Classen Immunotherapies v. Somaxon Pharmaceuticals

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Sonia S. Figueroa (SBN: 0269785) sfigueroa@dnlzito.com Joseph J. Zito j zito@dnlzito. com Emerson Briggs rbriggs@dnlzito.com DNL ZITO 355 South Grand Avenue, Suite 2450 Los Angeles, CA 90071 Tel: 213-400-3344 Fax: 213-402-2476
UNITED STATES DISTRICT COURT CENTRAL DISTRICT OF CALIFORNIA WESTERN DIVISION
CLASSEN IMMUNOTHERAPIES, INC. Plaintiff,
OV12-06643
Case No.: COMPLAINT FOR PATENT INFRINGEMENT JURY TRIAL DEMANDED
SOMAXON PHARMACEUTICALS Defendants.
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1 COMPLAINT FOR PATENT INFRINGEMENT
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Plaintiff, Classen Immunotherapies, Inc. ("Classen"), brings this Complaint for patent infringement against Defendant Somaxon Pharmaceuticals ("Defendant") as outlined below. JURISDICTION AND VENUE 1. 2. This is an action for patent infringement under Title 35 of the United States This Court has jurisdiction over patent claims under 28 U.S.C. 1331, Code "271 (a) (b) (c) and/or (f). 1338(a) providing for federal question jurisdiction of actions relating to patents and trademarks. 3. Defendant is engaged in making, using, offering for sale and selling, inducing to use and contributing to the infringing practicing of methods and systems covered under the claims of the patents in suit and engaged in the distribution of product which infringes the patents in suit. Venue is proper in this District pursuant to 28 U.S.C. ' 1391(b) (c) and (d) and ' 1400(a) and (b). Defendant Somaxon Pharmaceuticals, Inc. sells products in this District.
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THE PARTIES AND GENERAL ALLEGATIONS

Plaintiff, Classen Immunotherapies, Inc. is a corporation existing in the State of Maryland and is the owner of United States Letters Patent Numbers 7,653,639 and 7,984,069 (the "patents in suit"). 5. 6. Defendant Somaxon Pharmaceuticals, Inc. is a corporation existing under Defendant Somaxon manufactures and distributes a pharmaceutical the laws of the state of Delaware, with its headquarters in San Diego, California. product known as Silenor7 which it markets and sells nationwide. Defendant conducted drug interaction studies on its product Silenor7 and identified adverse event information which Somaxon commercialized and associated with its product Silenor7. 7. Somaxon determined that Silenor7 should not be taken with 3 hours of the consumption of a meal and protected, this development through proprietary filings,
including patent applications 20080058407; 20110166215; 20110077200; 20100105614; and U.S. Patent 7,915,307.
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THE PATENTS IN SUIT U.S. Patent No. 7,653,639 8. The 7,653,639 Classen patent in suit (the '"639 Patent") is entitled "COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY" and includes independent claim 1 as follows: 1. A method of generating and commercializing newly identified proprietary data about a proprietary or nonproprietary product or device, wherein the method comprises the steps of: accessing at least one adverse event data source that stores adverse event data associated with the product or device; analyzing the adverse event data to identify at least one new essential adverse event associated with the product or device, wherein the essential adverse event is one regulated by a regulatory agency requiring disclosure of the event in a package insert or data sheet accompanying the product or device; creating at least one essential adverse event information database, wherein the creating step comprises analyzing data from the at least one adverse event data source to identify at least one new proprietary characteristic or use for the product or device responsive to identification of the at least one new essential adverse event associated with the product or device, wherein the creating step further comprises storing essential adverse event information, and wherein the essential adverse event information includes the at least one proprietary new use or characteristic and data related thereto; and commercializing the proprietary essential adverse event information stored at the essential adverse event information database, which step comprises exclusive disclosure of the newly-identified proprietary essential adverse event information which, once identified, must then accompany the product or device. A copy of the '639 Patent is attached hereto as Exhibit "A"
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Somaxon has practiced a method by which Somaxon generated and
commercialized newly identified proprietary data about Silenor7. Somaxon accessed at least one adverse event data source; analyzed the adverse event data and identified a food related adverse event associated with Silenor7 regulated by the FDA requiring disclosure in a package insert or data sheet accompanying Silenor7. Somaxon identified a new proprietary dosing characteristic for Silenor7 and stored the adverse event information, including the new dosing characteristic and data related thereto; and commercialized the proprietary information by the requirement of disclosure of the information accompanying Silenor7. 10. Somaxon infringes one or more claims of the '639 patent, U.S. Patent No. 7,984,069 11. The 7,984,069 Classen patent in suit ("the '069 Patent) is entitled "COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY" and includes independent claim 1 as follows: 1. A method of commercializing at least one previously unreported proprietary method of using a product of manufacture or device, wherein the proprietary method of using the product or device is established according to the steps comprising: accessing one or more data sources, wherein at least one data source stores adverse event data associated with the product or device; analyzing and comparing the stored adverse event data, with at least one previously-known adverse event associated with the product or device; identifying at least one previously unreported essential adverse event associated with the product or device from the adverse event data, wherein an essential adverse event is one regulated by a regulatory agency requiring disclosure of the event in a package insert or data sheet accompanying the product or device, and then responsive to identifying of the previously unreported essential adverse event, identifying at least one previously unreported method of use for the product or device associated with said identified essential adverse event; documenting inventorship of the at least one previously unreported method of use for the product or device; and
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COMPLAINT FOR PATENT INFRINGEMENT
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creating a database of proprietary essential adverse event information, wherein the database stores at least one record related to at least one of: a patent, patent application, patent publication, or data contained in at least one patent, patent application or patent publication, wherein said at least one patent, patent application, patent publication, or data contained in at least one patent, patent application or patent publication, discloses and relates to at least one of the at least one previously unreported method of use and the at least one essential adverse event, and wherein the at least one previously unreported proprietary method of using a product or device consists of a use selected from the group consisting of a restricted use of said product or device, providing warning(s) about the essential adverse event, providing instruction( s) for avoiding an essential adverse event, and any combination thereof; and commercializing the at least one previously unreported proprietary method of using a product or device, the commercializing comprising exclusively disclosing the at least one previously unreported proprietary method of use and the associated at least one previously unreported essential adverse event information, which information, once identified, must then accompany the product or device, wherein commercializing means creating profit from the exclusive disclosure. A copy of the '069 Patent is attached hereto as Exhibit "B" 12. Somaxon has practiced a method of commercializing at least one
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previously unreported proprietary method of using Silenor7 by accessing data sources with adverse event data associated with Silenor7, analyzing and comparing the adverse event data to identify a food related, previously unreported essential adverse event associated with Silenor7 that is regulated by the FDA, and requires disclosure accompanying Silenor7. Somaxon developed a dosage requirement for Silenor7 and documented inventorship of the new dosage and established a patent application and publication containing disclosure related to said new restricted use dosage and said food related adverse event. Somaxon commercialized the new dosage requirement through the requirement for the information, to mandatorily accompany Silenor7. 13. Somaxon infringes one or more of the claims of the 7,984,069 patent.
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COUNT I PATENT INFRINGEMENT OF 7,653,639 14. Plaintiff re-alleges each and every allegation set forth above and incorporates them herein by reference. 15. Plaintiff owns and has at all times owned and has had standing to sue for infringement of United States Letters Patent 7,653,639 (the '639 patent) which was duly and legally issued on January 26, 2010. 16. The '639 patent properly names John B. Classen as inventor, is entitled COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY," and is properly assigned to Plaintiff Classen Immunotherapies, Inc. 17. Upon information and belief, Defendant Somaxon infringes and has infringed the '639 patent by commercializing information related to Silenor7 as described above. 18. Plaintiff is entitled to recover damages from Defendant Somaxon, including reasonable royalties, sustained as a result of Defendant's infringing acts. 19. Defendant has been aware of Plaintiff s rights in the patents in suit and of Plaintiffs' intent to enforce those rights. Defendant has, with full knowledge of those rights, willfully proceeded to infringe, in disregard of Plaintiff s rights. COUNT II PATENT INFRINGEMENT OF 7,984,069 20. Plaintiff re-alleges each and every allegation set forth above and
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incorporates them herein by reference. 21. Plaintiff owns and has at all times owned and has had standing to sue for infringement of United States Letters Patent 7,984,069 (the '069 patent), which was duly and legally issued on July 19, 2011.
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The '069 patent properly names John B. Classen as inventor, is entitled
"COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY," and is properly assigned to Plaintiff Classen Immunotherapies, Inc. 23. Upon information and belief, Defendant Somaxon infringes and has infringed the '069 patent by commercializing information related to Silenor7 as described above. 24. 25. Plaintiff is entitled to recover damages from Defendant Somaxon, Defendant has been aware of Plaintiff s rights in the patents in suit and of including reasonable royalties, sustained as a result of Defendant's infringing acts. Plaintiffs' intent to enforce those rights. Defendant has, with full knowledge of those rights, willfully proceeded to infringe, in disregard of Plaintiff s rights. PRAYER FOR RELIEF WHEREFORE, Plaintiff prays for judgment against Defendant as follows: 26. 27. 28. suit. 29. That judgment be entered for Plaintiff against Defendant, for Plaintiffs actual damages according to proof, and for any additional profits attributable to infringements of Plaintiffs' patent rights, in accordance with proof. 30. That judgment be entered for Plaintiff against Defendant, for reasonable royalties and/or other statutory damages based upon Defendant's acts of patent infringement and for their other violations of law. 31. That Defendant be required to account for all gains, profits, and advantages derived from their acts of infringement and for their other violations of law and that Plaintiff be awarded damages in the amount of such profits. 32. That the actions of Defendant be found willful.
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That Defendant be held to have infringed the 7,653,639 patent. That Defendant be held to have infringed the 7,984,069 patent. That Defendant acted with knowledge of one or more of the patents in
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33. 3 4 34, 35. That judgment he entered for Plaintiff and against Defendant, for trebling That the actions of Defendant be found exceptional. That Plaintiff be granted judgment against the Defendant for Plaintiffs That the Court grant such other, further, and different relief as the Court deems proper under the circumstances.
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of the damages awarded for patent infringement.
costs and attorney's fees.36.
DATED: August U2012
Respectfully submitted,
Sonia S, Figueroa, Escf. Attorneys for Plaintiff Classen Immunotherapies, Inc.
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DEMAND FOR JURY TRIAL Pursuant to Fed. R. Civ. P. 38(b), Plaintiff hereby demands a trial by jury on all issues raised by the complaint which are properly triable to a jury. DATED: August 1,2012 Respectfully submitted,
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Sonla S. Figueroa, Esq. Attorneys for Plaintiff Classen Immunotherapies, Inc.
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EXHIBIT A
U*rt)7653639B2
United States Patent

Classen
(54) COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY (75) Inventor: John Barthelow Classen, Baltimore, MD (US) (73) Assignee: Classen Immunotherapies, Inc.. Baltimore, MD (US) ( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b)by374days.
(io) Patent No.: US 7,653,639 B2 (45) Date of Patent: Jan. 26,2010

5,908,383 A 6/1999 Brynjestad 5,922,575 A * 7/1999 Cockerill et al. 5,970,463 A 10/1999 Cave et at.
435/91.2
(Continued) OTHER PUBLICATIONS

U.S. Appl. Np. 90/007.638, filed Jul. 22, 2005, Classen. Parent Supp IDS Jan. 30, 2006.
(21) Appl. No.: 11/355,763 (22) (65) Filed: May 15, 2006 Prior Publication Data US 2006/0195418 Al Aug. 31, 2006
(Continued) Primary ExaminerEtierme P LeRoux (74) Attorney, Agent, or FirmMontgomery. McCracken. Walker & Rhoads, LLP; Evelyn H. McConathy
(57)
ABSTRACT
Related U.S. Application Data (62) (60) (51) Division of application No. 10/081.705, filed on Feb. 21,2002. Provisional application No. 60/270,697, filed on Feb. 22,2001. The invention comprises systems, methods and a computerized data management device for creating and using data relating to a medical or non-medical product or device to enhance the safety of the product or device. A vast amount of data regarding adverse events associated with a particular product or device is analyzed to identify new essential adverse events associated with the product or device. At least one database of new essential adverse event information is created and utilized, and new characteristics of or uses for the product or device related to the new essential adverse event information are determined. Adverse event information is gathered for a large number of population sub-groups. 'Hie system may also be programmed to incorporate the information into intellectual property and contract documents. Manufacturers and/or distributors can include the proprietary information in consumer safety information, which accompanies the product or device, or which is provided to patients, users, consumers and the like, or in the case of certain medical products or devices, to prescribers of those products or devices. The system and methods also provide for commercializing the essential adverse event information. 65 Claims, 6 Drawing Sheets
Int.Cl. G06F 17/30 (2006.01) (52) U.S.CI 707/100 (58) Field of Classification Search 707/2, 707/102, 104.1. 100: 705/3 See application file for complete search history. (56) References Cited U.S. PATENT DOCUMENTS
5.181,394 5,642.731 5,723.283 5,728.385 5,737,539 A A A A A 1/1993 7/1997 3/1998 3/1998 4/1998 11/1998 12/1998 3/1999 Schea et al. Kehr C'lassen Classen Edelson et al. Schrier et at. Mayaud Beecham
. . . . 435/4 4">4/201 I
5,833,599 A
5,845,255 A 5,876,926 A
US 7,653,639 B2
Page 2 U.S. PATENT DOCUMENTS
6.000,828 6,097.995 6,112,182 6,219.674 6,323.242 6,421,650 6,465.463 6.584,472 6.696,924 6,784,177 6,867.236 2001/0001144 2002/0064765 2002/0082930 2002/0138305 2003/0004965
A 12/1999 Leet A * 8/2000 Tipton et al A 8/2000 Akers et al.
700/266
Bl 4/2001 Classen Bl 11/2001 Mueller Bl * 7/2002 Goetz et al Bl 10/2002 Cohn et al. B2 6/2003 Classen 2/2004 Socinski Bl B2 8/2004 Cohn et al, Bl * 3/2005 Breitner et al Al 5/2001 Kapp A l * 5/2002 Yoshihara et al Al 6/2002 Park Al 9/2002 Watanabe et al. Al 1/2003 Fanner etal.
705/3
5 14/570 434/276
OTHER PUBLICATIONS
U.S. Appl. No. 90/007.639, filed Jul. 22, 2005. Classen, Parent Supp IDS Jan. 30, 2006. Baker v. Secy ofDept. of Health and Human Servs.. No. 99-6 5 3V, 2003 WL 22416622. (Ct. Fed. Cl. Sep. 26. 2003) [Parent Supp IDS Jan. 30, 2006J. A. Bate, et al.. "A Bayesian neural network method for adverse drug reaction signal generation." EurJClui Pharmacol 54(4) (Jim. 1998) 315-321 [Parent Supp IDS Jan. 30, 2006], C. Baum, et al.. "The Spontaneous Reporting System in the United States," Pharmacoepidemiology, 2nd ed. New York. John Wiley & Sons, .1994, 125-137[Parent Supp IDS Jan. 30, 2006]. D. Bradbury, "A Bitter Pill to Swallow." Computing, 34-35, Feb. 9, 1995[Parent Supp IDS Jan. 30, 2006], D. Classen et al., "Adverse Drug Events in Hospitalized Patients," 277 JAMA. 301-306 (1997) [Parent Supp IDS Jan. 30, 2006]. D. Classen et al., "Computerized Surveillance of Adverse Drug Events in Hospital Patients," 266 JAMA 2847-2851 (1991) [Parent Supp IDS Jan. 30, 2006]. D. Classen et al.. "Description of a Computerized Adverse Drug Event Monitor Using a Hospital Information System," 27 Hosp. Pharm. 774, 776-779, 783 (1992) [Parent Supp IDS Jan. 30, 2006]. D. Classen S. Pestotnik, "The Computer-Based Patient Record," Hospital Epidemiology and Infection Control. 141-154 (2nd Ed., New York: Lippincott Williams & Williams 1999) [Parent Supp IDS Jan. 30, 2006]. R. Evans et al., "A Computer-Assisted Management Program for Antibiotics and Other Antiinfective Agents." 338 The New England Journal of Medicine, 232-238 (1998) [Parent Supp IDS Jan. 30. 2006]. R. Evans et al., "Development of Computerized Adverse Drag Event Monitor." 15th Annual Svmposium on Compute!' Applications in Medical Care, 23-27 (1992) [Parent Supp IDS Jan. 30, 2006]. R. Evans et al., "Evaluation of a Computer-Assisted Antibiotic-Dose Monitor," W,Annals. Pharm., 1026-1031 (1999) (Parent Supp IDS Jan. 30, 2006]. R. Evans et al., "Preventing Adverse Drug Events in Hospitalized Patients," 28 Ann. Pharm. 523-527 (1994) [Parent Supp IDS Jan. 30, 2006]. R. Evans et al., "Prevention of Adverse Drug Events through Computerized Surveillance," 16th Animal Symposium of Computer Applications in Medical Care, 437-441 (1993) [Parent Supp IDS Jan. 30, 2006].
R. Evans et al.. "Using a Hospital Information System to Assess the Effects of Adverse Dmg Events," Se\>enteenth Annual Symposium on Computer Applications in Medical Care. 161-165 (1994) [Parent Supp IDS Jan. 30.2006]. G. Faich, US Adverse Drug Reaction Surveillance 1989-1994, Pliarmacoepidemiolog}' and Drug Safety 5:393-398 (1996) [Parent Supp IDS Jan. 30.2006]. Federal Register, vol. 58. No. 105. (Jun. 3, 1993) (Parent Supp IDS Jan. 30, 2006]. Finney, D. J. Systematic Signalling of Adverse Reactions to Drugs, Methods of Information in Medicine, 13 (1974) l-10[Parent Supp IDS Jan. 30, 2006]. International Reporting of Adverse Drug Reactions. Final Report of CIOMS Working Group, 1990[Parent Supp IDS Jan. 30, 2006]. Jim Kling, "From hypertension to angina to Viagra," Modern Dmg Discovery 1(2) (1998), available at http://pubs.acs.org/hotartcl/mdd/ 98/novdec/viagra.htm[Parent Supp IDS Jan. 30. 2006]. M, Lindqulst et al.. "From Association to Alert A Revised Approach to International Signal Analysis," Pharmacoepidemiology and Drug Safety 8:S15-S25 (Apr. 1999) [Parent Supp IDS Jan. 30, 2006]. David J. Morrow, "New Profit s in Old Bottles," N. Y. Times. Mar. 19, 1999[Parent Supp IDS Jan. 30, 2006]. C.A. Naranjo et al., "A method for estimating the probability of adverse drug reactions," 30 Clin. Pharmacol Ther. (2):239-45 (1981) [Parent Supp IDS Jan. 30, 2006]. V. Pinkston & E. J. Swain. "Management of Adverse Drug Reaction and Adverse Event Data through Collection, Storage and Retrieval," Detection of New A dverse Drug Reactions. 281-296 (Apr. 1998) (4th Ed., London: Macmillan Reference Ltd.) [Parent Supp IDS Jan. 30, 2006]. "Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)." MEDWATCH Continuing Education Article (1998) [Parent Supp IDS Jan. 30. 2006]. Statement of Susan S. Ellenberg before the U.S. House of Representatives, available at www.fda.gov/ola/l999/anthrax.hrml (Jul. 21, 1999) [Parent Supp IDS Jan. 30, 2006]. A. Szarfman, "Discussion: A Report on the Activities of the Adverse Events Working Groups: Focus on Improving the Detection of Rare but Serious Events," 1999 Proceedings of the Biopharmaceutical Section, American Statistical Association. Alexandria (VA), American Statistical Association, 12-13 (1999)(Szarfman/abstract) [Parent Supp IDS Jan. 30, 2006]. A. Szarfman, "New Methods for Signal Detection," 15"' International Conference on Pharmacoepidemiology, Boston, Mass., Aug. 28, 1999 (Szarfman/ppt) [Parent Supp IDS Jan. 30, 2006]. Vaccine Safety Forum, Summaries of Two Workshops, Washington, DC (National Academy Press 1997) [Parent Supp IDS Jan. 30,2006]. Classen. J.B., "New Patents for Older Products Through Patenting Product Safety Information," www.vaccines.net, (2005). [Filed in Parent Supp IDS on Jul. 28, 2005]. Fiala, T.C. and Wright, .I.E., "Drug Labeling Patents: A New Line of Defense for Protecting Old Drugs?," The Intellectual Property Strategist, LJN (2005). [Filed in Parent Supp IDS on Jul. 28, 2005]. Bradbury, D., A Bitter Pill to Swallow. Computing 34-35 (1995). [Filed in Parent IDS Sep. 23, 2004]. R. T. Chen, et al. Vaccine Safety Datalink Project: A New Tool for Imroving Vaccine Safety Monitoring in the United States, Pediatrics, 99:[6] 765-773, 1997. [File in Parent IDS Sep. 23, 2004]. DeStefano, et al. Timing of Hepatitis B Vaccination and Risk of Insulin Dependent Diabetes Mellites. Pharma and Drug Safety 6[2] (1997). [File in Parent IDS Sep. 23, 2004],
* cited by examiner
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ESSENTIAL ADVERSE EVENT DATABASE
SHADOW STORAGE DEVICE
PROCESSOR
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U.S. Patent
Jan. 26,2010
Sheet 4 of 6
US 7,653,639 B2
START
ACCESS ADVERSE EVENT DATA SOURCE
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ANALYZE ADVERSE EVENT DATA
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CREATE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE
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COMMERCIALIZE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE
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END
FIG. 4
U.S. Patent
Jan. 26,2010
Sheet 5 of 6
US 7,653,639 B2
START SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12
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SERVER 14,114 OR 214 ANALYZES ADVERSE EVENT DATA FOR ESSENTIAL ADVERSE EVENT DATA
SERVER 14,114 OR 214 CREATE PROPRIETARY ESSENTIAL ADVERSE EVENT INFORMATION DATABASE
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SERVER 14,114 OR 214 GENERATES PROPRIETARY INFORMATION THAT CAN BE INCORPORATED INTO INTELLECTUAL PROPERTY, SALE AND/OR LICENSING DOCUMENTS
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SERVER 14,114 OR 214 GENERATES PRINTED WARNING INFORMATION DERIVED FROM ADVERSE EVENT INFORMATION DATABASE
OWNER OF PROPRIETARY ESSENTIAL ADVERSE EVENT INFORMATION DATABASE SELLS OR LICENSES PROPRIETARY INFORMATION TO A THIRD PARTY
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OWNER OF PROPRIETARY INFORMATION OR THIRD PARTY GENERATES PRINTED PRODUCT WARNING INFORMATION DERIVED FROM ADVERSE INFORMATION DATABASE
( END
FIG. 5
U.S. Patent
Jan. 26,2010 START
Sheet 6 of 6
US 7,653,639 B2
SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12
26'
SERVER 14,114 OR 214 ANALYZES
ADVERSE EVENT DATA FOR ESSENTIAL ADVERSE EVENT DATA

