IN THE UNITED STATES DISTRICT COURT FOR THE DISTRICT OF DELAWARE TET SYSTEMS GMBH & CO.

KG, Plaintiff, Civil Action No. _____ v. AERPIO THERAPEUTICS, INC.; AKEBIA THERAPEUTICS, INC.; KEVIN GENE PETERS AND ROBERT SHALWITZ, Defendants. COMPLAINT FOR PATENT INFRINGEMENT AND JURY DEMAND Plaintiff TET Systems GMBH & Co. KG (“TET” or “Plaintiff”), by and through its undersigned attorneys, Gibbons P.C., as for its Complaint against Defendants Aerpio Therapeutics, Inc. (“Aerpio”); Akebia Therapeutics, Inc. (“Akebia”); Kevin Gene Peters (“Dr. Peters”) and Robert Shalwitz (“Dr. Shalwitz”); (Aerpio, Akebia, Dr. Peters and Dr. Shalwitz collectively referred to herein as “Defendants”), alleges as follows: OVERVIEW 1. TET was founded by prominent academic researchers, two of whom -- Dr. JURY TRIAL DEMANDED

Hermann Bujard and Dr. Manfred Gossen -- invented and patented a system to modify cells to control gene expression. 2. Using the invention made by Professors Dr. Bujard and Dr. Gossen, higher cells

and entire organisms can be used as hosts in assays, or screening tests, that control target gene expression via external stimuli.

3.

In particular, cell-based screening assays can be useful in discovering and

profiling the activity of chemical compounds versus medically-relevant targets, including, for example, antiviral activity against the Hepatitis virus. 4. TET’s patented technology has proven to be so commercially valuable that

academic institutions, pharmaceutical companies and other drug development companies worldwide, of varying sizes, license its use from TET. 5. Indeed, ~85% of the world’s leading pharmaceutical companies license TET’s

patented technology, and its broad usage is demonstrated by more than 10,000 publications in peer-reviewed journals. 6. Drs. Bujard and Gossen and TET’s patented technology have been recognized in

numerous peer-reviewed scientific journals throughout the world. 7. TET brings this action for patent infringement under 35 U.S.C. § 271 et seq., as a

result of Defendants’ continued and willful unauthorized use of TET’s patented technology. THE PARTIES 8. TET is a corporation organized and existing under the laws of Germany, having

its principal place of business at Im Neuenheimer Feld 582, 69120 Heidelberg, Germany. 9. Patent No. TET is the owner, by assignment, of all rights, title and interest in United States 5,654,168 entitled “Tetracycline-Inducible Transcriptional Activator and

Tetracycline-Regulated Transcription Units” (“the ‘168 Patent”); and United States Patent No. 5,912,411 entitled “Mice Transgenic For a Tetracycline-Inducible Transcriptional Activator” (“the ‘411 Patent”). 10. TET is the owner, by assignment, of all rights, title and interest in United States

United States No. 5,464,758 entitled “Tight Control of Gene Expression in Eucaryotic Cells by Tetracycline- Responsive Promoters” (“the ‘758 Patent”), which expired on June 14, 2013. 2

11.

Aerpio is a domestic corporation organized under the laws of, and in good

standing in, the State of Delaware, with a principal place of business located at 9987 Carver Road, Suite 420 Cincinnati, Ohio 45242. 12. Akebia is a domestic corporation organized under the laws of, and in good

standing in, the State of Delaware, with a principal place of business located at 9987 Carver Road, Suite 420 Cincinnati, Ohio 45242. 13. Dr. Peters is a resident of Ohio with a principal residence at 9160 Given Road,

Cincinnati, Ohio 45243-1148. Dr. Peters is the Chief Scientific Officer at both Aerpio and Akebia. 14. Dr. Shalwitz is a resident of Ohio with a principle residence at 2549 Bryden Road,

Columbus, Ohio 43209-2135. Dr. Shalwitz is the Chief Medical Officer at both Aerpio and Akebia. JURISDICTION AND VENUE 15. This Court has original jurisdiction over the subject matter of this action pursuant

to 28 U.S.C. §§ 1331 and 1338(a). 16. This Court has personal jurisdiction over Aerpio by virtue of, inter alia, Aerpio

being organized under and existing under the laws of the State of Delaware. 17. This Court has personal jurisdiction over Akebia by virtue of, inter alia, Akebia

being organized under and existing under the laws of the State of Delaware. 18. This Court has personal jurisdiction over Dr. Peters by virtue of, inter alia, his

role as an Officer of both Aerpio and Akebia. 19. This Court has personal jurisdiction over Dr. Shalwitz by virtue of, inter alia, his

role as an Officer of both Aerpio and Akebia.

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20.

