Patenting Biotechnology Inventions

Author: Dr. Kalyan C. Kankanala1 Introduction

Biotechnology has the potential to transform humanity provided humanity wishes to be transformed.2 It promises better drugs, medical treatment tailored to the individual patient's biological make-up, new crops and new industrial processes. Biotechnology companies spend hundreds of millions of dollars and sometimes decades to develop a product.3 Patents provide the needed assurance for investors to risk the capital necessary in the long development process, so that investment cannot only be recouped but also generates profits. In the absence of patent regime, investor’s would not be interested in investing millions on long term R and D because their research output can be exploited by any person, which jeopardizes their returns and profits. In this context, biotechnology assumes very high importance when seen in the light of patent regime because of its research and investment intensive nature. However, the application of patent system to biotechnology as a field has been fraught with uncertainty and ambiguity because of the nature of the field. Unique nature of Biotechnology One of the most unique features of biotechnology is its diversity. Biotechnology as a field has number of sub fields. Though there is a common line running through all of them, each sub field has characteristics and features which are different from the others that a broad set of general rules cannot be framed for biotechnology as a whole. For example, genomics is different from tissue culture in characteristics, applications, processes and products and even in tissue culture; plant tissue culture has different characteristics when compared to animal tissue culture. Figure 3.1 provides an example of the diverse sub-fields that fall under the scope of biotechnology. As the field is growing and evolving at a rapid pace, the list is a non-exhaustive one.

1

Email: kalyan@brainleague.com, Blog: www.sinapseblog.com 1Climbing the Helical Staircase, Geoffrey Carr, The Economist, March 27, 2003. 3 Biotechnology Industries Organization, USA, http://www.bio.org/ip/, visited on September 21, 2005.

BIOTECHNOL

(1) BIOPROC

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

(2) HYBRIDO MA AND MONOCLON

(1) CELL

(2) RECOMBI

b)

(3) CLONING

(4) GENOMIC

(5) MICROAR
14. 15.

(6) DNA

16. Figure 3.1 – Examples of sub-fields in Biotechnology Source : www.bio.org visited on 21st September, 2005. Because of diversity in the field and varying characteristics of its sub fields, it is very difficult to devise or establish patent principles or rules for biotechnology as a whole and therefore, the application of patent law to biotechnology is very complex. As biotechnology has a direct interface with life, it gives rise to lot of moral, ethical and religious issues. Most issues in biotechnology, from patenting of genes or genetically modified crops to patenting life has been fraught with moral, ethical and religious controversies. Due to this reason, public consciousness has for long been intertwined with the progress of biotechnology and policy framers have been skeptical in applying the patent regime to promote a field that has the potential of disturbing ethics and values that have been built into the society. Furthermore, there has always been fear among people that biotechnology research might result in environment hazards and the progress of the field has been controversial. One issue that expounded

moral, ethical and environmental controversies was the recombinant DNA controversy, which led to promulgation of safety guidelines for biotech research.4 In addition to the aforesaid issues, the meaning of the term biotechnology has since long been very vague and ambiguous. It has been attributed different meanings based on context, place, etc. The World Intellectual Property Organization (WIPO) defines biotechnology as any technology using living entities, in particular animals, plants, or microorganisms, or causing change in them."5 The United States Office of Technology Assessment has defined Biotechnology as "any technique that uses living organisms or substances from those organisms to make or modify a product, to improve plants or animals, or to develop microorganisms for specific uses."6 The Organisation for Economic Co-operation and Development (OECD) has defined biotechnology as: 'The application of science and technology to living organisms, as well as parts, products and models thereof, to alter living or non-living materials for the production of knowledge, goods and services.7 On review of the afore-mentioned definitions, it can be observed that each of the definitions have different meaning and scope when compared to the others. While the WIPO definition is very broad and covers any technology that uses living organisms, the definition of Office of Technology is narrower as it is limited to only techniques using living organisms to make or modify products and to improve plants or animals. On the other hand, the OECD definition has a different scope when compared to other definitions because it defines the scope of biotechnology to include techniques using living organisms for production of knowledge, goods or services, which is an economic view of the field. Due to differences in the meaning attributed by different organisations or groups, the scope of the field is not clear and therefore poses challenges for application of patent principles. Patentability Requirements and Biotechnology Inventions Any invention will be eligible for a patent grant only if it satisfies the patentability requirements. The following section explains the scope of patentability requirements from the perspective of biotechnology inventions. The principles underlying patentability of biotechnology inventions in USA, Europe and India have been elaborated. Patentable Subject Matter USA To be patentable subject matter in USA, an invention should be a process, machine, manufacture or composition of matter or any improvement thereof.8 There are three judicially created exclusions to patentable subject matter in USA. They are Laws of nature, physical phenomena, and abstract
4