30'
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31"
32"-
SERVER 14,114 OR 214 GENERATES PROPRIETARY INFORMATION THAT CAN BE INCORPORATED INTO INTELLECTUAL PROPERTY AND/OR SALE DOCUMENTS
OWNER OF PROPRIETARY ESSENTIAL ADVERSE EVENT INFORMATION DATABASE MANUFACTURES AND SELLS PRODUCTS INCORPORATING THE PROPRIETARY INFORMATION
OWNER-MANUFACTURER OF PROPRIETARY INFORMATION GENERATES PRINTED PRODUCT WARNING INFORMATION DERIVED FROM ADVERSE INFORMATION DATABASE END )
FIG. 6
US 7,653,639 B2
COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY REFERENCE TO RELATED APPLICATIONS
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This application is a divisional of U.S. Utility application Ser. No. 10/081,705 filed Feb. 21,2002 and claims the benefit ofU.S. Provisional Application No. 60/270,697 filedFeb. 22. 2001, which filing dates are claimed herein, and the contents of which are herein incorporated by reference. 10 FIELD OF THE INVENTION The present invention involves the fields of products, including drugs, medicaments, biologicals, devices, food 15 additives, chemicals and other products or devices, that may have essential adverse events, as well as computer databases for generating, storing, analyzing and processing information related thereto.
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BACKGROUND OF THE INVENTION Computers, systems and methods for screening databases to determine new adverse events and to develop proprietary new uses and proprietary kits containing warnings pertaining 25 to the new adverse event information have been described in U.S. Pat. No. 6,219,674 and U.S. patent application Ser. No. 09/804,289. However, the systems and methods described in the '674 patent were less than ideal because not all adverse event information is commercially valuable, hi order for 30 adverse event information to be valuable it must be patentable (i.e. proprietary) by being novel, non obvious and having utility. Likewise, the systems and methods described in the '289 patent were less than ideal because, even if the adverse event data is patentable, it is not commercially valuable 35 unless it is essential, that is, the information must be such that all manulacttirers would need to include it with the sale of the corresponding product. Otherwise, manufacturers would continue to sell their products without the subject information. Conversely, if one were to simply patent all new uses for 40 the product, drug, and the like, considerable time and money would be consumed, but there would by a low probability for commercial or financial return on the whole. The government has carefully established codes and rules under which, for example in the medical field, manufacturers 45 and/or distributors are required to notify or warn the public of known adverse events which could occur when certain products, including drugs, medicaments and the like, are ingested or used by human or veterinary patients. Regulations also apply to chemical products, including food supplements, so which may be absorbed, ingested or inhaled. Similar notice or warnings must be attached to devices, particularly to medical devices. Moreover, if the warnings are not present, the product or device not only must be immediately removed from use by, and availability to, the public, but also significant fines and 55 penalties can be levied against the manufacturer and/or distributor of the product or device for its failure to provide adequate notice and warning to the public. In addition, because such manufacture and/or distribution was permitted without the required notice or warning, the manufacture and/ 60 or distribution was practiced in violation of the law. As a result, those manufacturers and/or distributors risk criminal and/or civil liability to anyone adversely affected by the product or device during the time when it was on die market. The government has failed to establish mechanisms by 65 which products and devices are adequately screened for safety, i.e.. for the possibility of essential adverse events
which could affect the safety of the patient using the product or device. This is particularly true for medical products and devices. The screening that is conducted by manufacturers and/or distributors of such products and devices is typically small in scale and incomplete for all possible adverse events. Consequently, until the present invention, mere has been a need in the art for reliable screening methods to eliminate or minimize the possibility of an essential adverse event that could affect a patient or consumer using a product or device, so that the consumer can trust that the product or device is "safe." In addition, the prior art has failed to contemplate business methods which involve detecting essential adverse events relating to a product or device, and then offering the refined proprietary data from such screens to the manufacturers and/ or distributors of the product or device. Once the existence of such essential adverse data is known to the manufacturer and/or distributor, they are obligated to inform the public of the potential adverse event, or they must remove the product or device from the market. Because manufacturers are currently producing and distributing products and devices without restrictions on their use, they are available for use in screens to develop essential adverse event data, which when refined, would become proprietary. Thus, there also exists a substantial market for such refined, proprietary, essential adverse event data, and for the methods, systems and devices by which it is obtained, which would (1) meet the need in the art for steps which would enhance public sa fety with regard to the use of products and devices, and (2) offer to manufacturers and/or distributors of product and/or devices a way to (a) significantly improve public safety, (b) permit their products and devices to remain on the market, and (c) reduce their risk of liability for the occurrence of an adverse event with the use of their products or devices. SUMMARY OF THE INVENTION The current invention permits not only ways of screening for new, previously unrecognized adverse events associated with the use of a product or device, but also a method, system and device for determining which new adverse events and new uses are "essential." The method, system and device permit a technician or computerized system to detect new essential adverse events and identify new useful characteristics or uses for a product or device, and commercialize the essential adverse data information. In some instances a manufacture or distributor is given the option of adding notifications or warnings that a product or device is associated with an essential adverse event, or they can perform safety studies to show the product is safe in light of the newly recognized, essential adverse event (essential methods of screening a product for safety). Thus, the invention relates to data processing methods and system for developing product safety information to be included in the package information which would accompany a commercial product or device. The current methods and system further provide for the detection and development of methods of screening a product or device for consumer safety. In preferred embodiments, the data processing system comprises: at least one adverse event database for storing adverse event data associated with a product or device; a processor for accessing and analyzing the data to assist in identifying new essential adverse events associated with the product or device and to assist in identifying at least one new useful characteristic of, or use for, the product or device responsive to identification of at least one new essential adverse event associated with the product or device; an
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adverse event information storage device for storing the new The invention also provides a kit containing the product or essential adverse event data identified by the processor; a device, and labeling notifying the user of at least one new computer for requesting and receiving adverse event iuforessential adverse eventfortheproductordevice. Additionally mation from the processor; and a user interface for interfacing provided are methods comprising using the kit in accordance with the processor and the computer. 5 with a new characteristic of. or use for, the product or device. The present invention is further embodied by a method for The invention is especially useful in detecting and preventcreating and using data associated with a product or device ing essential adverse events related to. or caused by. medical comprising: accessing at least one adverse event data source products including drags, medicaments and biologicals, and that stores adverse event data associated with a product or medical devices. device; analyzing the adverse event data to identify new 10 Other objects, features and advantages of the present essential adverse events associated with the product or invention will be clear to those skilled in one or more of the device; analyzing data from the data source to identify at least relevant arts, based on the teachings and guidance presented one new useful characteristic or use for the product or device herein, responsive to identification of at least one new essential adverse event: creating at least one essential adverse event is DESCRIPTION OF THE DRAWINGS information database, wherein the adverse event information includes at least one new characteristic or use; and commerT116 foregoing summary, as well as the following detailed cializing essential adverse event data stored in the essential description of the invention, will be better understood when adverse event information database. read ia conjunction with the appended drawings. For the The invention is also embodied by a method of establishing 20 PurPose of '"^rating the invention, there are shown in the at least one new use for a product or device comprising: drawings certain embodiment s) which are presently precomparing adverse event data associated with a product or ferred Ir shoulf be understood, however, that the invention is device with previously known adverse event data associated not hmlted to ^ Preclse arrangements and instrumentalities withtheproductordevice;observingatleastonenewadverse siowii. , . . , , ,. event associated with the product or device: determining 25 FIG' J ls * schematlc Vlew of a faret embodiment ol a whether the new adverse event associated with the product or system according to the present invention, device is an essential adverse event: and identifying at least H& 2 ls a schematic view of a further embodiment oi a one new useful characteristic of. or use for. the product or svstem ***" to me Present invention, device responsive to the determination that the at least one FIG ' 3 is a schematic view ol a further embodiment of a new adverse event associated with the product or device is an 3" s>'stem ^cording to the present invention, new essential adverse event. FIG - 4 ls a flow chart '""stratmg ê method according to , , , . . . , . . . . ,. , , , the present invention. In addition, the invention is embodied by a computer for ,,,, ,. ,- , F , -r r .. r ., .. , , , . . ,, } .. t . MG. 5 is a first preferred specific application of die method managing product or device related data comprising: at least , .>.., ,.,j- pip 4 one adverse event database .storing adverse,event data asso- 3s FIG. 6 is a further preferred specific * r-T/--- t t. ^\ j -c r application of the rû , .. , , e . , ciated with a product or device; a processor for accessing and - method nted in ^1G 4 analyzing the data to assist m identifying new essential ' adverse events associated with the product or device and to DETAILED DESCRIPTION OF THE INVENTION assist in identifying at least one new useful characteristic of, oruse for, the product or device responsive to identification of -n T r o r. c xr nniAtn ., * ., , t , .. . 40 Tlie inventor s pnor invention, U.S. Pat. Ser. No. 09/449. at least one new essential adverse event associated with the ng . ^ ^ y s p,it NQ g 2]9 ^^^ & product or device; and an essential adverse event information uter tera an(1method for deriving llew uses based on storage device for storing essentia adverse event data mclud^ ^^ ^^ ^.^ ^ findsb lication in the ing the at least one new essential adverse event associated t ^^ Howev.gr ^ mrf^h. ^bM system with the product or device, and the at least one new charac, ,, , r,, ,. ' , ,. "., , - _ . .,. . . ;. ,, , ' . . . , . , , , , . 45 and method of the invention provides for the further pun ficatenstic oi, or use for, the product or device identified by the " . ,. . r , . . ,. .. , , ,, , ' , , , ,. , ., tiou or refinement of adverse event information to develop processor. Moreover, the method and system further provide . . ,. , . , , ,r . . . . . . . , J . .. F . new proprietary uses for a product, such as a drug, or tor a for commercializing the essential adverse event information. , . , " , ., , , , . 0 device. I he system and methods provide detecting essenFurther, the invention is embodied by methods and systems tia],.adverse evellt information or "essential" new uses based by which the detected information is formatted and compiled J(| onmeadverseevents Q[ "essentia]"new methods of screening into contract documents, which are then used in licensing the a produc( f or safety essential adverse event information to manufecturers and/or Referring to the drawings wherein like references indicate distributors, who can then include the essential adverse event ]ike elemenls throughout the several views, there is shown in infomiationintheirproductinformation, whichisprovidedto ,,IG j a first system , Q constructecl iu accordance with the consumers or prescnbers of the product or device. Moreover, ^ invention. System 10 inchldes at least one adverse such contract documents can be used to license the essential evem database 12, at least one essential adverse event dataadverse event information to potential competitors of the base iy and fl server 14 Depending upon the source, the manufacturer and/or distributor. adverse eyent database(s) 12 may be accessed by server 14 The embodied invention also provides marketing and free of charge or for a fee. Essential adverse event database packaging methods, in which the use of the subject product or 60 12', preferably contains large amounts of data regarding a device is restricted by a licensing agreement or contract. particular "essential" medical or non-medical product or which would exclude using the product or device for the device. detection and patenting of essential new adverse event inforThe term "medical" as used herein shall be construed to mation. mean drugs, vaccines, non-vaccine biologicals. medical The invention also pertains to any product or device created 65 devices and any other medically-related goods and therapies, using the essential adverse event data of the method, system Dmgs and biologicals as the terms are herein used within the or device of the present invention; as well as uses therefore. term "medical product," are intended to encompass any
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known, or as yet unknown, class of drug, medication or biological therapeutic (including inhibitors, preventers, enhancers activators, stimulants, catalysts, promoters, regulators, and the like). These can be categorized by their effects oil an organ system, such as cardiac, respiratory, renal etc. Dnigs 5 and biologicals are also classified by their chemical composition, e.g., sulfa drugs, penicillin derivatives, vaccines, immune stimulants, antibiotics, etc. In addition, they can be classified according to their activity, e.g.. diuretic, antibiotic, beta-blocker, etc. 10 Medical devices can be similarly classified by those of ordinary skill in the art, e.g.. medical devices may be grouped as defibrillators, EKG machines, infusion pumps, CT machines, etc. To further assist in the categorization process, those skilled in the art may consult medical science resources ] 5 such as medical libraries or online authorities such as ME 13LINE and the like to locate articles, books or other printed or electronic publications on the subject of interest such as the non-limiting example of Goodman and Oilman's "The Pharmacological Basis of Therapeutics." 20 "Non-medical product or device" shall be construed to mean any non-medically-related product or device that may cause harm to a consumer including, without limitation, foods, food additives, beverages, vitamins, alcohol, tobacco, cosmetics, mechanical devices and children's toys, personal and household cleaning products, and other chemicals such as paints and related coatings, insecticides, herbicides and industrial chemicals. Because of the large volume of data that they contain, 30 preferred adverse event databases may include those of insurance companies, managed care organizations, pharmaceutical and medical device manufacturers and/or distributors, public health departments, hospitals and the like. Typically, each adverse event recorded in such databases links the 35 adverse event with demographic information such as but not limited to, the age, sex and race and, frequently, one or more physical condition factors of the individual that experienced the essential adverse event. The result is that adverse event database 12 may contain thousands or even millions of items 4Q of data. Such vast repositories of information enable the data to be analyzed to generate statistically relevant and reliable information relating to age, gender, racial, physical condition or other subgroup. The essential adverse event database 12' is a refinement of the adverse event data procured from the 45 adverse event database 12, based upon selection of adverse data that is "essential" as defined below. Server 14 preferably includes a shadow storage device 16, a processor 18. a user interface 20 and an essential adverse event information storage device 22. Shadow storage device 50 16 gathers and stores essential adverse event data received from the adverse event database(s) 12. Processor 18 comprises any computer processing means suitable for executing the operations of the present method as described hereinafter. User interface 20 includes any suitable input/output (I/O) 55 equipment. Essential adverse event information storage device 22 stores adverse event information that is generated by processor 18 responsive to analysis of the essential adverse event data stored in shadow storage device 16. The shadow and essential adverse event information storage devices 16, 60 22 may be any memory devices capable of storing large amounts of information. Lastly, system 10 includes a user computer 24 for interfacing with user interface 20. User computer 24 is preferably any commercially available personal computer, workstation or the like which can exchange infor- 65 mation with user interface 20 in the manner well known in the art. If the event data relating to a product or device is both essential and desired, the essential adverse event data in adverse event database 12' can be collected using the ICD and other disease codes 011 admission, discharge, pharmaceutical sales, physician visit records or other known sources. The system of the present invention also accommodates and processes animal safety test data such as animal toxicity data. Through operation of system 10 and the other systems described herein, the data extracted from the adverse event database 12 is analyzed by suitable programming of processor 18 to produce useful essential adverse event information that collected into essential adverse event database 12' and is storable in essential adverse event information storage device 22. For example, the adverse event database stores information on frequency of essential adverse events, such as but not limited to, death, illness, hospitalization, office visits, disability, missed work, medical costs, abnormal lab results and surgeries in individuals receiving the product or device in question, and this information can be compared to the observed adverse event rate in the same persons before receiving the medical product or in persons of similar characteristics (i.e.. a control group). The analysis is performed on different exposure rates including, but not limited to the amount, duration and timing of exposure to the product or device. The "adverse events" refer to, for example, damage or alteration to any organ system, including the non limiting examples of cardiac, respiratory, gastrointestinal, endocrine, muscular, skeletal, liver, renal, spleen, neurological, skin, blood, immune, and bone marrow. These adverse events further include the development of new diseases, including the non limiting examples of seizures, cancers, heart disease, arrhythmia, autoimmune disease, and allergy. Moreover, failure of a person to respond beneficially to a drug can be considered an adverse event. Preferably, the adverse event (or new use) is one other than one related to dosing including the timing of dosing (or optimizing dosing). The database to be screened for new adverse events comprises adverse event information relating to the use of products in or devices on humans or animals. While human data is more valuable for determining new uses in humans, it is possible that new adverse events detected in animals can be used to develop new product characteristics or uses in humans. An example is detection of birth delects, or drug interactions in animals, which preferably leads to new uses comprising restricted use in pregnant humans or humans taking certain drugs. Databases of adverse event information can be created by screening animal models of specific human diseases and cell culture models of human diseases for the potential newadverse events. In this situation an animal model of human disease is exposed to the product and the frequency or severity of the disease is recorded compared to a control group. Ideally the product is exposed to as many different animal models of human diseases as possible or feasible. In a similar manner a culture of cells can be exposed to a product in many instances. This is easily accomplished if the product is a drug, chemical, or emits radiation. The cells may be normal cells, premalignant or malignant cells. One can compare the outcome of product on the cells to that of the effect on control cells. Endpoints include the non limiting examples of cell death, cell mutation and cell division. Ideally the product or device is exposed to as many different animal models of human diseases as possible or economically feasible. One can use the data from the database to compare to previously known adverse events to detennine new adverse
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event information. The order by which one checks for an adverse event can vary, and any order that is suitable is acceptable. For example, one can hypothesize that a product causes one or more adverse events. One can then analyze the data to see if the product causes an adverse event, and then determine if the adverse event is new. Alternatively, one can hypothesize that a product causes an adverse event and then check databases to see if it has been reported that the product is associated with an adverse event. If the association has not been reported, then one can screen raw adverse event data/databases to see if the product is associated with the adverse event. If data does not exist to test the hypothesis using available rawadverse event data, then new data can be generated in the form of a study. In most cases, this would involve animal toxicity studies since performing prospective studies in humans to prove adverse events is generally unethical. By "raw data." as used herein, means data before it is processed and analyzed. For example, the raw efficacy or adverse event data relating to a drug would include all of the collected data, which is linked to individuals who used the drug, or in some instances for a product such as tobacco, for those exposed to the product. This raw data comprises, e.g., the individual's weight, height, race, lab results, medical conditions and length of use or exposure to a product or device. By contrast, "processed data" means analyzed data that has been categorized or qualified to meet the requirements or standards of a particular situation. In a preferred embodiment, one searches existing adverse event databases for adverse events, then determines if associations discovered are new. An additional study can be performed to verify the finding. In another preferred embodiment, one can hypothesize about certain adverse events, and then determine if they have been reported. If they have not, then raw adverse event data would be analyzed to determine if there is an association. Additional adverse event information may also be derived from subgroup analysis. Subgroup analysis is performed to determine specific high risk groups who may be at increased risk of having an essential adverse event. Subgroups include persons with similar characteristics, such as but not limited to, sex. age, race, weight, height, percent body fat, genetic characteristics, pregnancy status, allergies, additional medical problems, use of additional medical products (including devices), past medical liistory, family history, social history, occupation, use of alcohol, tobacco, recreational drugs, and history of abnormal lab tests such as EKG, chest x-ray, liver function test and kidney function test. Similarly, subgroups are intended to include without limitation high risk associated groups such as high or low temperatures, chemicals, surfaces, pressures, electricity and sparks; or contact of the product or device with one of the group consisting of skin, eyes, ears, respiratory surfaces, gastrointestinal surfaces and mucous membranes of the consumer, or to a subpopulalion group selected from the group consisting of children, pregnant women, consumers with specific allergies or medical conditions and animals. Preferably this demographic data, i.e.. sub group information, is available through history and physical, where no additional laboratory test is needed for a new use. The subgroup analysis can include groups that were not represented or were under-represented in safety studies that were required for marketing appawal or were done around the time of market introduction. For example, a drug may be approved for use in persons over the age of 18. However, people under 18 may also receive the drug. In such case, packaging for the drug may not include sufficient warnings for persons under 18, in general, and subgroups of persons under 18. in particular, that are at greater risk of essential adverse events linked to usage of the product or device. Studies, as described above and in other sections of this document, however do not prove a product or device causes an adverse event, only that the adverse event and the product or device are associated. In some instances there may be a direct link. For example, wealth or standard ofliving is associated with certain adverse events. Money does not cause the adverse events, but it allows wealthy individuals to buy products that cause a specific adverse event. If an epidemiology study does show an association between an adverse event and a product or device, then there is a risk that the associated product or device caused the adverse event. This risk exists even if the association is not statistically significant. However the risk is greater if a statistically significant association exists. Since some of the associations are true causal relations, knowledge that a risk exists has utility since one can avoid the risk when one knows it exists. Ideally, systems according to the invention track large numbers of variables to locate groups at high risk of essential adverse events. As a non-limiting example, the systems are configured to track people taking multiple different drugs to determine whether a toxic adverse event occurs in people taking all of the drugs at once. The systems utilize statistical formulae to identify groups at high or low risk of essential adverse events. Preferably the database of adverse events associated with a product contains multiple different adverse events and is not limited to a single type, such as diabetes, birth defects, or the like. The systems according to the invention also optionally collect mid analyze efficacy data. The benefit of the product or device in certain subgroups can thus be measured by observing the frequency of the intended benefit (e.g.. decreased death, stroke, kidney failure, and so on). Benefits also include reductions in costs where the costs may include, without limitation, costs of the product or device, expenses and lost productivity. By using the data from the risks and benefits, one can determine the risk/benefit for persons in any particular subgroup. This information can be highly stratified to enable, in addition to previously known uses. new. different or more precise uses for a product or device. For example, a dose of a dnig or biologic, the frequency or manner of use of a device, or the setting of a device such as a pacemaker may be precisely prescribed to accommodate the individual needs of particular subgroups. Targeted searches can be performed and their data analy/ed by the systems of the present invention. For example, if it is discovered from one adverse event database 12 that persons receiving a medical product are at increased risk of dying of liver failure at a certain dose of medication or when taking the drug in combination with other drugs, then one can verify the findings using a second adverse event database 12. Adverse event data from either adverse event database can also be confirmed in animals or by prospective clinical trials in humans. Targeted searches can also be done after case reports of adverse reactions, discovery of adverse events in animals, adverse events discovered in similar products and possible adverse found in small studies. Consistent with the invention, any number or variety of proprietary databases are storable on essential adverse event information storage device 22. For instance, a first proprietary database created containing information about a particular product's or device's adverse events and, optionally, risk benefits and cost benefits of the product or device. The data from that database is crossed, linked or compared with a database of knowledge already accumulated on the product or
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device that may also be stored on essential adverse event information storage device 22. Sources of prior known essential adverse events can include package inserts, the Physician's Desk Reference, The Merck Manual, data from regulatory agencies such as the FDA, and published literature found on databases such as MEDLINE. In the future it is contemplated that databases of patents and patent applications will also contain known adverse events. Likewise, the databases can comprise commercial or sales data. New findings on essential adverse reactions can thus be determined through appropriate comparison and/or interpretation of the databases. The newly derived knowledge can include, without limitation, catalogs of new adverse events, specific frequency of adverse events, drug interactions and side effects in specific subgroups such as those mentioned above. For instance, a new essential adverse event can mean a newly discovered adverse reaction such as the discovery of an increased rate of seizures associated with a drug, improved information such as more accurate calculation of the rates of seizures in a group or subgroup, or the discovery of an increased rate of seizures in patients taking the drug along with one or more additional drugs. FIG. 2 represents a further preferred embodiment of a system according to the invention identified by reference numeral 110. System 110 is constructed and functions substantially similarly to system 10 of FIG. 1 with the exception being that the shadow storage device 16 and essential adverse event information storage device 22 of system 10 are integrated into a single shadow storage device and essential adverse event information storage device 16, 22 on server 114. FIG. 3 represents a further preferred embodiment of a system according to the invention identified by reference numeral 210. System 110 also is constructed and functions substantially similarly to system 10 of FIG. 1. However. unlike systems 10 and 110, system 210 draws its essential adverse event data from an internal rather than an external source; that is, server 214 of system 210 directly supports essential adverse event database(s) 12'. System 210 graphically depicts a situation wherein a holder of a substantial body of adverse event data itself analyzes such data using processor 18 and creates one or more adverse event information databases that are stored on essential adverse event information storage device 22. Exemplary users of system 210 may include, for example, insurance companies, managed care organizations, pharmaceutical and medical device manufacturers and/or distributors, public health departments, hospitals and the like. Although illustrated as separated devices, it is also contemplated that essential adverse event dauibase(s) 12' and essential adverse event information storage device 22 may be integrated into a single storage device. FIG. 4 is a flow-chart that embodies the essential method steps of the present invention that are executed by each of systems 10, 110 and 210. At step 26, the adverse event database(s) 12 are accessed by server 10, 110 or 210 (at a fee or free of charge) to obtain desired adverse event data therefrom. In systems 10 and 110, the adverse event database(s) 12 are external to the servers 14 and 114. Hence, servers 14 and 114 desirably store the data received from databases 12 in shadowstorage devices 16. Server 214, by contrast, accesses its internal adverse event database(s) 12 for the desired data. The desired adverse event data having been accessed, the processor 18 of systems 10, 110 and 210 then analyzes the data, as described above, to identify previously known and new essential adverse events, as indicated at step 28. At step 30, the processor 18 further processes the analyzed adverse event data to create useful proprietary essential adverse event information, such as any of the kinds mentioned above. More particularly, in creating the proprietary adverse event information database at step 30, or more preferably an essential adverse event information database, at step 30' (not shown), processor 18 preferably possesses logic whereby it categorizes the newly-discovered essential adverse event(s) associated with a particular product or device that are identified at step 28 and also identifies at least one new use for the product or device responsive to the identification of at least one new essential adverse event(s) associated with the product or device. The processor 18 then stores the essential adverse event information as one or more databases in essential adverse event information storage device 22. According to presently preferred embodiments of the invention, the data retrieved from adverse event database(s) 12 is processed and analyzed by a centralized processor 18 on server 14. 114 or 214 and the analyzed data is stored at an essential adverse event information storage device also supported by server 14,114 or 21.4. Alternatively, the proprietors of servers 14,114or214 license proprietary software to users of user computers 24 that perform the functions of processor 18. Such software is loaded onto the user computers 24 to execute the adverse event data analyzing and other processing functions of processor 18 described above and the generated useful adverse event information may be stored at the user computers 24. hi any case, servers 14, 114 and 214 can be directly connected by a user interface 24 such as but not limited to a modem. It will be understood that the servers 14.114 and 214 may also be indirectly connected to user computers 24 via one or more other servers, a central computer or other system designed to link computers or other processing machines. Ideally, the information is transferred digitally between servers 14, 114 and 214 and user computers 24. Alternatively, however, it is transmitted in analog form by a modem along standard telephone lines. It is further understood that the information can also be transferred by disk, printed and then scanned in or. alternatively, manually re-keyed. Preferably, the user computers 24 and their associated printers (not illustrated) are sufficiently sophisticated to organize and print all information generated by the systems 10, 110 and 210 in virtually any desired format and on essentially any desired printable medium that is printed by the printers. However, certain product labels and package inserts that incorporate the information can be manually type faced using typesetting or other conventional printing techniques. The system also formats the data for submission to regulatory agencies such as the FDA.
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The proprietary information that is generated by the systems of the present invention is superior in many ways to the limited, and generally static, adverse event data and databases 55 heretofore known in the art. In respect to medical products in particular, the volume of data and the degree to which the data may be stratified and studied, the systems according to the invention far exceed the capabilities of FDA-required premarketing studies for medical products. To illustrate, a typical 60 FDA pre-marketing study generally involves study populations of less than about 5000 and normally less than about 2000 participants. In contrast, the adverse event data that is amassed and analyzed pursuant to the invention contains information on far larger numbers of people receiving the 65 medical product. Representative populations studied using the present system in virtually all practical medical product scenarios comprises at least 5000 and is analyzed in any
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desired increment such as, for example, 5,000; 10,000; 50,000; 100.000; 200,000; 1 million or more. Hie systems of the present invention will additionally provide a better appreciation of delayed or latent essential adverse events caused by products or devices long after ini- 5 tiation of treatment or after treatment has been discontinued. Using the present systems, post-exposure follow-up of a product or device is analyzed in any desired increments of time. For instance, selected post-exposure study periods maybe as brief as a few minutes or hours to considerably lengthier l periods, such as 1 day, 2 days, 7 days, 10 days, 30 days. 90 days, 180 days, 1 year. 3 years, 5 years. 10 years or more. Risk/benefit analyses may also be readily performed using the methods and systems described herein. Acceptable essential adverse event thresholds may be established and studied 15 for a product or device. 'Hie essential adverse event thresholds may be selected to be at any desired incidence level, e.g., 1:10,000,000; 1:1,000,000; 1:100,000; 1:10,000; 1:1,000; 1:100, above which use of a product or device may exceed its benefit for a general or specific population group. The essen- " tial adverse event thresholds serve as limits for single or aggregated newly discovered adverse events. For example, an essential adverse event threshold of 1 occurrence in 1000 persons may be established as an acceptable level of occurrences. If 2 occurrences are observed in the target population then the essential adverse event threshold is exceeded and the product or device is deemed unsafe or commercially impractical for use by persons in that group. Likewise, 10 new similar or dissimilar essential adverse events relating to the product or device may be observed in the target group, but none of the individual new essential adverse events occurs more than once in 10.000 persons. In the aggregate, therefore, the 10 occurrences detected in a total study population of 10,000 persons corresponds to a ratio of 1:1000 which equals, but does not exceed the acceptable essential adverse event threshold for the product or device under scrutiny. In this instance, the product is deemed safe and commercially viable for use in the targeted population group. 4(| The present systems and methods also enable ready comparisons between target populations that receive treatment with a product or device, and experience essential adverse events, with untreated control groups that experience similar essential adverse events. For example, a target group treated 45 with a certain vaccine that acquires diabetes may be compared with an otherwise identical but unvaccinated control group that also acquires diabetes. Increased incidences of diabetes in the target group thus may be attributable to the vaccine. 50 Systems 10.110 and 210 may be programmed to establish any desired acceptable increased rates of essential adverse event occurrences in the treated target group versus the untreated control group, e.g., 2%, 5%. 10%", 20%, 30%, 50%. 75%, 100%. 150%, 200%, 300%, 400%, 600%, 800%, 55 1,000% or more, above which treatment would be contraindicated in the target group. Preferably, the system analyzes data using any desired study design. For example, a case control study design may be used where the frequency of using a product or device in a group with the target disease is 60 compared to the frequency of using a product or device in a group of controls. The studies may include prospective clinical trials and retrospective follow-up of clinical trials, as well as cohort analysis of people not in clinical trials. The studies may, or may not. include efficacy for the intended use as in 65 treatment of a specific disease. The studies may also be part of a pre-approval or post-marketing study regulated by the FDA
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or similar regulatory body. Conversely, the studies may be unaffiliated with FDA-sanctioned clinical trials. Returning to FIG. 4, the adverse event information stored in essential adverse event information storage device 22 is commercialized. Commercialization of the useful essential adverse event information may take on an assortment of forms as indicated in FIGS. 5 and 6. Users of servers 10.110 and 210 may include individual, a corporation, partnership, government agencies, research institutions or any other persons or entities that may have an interest in or need for new and useful essential adverse event information. Non-limiting examples include manufacturers and/or distributors of products or devices, insurance companies, health maintenance organizations and public health departments. In the case of manufacturers and/or distributors of products or devices, such manufacturers and/or distributors may use the information in the manufacture and/or distribution of their own products, or may license the information to their competitors. As indicated by step 26' in FIGS, 5 and 6, at the request any of these persons or entities or on its own behalf, the owner or licensee of server, 14, 114 or 214 accesses and retrieves raw adverse event product data from adverse event database(s) 12. At step 28' the server analyzes the retrieved data to identify new essential adverse events regarding a product or device, to conduct cost/benefit analyses related to the newly discovered essential adverse events or to perform any other desired analysis of the raw data. At step 30' the server creates one or more proprietary essential adverse information databases that are stored in essential adverse information storage device 22. At step 32' in FIG. 5 the licensee or owner or owner of server 14, 114 or 214 commercializes the essential adverse event information in essential adverse information storage device 22 by selling or licensing the proprietary information to a third party. The third party communicates with system 10, 110 or 210 through user computer 24. The user computer interfaces with user interface 20 to make requests for information to and to receive information from the processor 18 of server 14.114 or 214. Interpretation of the received information may be performed by the third party, an independent contractor, the owners or licensees of server 14,114 or 214 or the owner(s) or licensees of the essential adverse event database^) 12. Practical, but non-limiting, examples of possible users of systems 10, 110 or 210 and the method depicted in FIG. 5 include manufacturers and'or distributors of products or devices, holding companies, venture capital companies or other companies or individuals seeking to capitalize on ownership of a portfolio of new product information that may be of commercial value. The users may use the information to seek patent, or other intellectual property protection for the information. The systems 10. 110 and 210 and the methods depicted in FIGS. 5 and 6 are especially useful for creating proprietary information and products ordevices. The systems and methods of the present invention can assist in preparing information for a patent application and can assist in documentation of the invention, including inventors, date of invention, progress of the development of invention. As used herein, proprietary information shall be construed to mean information-thai is used or intended to be used for establishing or claiming specific intellectual property rights. For example, the proprietary information can be used in the creation of intellectual property, sale or licensing documents; that is, the proprietary information may comprise textual or graphical content that may be incorporated into patent applications. A 'proprietary new use' means a new use, in which one has or is seeking intellectual property rights, i.e., a patent.