Dr. Peters’ and Dr. Shalwitz’s acts are attributable to Aerpio and Akebia for

jurisdictional purposes. 21. Venue is proper in this Court under 28 U.S.C. §§ 1391(b), 1391(c) and 1400(b). TET’S PATENTED TECHNOLOGY 22. The ‘758, ‘168 and ‘411 Patents alone, or in combination, are also referred to as

the “TET Patents” and the claimed features of the TET Patents are also referred to as the “TET System.” 23. The ‘758 Patent was duly and legally issued by the United States Patent and

Trademark Office on November 7, 1995. A copy of the ‘758 Patent is attached hereto as Exhibit A. 24. The ’168 Patent was duly and legally issued by the United States Patent and

Trademark Office on August 5, 1997. A copy of the ’168 Patent is attached hereto as Exhibit B. 25. The ’411 Patent was duly and legally issued by the United States Patent and

Trademark Office on June 15, 1999. A copy of the ’411 Patent is attached hereto as Exhibit C. 26. Broadly speaking, the ‘758 and ‘168 Patents disclose and claim a system and

method of providing accurate and reproducible control of expression of a gene of interest using tetracycline or a tetracycline analogue (‘tet”) as the controlling effector molecule, in order to screen new drug compounds in animal models and to identify the activity of compounds to evaluate their potential use as drugs. Claims of the ’411 Patent disclose and claim, inter alia, a transgenic mouse useful for regulating the expression of genes in cells. 27. Practicing the invention claimed in the TET Patents enables users to determine,

for example, methods of treating diseases or conditions of the eye which are characterized by neovascularization, vascular instability and vascular leakage, among others.

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28.

The TET System has been recognized in the scientific literature as a broadly and

successfully applied system for controlled gene expression in eukaryotes, i.e., organisms made up of cells that possess a membrane-bound nucleus containing genetic material. 29. TET’s novel technology allows users to control the activity of a target gene both

in vivo and in vitro. 30. The TET System has been applied in cultured cells, as well as in a wide spectrum

of organisms, from animals and plants to various unicellular systems. 31. The TET System has also been employed in the development of new animal

models for human diseases, such as Tet/opsin/VEGF mice, or transgenic mice. 32. The advantages of the TET System have provided users with new insights into

complex biological processes of development, disease and behavior, including diseases or conditions of the eye. 33. TET has commercially embodied features claimed in the ’758 Patent, ‘168 Patent

and ‘411 Patent. DEFENDANTS’ INFRINGING ACTIVITIES 34. Upon information and belief, Defendants are developing therapeutics, including,

inter alia, for the treatment of diseases or conditions of the eye, including retinopathies, ocular edema, ocular neovascularization and diabetic macular edema. 35. Upon information and belief, Defendants have used, and continue to use

transgenic mice, such as Tet/opsin/VEGF mice, as models for developing therapeutics for the treatment of these diseases or conditions of the eye, including ocular neovascularization. 36. Upon information and belief, Defendants use of Tet/opsin/VEGF mice took place

in the United States.

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37.

Defendants have published their use of Tet/opsin/VEGF mice in United States

Patent Application Publication US 2012/0129847, published May 24, 2012, in which the uses of Tet/opsin/VEGF mice were described in experiments related to developing treatments for ocular neovascularization. 38. Dr. Peters and Dr. Shalwitz filed the application leading to the foregoing patent

application publication on October 5, 2011. 39. Dr. Peters and Dr. Shalwitz assigned the application leading to the foregoing

patent application publication to Akebia on October 6, 2011. 40. Akebia assigned the application leading to the foregoing patent application

publication to Aerpio on February 8, 2012. 41. ‘411 Patents. 42. 43. 44. Defendants do not have a license to the TET Patents. Defendants used the Tet/opsin/VEGF mice without the authorization of TET. Upon information and belief, Defendants continue to use the Tet/opsin/VEGF Each of paragraphs 34 to 36 above constitutes infringement of the ‘758, ‘168 and

mice without compensating TET for their use. EVIDENCE OF DEFENDANTS’ WILLFULNESS 45. TET put Defendants on notice that Defendants’ use of the inventions described in

the TET Patents was unauthorized. 46. 47. Defendants are aware of the existence of the TET Patents. Defendants have ignored TET and its offers to license the TET Patents. COUNT I: DIRECT INFRINGEMENT UNDER 35 U.S.C. § 271(a) 48. TET realleges paragraphs 1 to 47 as if fully set forth herein.

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49.

In violation of 35 U.S.C. § 271(a), and as evidenced above, Defendants have

infringed and continue to infringe, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘168 Patent and the ‘411 Patent, without license from TET, by making, selling, offering to sell and/or using Tet/opsin/VEGF mice. 50. In further violation of 35 U.S.C. § 271(a), and as evidenced above, Defendants

have infringed, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘758 Patent, without license from TET, by making, selling, offering to sell and/or using Tet/opsin/VEGF mice. 51. 52. Defendants’ infringement of the TET Patents has been knowing and willful. Defendants’ infringing activities will continue unless enjoined by this Court.