US 7,653,63962 13
It is not the intent of this invention to encompass an "expanded use" relating to an unexpected phenomenon associated with a product or device. "Expanded use" is used herein to mean other uses for a product or device in addition to currently known uses for the product or device. For example, if an unexpected phenomenon associated with blood pressure medicine is hair growth, then the use of blood pressure medicine may be expanded to include use as a hair tonic. By comparison, expandeduses fora medical product or device are not created by discovery of adverse events, rather such uses are determined by performing extensive clinical trials and obtaining regulatory approval for marketing the new use of the product or device. On die other hand, the invention is intended to encompass a restricted use. i.e., avoiding, when possible, use of the product or device by methods involving same, or by using same, that are at increased risk for an adverse event. A new useful characteristic of a product or device responsive to identifying an essential adverse event, e.g., providing a written warning with the product to a consumer, is also encompassed by the invention. New restricted uses are primarily derived by discovering an adverse event because manufacturers are required to disclose possible adverse events associated with use of a product or device, even if the adverse event has not been proven to occur in a specific risk group or situation. However, the invention is intended to encompass a use that allows a group, previously considered to be at high risk, to use a product by better defining the high risk group, although, this is neither an expanded nor a restricted use. It is also not the intent of this invention to encompass the simple copyrighting of package inserts that may contain adverse event information. A manufacturer and/or distributor is entitled to the copyright associated with any creative work that it produces, including package inserts. Of course, package inserts may contain adverse event information or product uses that are not proprietary and are in the public domain. Thi s invention is, therefore, not intended to encompass this practice. It is also not the intended purpose of the present invention to encompass proprietary kits (i.e., patented), wherein the kit is proprietary solely because of pre-existing intellectual property rights. Rather, it is the intent of the invention to claim proprietary kits containing new proprietary adverse event information and/or instructions to use the product according to a proprietary new use based on new adverse event information, wherein that new adverse event information is the product of a system, device or method of the present invention. Users might seek patent protection for new therapeutic uses for existing products or devices based on newly discovered essential adverse event information. Similarly, users might seek protection for new labeling necessitated by the discovery of the new essential adverse event information. For any new use discovered by the systems according to the present invention, the instructions accompanying the product or device for which the new use is identified should desirably warn newly-identified high risk users of the product or device to avoid using the product or device. Likewise, the instructions also inform users who were previously but wrongly identified as high risk users that the product or device may be safely used by them. Preferably, systems 10.110 and 210 are capable of formatting the proprietary information data such that it is suitable for incorporation into the aforementioned intellectual property documents. In FIG. 6, method steps 26', 28' and 30' are identical to their counterparts in FIG. 5. However, as indicated at step 32" of FIG. 6, the owner or user of the proprietary essential adverse information commercializes the proprietary information by
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manufacturing (or causing to be manufactured) products or devices incorporating the proprietary information and then selling the products and devices. In addition to the functions represented by method steps 26', 28', 30', 32' and 32". additional tasks are preferably performed to more completely fulfill the purposes of the present invention, as reflected in FIGS. 5 and 6. For example, as indicated by step 29' in FIG. 5. server 14,114 or 214 may be programmed to generate proprietary information, typically in textual and/or graphic form, that is incorporated into intellectual property, sale and/or licensing documents. The documents then are used in negotiations with product or device manufacturers and/or distributors or other interested third parties. Additionally, FIG. 5 reveals in step 31' that server 14, 114 or 214 may optionally generate printed product warning information derived from the essential adverse information database(s). The printed warning information may be used in connection with packaging such as. for example, as product labeling or as product packaging inserts to advise the consumer (or product prescriber in the case of products or devices requiring a prescription) of contraindications or other adverse events associated with use of the product or device. Alternatively, as shown in step 33' of FIG. 5. the owner of the proprietary information or its licensee may generate the aforesaid printed warning information. Similarly, in FIG. 6. the server 14,114 or 214 may generate proprietary information that may be incorporated into intellectual property and/or sale documents (step 31"). Printed product warning or safety information is generated by the servers 14. 114 or 214. Alternatively, as shown at step 33", this step is performed by the owner or licensee of the proprietary information (who also manufactures and/or distributes the product or device or causes it to be manufactured and/or distributed). Equipped with the new essential adverse information generated by systems 10,110 and 210, a user might also urge the FDA to compel existing manufacturers and/or distributors of a product to remove the product from the market if it does not have adequate safety warnings or to prevent those contemplating marketing the product from entering the market without providing adequate safety labeling. In a preferred application, the systems described herein are used to develop new proprietary safer uses for drugs that are already generic or soon to become generic. A generic drug is one where the active compound either is not protected by a composition of matter patent, or the patent will very soon expire. Therefore the active compound is commercially available and adverse event data may be available from one or more sources. In some instances there are drugs that are on the market but protected by orphan drug status, such as thalidomide or by a use patent such as AZT. In these instances the composition of matter patent had expired but competitors have not entered the market because there are only a few known existing uses for the product, and these are covered by use patents or orphan drug provisions. However, these drugs may have been on the market for ten or more years and little research has been conducted before or during that time to identify and optimize the fullest extent of their potential ranges of safe use. Moreover, they have probably been tested for other indications, and adverse event information exists on them. In varying degrees, generics of a proprietary' dmg often differ from the proprietary drug itself, and from one another. More particularly, although their active ingredients may be the same, generic drugs may include impurities, inert substances, carriers and other agents that are not present in their corresponding proprietary drugs or other generic alternatives
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thereof. When considering generics and their proprietary counterparts based solely on their active ingredients, the generics would be expected to exhibit similar adverse events. However, through implementation of the present invention, generic drugs can be precisely compared against their propri- 5 etary drag counterparts, and alternative generics. to determine the impact of their inactive ingredients on adverse events, despite the variability of such inactive ingredients. For instance, drugs with agents which delay the release of an active agent can be expected to exhibit many of the same side i o effects as drugs with the same active ingredient, but that release it over a shorter period of time. In this context, therefore, a generic and a proprietary drug is considered to be the same product if the adverse event(s) and/or new use(s) for the drugs would be expected to be consistent for both. 15 The "new use" derived from die new adverse event may involve restricting the use of the product or device in ways that are now discovered to be dangerous. For example, if a product is determined to be flammable or explosive, the "new proprietary use" would restrict its use in conditions that could 20 lead to combustion or explosion, which may occur when used ill the presence of an open flame or near a fire. Substances discovered to emit toxic fumes would, as a new use, only be utilized in well-ventilated areas, or under safety hoods. The new use may include providing a kit which contains warnings 25 about a new adverse event relating to use of the product or device The term 'commercially available' pertains to products or devices that are available to more than one group or company. The product can be a substance, such as a drug, which is 30 known by more than one company or research group. With such a product or device, adverse event data may have been generated by more than one group, and adverse event data although generated by one group, may not be new. This is because another earlier group may have discovered the 35 adverse event first. This is especially true when the product has been sold commercially, and is known to have been used by a number of different groups over time. Studies may be performed with non-commercially available products, wherein a non limiting example would be 40 drugs. In this example, the uon-commercially available drug may also be tested in patients receiving commercially available drugs. Drug interactions may be detected between the commercially available drug and the non-commercially available chug. In this situation the purpose of the study is to 45 screen a database for adverse events of the non-commercially available product, not the commercially available product. A manufacturer and/or distributor of a commercially available product or device is not required to warn potential users about an interaction mat may occur with their product or device and 50 a product or device that is not yet available, or that the manufacturer or distributor does not even know exists. The present invention is intended for screening of products that are both commercially available and those that are not, unless otherwise specified. 55 Many entities, large and small, may beneficially utilize the systems described herein. A representative, although nonlimiting, example would be an independent non-manufacturing company that procures access to one or more essential adverse event databases to analyze the data contained therein 60 and identify new uses for existing drugs. The independent company could then license the "new use" technology or new characteristic it discovers to pharmaceutical manufacturers. The content of the licensing agreements may be agreed upon before or after the data has been analyzed. The independent 65 company may opt to file appropriate intellectual property documents such as patent applications covering the newly-
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discovered uses for the product and/or their attendant product warning information and receive monies derived from the sale of the drug ill the form of royalties or a lump sum fee. Alternatively, the independent company may utilize the services of a contract manufacturer that will make the drug for the independent company which will reserve the right to sell the product on its own behalf. The independent company may also be a large insurer or pharmaceutical company that has access to its own extensive adverse event information database^) from which may identify and commercially exploit new uses for existing products or devices. As mentioned above, the present systems and methods are also utilized to develop proprietary safety information on products or devices unrelated to the medical fields since manufacturers and/or distributors in other fields of endeavor generally are required to provide consumers with safety information regarding their products. Essential Adverse Event Information The final determination of what is "essential" information is determined by a regulatory agency such as the FDA. New adverse event information that is "essential" is of great commercial value since if this information is proprietary, for example patented in the form a new use, it can be used to exclude potential competitors from selling a product which would require the essential information. In order for a company searching through raw adverse new uses, to maximize profits from such a search, the "essential" new uses should ideally be separated from other new uses. By limiting the protection for such new data, e.g., patenting, and limiting petitions to regulatory agencies to only the "essential" newuses, a company saves time and money by avoiding expending lime on adverse event information that has little commercial value. Methods of Determining Essential Adverse Events A computer system can assist in identifying essential adverse event information. Preferably the first step is to identify adverse events associated with a group or subgroup using or exposed to the product in question. In accordance with the embodied invention, comparisons are made regarding the risk of the occurrence of a new adverse event in a group of subjects exposed to the product or device, with the occurrence of the same event in a control group. One type of control could be a group exposed to a competing technology (drug, product). For example, if the system is evaluating the use of a fuel, then the control group would be exposed lo a competing fuel, such as oil vs. coal vs. natural gas versus electricity. In a like manner, the system could compare those exposed to an oil-based paint versus a latexbased paint as a non-limiting example. Another type of control group could be a group that receives no exposure to a competing technology. For example, comparing a group receiving a drug, to a group receiving no drug. A third possible control situation would be a population exposed to the product in question, but selecting a subpopulation, which does not contain people in the same subgroup in which the adverse event is thought to occur more frequently. An example would compare a population receiving 4 doses of a vaccine, to a population receiving only one dose of a vaccine, which is either equal to a bolus of all 4 of the comparable doses, or which is equal to only one of the comparable four doses. Another example would compare a group of people with liver problems, receiving a drug for a non liver ailment, to a group with healthy livers who receive the same drag. A fourth type of control would use the group members as their own control. In this case the incidence of an essential
US 7,653,639 B2 17 18
adverse event occurring prior to exposure to the product or the adverse event, or of performing a study to disprove the device, is compared to essential adverse events following product is related to or causes the adverse event, or disprove exposure to the subject product or device. the that adverse event is essential. In the later case this Having estimated the risk of an adverse event associated embodiment pertains to specific tests to insure a product is with a product, such as a drug, one can determine if the 5 safe, which comprises specifically checking to see if the adverse events are essential. Several different criteria can be product is associated with or causes the adverse event which utilized to determine if the adverse reaction is essential. Such is also associated with the competing product, criteria include the non limiting examples, comprising: deterA competitor can perform specific tests to try to disprove mining whether the adverse event is unnecessary, if the risk the existence of an essential adverse event. This can be of exceeds benefit, if causation has been proven, or if the risk is 10 value to a competitor when an adverse event information is frequent and or severe. These factors can be determined, and covered in a patent (i.e., proprietary adverse event), and inclucompared or compiled with the assistance of a computer. sion of this adverse event in a product data safety sheet (for An 'unnecessary adverse event' would be an essential example pharmaceutical labeling/package insert or an adveradverse event that could be or could have been easily avoided. tiseinent) or an instruction brochure, pamphlet or book for a One example would be a drug interaction, which could be 15 device, would constitute an act of infringement. Alternatively, avoided by withholding one of the interacting drugs. Mother a competitor can perform a study to either try to disprove the example of an unnecessary adverse event is one in which the existence of an adverse event or try to disprove that the adverse event can be or could have been avoided by using a adverse event is 'essential.' In the later case the competitor different product, or even a different brand. For example, if a may use the same or different data as was used in establishing drug is very toxic in a subgroup of people, e.g., people of a -0 the adverse event in the first place, or that established that the certain age, or those who have a preexisting condition, then adverse event is essential. The competitor can also use the the adverse event in such individuals groups can be or could same or different epidemiological method, and the same or have been easily avoided by using a different drug or different different statistical tests. Moreover, the competitor can prc>treatment. for example, surgery. vide additional data to supplement the initial data, such as Another type of essential adverse event information is one 25 information regarding confounding variables that may be in which the risk 'exceeds the benefit.'For example, in certain useful for disproving the essential adverse went information, subgroups of patients, the risk of disease or complications Computers can assist in this process as provided above, exceeds the benefit provided by the product or device. By avoiding the placement of proprietary adverse event A third type of essen tial adverse event in formation is where information in a product data safety sheet or the like, a comthe frequency of the adverse event is so high, or the event so 30 petitor avoids infringement of patents. This is because what severe, that a significant health concern or medical managewas claimed as an essential element in the patent or what meut issue. In a situation the adverse event may occur graduappeared to be inherent in the claimed invention, is no longer ally, but laboratory testing could pick up the damage early, so required in the competitors product. Such an improvement that further damage need not occur. The frequency of the will avoid costly patent litigation and lead to lower costs of events that render an adverse event essential depends in part 35 development of a product or device, quicker time from develon the severity. Association between death, hospitalization. opmeut to market, or an expected higher return for developlife threatening events, permanent organ damage, disability, ment costs. cancer, or birth defect and a product or device, becomes Nevertheless, the present invention is not intended to essential adverse event information at a lower frequency than encompass pharmacogenomic techniques for screening. would the information relating to a potentially benign adverse 40 . event, such as but not limited to minor pain, swelling, and Licensing Agreements. fever. Other adverse events that are included in mis essential "I1le mvendon provides new methods of business that procategory include marked abnormalities in laboratory values, vlde to a manufacturer and/or distributor the ability to prevent vital signs FKG and seizures a Ami-party, potential competitor from generating propnA fourth tvpe of essential adverse event information occurs 45 etai? 'essential' information with regard to the manufactured when the adverse event is so well characterized that causation or distributed product or device, thereby preventing the is generally believed to exist. For example, such a situation manufacturer s and/or distributor's exclusion from the marcan occur when the adverse event is detected in two separate, ket A Pref erred embodiment of tins method involves using a well-controlled clinical trials, i.e. the adverse events are licensing agreement/contract for sales of the product or duplicated. An example would be an industrial chemical, device- wllich states <** ** Product or device can only be wherein exposure is unintended, but for which exposure is used for certaln PurPses. s^ a license would exclude the known to cause severe adverse events. By providing warnllceusee s nht to the use the Product or device to determine uuts, one can alert those who may be exposed of the risks new PP"ctary characteristics or uses lor the subject product associated with accidental exposure, and the treatment that or device' for the smjauon m wmch lhe new characteristic or should be under taken to minimize an adverse event following ** use ls ^covered by screening for the occurrences of new exposure ' adverse events related to the use of the product or device. The license or agreement could be similar to that used with Method of Screening fora Specific Adverse Event, Especially software (e.g., a shrink-wrap license), where the breaking of an Essential Adverse Event. the wrapper or of a seal indicates one's acceptance of the The methodofthe preferred embodiment can be utilized to 60 contract. Such a licensing agreement could be affixed to or develop new methods of screening drugs for adverse events, accompany the product or device, by methods well known in particularly essential adverse events. The discovery of an the art. Alternatively, it could be signed by a responsible party essential adverse event warrants that all manufacturers and/or prior to delivery of the product or device to a purchaser, distributors of the product or generic version to warn of the end-user, distributor, etc. Moreover, as part of the contract/ adverse event. In certain circumstances where a competitor 65 licensing agreement, the purchaser, end-user, distributor, or produces a similar or even identical (generic) the competitor the like, would agree for a predetermined period of time not to may be given the choice of warning potential consumers of use the product or device in any attempt to discredit the
US 7,653,639 B2
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existence of one or more new. essential adverse events, or the utility of the existing subject proprietary use. This will prevent competitor licensees from trying to block the original owner's rights to the product or device by 'discovering' through the use of essential adverse event information, proprietary new characteristics or uses of the product or device. For example, if the competitor were to find or become aware of a previously unknown, essential adverse event, and if that information were proprietary to the competitor, such a competitor could have a basis for claiming exclusive rights to a novel product or device, which would be just like the original, except it claims a new characteristic based upon the newly discovered essential adverse event information. However, the agreement controlling rights to use the product or device would preclude such behavior. Alternatively, or in addition to an end-user agreement, a licensing agreement can be made at the time of intermediate sales of products or devices to wholesalers, retailers, distributors or other who purchase the product or device with the intent of reselling it to third parties. Such an agreement can be in the form of, or include, an electronic monitoring system. In one such embodied electronic system, a window would appear or a button would require activation, acknowledging acceptance of, and intent to comply with, the contract/licensing agreement. In an alternative embodiment, an electronic signature, acknowledging acceptance of and compliance with the agreement would be stored. In a third possible electronic method, an electronic image of an 'executed' agreement document would be saved. A manual packaging system can also be established which could be utilized in shipments to purchasers of large quantities of the product or device, such as but not limited to wholesalers, retailers, middleman, merchandisers, distributors and the like. A seal could be applied to the bulk package, that when broken, would certify agreement with a licensing agreement of the type(s) described above. Based upon this disclosure, one skilled in the art can devise any of a number of different methods or systems to accomplish the task of creating and/or verifying an agreement, electronically or otherwise, that would prevent the purchaser and/or the end-user from using the product or device in certain ways or for certain purposes, specifically for generating proprietary new, essential adverse event information to be used for the identification and/or development of new characteristics oruses of the subject product or device, and/or new methods of screening such products or devices for such new. essential adverse event information. Methods of Screening Adverse Events for Commercial Value. All essential adverse event information is not of equal value. Value depends on the potential value of making a generic product or device into a proprietary product or device, or preventing a proprietary product or device from becoming a generic product or device. If a proprietary product or device is loosing money or marginally profitable, then extending its proprietary status by discovering essential adverse events will add little value. For example, discovering an essential adverse event in a generic aluminum-containing antacid may not bring much added profit, even if the product were to become proprietary, if consumers were more interested in switching to other antacids lacking aluminum, such as calcium-based antacids or magnesium-based antacids. Alternatively, a consumer with gastritis who is faced with the proposition of buying expensive antacids, may prefer to use alternative newer, more expensive, and more effective products, such as histamine blockers or hydrogen pump inhibitors. Alternatively, large profits can be made on a highly profitable pat-
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ented product or device by extending its proprietary status by obtaining one or more new patents based upon the discovery of essential adverse events associated with use of the product or device. In a preferred embodiment of the invention, a product or device for which an essential adverse event is discovered, is also one that is highly profitable, but would face a marked decrease in profitability if the product or device were to lose its proprietary status. One skilled in the art can screen products or devices by recognized methods to determine the potential value of discovering proprietary essential adverse events. Those skilled in e.g., sales, marketing, licensing, statistics or business practices, will know how to use recognized methods to calculate or estimate such parameters as, in the non limiting examples of, current market share, potential market share, total market share in unit volume or sales, marketing costs, elasticity of demand, cost of production, cost of marketing, number of competitors, market potential, cost of discovering a new adverse event, product liability costs, growth of market and the like. Mathematical modeling, with or without the use of computers, can be performed to evaluate whether it would be profitable to develop a proprietary essential new use based on an essential new adverse event. In addition to profitability, an entity may desire to determine cost of capital and opportunity costs before deciding to move forward with the project. All references cited herein, including journal articles or abstracts, U.S. or foreign patents, published patent applications, or any other references, are entirely incorporated by reference herein, including all data, tables, figures, and text presented in the cited references. Additionally, the entire contents of the references cited within the references cited herein are also entirely incorporated by reference. It is to be understood that the phraseology or terminology herein is for the purpose of description and not of limitation, s uch that the terniino logy or p hraseol ogy of the present specification is to be interpreted by the skilled artisan in light of the teachings and guidance presented herein, in combination with the knowledge of one of ordinary skill in the art. Reference to known method steps, conventional methods steps, known methods or conventional methods is not in any way an admission that any aspect, description or embodiment of the present invention is disclosed, taught or suggested in the relevant art. While the foregoing specification has been described with regard to certain preferred embodiments, and many details have been set forth for the purpose of illustration, it will be apparent to those skilled in the art that the invention may be subject to various modifications and additional embodiments, and that certain of the details described herein can be varied considerably without departing from the spirit and scope of the invention. Such modifications, equivalent variations and additional embodiments are also intended to fall within the scope of the appended claims. What is claimed is: 1. A method of generating and commercializing newlyidentified proprietary- data about a proprietary or nonproprietary product or device, wherein the method comprises the steps of: accessing at least one adverse event data source that stores adverse event data associated with the product or device; analyzing the adverse event data to identify at least one new essential adverse event associated with the product or device, wherein the essential adverse event is one regulated by a regulatory agency requiring disclosure of the event in a package insert or data sheet accompanying the product or device;
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creating at least one essential adverse event information database, wherein the creating step comprises analyzing data from the at least one adverse event data source to identify at least one new proprietary characteristic or use for the product or device responsive to identification of 5 the at least one new essential adverse event associated with the product or device, wherein the creating step further comprises storing essential adverse event information, and wherein the essential adverse event information includes the at least one proprietary new use or 10 characteristic and data related thereto: and commercializing the proprietary essential adverse event information stored at the essential adverse event information database, which step comprises exclusive disclosure of the newly-identified proprietary essential 15 adverse event information which, once identified, must then accompany the product or device. 2. The method of claim 1, wherein accessing further comprises accessing the at least one adverse event data source comprising raw data from a plurality of different adverse 20 events. 3. The method of claim 1, wherein accessing further comprises accessing data from the at least one adverse event data source comprising adverse event information regarding exposure to or use of the product or device. 25 4. The method of claim 3, wherein accessing further comprises accessing the at least one adverse event data source further comprising information regarding adverse events selected from at least two categories selected from the group consisting of death, illness, hospitalization, missed work, 30 medical costs, abnormal laboratory results and surgeries. 5. The method of claim 1, further accessing at least one data source comprising information relating to patents and patent applications. 6. The method of claim 1. further accessing at least one data 35 source comprising information relating to raw commercial or sales data. 7. The method of claim 1, further comprising providing the at least one adverse event data source comprising adverse event data gathered from at least 5000 subjects. 40 8. The method of claim 7, further comprising providing the at least one adverse event data source comprising information regarding amount of use of the product or device or duration of exposure to the product or device by each subject. 9. The method of claim 7, further comprising providing the 45 at least one adverse event data source comprising information regarding product post-exposure adverse event data, which is recorded in selected time increments, ranging from less than one hour to more than ten years. 10. The method of claim 1. wherein commercializing fur- 50 ther comprises selling, leasing or licensing the newly identified product information. 11. The method of claim 1, wherein commercializing farther comprises protecting the intellectual property interest in the newly identified product information. 55 12. The method of claim 1, wherein commercializing further comprises formatting the data relating to at least one new adverse event associated with exposure to, or use of the product or device, or documenting same, such that a manufacturer or distributor of the product or device must inform consum- 60 ers, users or individuals responsible for the user, physicians or prescribers about at least one new adverse event associated with exposure to or use of the product or device. 13. The method of claim 1, further compri sing determi ning the value of commercializing the at least one new character- 65 istic or use determined from the at least one identified essential adverse event.
22
14. The method of claim 1, further identifying the at least one new use of the product or device as a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 15. The method of claim 1, wherein the product or device is commercially available, and further identifying the new use as comprising restricting exposure of the product or device to one of the high risk associated groups selected from the group consisting of high or low temperatures, chemicals, surfaces, pressures, electricity and sparks; or contact of the product or device with one of the group selected from the group consisting of skin, eyes, ears, respiratory surfaces, gastrointestinal surfaces and mucous membranes of the consumer; or exposure to a subpopulation group selected from the group consisting of children, pregnant women, consumers with specific allergies or medical conditions and animals; or exposure to a subpopulation defined by at least one consumer-identifying characteristic selected from the group consisting of sex, weight, age, race, genetic characteristics, medical condition, pregnancy status, presence of allergies, and use of medicines or medical devices. 16. A proprietary product or device created using the method of claim 1. 17. The product of claim 1. wherein the product is medical. 18. The product of claim 16, wherein the product is medical. 19. The product of claim 17, wherein the medical product is a generic drug. 20. The product of claim 18, wherein the medical product is a generic drug. 21. The product of claim 1, wherein the product is nonmedical. 22. The product of claim 16, wherein the product is nonmedical. 23. The device of claim 1. wherein the device is medical. 24. The device of claim 16, wherein the device is medical. 25. The device of claim 1, wherein the device is nonmedical. 26. The device of claim 16, wherein the device is nonmedical. 27. A proprietary kit containing a product or device, and labeling notifying a user of at least one new essential adverse event for the product or device, wherein the kit is created in accordance with claim 1. 28. A proprietary kit containing a product or device, and labeling notifying a user of at least one new essential adverse event for the product or device, wherein the kit is created in accordance with claim 14. 29. The method comprising using the proprietary kit of claim 27 in accordance with a proprietary new characteristic of, or use for. a product or device. 30. The method comprising using the proprietary kit of claim 28 in accordance with a proprietary new characteristic of, or use for, a product or device. 31. A proprietary new use for a commercially available product or device, wherein the new use is determined from the data provided by the method of claim 1. 32. The proprietary new use for a commercially available product or device according to claim 31, wherein the new use is protected as an intellectual property. 33. The proprietary new use for a commercially available product or device according to claim 31, wherein the new use comprises a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device.
US 7,653,639 B2 23 24
34. The proprietary new use of the product or device 51. The method of using the proprietary kit of claim 27 according to claim 33, wherein at least one new adverse event comprising providing a proprietary new characteristic of, or comprises a drug interaction. use for the product of device, wherein the product or device is 35. The proprietary new use of the product or device commercially available, and wherein the new use comprises a according to claim 33, wherein at least one new adverse event 5 restricted use in at least one population subgroup when there is based upon neither a drug interaction, nor a chronic js observed to be a high risk of at least one adverse event immune mediated disorder. associated with exposure to or use of the product or device. 36. The method of claim 1, further comprising establishing 52 Themethod ofdaim ^ whereiu thfi at ,east oneadverse a new saiety data sheet lor a commercially available product . , . , ,. . . . ... , , . u u f < i < i - I T i i event data source is part ol a system lor creating and using or device, whereinthesalely data sheet identifies at least one 10 . j , j " j , ,. , , , ,- ,, ,, . , data associated with a product or device, comprising: at least new essential adverse event tor the at least one product or , , F , , device one a<*verse evenl data source for storing adverse event data 37. The methodof claim 1, further comprising establishing associated with a commercially available product or device; a new safety data sheet, removed from which is at least one processor for accessing and analyzing data from the at least proprietary- non-essential adverse event for the at least one 15 one adverse event data source to assist in identifying new product or device essential adverse events associated with the product or device 38. The safety data sheet produced in accordance with and to assist in identifying at least one new useful characterclaim 36. istic f- or use fr! me product or device responsive to iden39. The safety data sheet produced in accordance with tificalion of at least one new essential adverse event associclaim 37. - ated with the product or device; adverse event information 40. The method of claim 1. further comprising using the database storage device for storing the new essential adverse method to produce lower costs for development of the product event data identified with the assistance of the processor; user or device, or quicker time to market, or an expected higher computer for making requests for essential adverse event return for development costs associated with the product or information to, and for receiving adverse event information device, or any combination thereof. 25 from, the processor: and user interface for interfacing the 41. The method of claim 36, further comprising using the processor and the user computer. methodtoproducelowercostsfordevelopmentoftheproduct 53 -^ melhod of c]aim 52 wherein accessing furmer or device, or quicker time to market, or an expected higher C0lnprises accessing the at least one adverse event data source return for development costs associated with the product or fi]rther rism information regarding adverse events device or any combination ttereot selected from at least two categories selected from the group 42. I he method ol claim 37 further comprising using the consisting of dea,hj iUness , hospitalization. missed work, metoodtoproducelowercostsfordevelopment oltheproduct ^^ abnormal laboratory results and surgeries, or device, or quicker time to market, or an expected higher , , , - . - . . , return for development costs associated with the product or 54 llle m<illlodo1 claim 52, farther accessing at least one device, or any combination thereof. 35 data source comprising information relating to raw conimer43. The method of claim 1. further comprising using the clal or sales data" method to develop at least one essential proprietary new 55. The method ol claim 52, further identifying the at least method of screening a product or device for safety. one new use of the product or device as a restricted use in at 44. The method of claim 36, further comprising using the least one population subgroup when there is observed to be a method to develop at least one essential proprietary new 4U high risk of at least one adverse event associated with expomethod of screening a product or device for safety. sure to or use ofthe Product or device. 45. The method of claim 37, further comprising using the 56. The method of claim 52, wherein the product or device method to develop at least one essential proprietary new is commercially available, and further identifying the new use method of screening a product or device for safety. s as comprising restricting exposure ofthe product or device to 46. The method of claim 1, wherein commercialization " oneofthehighriskassociatedgroupsselectedfromthegroup comprises facilitating documentation of inventorship. consisting of high or low temperatures, chemicals, surfaces, 47. The method of claim 46. further comprising documentpressures, electricity and sparks; or contact of the product or in" date of iuveutorship device with one ot the group selected from the group consist48. The method of claim 46. wherein the product or device ,0 m of skin' ***< **, respiratory surfaces, gastrointestinal is commercially available and further comprising identifying ' surfaces and mucous membranes ol the consumer; or expotrie new use as a restricted use in at least one population sure lo a subpopulation group selected Irom the group coilsubgroup when there is observed to be a high risk of at least s f m ? of children, pregnant women, consumers with specific one adverse event associated with exposure to or use of the alleies or raedlcal co"dltMns and "mals: or exposure to a product or device subpopulation denned by at least one consumer-identifying . , ., , c , .- , - ,, , , . x cliaracteristic selected from the group consisting of sex, 49. fhe method ot claim 47. wherein the product or device . . . . . . , . , , . . is commercially available and'further comprising identifying weight, age, race, genetic characteristics, medicd condition, the new use as a restricted use in at least one population Pre8nailcy **tus- Pre^nce of allergies, and use ol medicines u i there is observed to t. a highi risk of at i - u j 4. be i - . - i r least o r medical devices, subgroup when u one adverse event associated with exposure to or use of the 6o 57'The product of daim 52' wherein the Product is mediproduct or device. ca ^50. The product or device of claim 16, wherein the product 58- The product of claim 57, wherein the medical product or device is commercially available and wherein the new use ls a generic drug. comprises a restricted use in at least one population subgroup 59. A proprietary kit containing a product or device, and when there is observed to be a high risk of at least one adverse 65 labeling notifying a user of at least one new essential adverse event associated with exposure to or use of the product or event for the product or device, wherein the kit is created in device. accordance with claim 52.
US 7,653,639 B2 25
60. A proprietary kit containing a product or device, and labeling notifying a user of at least one new essential adverse event for the product or device, wherein the kit is created in accordance with claim 55. 61. A proprietary new use for a commercially available product or device, wherein the new use is determined from the data provided by the method of claim 52. 62. The proprietary new use for a commercially available product or device according to claim 61. wherein the new use comprises a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device.
26
63. The method of claim 52, wherein commercialization comprises facilitating documentation of inventorship. 64. The method of claim 63, wherein the product or device is commercially available and further comprising identifying the new use as a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 65. The method of claim 1. wherein the commercializing step further comprises profiting from use of the method wherein the required disclosure of the newly-identified proprietary essential adverse event information accompanying the product or device is not freely available to a competitor.
EXHIBIT B
USW7984069B2
United States Patent

Classen
(54) COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY (75) Inventor: (73) (*) John Barthelow Classen, Baltimore, MD (US)
US 7,984,069 B2 (io) Patent No.: Jul. 19, 2011 (45) Date of Patent:
5,845,255 A 5,876.926 A 5,908,383 A 5,950,630 A * 5,970,463 A 5 991 751 \ 6.000.828 A * 12/1998 3/1999 6/1999 9; 1 999 10/1999 11 1999 12/1999 Mayaud Beecham Brynjestad Portwood et al Caveetal, Rjvetteetal Leet
128/897 707/1 705/2
Assignee: Classen Immunotherapies, Inc., Baltimore, MD (US) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 1911 days.
(Continued) OTHER PUBLICATIONS

R.T. Chen, et al.. "Vaccine Safety Datalink Project: A New Tool For Improving Vaccine Safely Monitoring in the United States," Pediatrics, 99:|6] 765-773. 1997.
(21) Appl.No.: 10/081,705 (22) (65) Filed: Feb. 21, 2002 Prior Publication Data US 2002/0083080 A1 Jun. 27, 2002
(Continued) Primary Examiner Etienne P LeRoux (74) Attorney, Agent, or Firm Browdy and Neimark, PLLC
(57)
Related U.S. Application Data (60)

(51)
ABSTRACT
Provisional application No. 60/270.697, filed on Feb. 22,2001.
Int. Cl. G06F17/30 (2006.01) (52) U.S.C1 707/790 (58) Field of Classification Search 707/1.2, 707/10, 104.1, 200, 9, 5, 3, 790; 705/3, 26; 700/108 See application file for complete search history.
(56)
3.885.566 5J81.394 5,386,829 5.642,731 5.678.234 5.723.283 5J26.884 5.728385 5J37.539 5,833.599 A A A A A A A A A A * * *
References Cited U.S. PATENT DOCUMENTS