COUNT II: INDIRECT INFRINGEMENT UNDER 35 U.S.C. § 271(b) 53. 54. 55. TET realleges paragraphs 1 to 52 as if fully set forth herein. Prior to this lawsuit, Defendants had knowledge of the TET Patents. In violation of 35 U.S.C. § 271(b), and as evidenced above, Defendants have

induced and continue to induce others to infringe, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘168 Patent and the ‘411 Patent without license from TET, by inter alia, making, and upon information and belief, selling, offering to sell and/or using Tet/opsin/VEGF mice. 56. In further violation of 35 U.S.C. § 271(b), and as evidenced above, Defendants

have induced others to infringe, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘758 Patent without license from TET, by inter alia, making, and upon information and belief, selling, offering to sell and/or using Tet/opsin/VEGF mice.

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57.

Defendants knew, or should have known that making, selling, offering to sell

and/or using Tet/opsin/VEGF mice induced infringement of the TET Patents. 58. Upon information and belief, Defendants’ induced infringement has been

knowing and willful. COUNT III: INFRINGEMENT UNDER 35 U.S.C. § 271(c) 59. 60. TET realleges paragraphs 1 through 58 above as if fully set forth herein. Upon information and belief and as evidenced above, Defendants have

contributorily infringed and continue to contributorily infringe, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘168 Patent and the ‘411 Patent, without license from TET. 61. Upon information and belief and as evidenced above, Defendants have

contributorily infringed, literally or under the doctrine of equivalents, each of the elements of one or more claims of the ‘758, without license from TET. 62. Upon information and belief, Defendants have made, used, offered for sale, sold,

or imported into the United States a material or apparatus for use in practicing the invention disclosed in the TET Patents, namely, Tet/opsin/VEGF mice, and such constitutes a material part of the invention disclosed in the TET Patents. 63. Upon information and belief, Defendants had knowledge that the Tet/opsin/VEGF

mice described above, which Defendants made, used, offered for sale, sold, or imported into the United States, was especially made or especially adapted for use in practicing the invention disclosed in the TET Patents, and such material or apparatus was and is not a staple article or commodity of commerce suitable for substantial noninfringing use. DEFENDANTS’ HARM TO TET 64. TET realleges paragraphs 1 to 63 as if fully set forth herein. 8

65.

As a direct and proximate cause of Defendants’ infringing acts, TET has been

injured and, unless such infringing acts are enjoined by this Court, will continue to be injured in its business and property rights, and has suffered and will continue to suffer injury and damages for which it is entitled to relief under 35 U.S.C. § 284. 66. As a direct and proximate cause of Defendants’ infringing acts, Defendants have

caused and, unless such acts are enjoined by this Court, will continue to cause, irreparable harm to TET for which there is no adequate remedy at law, and for which TET is entitled to preliminary and permanent injunctive relief under 35 U.S.C. § 283. PRAYER FOR RELIEF WHEREFORE, Plaintiff respectfully requests of this Court the following relief: (a) A judgment and decree that Defendants have infringed one or more claims of the

‘758 Patent, the ‘168 Patent and the ‘411 Patent; (b) A judgment and decree that Defendants have induced infringement of one or more

claims of the ‘758 Patent, the ‘168 Patent and the ‘411 Patent; (c) A judgment and decree that Defendants have contributorily infringed one or more

claims of the ‘758 Patent, the ‘168 Patent and the ‘411 Patent; (d) An Order preliminarily and permanently restraining and enjoining Defendants,

and each of their officers, agents, servants and employees and all others in concert or participation with them, from committing further acts of infringement under 35 U.S.C. § 271 of any one or more claims of the ‘168 Patent and the ‘411 Patent, pursuant to 35 U.S.C. § 283; (e) An award of damages for Defendants’ infringement, which should be trebled

pursuant to 35 U.S.C. § 284; (f) That this case be declared “exceptional” and award TET its reasonable attorney

fees, expenses, and costs in this action pursuant to 35 U.S.C. § 285; and 9

(g)

Such other and further relief as the Court may deem just and proper.

Dated: June 27, 2013

Respectfully submitted,

/s/ Christopher Viceconte Christopher Viceconte (No. 5568) GIBBONS P.C. 1000 N. West Street, Suite 1200 Wilmington, DE 19801-1058 Phone: 302-295-4875 Fax: 302-295-4876 David E. De Lorenzi pro hac vice to be filed Ralph A. Dengler pro hac vice to be filed Todd M. Nosher pro hac vice to be filed GIBBONS P.C. One Gateway Center Newark, NJ 07102 Phone: 973-596-4500 Fax: 973-596-0545 Attorneys for Plaintiff TET Systems GMBH & Co. KG

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JURY DEMAND TET hereby demands a jury trial on all issues so triable in this action. /s/ Christopher Viceconte Christopher Viceconte (No. 5568) GIBBONS P.C. 1000 N. West Street, Suite 1200 Wilmington, DE 19801-1058 Phone: 302-295-4875 Fax: 302-295-4876 David E. De Lorenzi pro hac vice to be filed Ralph A. Dengler pro hac vice to be filed Todd M. Nosher pro hac vice to be filed GIBBONS P.C. One Gateway Center Newark, NJ 07102 Phone: 973-596-4500 Fax: 973-596-0545 Attorneys for Plaintiff TET Systems GMBH & Co. KG Dated: June 27, 2013

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