5/1975 1/1993 2/1995 7/1997 * 10/1997 3/1998 * 3/1998 3/1998 4/1998 11/1998 Jacob Scheaetal Diamond Kehr Colombo etal Classen Sturgeon et al Classen Edelsonetal. Schrier et al. 604/390 62/371 600/425 588/318 435/4 705/9 424/201.1
The invention comprises systems, methods and a computerized data management device for creating and using data relating to a medical or non-medical product or device to enhance the safety of the product or device. A vast amount o f data regarding adverse events associated with a particular product or device is analyzed to identify new essential adverse events associated with the product or device. At least one database of new essential adverse event information is created and utilized, and new characteristics of or uses for the product or device related to the new essential adverse event information are determined. Adverse event information is gathered for a large number of population sub-groups. The system may also be programmed to incorporate the information into intellectual property and contract documents. Manufacturers and/or distributors can include the proprietary information in consumer safely information, which accompanies the product or device, or which is provided to patients, users, consumers and the like, or in the case of certain medical products or devices, to prescribers of those products or devices. The system and methods also provide for commercializing the essential adverse event information. 50 Claims, 6 Drawing Sheets
US 7,984,069 B2
Page 2 U.S. PATENT DOCUMENTS
6.018.714 6.097^995 6,1 12,182 6,219.674 6,221.851 6^243.6 15 6.323.242 6/158.958 6,465.463 6.584,472 6.696,924 6.784.177 6,944,776 2001/0001144 2002/0039990 2002/0082930 2002/0138305 2003/0004965 A * 1/2000 Risen et al A * 8/2000 Tipton et al A 8/2000 Akers et al. Bl 4/2001 Classen Bl * 4/2001 Feldman Bl * 6/200 1 Neway et al Bl * 1 1/2001 Mueller B l * 10/2002 D'Ambra et al Bl 10/2002 Cohn et al. B2 6/2003 Classen B l * 2/2004 Socinski B2 8/2004 Cohn et al. B l * 9/2005 Lockhartetal A l * 5/2001 Kapp Al* 4/2002 Stanton, Jr A l * 6/2002 Park Al 9/2002 Watanabe et al. A l * 1/2003 Farmer etal 705/4 700/266 707/104 51446 700/108 5 14/646 546/239 707/104 1 221/15 705/59 705/3 514/1 705/26 707/104.1 R. Evans et al.. "Evaluation of a Computer-Assisted Antibiotic-Dose Monitor," 33, Annals. Pharm., 1026-1031 (1999). R. Evans et al., "Preventing Adverse Drug Events in Hospitalized Patients," 2% Ann. Pharm. 523-527 (1994). R. Evans et al.. "Prevention of Adverse Drug Events through Computerized Surveillance," 16"1 Annual Symposium of Computer Applications in Medical Care. 437-441 (1993). R. Evans et al., "Using a Hospital Information System to Assess the Effects of Adverse Drug Events." Seventeemli Annual Symposium on Computer Applications in Medical Care, 161-165 (1994). G. Faich, US Adverse Drug Reaction Surveillance 1989-1994, Pharmacoepidemiology and Drug Safety 5:393-398 (1996). Federal Register, vol. 58, No. 105, (Jun's, 1993). Finney, D. J, Systematic Signalling of Adverse Reactions to Drugs, Methods of Information in Medicine, 13 (1974) 1-10. International Reporting of Adverse Drug Reactions. Final Report of CIOMS Working Group, 1990. Jim Kling, "From hypertension to angina to Viagra." Modern Drug Discovery 1(2) (1998). available at http://pubs.acs.org/hotartcl/mdd/ 98/novdec/viagra.htm. M. Lindquist et al., "From Association to Alert A Revised Approach lo International Signal Analysis," Pharmacoepidetniolog)' and Drug Safety 8:S15-S25 (Apr. 1999). David J. Morrow, "New Profits in Old Bottles." N. Y. Times, Mar. 19, 1999. U.S. Appl. No. 90/007,638, filed Jul. 22, 2005, Classen. U.S. Appl. No. 90/007,639, filed Jul. 22. 2005, Classen. C.A. Naranjo et al., "A method for estimating the probability of adverse drug reactions," 30 Clin. Pharmacol. Ther. (2):239-45 (1981). V. Pinkston & E. J. Swain, "Management of Adverse Drug Reaction and Adverse Event Data through Collection, Storage and Retrieval," Detection of New Adverse Drug Reactions. 281 -296 (Apr. 1998) (4th Ed.. London: Macmillan Reference Ltd.). "Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)." MEDWATCH Continuing Education Article (1998). Statement of Susan S. Ellenberg before the U.S. House of Representatives, available at www.fda.gov/ola/l999/anthrax.html (Jul. 21, 1999). A. Szarfinan, "Discussion: A Report on the Activities of the Adverse Events Working Groups: Focus on Improving the Detection of Rare but Serious Events," 1999 Proceedings of the Biopharmaceutical Section, American Statistical Association. Alexandria (VA), American Statistical Association, 12-13 (1999) (Szarfman/abstract). A. Szarfman, "New Methods for Signal Detection." IS'1' International Conference on Pharmacoepidemiology, Boston, Mass., Aug. 28, 1999 (Szarfman/ppt). U.S. Food and Drug Administration, "What Is A Serious Adverse Event?." http://mvw.fda.gov/medwatch/report/DESK/advevnt.htm. Vaccine Safety Forum, Summaries of Two Workshops, Washington, DC (National Academy Press 1997).
OTHER PUBLICATIONS
DeStefano, et al., "Timing of Hepatitis B Vaccination and Risk of Insulin-Dependent Diabetes Mellites," Pharma. And Drug Safely 6[2] (1997). Classen. J.B.. "New Patents for Older Products Through Patenting Product Safety Information," www.vaccines.net. (2005). Fiala, T.C. andWright, .I.E.. "Drug Labeling Patents: ANew Line of Defense for Protecting Old Drugs?," The Intellectual Property Strategist, UN (2005). Baker \ Secy ofDept. of Health and Human Sen's., No. 99-6 53V . 2003 WI. 22416622, (Ct. Fed. Cl. Sep. 26, 2003). A. Bate, et al.. "A Bayesian neural network method for adverse drug reaction signal generation." EurJClin Pharmacol 54(4) (Jun. 1998) 315-321. C. Baum, et al., "The Spontaneous Reporting System in the United States," Phartnacoepideniiology, 2nd ed. New York: John Wiley & Sons, 1994, 125-137. D. Bradbury, "A Bitter Pill to Swallow." Computing, 34-35, Feb. 9. 1995. D. Classen et al., "Adverse Drug Events in Hospitalized Patients," 277 JAMA, 301-306 (1997). D. Classen et al., "Computerized Surveillance of Adverse Drug Events in Hospital Patients," 266 JAMA 2847-2851 (1991). D. Classen et. al., "Description of a Computerized Adverse Drug Event Monitor Using a Hospital Information System," 27 Hasp. Pharm. 774, 776-779, 783 (1992). D. Classen & S. Pestotnik, "The Computer-Based Patient Record" Hospital Epidemiology and Infection Control, 141-154 (2nd Ed., New York: Lippincolt Williams & Williams 1999). R. Evans et al.. "A Computer-Assisted Management Program for Antibiotics and Other Antiinfective Agents," 338 The New England Journal of Medicine, 232-238 (1998). R. Evans et al., "Development of Computerized Adverse Drug Event Monitor," I?"1 Annual Symposium on Computer Applications in Medical Care, 23-27 (1992).
* cited by examiner
10
14
ESSENTIAL 12'
ESSENTIAL
SHADOW STORAGE DEVICE
PROCESSOR
18
USER INTERFACE
ADVERSE EVENT INFORMATION STORAGE DEVICE
20 22
16-
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114
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SHADOW STORAGE DEVICE AND ADVERSE EVENT INFORMATION STORAGE ^J)EVICE_^ 16,22-J
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PROCESSOR
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USER INTERFACE
20
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ESSENTIAL
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USER COMPUTER
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FIG. 2
00
O
03
210
-214
ESSENTIAL
PROCESSOR
ESSENTIAL
\ VO
12'
ADVERSE
ADVERSE
18
USER INTERFACE EVENT INFORMATION
K O
EVENT DATABASE
STORAGE DEVICE
20 22
sr
U> O
ON
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24
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FIG. 3
"o ^ OS
"sO
bd
U.S.
Patent
Jul. 19,2011
Sheet 4 of 6
US 7,984,069 B2
START
ACCESS ADVERSE EVENT DATA SOURCE
ANALYZE ADVERSE EVENT DATA
-28
CREATE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE
30
COMMERCIALIZE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE
32
END
FIG. 4
U.S. Patent
Jul. 19,2011
Sheet 5 of 6
US 7,984,069 B2
( START ) SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12
-26'
SERVER 14, 114 OR 214 ANALYZES ADVERSE EVENT DATA FOR ESSENTIAL ADVERSE EVENT DATA
-28'
-30'
29'
JL
SERVER 14,114 OR 214 GENERATES PROPRIETARY INFORMATION THAT CAN BE INCORPORATED INTO INTELLECTUAL PROPERTY, SALE AND/OR LICENSING DOCUMENTS
32'-
SERVER 14,114 OR 214 GENERATES PRINTED WARNING INFORMATION DERIVED FROM ADVERSE EVENT INFORMATION DATABASE
31'
OWNER OF PROPRIETARY ESSENTIAL ADVERSE EVENT INFORMATION DATABASE SELLS OR LICENSES PROPRIETARY INFORMATION TO A THIRD PARTY
OWNER OF PROPRIETARY INFORMATION OR THIRD PARTY GENERATES PRINTED PRODUCT WARNING INFORMATION DERIVED FROM ADVERSE INFORMATION DATABASE
END
FIG. 5
U.S. Patent
Jul. 19,2011
Sheet 6 of 6
US 7,984,069 B2
( START
SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12
-26'
SERVER 14, 114 OR 214 ANALYZES ADVERSE EVENT DATA FOR ESSENTIAL ADVERSE EVENT DATA
-28'
-30'
31"
SERVER 14,114 OR 214 GENERATES PROPRIETARY INFORMATION THAT CAN BE INCORPORATED INTO INTELLECTUAL PROPERTY AND/OR SALE DOCUMENTS
32"-
OWNER OF PROPRIETARY ESSENTIAL ADVERSE EVENT INFORMATION DATABASE MANUFACTURES AND SELLS PRODUCTS INCORPORATING THE PROPRIETARY INFORMATION
OWNER-MANUFACTURER OF PROPRIETARY INFORMATION GENERATES PRINTED PRODUCT WARNING INFORMATION DERIVED FROM ADVERSE INFORMATION DATABASE
( END )
FIG. 6
US 7,984,069 B2
COMPUTER ALGORITHMS AND METHODS FOR PRODUCT SAFETY REFERENCE TO RELATED APPLICATIONS s Tills application claims the benefit of U.S. Provisional Application No. 60/270,697, filed Feb. 22, 2001. which filing date is claimed herein, and the content of which is herein incorporated by reference. 10 FIELD OF THE INVENTION The present invention involves the fields of products, including drugs, medicaments, biologicals, devices, food additives, chemicals and other products or devices, that may i 5 have essential adverse events, as well as computer databases for generating, storing, analyzing and processing information related thereto. BACKGROUND OF THE INVENTION Computers, systems and methods for screening databases to determine new adverse events and to develop proprietary new uses and proprietary kits containing warnings pertaining to the new adverse event information have been described in U.S. Pat. No. 6,219.674 and U.S. patent application Ser. No. 09/804,289. However, the systems and methods described in the '674 patent were less than ideal because not all adverse event information is commercially valuable. In order for adverse event information to be valuable it must be patentable (i.e. proprietary) by being novel, uon obvious and having utility. Likewise, the systems and methods described in the '289 patent were less than ideal because, even if the adverse event data is pateiitable, it is not commercially valuable unless it is essential, that is, the information must be such that all manufacturers would need to include it with the sale of the corresponding product. Otherwise, manufacturers would continue to sell their products without the subject information. Conversely, if one were to simply patent all new uses for the product, drug, and the like, considerable time and money would be consumed, but there would by a low probability for commercial or financial return on the whole. The government has carefully established codes and rales under which, for example in the medical field, manufacturers and/or distributors are required to notify or warn the public of known adverse events which could occur when certain products, including drugs, medicaments and the like, are ingested or used by human or veterinary patients. Regulations also apply to chemical products, including food supplements, which may be absorbed, ingested or inhaled. Similar notice or warnings must be attached to devices, particularly to medical devices. Moreover, if the warnings are not present, the product or device not only must be immediately removed from use by, and availability to, the public, but also significant fines and penalties can be levied against the manufacturer and/or distributor of the product or device for its failure to provide adequate notice and warning to the public. In addition, because such manufacture and/or distribution was permitted without the required notice or warning, the manufacture and/ or distribution was practiced in violation of the law. As a result, those manufacturers and/or distributors risk criminal and/or civil liability to anyone adversely affected by the product or device during the time when it was on the market. The government has failed to establish mechanisms by which products and devices are adequately screened for safety, i.e., for the possibility of essential adverse events which could affect the safety of the patient using the product -(> or device. This is particularly true for medical products and devices. The screening that is conducted by manufacturers and/or distributors of such products and devices is typically small in scale and incomplete for all possible adverse events. Consequently, until the present invention, there has been a need in the art for reliable screening methods to eliminate or minimize the possibility of an essential adverse event that could affect a patient or consumer using a product or device, so that the consumer can trust that the product or device is "safe." In addition, the prior art has failed to contemplate business methods which involve detecting essential adverse events relating to a product or device, and then offering the refined proprietary data from such screens to the manufacturers and/ or distributors of the product or device. Once the existence of such essential adverse data is known to the manufacturer and/or distributor, they are obligated to inform the public of the potential adverse event, or they must remove the product or device from the market. Because manufacturers are currently producing and distributing products and devices without restrictions on their use, they are available for use in screens to develop essential adverse event data, which when refined, would become proprietary. Thus, there also exists a substantial market for such refined, proprietary, essential adverse event data, and for the methods, systems and devices by which it is obtained, which would (1) meet the need in the art for steps which would enhance public safety with regard to the use of products and devices, and (2) offer to manufacturers and/or distributors of product and/or devices a way to (a) significantly improve public safety, (b) permit their products and devices to remain on the market, and (c) reduce their risk of liability for the occurrence of an adverse event with the use of their products or devices. SUMMARY OF THE INVENTION The current invention permits not only ways of screening for new. previously unrecognized adverse events associated with the use of a product or device, but also a method, system and device for determining which new adverse events and new uses are "essential." The method, system and device permit a technician or computerised system to detect new essential adverse events and identify new useful characteristics or uses for a product or device, and commercialize the essential adverse data information. In some instances a manufacture or distributor is given the option of adding notifications or warnings that a product or device is associated with an essential adverse event, or they can perform safety studies to show the product is safe in light of the newly recognized, essential adverse event (essential methods of screening a product for safety). Thus, the invention relates to data processing methods and system for developing product safety information to be included in the package information which would accompany a commercial product or device. The current methods and system further provide for the detection and development of methods of screening a product or device for consumer safety. In preferred embodiments, the data processing system comprises: at least one adverse event database for storing adverse event data associated with a product or device: a processor for accessing and analyzing the data to assist in identifying new essential adverse events associated with the product or device and to assist in identifying at least one new useful characteristic of, or use for. the product or device responsive to identification of at least one new essential adverse event associated with the product or device; an adverse event information storage device for storing the new
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essential adverse event data identified by the processor; a computer for requesting and receiving adverse event iiiformation from the processor: and a user interface for interfacing with the processor and the computer. The present invention is further embodied by a method for creating and using data associated with a product or device comprising: accessing at least one adverse event data source that stores adverse event data associated with a product or device; analyzing the adverse event data to identify new essential adverse events associated with the product or device; analyzing data from the data source to identify at least one new useful characteristic or use for the product or device responsive to identification of at least one new essential adverse event; creating at least one essential adverse event information database, wherein the adverse event information includes at least one new characteristic or use; and commercialmng essential adverse event data stored in the essential adverse event information database. The invention is also embodied by a method of establishing at least one new use for a product or device comprising: comparing adverse event data associated with a product or device with previously known adverse event data associated with the product or device; observing at least one new adverse event associated with the product or device; determining whether the new adverse event associated with the product or device is an essential adverse event: and identifying at least one new useful characteristic of. or use for, the product or device responsive to the determination that the at least one new adverse event associated with the product or device is an new essential adverse event. In addition, the invention is embodied by a computer for managing product or device related data comprising: at least one adverse event database storing adverse event data associated with a product or device; a processor for accessing and analyzing the data to assist in identifying new essential adverse events associated with the product or device and to assist in identifying at least one new useful characteristic of, or use for, the product or device responsive to identification of at least one new essential adverse event associated with the product or device; and an essential adverse event information storage device for storing essential adverse event data including the at least one new essential adverse event associated with the product or device, and the at least one new characteristic of, or use for. the product or device identified by the processor. Moreover, the method and system further provide for commercializing the essential adverse event information. Further, the invention is embodied by methods and systems by which the detected information is formatted and compiled into contract documents, which are then used in licensing the essential adverse event information to manufacturers and/or distributors, who can then include the essential adverse event information in their product information, which is provided to consumers or prescribers of the product or device. Moreover, such contract documents can be used to license the essential adverse event information to potential competitors of the manufacturer and/or distributor. The embodied invention also provides marketing and packaging methods, in which the use of the subject product or device is restricted by a licensing agreement or contract, which would exclude using the product or device for the detection and patenting of essential new adverse event information. The invention also pertains to any product or device created using the essential adverse event data of the method, system or device of the present invention; as well as uses therefore.
4
The invention also provides a kit containing the product or device, and labeling notifying the user of at least one new essential adverse event for the product or device. Additionally provided are methods comprising using the kit in accordance with a new characteristic of. or use for, the product or device, The invention is especially useful in detecting and prevent ing essential adverse events related to, or caused by, medical products including drags, medicaments and biologicals, and medical devices. ()ther objects, features and advantages of the present invention will be clear to those skilled in one or more of the relevant arte-based on the teachings and guidance presented erem. DESCRIPTION OF THE DRAWINGS
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-The foregoing summary, as well as the following detailed description of the invention, will be better understood when read in conjunction with the appended drawings. For the 20 purpose of illustrating the invention, there are shown in the drawings, certain embodiment(s) which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown. 25 FIG. 1 is a schematic view of a first embodiment of a system according to the present invention, FIG. 2 is a schematic view of a further embodiment of a system according to the present invention, FIG. 3 is a schematic view of a further embodiment of a 30 system according to the present invention, FIG. 4 is a flow chart illustrating the method according to the present invention. FIG. 5 is a first preferred specific application of the method represented in FIG. 4. 35 FIG. 6 is a further preferred specific application of the method represented in FIG. 4. DETAILED DESCRIPTION OF THE INVENTION 40 The inventor's prior invention, U.S. patent Sen No. 09/449, 178 (now allowed) describes a computer system and method for deriving new uses based on new adverse events, which also finds application in the present invention. However, the currently embodied system and method of the invention provides for the further purification or refinement of adverse event information to develop new proprietary uses for a product, such as a drug, or for a device. The system and methods provide detecting "essential" adverse event information or "essential" new uses based on the adverse events or "esseutial" new methods of screening a product for safety, Referring to the drawings wherein like references indicate like elements throughout the several views, there is shown in FIG. 1 a first system 10 constructed in accordance with the present invention. System 10 includes at least one adverse event database 12, at least one essential adverse event database 1.2' and a server 14. Depending upon the source, the adverse event database(s) 12 may be accessed by server 14 free of charge or for a fee. Essential adverse event database 12'. preferably contains large amounts of data regarding a particular "essential" medical or non-medical product or device. The term "medical" as used herein shall be construed to mean drugs, vaccines, non-vaccine biologicals, medical devices and any other medically-related goods and therapies. Drugs and biologicals as the terms are herein used within the term "medical product," are intended to encompass any known, or as yet unknown, class of drug, medication or bio-
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logical therapeutic (including inhibitors, preventers, enhancers activators, stimulants, catalysts, promoters, regulators, and the like). These can be categorized by their effects oil ail organ system, such as cardiac, respiratory, renal etc. Dnigs and biologicals are also classified by their chemical composition, e.g., sulfa drugs, penicillin derivatives, vaccines, immune stimulants, antibiotics, etc. In addition, they can be classified according to their activity, e.g., diuretic, antibiotic, beta-blocker. etc. Medical devices can be similarly classified by those of ordinary skill in the art. e.g., medical devices may be grouped as defibrillators, EKG machines, inliision pumps. CT machines, etc. To further assist in the categorization process, those skilled in the art may consult medical science resources such as medical libraries or online authorities such as MEDLINE and the like to locate articles, books or other printed or electronic publications on the subject of interest suchas the non-limiting example of Goodman and Oilman's "The Pharmacological Basis of Therapeutics." "Non-medical product or device" shall be construed to mean any non-medically-related product or device that may cause harm to a consumer including, without limitation, foods, food additives, beverages, vitamins, alcohol, tobacco, cosmetics, mechanical devices and children's toys, personal and household cleaning products, and other chemicals such as paints and related coatings, insecticides, herbicides and industrial chemicals. Because of the large volume of data that they contain, preferred adverse event databases may include those of insurance companies, managed care organizations, pharmaceutical and medical device manufacturers and'or distributors, public health departments, hospitals and the like. Typically, each adverse event recorded in such databases links the adverse event with demographic information such as but not limited to, the age, sex and race and, frequently, one or more physical condition factors of the individual that experienced the essential adverse event. The result is that adverse event database 12 may contain thousands or even millions of items of date. Such vast repositories of information enable the data to be analyzed to generate statistically relevant and reliable information relating to age. gender, racial, physical condition or other subgroup. The essential adverse event database 12' is a refinement of the adverse event data procured from the adverse event database 1.2, based upon selection of adverse data that is "essential" as defined below. Server 14 preferably includes a shadow storage device 16. a processor 18, a user interface 20 and an essential adverse event information storage device 22. Shadow storage device 16 gathers and stores essential adverse event delta received from the adverse event database(s) 12. Processor 18 comprises any computer processing means suitable for executing the operations of the present method as described hereinafter. User interface 20 includes any suitable input/output (I/O) equipment. Essential adverse event information storage device 22 stores adverse event information that is generated by processor 18 responsive to analysis of the essential adverse event data stored in shadow storage device 16. The shadow and essential adverse event information storage devices 16, 22 may be any memory devices capable of storing large amounts of information. Lastly, system 10 includes a user computer 24 for interfacing with user interlace 20. User computer 24 is preferably any commercially available personal computer, workstation or the like which can exchange information with user interface 20 in the manner well known in the art. If the event data relating to a product or device is both essential and desired, the essential adverse event data in adverse event database 12' can be collected using the ICD and other disease codes on admission, discharge, pharmaceutical sales, physician visit records or other known sources. The system of the present invention also accommodates and processes animal safety test data such as animal toxicity data. Through operation of system 10 and the other systems described herein, the data extracted from the adverse event database 12 is analyzed by suitable programming of processor 18 to produce useful essential adverse event information that collected into essential adverse event database 12' and is storable in essential adverse event information storage device 22. For example, the adverse event database stores information on frequency of essential adverse events, such as but not limited to, death, illness, hospital!zation, office visits, disability, missed work, medical costs, abnormal lab results and surgeries in individuals receiving the product or device in question, and this information can be compared to the observed adverse event rate in the same persons before receiving the medical product or in persons of similar characteristics (i.e.. a control group). The analysis is performed on different exposure rates including, but not limited to the amount, duration and timing of exposure to the product or device. The "adverse events" refer to, for example, damage or alteration to any organ system, including the non limiting examples of cardiac, respiratory, gastrointestinal, endocrine, muscular, skeletal, liver, renal, spleen, neurological, skin, blood, immune, and bone marrow, 'fhese adverse events further include the development of new diseases, including the noil limiting examples of seizures, cancers, heart disease, arrhythmia, autoimmune disease, and allergy. Moreover, failure of a person to respond beneficially to a drug can be considered an adverse event. Preferably, the adverse event (or new use) is one other than one related to dosing including the timing of dosing (or optimizing dosing). The database to be screened for new adverse events comprises adverse event information relating to the use of products in or devices on humans or animals. While human data is more valuable for determining new uses in humans, it is possible that new adverse events detected in animals can be used to develop new product characteristics or uses in humans. An example is detection of birth defects, or drug interactions in animals, which preferably leads to new uses comprising restricted use in pregnant humans or humans taking certain drugs. Databases of adverse event information can be created by screening animal models of specific human diseases and cell culture models of human diseases for the potential new adverse events. In this situation an animal model of human disease is exposed to the product and the frequency or severity of the disease is recorded compared to a control group. Ideally the product is exposed to as many different animal models of human diseases as possible or feasible. In a similar manner a culture of cells can be exposed to a product in many instances. This is easily accomplished if the product is a drug, chemical, or emits radiation. The cells may be normal cells, premalignant or malignant cells. One can compare the outcome of product on the cells to that of the effect on control cells. Endpoints include the non limiting examples of cell death, cell mutation and cell division. Ideally the product or device is exposed to as many different animal models of human diseases as possible or economically feasible. One can use the data from the database to compare to previously known adverse events to determine new adverse event information. The order by which one checks for an adverse event can vary, and any order that is suitable is accept-
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US 7,984,069 B2 7
able. For example, one can hypothesize that a product causes one or more adverse events. One can then analyze the data to see if the product causes an adverse event, and then determine if the adverse event is new. Alternatively, one can hypothesize that a product causes an adverse event and then check databases to see if it has been reported that the product is associated with an adverse event. If the association has not been reported then one can screen raw adverse event data/databases to see if the product is associated with the adverse event. Ifdatadoesnotexisttotestthehypothesisusingavailableraw , ., , , , j 41 r adverse event data, then new data can be generated in the form .. , T ,. ,, . , , of a study. In most cases, this would involve animal toxicity studies since performing prospective studies in humans to prove adverse events is generally unethical. By "raw data," as used herein, means data beiore it is processed and analyzed. For example, the raw efficacy or adverse event data relating to a drug would include all of the collected data, which is linked to individuals who used the drug, or in some instances for a product such as tobacco, for those exposed to the product. This raw data comprises, e.g., the individual's weight, height, race, lab results, medical conditions and length of use or exposure to a product or device. By contrast, "processed data" means analyzed data that lias been categorized or qualified to meet the requirements or standards of a particular situation. In a preferred embodiment, one searches existing adverse event databases for adverse events, then determines if associations discovered are new. An additional study can be performed to verify the finding. In another preferred embodiinent, one can hypothesize about certain adverse events, and then determine if they have been reported. If they have not, then raw adverse event data would be analyzed to determine if there is an association. Additional adverse event information may also be derived from subgroup analysis. Subgroup analysis is performed to determiiie specific high risk groups who may be at increased risk of having an essential adverse event. Subgroups include persons with similar characteristics, such as but not limited to, sex, age. race, weight, height, percent body fat, genetic characteristics, pregnancy status, allergies, additional medical problems, use of additional medical products (including devices), past medical history, family history, social history, occupation, use of alcohol, tobacco, recreational drugs, and history of abnormal lab tests such as EKG. chest x-ray, liver function test and kidney function test. Similarly, subgroups are intended to include without limitation high risk associated groups such as high or low temperatures, chemicals, surfaces, pressures, electricity and sparks; or contact of the product or device with one of the group consisting of skin, eyes, ears, respiratory surfaces, gastrointestinal surfaces and mucous membranes of the consumer, or to a subpopulation group selected from the group consisting of children, pregnant women, consumers with specific allergies or medical condilions and animals. Preferably this demographic data, i.e., sub group information, is available through history and physical, where no additional laboratory test is needed for a new use. The subgroup analysis can include groups that were not represented or were under-represented in safety studies that were required for marketing approval or were done around the time of market introduction. For example, a drug may be approved for use in persons over the age of 18. However, people under 18 may also receive the dmg. In such case, packaging for the drug may not include sufficient warnings for persons under 18. in general, and subgroups of persons under 18, in particular, that are at greater risk of essential adverse events linked to usage of the product or device.
8
Studies, as described above and in other sections of this document, however do not prove a product or device causes an adverse event, only that the adverse event and the product or device are associated. In some instances there may be a -s direct link. For example, wealth or standard of living is associated with certain adverse events. Money does not cause the adverse events'but il allows wealth>' individuals to buy products that cause a sPec]fic adverse evenl' If al1 epidemiology study does show an association between an adverse event and I 0 a Prduct f device' thef *** ls a nsk to the assoclated product or device caused the adverse event, -n i -ri . . . .. .. This nsk exists even il the association is not statistically si mficallt However the risk is ter if a surtistically sig. ^Scant associatioil ^^ since some of me associations are ., tn]e causa, relations< knowledge that a risk exists has utility
since one can avoid the risk when one knows it exists
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Ideally, systems according to the invention track large numbers of variables to locate groups at high risk of essential adverse events. As a non-limiting example, the systems are configured to track people taking multiple different drugs to determine whether a toxic adverse event occurs in people taking all of the drugs at once. The systems utilize statistical formulae to identify groups at high or low risk of essential adverse events. Preferably the database of adverse events associated with a product contains multiple different adverse events and is not limited to a single type, such as diabetes, birth defects, or the like. The systems according to the invention also optionally collect and analyze efficacy data. The benefit of the product or device in certain subgroups can thus be measured by observing the frequency of the intended benefit (e.g., decreased death, stroke, kidney failure, and so oil). Benefits also include reductions in costs where the costs may include, without limitation, costs of the product or device, expenses and lost productivity. By using the data from the risks and benefits, one can determine the risk/benefit for persons in any particular subgroup. This information can be highly stratified to enable, in addition to previously known uses, new. different or more precise uses for a product or device. For example, a dose of a drug or biologic, me frequency or manner of use of a device, or the setting of a device such as a pacemaker may be precisely prescribed to accommodate the individual needs of particular subgroups. Targeted searches can be performed and their data analyzed by the systems of the present invention. For example, if it is discovered from one adverse event database 12 that persons receiving a medical product are at increased risk of dying of liver failure at a certain dose of medication or when taking the drug in combination with other drugs, then one can verify the findings using a second adverse event database 12. Adverse event data from either adverse event database can also be confirmed in animals or by prospective clinical trials in humans. Targeted searches can also be done after case reports of adverse reactions, discovery of adverse events in animals, adverse events discovered in similar products and possible adverse found in small studies. Consistent with the invention, any number or variety of proprietary databases are storable on essential adverse event information storage device 22. For instance, a first proprietary' database created containing information about a particular product's or device's adverse events and, optionally, risk benefits and cost benefits of die product or device. The data from that database is crossed, linked or compared with a database of knowledge already accumulated on the product or device that may also be stored on essential adverse event information storage device 22. Sources of prior known essen-
US 7,984,069 B2 10
tial adverse events can include package inserts, the Physician's Desk Reference, The Merck Manual, data from regulatory agencies such as the FDA, and published literature found on databases such as MEDLINE. In the future it is contemplated that databases of patents and patent applica- 5 tions will also contain known adverse events. Likewise, the databases can comprise commercial or sales data. New findings on essential adverse reactions can thus be determined through appropriate comparison and/or interpretation of the databases. 10 The newly derived knowledge can include, without limitation, catalogs of new adverse events, specific frequency of adverse events, drug interactions and side effects in specific subgroups such as those mentioned above. For instance, a new essential adverse event can mean a newly discovered 15 adverse reaction such as the discovery of an increased rate of seizures associated with a drug, improved information such a s more accurate calculation of the rates of sei zures in a group or subgroup, or the discovery of an increased rate of seizures in patients taking the drug along with one or more additional 20 drugs. FIG. 2 represents a further preferred embodiment of a system according to the invention identified by reference numeral 110. System 110 is constructed and functions substantially similarly to system 10 of FIG. 1 with the exception 25 being that the shadow storage device 16 and essential adverse event information storage device 22 of system 10 are integrated into a single shadow storage device and essential adverse event information storage device 16, 22 on server
114. 30
FIG. 3 represents a further preferred embodiment of a system according to the invention identified by reference numeral 210. System 110 also is constructed and functions substantially similarly to system 10 of FIG. 1. However, unlike systems 10 and 110. system 210 draws its essential 35 adverse event data from an internal rather than an external source; that is, server 214 of system 210 directly supports essential adverse event database(s) 12'. System 210 graphically depicts a situation wherein a holder of a substantial body of adverse event data itself analyzes such data using processor 40 18 and creates one or more adverse event information datebases that are stored on essential adverse event information storage device 22. Exemplary users of system 210 may include, for example, insurance companies, managed care organizations, pharma- 45 ceutical and medical device manufacturers and/or distributors, public health departments, hospitals and the like. Although illustrated as separated devices, it is also contemplated that essential adverse event database(s) 12' and essential adverse event information storage device 22 may be inte- 50 grated into a single storage device. FIG. 4 is a flow-chart that embodies the essential method steps of the present invention that are executed by each of systems 10. 110 and 210. At step 26, the adverse event datebase(s) 12 are accessed by server 10,110 or 210 (at a fee or 55 free of charge) to obtain desired adverse event data therefrom. In systems 10 and 110, the adverse event database(s) 12 are external to the servers 14 and 114. Hence, servers 14 and 114 desirably store the date received from databases 12 in shadow storage devices 16. Server 214. by contrast, accesses its inter- 60 ual adverse event database(s) 12 for the desired data. The desired adverse event data having been accessed, the processor 18 of systems 10. 110 and 210 then analyzes the data, as described above, to identify previously known and new essential adverse events, as indicated at step 28. At step 65 30, the processor 18 further processes the analyzed adverse event data to create useful proprietary essential adverse event
information, such as any of the kinds mentioned above. More particularly, in creating the proprietary adverse event information database at step 30. or more preferably an essential adverse event information database, at step 30' (not shown), processor 18 preferably possesses logic whereby it categorizes the newly-discovered essential adverse event(s) associated with a particular product or device that are identified at step 28 and also identifies at least one new use for the product or device responsive to the identification of at least one new essential adverse event(s) associated with the product or device. The processor 18 then stores the essential adverse event information as one or more databases in essential adverse event information storage device 22. According to presently preferred embodiments of the invention, the data retrieved from adverse event database(s) 12 is processed and analyzed by a centralized processor 18 on server 14, 114 or 214 and the analyzed data is stored at an essential adverse event information storage device also supported by server 14,114 or 214. Alternatively, the proprietors of servers 14,114 or 214 license proprietary software to users of user computers 24 that perform the functions of processor 18. Such software is loaded onto the user computers 24 to execute the adverse event date analyzing and other processing functions of processor 18 described above and the generated useful adverse event information may be stored at the user computers 24. In any case, servers 14, 114 and 214 can be directly connected by a user interface 24 such as but not limited to a modem. It will be understood that the servers 14.114 and 214 may also be indirectly connected to user computers 24 via one or more other servers, a central computer or other system designed to link computers or other processing machines. Ideally, the information is transferred digitally between servers 14, 114 and 214 and user computers 24. Alternatively, however, it is transmitted in analog form by a modem along standard telephone lines. It is further understood that the information can also be transferred by disk, printed and then scanned in or. alternatively, manually re-keyed. Preferably, the user computers 24 and their associated printers (not illustrated) are sufficiently sophisticated to organize and print all information generated by the systems 10, 110 and 210 in virtually any desired format and on essentially any desired printable medium that is printed by the printers. However, certain product labels and package inserts that incorporate the information can be manually type faced using typesetting or other conventional printing techniques. The system also formats the data for submission to regulatory agencies such as the FDA. The proprietary information that is generated by the systems of the present invention is superior in many ways to the limited, and generally static, adverse event da to and databases heretofore known in the art. In respect to medical products in particular, the volume of data and the degree to which the data may be stratified and studied, the systems according to the invention far exceed the capabilities of FDA-required premarketing studies for medical products. To illustrate, a typical FDA pre-marketiiig study generally involves study populations of less than about 5000 and normally less than about 2000 participants. In contrast, the adverse event data that is amassed and analyzed pursuant to the invention contains information on far larger numbers of people receiving the medical product. Representative populations studied using the present system in virtually all practical medical product scenarios comprises at least 5000 and is analyzed in any desired increment such as, for example, 5,000; 10.000; 50,000; 100,000; 200.000; 1 million or more.
US 7,984,069 B2 11 12
The systems of the present invention will additionally proReturning to FIG. 4, the adverse event information stored vide a better appreciation of delayed or latent essential in essential adverse event information storage device 22 is adverse events caused by products or devices long after inicommercialized. Commercialization of the useful essential tiation of treatment or after treatment has been discontinued. adverse event information may take on an assortment of Using the present systems, post-exposure follow-up of a 5 forms as indicated in FIGS. 5 and 6. product or device is "analyzed in any desired increments of Users of servers 10,110 and 210 may include individual, a time. For instance, selected post-exposure study periods may corporation, partnership, government agencies, research be as brief as a few minutes or hours to considerably lengthier institutions or any other persons or entities that may have an periods, such as 1 day, 2 days, 7 days, 10 days, 30 days. 90 lnteresl m or need lor new and useiy essentlal adverse event days. 180 days. 1 year. 3 years. 5 years. 10 years or more. ' inlon; Non-limiting examples include manufacturers . , r i i v i-i r i and/or distributors 01 products or devices, insurance compaRisk/benefat analyses may also be readily performed using - 1 1 1 j n- i 11. . . , , , ., .. . . ,, mes. health maintenance organizations and public health the,methods and systems . . described, herein. Acceptable essen-, , , TIn *i_ case ol manufacturers and/or distributors * * * . .i/ j- .. -i. * . , " . ,,. , , , .. departments. the tial adverse event thresholds may be established and studied ()f ^ m devices_ such manufactwers wd/or dislribu. foraproductordevice.Theessentialadverseeventthresholds tors may use the infornlation in the manufacture and/or dismay be selected to be at any desired incidence level, e.g.. tribution of their own products, or may license the informa1:10,000,000; 1:1,000,000; 1:100,000; 1:10.000; 1:1,000; tion to their competitors. 1:100, above which use of a product or device may exceed its As indicated by step 26' in FIGS. 5 and 6. at the request any benefit for a general or specific population group. The essenof these persons or entities or on its own behalf, the owner or tial adverse event thresholds serve as limits for single or 20 licensee of server, 14. 114 or 21.4 accesses and retrieves rawaggregated newly discovered adverse events. For example, an adverse event product data from adverse event database(s) 12. essential adverse event threshold of 1 occurrence in 1000 At step 28' the server analyzes the retrieved data to identify persons may be established as an acceptable level of occurnew essential adverse events regarding a product or device, to rences. conduct cost/benefit analyses related to the newly discovered If 2 occurrences are observed in the target population then 25 essential adverse events or to perform any other desired the essential adverse event threshold is exceeded and the analysis of the raw data. At step 30'the server creates one or product or device is deemed unsafe or commercially impracmore proprietary essential adverse information databases that tical for use by persons in that group. Likewise, 10 new are stored in essential adverse information storage device 22. similar or dissimilar essential adverse events relating to the At step 32' in FIG. 5 the licensee or owner or owner of server product or device may be observed in the target group, but 30 14, 114 or 214 commercializes the essential adverse event none of the individual new essential adverse events occurs information in essential adverse information storage device more than oncein 10.000 persons. In the aggregate, therefore, 22 by selling or licensing the proprietary information to a the 10 occurrences detected in a total study population of third party. The third party communicates with system 10, 10,000 persons corresponds to a ratio of 1:1000 which equals, 110 or 210 through user computer 24. The user computer but does not exceed the acceptable essential adverse event 35 interfaces with user interface 20 to make requests for inforthreshold for the product or device under scrutiny. In this uiation to and to receive information from the processor 18 of instance, the product is deemed safe and commercially viable server 14,114 or 214. Interpretation of the received informafor use in the targeted population group, tion may be performed by the third party, an independent The present systems and methods also enable ready comcontractor, the owners or licensees of server 14.114 or 214 or parisons between target populations that receive treatment 40 the owner(s) or licensees of the essential adverse event datawith a product or device, and experience essential adverse base(s) 12. events, with untreated control groups that experience similar Practical, but non-limiting, examples of possible users of essential adverse events. For example, a target group treated systems 10, 110 or 210 and the method depicted in FIG. 5 with a certain vaccine that acquires diabetes may be cominclude manufacturers and/or distributors of products or pared with an otherwise identical but unvaccinated control 45 devices, holding companies, venture capital companies or group that also acquires diabetes. Increased incidences of other companies or individuals seeking to capitalize on owndiabetes in the target group thus may be attributable to the ership of a portfolio of new product information that may be vaccine. of commercial value. The users may use the information to Systems 10,110 and 210 may be programmed to establish seek patent, or other intellectual property protection for the any desired acceptable increased rates of essential adverse so information. The systems 10, 110 and 210 and the methods event occurrences in the treated target group versus the depicted in FIGS. 5 and 6 are especially useful for creating untreated control group, e.g.. 2%, 5%, 10%, 20%, 30%, 50%. proprietary information and products or devices. The systems 75%, 100%, 150%, 200%, 300%, 400%. 600%, 800%, and methods of the present invention can assist in preparing 1,000% or more, above which treatment would be contraininformation for a patent application and can assist in docudicated in the target group. Preferably, the system analyzes 55 mentation of the invention, including inventors, date of invendata using any desired study design. For example, a case tion. progress of the development of invention. As used control study design may be used where the frequency of herein, proprietary information shall be construed to mean using a product or device in a group with the target disease is information that is used or intended to be used for establishing compared to the frequency of using a product or device in a or claiming specific intellectual property rights. For example, group of controls. The studies may include prospective clini- 60 the proprietary information can be used in the creation of cal trials and retrospective follow-up of clinical trials, as well intellectual property, sale or licensing documents; that is, the as cohort analysis of people not in clinical trials. The studies proprietary information may comprise textual or graphical may, or may not. include efficacy for the intended use as in content that may be incorporated into patent applications. A treatment of a specific disease. The studies may also be part of 'proprietary new use' means a new use, in which one has or is a pre-approval or post-marketing study regulated by the FDA 65 seeking intellectual property rights, i.e.. a patent, or similar regulatory body. Conversely, the studies may be It is not the intent of this invention to encompass an unaffiliated with FDA-sanctioned clinical trials. "expanded use" relating to an unexpected phenomenon asso-
US 7,984,069 B2 13 14
ciated with a product or device. "Expanded use" is used devices incorporating the proprietary information and then herein to mean other uses for a product or device m addition selling the products and devices. to currently known uses for the product or device. For In addition to the functions represented by method steps example, if an unexpected phenomenon associated with 26', 28', 30'. 32' and 32". additional tasks are preferably perblood pressure medicine is hair growth, then the use of blood -s formed to more completely fulfill the purposes of the present pressure medicine may be expanded to include use as a hair invention, as reflected in FIGS. 5 and 6. For example, as tonic. By comparison, expanded uses fora medical product or indicated by step 29' in FIG. 5, server 14,114 or 214 may be device are not created by discovery of adverse events, rather programmed to generate proprietary information, typically in such uses are determined bv performing extensive clinical textual and/or Î*10 form - thal ls incorporated into mtellectrials and obtaining regulatory approval for marketing the 10 tual PPerty' Sale and/Or llCensmS df melljs' "H* docuf., , . j . ments then are used m negotiations with product or device new use 01 the product or device. ,, ,. .. , . , .. , , i i . , . . . , , manufacturers and/or distnbutors or other interested third On the other hand, the invention is intended to encompass .. , ,,... ,, ,,,.-, , i . inu IA , . ' . .. , ... . parties.Additionally, FIG. Sreveals instep 31 that.server 14, a restricted use, i.e., avoiding, when possible, use of the 114 or 214 optionally gei]erate printed product warning product or device by methods involving same, or by using 1S information derived from the essential adverse information same, that are at increased risk for an adverse event. A new database(s). The printed warning information may be used in useful characteristic of a product or device responsive to connection with packaging such as, for example, as product identifying an essential adverse event, e.g., providing a writlabeling or as product packaging inserts to advise the conten warning with Hie product to a consumer, is also encomsumer (or product prescriber in the caseof products or devices passed by the invention. New restricted uses are primarily 20 requiring a prescription) of contraindications or other adverse derived by discovering an adverse event because manufacturevents associated with use of the product or device. Alternaers are required to disclose possible adverse events associated lively, as shown in step 33' of FIG. 5. the owner of the prowith use of a product or device, even if the adverse event has prietary information or its licensee may generate the aforenot been proven to occur in a specific risk group or situation. said printed warning information. However, the invention is intended to encompass a use that 25 Similarly, in FIG. 6, the server 14,114 or 214 may generate allowsagroup. previously consideredtobeathighrisk, to use proprietary information that may be incorporated into intela product by better defining the high risk group, although, this lectual property and/or sale documents (step 31"). Printed is neither an expanded nor a restricted use. product warning or safety information is generated by the It is also not the intent of this invention to encompass the servers 1.4,114 or 214. Alternatively, as shown atstep 33", this simple copyrighting of package inserts that may contain 30 step is performed by the owner or licensee of the proprietary adverse event information. A manufacturer and/or distributor information (who also manufactures and/or distributes the is entitled to the copyright associated with any creative work product or device or causes it to be manufactured and/or that it produces, including package inserts. Of course, packdistributed). age inserts may contain adverse event information or product Equipped with the new essential adverse information genuses that are not proprietary' and are in the public domain. This 35 crated by systems 10,110 and 210, a user might also urge the invention is, therefore, not intended to encompass this pracFDA to compel existing manufacturers and/or distributors of lice. It is also not the intended purpose of the present invena product to remove the product from the market if it does not tion to encompass proprietary kits (i.e., patented), wherein have adequate safety warnings or to prevent those contemthe kit is proprietary solely because of pre-existing intellecplating marketing the product from entering the market withttial property rights. Rather, it is the intent of the invention to 40 out providing adequate safety labeling, claim proprietary kits containing new proprietary adverse In a preferred application, the systems described herein are event information and/or instructions to use the product used to develop new proprietary safer uses for drags that are according to a proprietary new use based on new adverse already generic or soon to become generic. A generic drug is event information, wherein that new adverse event informaone where the active compound either is not protected by a tionistlieproductofasystem,deviceormethodofthepresent 45 composition of matter patent, or the patent will very soon invention. expire. Therefore the active compound is commercially availUsers might seek patent protection for new therapeutic able and adverse event data may be available from one or uses for existing products or devices based on newly discovmo re sources. In some instances there are drugs that are on the ered essential adverse event information. Similarly, users market but protected by orphan drug status, such as thalidomight seek protection for new labeling necessitated by the 50 mide or by a use patent such as AZT. In these instances the disco very of the new essential adverse event information. For composition of matter patent had expired but competitors any new use discovered by the systems according to the have not entered the market because there are only a few present invention, the instructions accompanying (he product known existing uses for the product, and these are covered by or device for which the new use is identified should desirably use patents or orphan drug provisions. However, these drugs warn newly-identified high risk users of the product or device 55 may have been on the market for ten or more years and little to avoid using the product or device. Likewise, the instrucresearch has been conducted before or during that time to tions also inform users who were previously but wrongly identify and optimize the fullest extent of their potential identified as high risk users that the product or device may be ranges of safe use. Moreover, they have probably been tested safely used by them. Preferably, systems 10,110 and 210 are for other indications, and adverse event information exists on capable of formatting the proprietary information data such 60 them. that it is suitable for incorporation into the aforementioned In varying degrees, generics of a proprietary drug often intellectual property documents. differ from the proprietary drug itself, and from one another. In FIG. 6, method steps 26', 28' and 30' are identical to their More particularly, although their active ingredients may be counterparts in FIG. 5. However, as indicated at step 32" of the same, generic drugs may include impurities, inert subFIG. 6, the owner or user of the proprietary essential adverse 65 stances, carriers and other agents that are not present in their information commercializes the proprietary information by corresponding proprietary drags or other generic alternatives manufacturing (or causing to be manufactured) products or thereof. When considering generics and their proprietary
US 7,984,069 B2 15 16
counterparts based solely on their active ingredients, the warning information and receive monies derived from the generics would be expected to exhibit similar adverse events. sale of the drug ill the form of royalties or a lump sum fee. However, through implementation of the present invention. Alternatively, the independent company may utilize the generic drugs can be precisely compared against their propriservices of a contract manufacturer that will"make the dmg for etary drug counterparts, and alternative generics, to deter- 5 me independent company which will reserve the right to sell mine the impact of their inactive ingredients on adverse the product on its own behalf. The independent company may events, despite the variability of such inactive ingredients. For a]so be a ,arge ilm)rer or pharmaceutical company that has instance, drugs with agents which delay the release of an accegg to its own extensive adverse event information dataactive agent can be expected to exhibit many of the same side base(s) from wWch may identjfv ^ commerciallv loit effects as drugs with the same active ingredient, but that 10 flew uges fofexisti roducts o'r devjces release it over a shorter period o f time. I n this context, there. - i i _ u * < 1 1 1 , ' . , i , ' i i As mentioned above, the present systems and methods are lore, a generic and a proprietary drug is considered to be the , .,. , , . . ,, .r i t-f.r. i <, \ , \f i. also utilized to develop proprietary salety information on same product if the adverse event(s) and/or new use(s) for the , , , ,drugs would be expected to be consistent for both. products or devices unrelated to the medical fields since The "new use" derived from the new adverse event may is manufacturers and/or distributors in other fields of endeavor involve restricting the use of the product or device in ways generally are required to provide consumers with safety miorthat are now discovered to be dangerous. For example, if a mation regarding their products, product is determined to be flammable or explosive, the "new Essential Adverse Event Information proprietary use" would restrict its use in conditions that could The final determination of what is "essential" information lead to combustion or explosion, which may occur when used 20 is determined by a regulatory agency such as the FDA. in the presence of an open flame or near a fire. Substances New adverse event information that is "essential" is of discovered to emit toxic fumes would, as a new use, only be great commercial value since if this information is propriutilized in well-ventilated areas, or under safety hoods. The etary, for example patented in the form a new use, it can be new use may include providing a kit which contains warnings used to exclude potential competitors from selling a product about a new adverse event relating to use of the product or 25 which would require the essential information. In order for a device. company searching through raw adverse new uses, to maxiThe term 'commercially available' pertains to products or mize profits from such a search, the "essential" new uses devices that are available to more than one group or company. should ideally be separated from other new uses. By limiting The product can be a substance, such as a drug, which is the protection for such new date, e.g.. patenting, and limiting known by more than one company or research group. With 30 petitions to regulatory agencies to only the "essential" new such a product or device, adverse event data may have been uses, a company saves time and money by avoiding expendgenerated by more than one group, and adverse event data ing time on adverse event information that has little commeralthough generated by one group, may not be new. This is cial value. because another earlier group may have discovered the Methods of Determining Essential Adverse Events adverse event first. This is especially true when the product 35 A computer system can assist in identifying essential has been sold commercially, and is known to have been used adverse event information. Preferably the first step is to idenby a number of different groups over time. tify adverse events associated with a group or subgroup using Studies may be performed with non-commercially availor exposed to the product in question. able products, wherein a non limiting example would be In accordance with the embodied invention, comparisons drugs. In this example, the non-commercially available drug 40 are made regarding the risk of the occurrence of a new adverse may also be tested in patients receiving commercially availevent in a group of subjects exposed to the product or device, able drugs. Drug interactions may be detected between the with the occurrence of the same event in a control group. One commercially available drug and the non-commercially type of control could be a group exposed to a competing available drug. In this situation the purpose of the study is to technology (drug, product). For example, if the system is screen a database for adverse events of the non-commercially 45 evaluating the use of a fuel, then the control group would be available product, not the commercially available product. A exposed to a competing fuel, such as oil vs. coal vs. natural manufacturer and/or distributor of a commercially available gas versus electricity. In a like manner, the system could product or device is not required to wani potential users about compare those exposed to an oil-based paint versus a latex an interaction that may occur with their product or device and based paint as a no 11-limiting example, a product or device that is not yet available, or that the manu- 50 Another type of control group could be a group that facturer or distributor does not even know exists. The present receives no exposure to a competing technology. For invention is intended for screening of products that are both example, comparing a group receiving a dmg, to a group commercially available and those that are not, unless otherreceiving no drug, wise specified. A third possible control situation would be a population Many entities, large and small, may beneficially utilize the 55 exposed to the product in question, but selecting a subpopusystems described herein. A representative, although nonlation, which does not contain people in the same subgroup in limiting, example would be an independent non-manufacturwhich the adverse event is thought to occur more frequently. ing company that procures access to one or more essential An example would compare a population receiving 4 doses of adverse event databases to analyze the data contained therein a vaccine, to a population receiving only one dose of a vacand identify new uses for existing drugs. The independent 60 cine, which is either equal to a bolus of all 4 of the comparable company could then license the "new use" technology or new doses, or which is equal to only one of the comparable four characteristic it discovers to pharmaceutical manufacturers. doses. Another example would compare a group of people The content of the licensing agreements may be agreed upon with liver problems, receiving a drug for a non liver ailment, before or after the data has been analyzed. The independent to a group with healthy livers who receive the same drug, company may opt to file appropriate intellectual property 65 A fourth type of control would use the group members as documents such as patent applications covering the newlytheir own control. In this case the incidence of an essential discovered uses for the product and/or their attendant product adverse event occurring prior to exposure to the product or
US 7,984,069 B2 17 18
device, is compared to essential adverse events following the that adverse event is essential. In the later case this exposure to the subject product or device. embodiment pertains to specific tests to insure a product is Having estimated the risk of an adverse event associated safe, which comprises specifically checking to see if the with a product, such as a drug, one can determine if the product is associated with or causes the adverse event which adverse events are essential. Several different criteria can be 5 js aiso associated with the competing product, utilized to determine if the adverse reaction is essential. Such A competitor can perform specific tests to try to disprove criteria include the non limiting examples, comprising: determe existence of all essential adverse event. This can be of mining whether the adverse event is unnecessary, if the risk va]ue ,0 a competitor when all adverse evellt information is exceeds benefit, it causation has been proven or if theriskis coyered ina (i e riet adverse event) îndu. frequent and or severe. I hese factors can be determined, and , o siofl of ^ ^^ ^ jn fl duc( dafa safety ^ (for compared or compiled with the assistance oi a computer. , u * 11 i_ i- / i _ j , . , , ,, , ... example pharmaceutical labeling/package insert or an adverAn unnecessary adverse event would be an essential ' * . . , , e .. , , ,adverseeventthatcouldbeorcouldhavebeeneasilvavoided. l;semellt) m ^truction brochure, pamphlet orbook tor a One example would be a drug interaction, which could be device, would constiuite an act of minngement. Alternatively, avoided by withholding one of the interacting drugs. Another 15 a competitor can perform a study to either try to disprove the example of an unnecessary adverse event is one in which the existence of an adverse event or try to disprove that the adverse event can be or could have been avoided by using a adverse event is 'essential.' In the later case the competitor different product, or even a different brand. For example, if a may use the same or different date as was used in establishing drug is very toxic in a subgroup of people, e.g., people of a the adverse event in the first place, or that established that the certain age, or those who have a preexisting condition, then 20 adverse event is essential. The competitor can also use the the adverse event in such individuals groups can be or could same or different epidemiological method, and the same or have been easily avoided by using a different drug or different different statistical tests. Moreover, the competitor can protreatment, for example, surgery. vide additional data to supplement the initial data, such as Another type of essential adverse event information is one information regarding confounding variables that may be in which the risk 'exceeds the benefit.' For example, in certain 25 useful for disproving the essential adverse event information, subgroups of patients, the risk of disease or complications Computers can assist in this process as provided above, exceeds the benefit provided by the product or device. By avoiding the placement of proprietary adverse event A tlii rd type of essential adverse event information is where information in a product data safety sheet or the like, a comthe frequency of the adverse event is so high, or the event so petitor avoids infringement of patents. This is because what severe, that a significant health concern or medical manage- 30 was claimed as an essential element in the patent or what ment issue. In a situation the adverse event may occur graduappeared to be inherent in the claimed invention, is no longer ally, but laboratory testing could pick up the damage early, so required in the competitors product. Such an improvement that further damage need not occur. The frequency of the will avoid costly patent litigation and lead to lower costs of events that render an adverse event essential depends in part development of a product or device, quicker time from develon the severity. Association between death, hospitalization, 35 opment to market, or an expected higher return for developlife threatening events, permanent organ damage, disability. ment costs. cancer, or birth defect and a product or device, becomes Nevertheless, the present invention is not intended to essential adverse event information at a lower frequency than encompass pharmacogenomic techniques for screening, would the information relating to a potentially benign adverse Licensing Agreements. event, such as but not limited to minor pain, swelling, and 40 The invention provides new methods of business that profever. Other adverse events that are included in this essential vide to a manufacturer and/or distributor the ability to prevent category include marked abnormalities in laboratory values, a third-party, potential competitor from generating proprivital signs. EK.G, and seizures. etary 'essential' information with regard to the manufactured A fourth type of essential adverse event information occurs or distributed product or device, thereby preventing the when the adverse event is so well characterized that causation 45 manufacturer's and/or distributor's exclusion from the maris generally believed to exist. For example, such a situation ket. A preferred embodiment of this method involves using a can occur when the adverse event is detected in two separate, licensing agreement/contract for sales of the product or well-controlled clinical trials, i.e. the adverse events are device, which suites that die product or device can only be duplicated. An example would be an industrial chemical. used for certain purposes. Such a license would exclude the wherein exposure is unintended, but for which exposure is 50 licensee's right to the use the product or device to determine known to cause severe adverse events. By providing warnnew proprietary characteristics or uses for the subject product ings, one can alert those who may be exposed of the risks or device, for the situation in which the new characteristic or associated with accidental exposure, and the treatment that use is discovered by screening for the occurrences of new should be undertaken to minimize ail adverse event following adverse events related to the use of the product or device, exposure. 55 The license or agreement could be similar to that used with Method of Screening fora Specific Adverse Event, Especially software (e.g.. a shrink-wrap license), where the breaking of an Essential Adverse Event. the wrapper or of a seal indicates one's acceptance of the The method of the preferred embodiment can be utilized to contract. Such a licensing agreement could be affixed to or develop new methods of screening drugs for adverse events, accompany the product or device, by methods well known in particularly essential adverse events. The discovery of an 60 theart.Alteraatively,itcouldbesignedbyaresponsibleparty essential adverse event warrants that all manufacturers and/or prior to delivery of the product or device to a purchaser, distributors of the product or generic version to warn of the end-user, distributor, etc. Moreover, as part of the contract/ adverse event. In certain circumstances where a competitor licensing agreement, the purchaser, end-user, distributor, or produces a similar or even identical (generic) the competitor the like, would agree for a predetermined period of time not to may be given the choice of warning potential consumers of 65 use the product or device in any attempt to discredit the the adverse event, or of performing a study to disprove-the existence of one or more new, essential adverse events, or the product is related to or causes the adverse event, or disprove utility of the existing subject proprietary use.
US 7,984,069 B2
19 20
This will prevent competitor licensees from trying to block obtaining one or more new patents based upon the discovery the original owner's rights to the product or device by 'disof essential adverse events associated with use of the product covering' through the use of essential adverse event infonnaor device. tion, proprietary new characteristics or uses of the product or In a preferred embodiment of the invention, a product or device. For example, if the competitor were to find or become -s device for which an essential adverse event is discovered, is aware of a previously unknown, essential adverse event, and also one mat is hig^Y profitable, but would face a marked if that information were proprietary to the competitor, such a decrease in profitability if the product or device were to lose competitor could have a basis for claiming exclusive rights to lts proprietary status. One skilled in the art can screen proda novel product or device, which would be just like the origiucts or devices b>' &d methods to determine the nal, except it claims a new characteristic based upon the 10 potentml value of discovermg propnetary essential adverse , ,, , , , f .. TT events. Those skilled in e.g.. sales, marketing, licensing, stanewly discovered essential adverse event information. How. . . . . ..., , . , . . . . . . , , tistics or business practices, will know how to use recognized ever, the agreement controlling rights to use the product or methflds IQ ca]cu,ate Qr ^^ such meters as _ in the device would preclude such behavior. n()n ]imili ^ les o currellt market share, polentia] Alternatively, or in addition to an end-user agreement, a ,_, market share total market ghare in unit volume Qt saleg< licensing agreement can be made at the tune of intermediate marketing costs, elasticity of demand, cost of production, cost sales of products or devices to wholesalers, retailers, distribuof marketing, number of competitors, market potential, cost tors or other who purchase the product or device with the of discovering a new adverse event, product liability costs, intent of reselling it to third parties. Such an agreement can be growth of market and the like. Mathematical modeling, with in the form of, or include, an electronic monitoring system. In 20 or without the use of computers, can be performed to evaluate one such embodied electronic system, a window would whether it would be profitable to develop a proprietary essenappear or a button would require activation, acknowledging tial new use based on ail essential new adverse event. In acceptance of, and intent to comply with, the contract/licensaddition to profitability, an entity may desire to determine ing agreement. In an alternative embodiment, an electronic cost of capital and opportunity costs before deciding to move signature, acknowledging acceptance of and compliance with 25 forward with the project. the agreement would be stored. In a third possible electronic All references cited herein, including journal articles or method, an electronic image of an 'executed' agreement abstracts, U.S. or foreign patents, published patent applicadocument would be saved. tions, or any other references, are entirely incorporated by A manual packaging system can also be established which reference herein, including all data, tables, figures, and text could be utilized ill shipments to purchasers of large quauti- 30 presented in the cited references. Additionally, the entire conties of the product or device, such as but not limited to wholetents of the references cited within the references cited herein salers, retailers, middleman, merchandisers, distributors and are also entirely incorporated by reference. the like. A seal could be applied to the bulk package, that It is to be understood that the phraseology or terminology when broken, would certify agreement with a licensing agreeherein is for the purpose of description and not of limitation, ment of the rype(s) described above. 35 such that the terminology or phraseology of the present speciBased upon this disclosure, one skilled in the art can devise fication is to be interpreted by the skilled artisan in light of the any of a number of different methods or systems to accomteachings and guidance presented herein, in combination plish the task of creating and/or verifying an agreement, elecwith the knowledge of one of ordinary skill in the art. Refertronically or otherwise, that would prevent the purchaser ence to known method steps, conventional methods steps, and/or the end-user from using the product or device in cer- 40 known methods or conventional methods is not in any way an Uiin ways or for certain purposes, specifically for generating admission that any aspect, description or embodiment of the proprietary new, essential adverse event information to be present invention is disclosed, taught or suggested in the used for the identification and/or development of new charrelevant art. acteristics or uses of the subject product or device, and/or new While the foregoing specification has been described with methods of screening such products or devices for such new, 45 regard to certain preferred embodiments, and many details essential adverse event information. have been set forth for the purpose of illustration, it will be Methods of Screening Adverse Events For Commercial apparent to those skilled in the art that the invention may be Value. subject to various modifications and additional embodiments. All essential adverse event information is not of equal and that certain of the details described herein can be varied value. Value depends on the potential value of making a 50 considerably without departing from the spirit and scope of generic product or device into a proprietary product or device. the invention. Such modifications, equivalent variations and or preventing a proprietary product or device from becoming additional embodiments are also intended to fall within the a generic product or device. If a proprietary product or device scope of the appended claims, is loosing money or marginally profitable, then extending its What is claimed is: proprietary'status by discovering essential adverse events will 55 1. A method of commercializing at least one previously add little value. For example, discovering an essential adverse unreported proprietary method of using a product of mauuevent in a generic aluminum-containing antacid may not facture or device, wherein the proprietary method of using the bring much added profit, even if the product were to become product or device is established according to the steps cornproprietary, if consumers were more interested in switching prising: to other antacids lacking aluminum, such as calcium-based 60 accessing one or more data sources, wherein at least one antacids or magnesium-based antacids. Alternatively, a condata source stores adverse event data associated with the simier with gastritis who is faced with the proposition of product or device; buying expensive antacids, may prefer to use alternative analyzing and comparing the stored adverse event data, newer, more expensive, and more effective products, such as with at least one previously-known adverse event assohistamine blockers or hydrogen pump inhibitors. Alterna- 65 ciated with the product or device; lively, large profits can be made on a highly profitable patidentifying at least one previously unreported essential ented product or device by extending its proprietary status by adverse event associated with the product or device from
US 7,984,069 B2 21
the adverse event data, wherein an essential adverse event is one regulated by a regulatory agency requiring disclosure of the event in a package insert or data sheet accompanying the product or device, and then responsive to identifying of the previously unreported essential adverse event, identifying at least one previously unreported method of use for the product or device associated with said identified essential adverse event; documenting inventorship of the at least one previously unreported method of use for the product or device; and creating a database of proprietary essential adverse event information, wherein the database stores at least one record related to at least one of: a patent, patent application, patent publication, or data contained in at least one patent, patent application or patent publication, wherein said at least one patent, patent application, patent publication, or data contained in at least one patent, patent application or patent publication, discloses and relates to at least one of the at least one previously unreported method of use and the at least one essential adverse event, and wherein the at least one previously unreported proprietary method of using a product or device consists of a use selected from the group consisting of a restricted use of said product or device, providing warning(s) about the essential adverse event, providing instruction(s) for avoiding an essential adverse event, and any combination thereof; and commercializing the at least one previously unreported proprietary method of using a product or device, the commercializing comprising exclusively disclosing the at least one previously unreported proprietary method of use and the associated at least one previously unreported essential adverse event information, which information, once identified, must then accompany the product or device, wherein commercializing means creating profit from the exclusive disclosure. 2. The method of claim 1, further comprises determining value of commercializing the at least one use determined from the at least one identified essential adverse event. wherein the value depends on a potential value of making a generic product or device inlo a proprietary product or device, or preventing a proprietary product or device from becoming a generic product or device. 3. The method of claim 2. wherein the commercializing step further comprises generating information for incorporation into documents for selling, leasing or licensing the identified product information. 4. The method of claim 2, wherein the product is commercially available at the time of the analyzing step. 5. The method of claim 2, wherein the step of commercializing further comprises formatting the data relating to at least one adverse event associated with exposure to. or use of the product or device, or documenting same, such that a manufacturer or distributor of the product or device must inform consumers, users or individuals responsible for the user, physicians orprescribers about at least one adverse event associated with exposure to or use of the product or device. 6. The method of claim 1, wherein the product or device is commercially available at the time of the analyzing step, and wherein the at least one data source comprises information relating to patents and patent applications. 7. The method of claim 1, wherein the product or device is commercially available at the time of the analyzing step, and wherein the at least one data source comprises information
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relating to raw commercial or sales data, wherein said raw data is commercial or sales data before being processed and analyzed. 8. The method of claim 2. wherein the at least one adverse event comprises a drug interaction. 9. The method of claim 8, wherein the at least one data source comprises information relating to raw commercial or sales data, wherein said raw data is commercial or sales data before being processed and analyzed. 10. The method of claim 1, wherein the steps of establishing the use of the essential adverse event data are proprietary. 11. The method of claim 1, wherein the product is medical. 12. The method of claim 2, wherein the product is medical. 13. The method of claim 12, wherein the medical product is a generic drug. 14. The method of claim 1, wherein the product is nonmedical. 15. The method of claim 2, wherein the product is nonmedical. 16. The method of claim 1, wherein the device is medical. 17. The method of claim 2, wherein the device is medical. 18. The method of claim 1, wherein the device is nonmedical. 19. The method of claim 2. wherein the device is nonmedical. 20. A proprietary kit containing a product or device, and labeling listing the information which once identified, must accompany the product or device thus notifying a user of at least one previously unreported essential adverse event for the product or device, wherein the information to be listed on the labeling is determined in accordance with the method of claim 1. 21. A proprietary kit containing a product or device, and labeling listing the information which once identified, must accompany the product or device thus notifying a user of at least one previously unreported essential adverse event for the product or device, wherein information to be listed on the labeling is determined in accordance with the method of claim 9. 22. The method of claim 1, wherein the proprietary method of use is a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 23. The method of claim 3, wherein the proprietary method of use is a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 24. The method of claim 1, wherein the at least one adverse event is a drug interaction. 25. The method of claim 24, wherein the product or device is commercially available at the time of the analyzing step. 26. The method of claim 25. wherein the proprietary method of use comprises a restricted use in at least one population subgroup when (here is observed to be a high risk of at least one adverse event associated with exposure to, or use of, the product or device. 27. The method of claim 25, wherein at least one data source comprises information relating to raw commercial or sales data, wherein said raw data is commercial or sales data before being processed and analyzed. 28. The method of claim 27, wherein at least one previously unreported essential adverse event is other than a chronic immune mediated disorder. 29. The method of claim 27, the steps further comprising determining value of commercializing the at least one propri-
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US 7,984,069 B2 23
etary method of use determined from the at least one identified essential adverse event, wherein the value depends on a potential value of making a generic product or device into a proprietary product or device, or preventing a proprietary product or device from becoming a generic product or device. 5 30. The method of claim 1, wherein at least one previously unreported essential adverse event comprises a drug interaction, wherein at least one data source comprises information relating to patents and patent applications, and wherein at least one data source comprises information relating to raw 10 commercial or sales data, wherein said raw data is commercial or sales data before being processed and analyzed. 31. The method of claim 2, wherein at least one previously unreported essential adverse event comprises a drug interac- s tion, wherein at least one data source comprises information relating to patents and patent applications, and wherein at least one data source comprises information relating to raw commercial or sales data, wherein said raw data is commercial or sales data before being processed and analyzed. 20 32. The method of claim 1, wherein the at least one adverse event data source comprises information regarding product postexposure adverse event data, which is recorded in selected time increments, ranging from less than one hour to more than ten years. 25 33. The method of claim 1, wherein the at least one adverse event data source comprises information regarding amount of use of the product or device or duration of exposure to the product or device by subjects. 34. The method of 1, wherein the at least one proprietary 30 method of using the product or device is a restricted use in at least one population subgroup, where there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device and the previously unreported essential adverse event is one other than a chronic 35 immune mediated disorder. 35. The method of claim 2. wherein the at least one proprietary method of using the product or device is a restricted use in at least one population subgroup, where there is observed to be a high risk of at least one adverse event asso- 40 ciated with exposure to or use of the product or device and the previously unreported essential adverse event is one other than a chronic immune mediated disorder. 36. The method of claim 1, wherein the product or device is commercially available, the steps further comprising iden- 45 tifying the proprietary method of use as a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 37. The method of use claim 2, wherein the product or 50 device is commercially available, the steps further comprising identifying the proprietary method of use as a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with exposure to or use of the product or device. 55 38. The method of claim 9, wherein the product or device is commercially available, the steps further comprising identifying the proprietary method of use as a restricted use in at least one population subgroup when there is observed to be a high risk of at least one adverse event associated with expo- 60 sure to or use of the product or device. 39. The method of claim 1. the steps further comprising documenting date of inventorship and storing information relating to the documented date of inventorship in the datebase of proprietary essential adverse event information. 65 40. The method of claim 1, wherein at least one adverse event data source comprises raw data from a plurality of
24
different adverse events, wherein said raw data is commercial or sales data before being processed and analyzed. 41. The method of claim 1, wherein the product or device is commercially available, and the proprietary method of use is further identified as comprising restricting exposure of the product or device to at least one factor selected from the group consisting of high temperatures, low temperatures, chemicals, surfaces, pressures, electricity sparks; contact with an anatomical element selected from the group consisting of skin, eyes, ears, respiratory surfaces, gastrointestinal surfaces and mucous membranes of the user; exposure to a subpopulation group selected from the group consisting of children, pregnant women, users with specific allergies, users with specific medical conditions, and animals; exposure to subpopulations defined by at least one user identifying characteristic selected from the group consisting of sex, weight, age, race, genetic characteristics, medical condition, pregnancy status, presence of allergies, use of drugs, use of tobacco, use of alcohol, and use of medical devices. 42. The method of claim 1, wherein at least one database of essential adverse event information is computerized. 43. The method of claim 1, wherein at least one data source comprises human adverse event date. 44. The method of claim 1. further comprising utilizing least one controlled clinical trial andorepidemiological study to discover at least one previously unreported essential adverse event. 45. The method of claim 1, wherein the step of establishing the adverse event is one other than an abnormal laboratory value. 46. The method of claim 1, wherein the use is one other than a new dosing regimen. 47. The method of claim 1, wherein the use further comprises providing printed product safety information in connection with product packaging. 48. The method of claim 2. wherein the use further comprises providing printed product warning information in connection with product packaging. 49. The method of claim 1, wherein the step of documenting the inventorship comprises storing information relating to the documented inveutorship in the database of proprietary essential adverse event information. 50. A method of commercializing at least one previously unreported proprietary method of using a product of manufacture or device, comprising: accessing one or more data sources, wherein at least one data source stores adverse event data associated with the product or device; analyzing and comparing the stored adverse event date, with at least one previously-known adverse event associated with the product or device; identifying at least one previously unreported essential adverse event associated with the product or device from the adverse event date, wherein an essential adverse event is one regulated by a regulatory agency requiring disclosure of the event in a package insert or data sheet accompanying the product or device, and then responsive to identifying of the previously unreported essential adverse event, identifying at least one previously unreported method of use for the product or device associated with said identified essential adverse event: documenting inventorship of the at least one previously unreported method of use for the product or device; and creating a database of proprietary essential adverse event information, wherein the database stores at least one record related to at least one of: a patent, patent application, patent publication, or data contained in at least
US 7,984,069 B2 25
one patent, patent application or patent publication, wherein said at least one patent, patent application, patent publication, or data contained in at least one patent, patent application or patent publication, which discloses and relates to the at least one previously unre- 5 ported method of use, and wherein the at least one previously unreported proprietary method of use consists of a use selected from the group consisting of a restricted use of said product or device, providing warning(s) about the essential adverse event, providing instruction(s) for avoiding an essential adverse event, and any combination thereof, wherein the at least one previously unreported proprietary method of use is not a pharmacogenoniic technique for screening: and
26
commercializing the at least one previously unreported proprietary method of use, the commercializing comprising exclusively disclosing the at least one previously unreported proprietary method of use and the associated at least one previously unreported essential adverse event information, which information, once identified, must then accompany the product or device, wherein commercializing means creating profit from the exclusive disclosure.
UNITED STATES DISTRICT COURT CENTRAL DISTRICT OF CALIFORNIA
NOTICE OF ASSIGNMENT TO UNITED STATES MAGISTRATE JUDGE FOR DISCOVERY This case has been assigned to District Judge Gary A. Feess and the assigned discovery Magistrate Judge is Paul Abrams. The case number on all documents filed with the Court should read as follows:
CV12- 6643 GAF (PLAx)

Pursuant to General Order 05-07 of the United States District Court for the Central District of California, the Magistrate Judge has been designated to hear discovery related motions.
All discovery related motions should be noticed on the calendar of the Magistrate Judge
NOTICE TO COUNSEL A copy of this notice must be served with the summons and complaint on all defendants (if a removal action is filed, a copy of this notice must be served on all plaintiffs). Subsequent documents must be filed at the following location: [_] Western Division 312 N. Spring St., Rm. G-8 Los Angeles, CA 90012 [ ] Southern Division 411 West Fourth St., Rm. 1 -053 Santa Ana, CA 92701 -4516 [_] Eastern Division 3470 Twelfth St., Rm. 134 Riverside, CA 92501
Failure to file at the proper location will result in your documents being returned to you.
CV-18 (03/06)
NOTICE OF ASSIGNMENT TO UNITED STATES MAGISTRATE JUDGE FOR DISCOVERY
Sonia S. Figueroa (SEN: 0269' , sfigueroa@dnlzito. com DNL ZITO 355 South Grand Avenue, Suite 2450 Los Angeles, CA 90071 Tel: 213-400-3344
UNITED STATES DISTRICT COURT CENTRAL DISTRICT OF CALIFORNIA
CLASSEN IMMUNOTHERAPIES, INC.,
CASE NUMBER
PLAINTIFF(S) V.
SOMAXON PHARMACEUTICALS SUMMONS

DEFEND ANT(S).
TO:
DEFENDANT(S): A lawsuit has been filed against you.
Within 21 days after service of this summons on you (not counting the day you received it), you must serve on the plaintiff an answer to the attached SI complaint D amended complaint D counterclaim D cross-claim or a motion under Rule 12 of the Federal Rules of Civil Procedure. The answer or motion must be served on the plaintiffs attorney, Sonia S. Figueroa, DNL Zito , whose address is 355 South Grand Avenue, Suite 2450 Los Angeles, CA 90071 If you fail to do so, judgment by default will be entered against you for the relief demanded in the complaint. You also must file your answer or motion with the court. Clerk, U.S. District Dated: August 1, 2012
(Seal ofthq
[Use 60 days if the defendant is the United States or a United States agency, or is an officer or employee of the United States. Allowed 60 days by Rule 12(a)(3)].
CV-01A (10/11
SUMMONS
UNITED ST' -~s DISTRICT COURT, CENTRAL DISTP"

CIVIL COVER SHEET 1 (a) PLAINTIFFS (Checkbox if you are representing yourself U) CLASSEN 1MMUNOTHERAP1ES, INC.
OF CALIFORNIA
DEFENDANTS SOM A XO N PH AR MACEUT1C A I.. S
(b) Attorneys (Firm Name. Address and Telephone Number. If you arc representing yourself, provide same.) Sonia S. Figueroa, Esq. DNL ZITO, 355 South Grand Avenue, Suite 2450. Los Angeles. CA 90071 Tel: 213-400-3344 II. BASIS OF JURISDICTION (Place an X in one box only.) P 1 U.S. Government Plaintiff 1/3 federal Question (U.S. Government Not a Party)
Attorneys f If Known)
III. CITIZENSHIP OF PRINCIPAL PARTIES - For Diversity Cases Only (Place an X in one box for plaintiff and one for defendant.) Citizen of This StatePIT D 1 P 2 DEF PI III 2 D3 Incorporated or Principal Place of Business in this State PTF DEF P4 P 4 P5
D6
D 2 U.S. Government Defendant
P 4 Diversity (Indicate Citizenship Citizen of Another State of Parties in Item 111)
Incorporated and Principal Place P 5 of Business in Another State Foreign Nation

06
Citizen or Subject of a Foreign Country D 3 IV. ORIGIN (Place an X in one box only.) BI1 Original Proceeding D 2 Removed from State Court D 3 Remanded from Appellate Court D 4 Reinstated or Reopened
P 5 Transferred from another district (specify):
D 6 MultiD 7 Appeal to District District Judge from Litigation Magistrate Judge
V. REQUESTED IN COMPLAINT:
JURY DEMAND: {/Yes
P No (Check 'Yes' only if demanded in complaint.) P MONEY DEMANDED IN COMPLAINT: $
CLASS ACTION under F.R.C.P. 23: P Yes t/No
VI. CAUSE OF ACTION (Cite the U.S. Civil Statute under which you are filing and write a brief statement of cause. Do not cite jurisdictional statutes unless diversity.) Patent infringement under Title 35 of the United States Code " 271 (a) (b) (c) and/or (f) VII. NATURE OF SUIT (Place an X in one box only.) OTHER STATUTES G 400 State Rcapportionmcnt Q 410 Antitrust a 430 Banks and Banking D450 Commerce/ICC Rates/etc. D460 Deportation D470 Racketeer Influenced and Corrupt Organizations D 480 Consumer Credit Q 490 Cable/Sat TV D810 Selective Service D 850 Securities/Commodities/ Exchange P875 Customer Challenge 12 USC 34 10 D 890 Other Statutory Actions P 891 Agricultural Act D 892 Economic Stabilization Act P 893 Environmental Matters P 894 Energy Allocation Act D 895 Freedom of Info. Act D 900 Appeal of Fee Determination Under Equal Access to Justice
P 950 Constitutionality of State Statutes CONTRACT P D D D D Insurance Marine Miller Aet Negotiable Instrument Recovery of Overpayment & Enforcement of Judgment P 1 5 1 Medicare Act P 152 Recovery' of Defaulted Student Loan (Excl. Veterans) P 1 53 Recovery of Overpayment of Veteran's Benefits D 160 Stockholders' Suits D 190 Other Contract D 1 95 Contract Product Liability D 196 Franchise REAL PROPERTY Q 21 0 Land Condemnation P 220 Foreclosure P 230 Rent Lease & Ejectment D240 Torts to Land D245 Tort Product Liability P 290 All Other Real Property 1 10 120 130 140 150 TORTS PERSONAL INJURY D310 Airplane P 3 1 5 Airplane Product Liability D 320 Assault. Libel & Slander D 330 Fed. Employers" Liability D 340 Marine Q 345 Marine Product L i abi 1 i L'v n 350 Motor Vehicle D 355 Motor Vehicle Product Liability D 360 Other Personal Injury D 362 Personal InjuryMed Malpractice D 365 Personal InjuryProduct Liability D 368 Asbestos Personal Injury Product Liability IMMIGRATION D 462 Naturalization Application D 463 Habeas CorpusAlien Detainee D 465 Other Immigration Actions TORTS PERSONAL PROPERTY 370 Other Fraud 37 1 Truth in Lending 380 Other Personal Property Damage 385 Property Damage Product Liability BANKRUPTCY 422 Appeal 28 USC
P D u D
158
P 423 Withdrawal 28 USC 157 CIVIL RIGHTS P 4 4 I Voting D 442 Employment n 443 Housing; Accommodations Q444 Welfare D 445 American with Disabilities Employment P 446 American with Disabilities Other U 440 Other Civil Rights
LABOR D 7 1 0 Fair Labor Standards Act P 720 Labor/Mgmt. Relations D730 Labor/Mgmt. Reporting & Disclosure Act P 740 Railway Labor Act D 550 Civil Rights D 790 Other Labor P 555 Prison Condition Litigation FORFEITURE / L1791 Empl. Ret. inc. PENALTY Security Aet P 610 Agriculture PROPERTY RIGHTS n 620 Other Food & LL820 Copyrights Drag H 830 Patent P 625 Drug Related P 840 Trademark Seizure of SOCIAL SECURITY Property 21 USC Q861 HIA(1395ff) D 862 Black Lung (923) 881 D 863 DIWC/DIWW n 630 Liquor Laws D 640 R.R. & Truck <40S(g)) P 864 SS1D Title XVI P650 Airline Regs Q 660 Occupational D 865 RSI (405(g)) Safety /Health FEDERAL TAX SUITS D 870 Taxes (U.S. Plaintiff D 690 Other or Defendant) D 87 1 IRS-Third Party 26 USC 7609
PRISONER PETITIONS P510 Motions to Vacate Sentence Habeas Corpus ill 530 General P 535 Death Penalty D 540 Mandamus/ Other
FOR OFFICE USE ONLY:
Case Nu JESTED BELOW. Page 1 of2
AFTER COMPLETING THE FRONT SIDE OF FORM CV-71, COMPLETE THE INFORMATION C'V-71 (05/08) CIVIL COVER SHEET
UNITED.
.TES DISTRICT COURT, CENTRAL DIST._...~T OF CALIFORNIA

CIVIL COVER SHEET
Vlli(a), IDENTICAL CASES: Has this action been previously filed in this court and dismissed, remanded or dosed? mNo D Yes If yes, list ease numher(s): V'III(b). RELATED CASES: Have any cases been previously filed in this court that are related to the present case? IB No If yes, list case numherjs): D Yes
Civil case* are deemed related if a previous); filed cast and the present case; (Check all boxes that apply) Q A. Arise from the same or closely related transactions, happenings, or events; or D B. Call for determination of the same or substantially related or similar questions of law and fact; or Q C, For other reasons would entail substantial duplication of labor if heard by different judges; or Q D. Involve the same patent, trademark or copyright, and one of the factors identified above in a, b or c also is present. IX. VENUE: (When completing the following information, use an additional sheet if necessary.) (a) List the County in this District; California County outside of this District; State if other than California; or Foreign Country, in which EACH named plaintiff resides. D Check here if the government, its agencies or employees is a named plaintiff. If this box is checked, go to item (b). County in this District:* California County outside of this District, State, if other than California; or Foreign Country
State of Maryland
<
(b) List the County in this District; California County outside of this District; Stale if other than California; or Foreign Country, in which EACH named defendant resides. G Check here if the government, its agencies or employees is a named defendant. If this box is checked, go to item (c). County in this District;* California County oytside of this District; State, if other than California; or Foreign Co San Diego County
(c) List the County in this District; California County outside of this District; State if other than Californig; or Foreign Country, in which EACH claim arose. Note; In land condemnation cases, use the location of the tract of land involved.
County in this District:* California County outside of this District; State, if other than California; or Foreign Country
Los Angeles County for all claims
* Los Angeles, Orange, Sn Bernardino, Riverside, Ventura, Santa Barbara, or San tuls Obispo Counties Note: in land condemnation cases, use the location of the trjfe of land involved X. SIGNATURE OF ATTORNEY (OR PRO PER):
Date
August 1,2012
Notice to Counsel/Parties: The CV-7 1 (JS-44) Civil Cover Sheet and the information contained herein neither replace nor supplement the filing and service of pleadings or other papers as required by law. This form, approved by the Judicial Conference of the United States in September 1 *>74, is required pursuant to l,oea! Rule 3- 1 is not filed but is used by the Clerk of the Court for the purpose of statistics, venue and initiating the civil docket sheet. (For more detailed instructions, see separate instructions sheet.) Key to Statistical codes relating to Social Security Cases: Nature of Suit Code
861
Abbreviation MIA
Substantive Statement of Cause of Action All claims for health insurance benefits (Medicare) under Title 18, Pan A, of the Social Security Act, as amended. Also, include claims by hospitals, skilled nursing facilities, clc., for certification as providers of services under the program. (42 U.S.C. I93SFF(b All claims for "Black Lung" benefits under Title 4, Part B, of the Federal Coal Mine Health and Safety Act of 1969. {30 U.S.C. 923) All claims filed by insured workers for disability insurance benefits under Title 2 of the Social Security Act, as amended; plus all claims filed for child's insurance benefits based on disability. (42 U.S.C. 405(g)) All claims filed for widow* or widowers insurance benefits based on disability under Title 2 of the Social Security Act, as amended, (42 U.S.C, 405(g) All claims for supplemental security income payments based upon disability filed under Title 16 of the Social Security
862 863 863 864
BL D1WC DIWW SSID RS!
Act, as amended,
865
All claims for retirement (old age) and survivors benefits under Title 2 of the Social Security Act, as amended, (42 U.S.C. (g)) Page 2 of2
CV-71 (05/08)
CIVIL COVER SHEET

Classen Immunotherapies v. Somaxon Pharmaceuticals

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Classen Immunotherapies v. Somaxon Pharmaceuticals

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UNITED STATES DISTRICT COURT CENTRAL DISTRICT OF CALIFORNIA WESTERN DIVISION

CLASSEN IMMUNOTHERAPIES, INC. Plaintiff,

SOMAXON PHARMACEUTICALS Defendants.

1 COMPLAINT FOR PATENT INFRINGEMENT

THE PARTIES AND GENERAL ALLEGATIONS

3 COMPLAINT FOR PATENT INFRINGEMENT

Somaxon has practiced a method by which Somaxon generated and

COMPLAINT FOR PATENT INFRINGEMENT

The '069 patent properly names John B. Classen as inventor, is entitled

of the damages awarded for patent infringement.

costs and attorney's fees.36.

DATED: August U2012

Sonia S, Figueroa, Escf. Attorneys for Plaintiff Classen Immunotherapies, Inc.

COMPLAINT FOR PATENT INFRINGEMENT

Sonla S. Figueroa, Esq. Attorneys for Plaintiff Classen Immunotherapies, Inc.

COMPLAINT FOR PATENT INFRINGEMENT

United States Patent

(io) Patent No.: US 7,653,639 B2 (45) Date of Patent: Jan. 26,2010

(Continued) OTHER PUBLICATIONS

ESSENTIAL ADVERSE EVENT DATABASE

SHADOW STORAGE DEVICE

ESSENTIAL ADVERSE EVENT INFORMATION STORAGE DEVICE 20

ADVERSE EVENT DATABASE

ESSENTIAL ADVERSE EVENT DATABASE

ESSENTIAL ADVERSE EVENT DATABASE

ESSENTIAL ADVERSE EVENT DATABASE

PROCESSOR 18 USER INTERFACE

ESSENTIAL ADVERSE EVENT INFORMATION STORAGE DEVICE 20

ACCESS ADVERSE EVENT DATA SOURCE

ANALYZE ADVERSE EVENT DATA

CREATE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE

COMMERCIALIZE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE

START SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12

Jan. 26,2010 START

SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12

SERVER 14,114 OR 214 ANALYZES

ADVERSE EVENT DATA FOR ESSENTIAL ADVERSE EVENT DATA

United States Patent

128/897 707/1 705/2

(Continued) OTHER PUBLICATIONS

Related U.S. Application Data (60)

Provisional application No. 60/270.697, filed on Feb. 22,2001.

References Cited U.S. PATENT DOCUMENTS

ADVERSE EVENT DATABASE

SHADOW STORAGE DEVICE

ADVERSE EVENT INFORMATION STORAGE DEVICE

ADVERSE EVENT DATABASE

ADVERSE EVENT DATABASE

ADVERSE EVENT DATABASE

ACCESS ADVERSE EVENT DATA SOURCE

ANALYZE ADVERSE EVENT DATA

CREATE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE

COMMERCIALIZE PROPRIETARY ADVERSE EVENT INFORMATION DATABASE

( START ) SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12

SERVER 14,114 OR 214 ACCESSES ADVERSE EVENT DATABASE(S) 12

UNITED STATES DISTRICT COURT CENTRAL DISTRICT OF CALIFORNIA

CV12- 6643 GAF (PLAx)

NOTICE OF ASSIGNMENT TO UNITED STATES MAGISTRATE JUDGE FOR DISCOVERY

CLASSEN IMMUNOTHERAPIES, INC.,

SOMAXON PHARMACEUTICALS SUMMONS

DEFENDANT(S): A lawsuit has been filed against you.

UNITED ST' -~s DISTRICT COURT, CENTRAL DISTP"

DEFENDANTS SOM A XO N PH AR MACEUT1C A I.. S