Genetic Alchemy, The Social History of the Recombinant DNA Controversy, Sheldon Krimsky, The MIT Press (1982). 5 Graeme T. Laurie, Biotechnology and Intellectual Property: A Marriage of Inconvenience?, in CONTEMPORARY ISSUES IN LAW, MEDICINE AND ETHICS 237, 238 (Sheila A. M. McLean ed., 1996) (citing Committee of Experts on Biotechnology Inventions and Industrial Property, Second Session (Geneva, Feb. 3-7, 1986), reported in INDUSTRIAL PROPERTY, June 1986, at 251, 256. 6 Jasemine Chambers, Patent Eligibility of Biotechnological Inventions in the United States, Europe, and Japan: How Much Patent Policy is Public Policy?, 34 Geo. Wash. Int'l L. Rev. 223 (2002). 7 http://www.stat.fi/tk/yr/ttbio_en.html?tulost visited on 16th September, 2005. 8 35 USC Section 101 (2005).

ideas.9 Biotechnology (Biotech) inventions are considered to be eligible subjects as Compositions of matter or manufactures. The exclusion most relevant for biotech inventions is 'Laws of nature' exclusion. US Courts have consistently held that s per the exclusion anything that naturally exists or is a 'product of nature' is not patentable. The question relating to patentability of micro-organisms first came before the US Supreme Court in Funk Bros. Seed Co. v. Kalo Inoculant Co.10The case involved an invention relating to a mixed culture of Rhizobium bacteria capable of simultaneously inoculating the seeds of plants belonging to several cross-inoculation groups.11 The court in this case held that the mere aggregation of species fell short of invention within the meaning of the patent statute because the combination of species produced no new bacteria and no change in the six species of bacteria.12 As there was no change in the species, the court stated that qualities of the non-inhibitive strains were the work of nature and therefore not patentable subject matter.13 Later, the US Supreme Court in Diamond v. Chakrabarty, a landmark biotech case, held that everything under the sun made by man is patentable.14 The case related to patentability of a genetically modified pseudomonas bacterium capable of degrading oil spills and a process by which four different plasmids, capable of degrading four different oil components, could be transferred to and maintained stably in a single Pseudomonas bacterium.15 The patent application relating to the bacterium was rejected on the ground that the bacterium was a product of nature and that it is a living organism.16 On appeal, the US Supreme Court held that the invention is patentable because it is a new bacterium with markedly different characteristics from any found in nature. The Supreme court further stated that the test for determining whether an invention falls within the scope of 'Product of nature' is whether the invention in question involves a hand of man. If yes, the invention is not product of nature or naturally existing. If No, it is naturally existing and therefore not patentable. As the pseudomonas bacterium in the case involved the hand of man in inserting four different plasmids into it, the court held that it was not naturally existing and therefore patentable.17 It also stated that living organisms were not excluded from the scope of patentable subject matter in USA.18 After the Chakrabarty’s decision, expounded the product of nature doctrine, patents have been granted to various multi-cellular organisms. Patents were granted to polyploid oysters, genetically modified mice, rabbits and so on. Furthermore, patents have also been held patentable.19 Furthermore, in USA, gene sequences, gene therapies and so on have also been held to be patentable subject matter.

9

Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980). 333 US 127 (1978) 11 Id. at 441. 12 Id. at 442. 13 Id. 14 Diamond v. Chakrabarty, 100 S.Ct. 2204 (1980). 15 Id. at 305. 16 Id. 17 Id. at 311. 18 Id. 19 Ag Supply, Inc. v. Pioneer Hi-Bred Int'l, Inc., 534 U.S. 124 (2001).
10

Though the scope of patentable subject matter is very broad in USA, human beings are not considered to be patentable subject matter. A patent application filed by Dr. Stuart Newman of New York Medical College covering fusion of embryonic human and animal cells to create chimeras for medical research was rejected by USPTO and such rejection was approved by the Court.20

Europe The discussion with respect to Europe has been limited to the European Patent Convention (EPC). As per the European Patent Convention, any invention is patentable unless it falls within the list of excluded inventions.21 According to Article 52 of EPC, any invention irrespective of the technology to which it belongs can be considered as patentable subject matter so long as it is new, inventive and has an industrial applicability and does not fall within the list of excluded inventions provided in Article 53 of the EPC.22

Along with inventions contrary to public order or morality, the list of exclusions also include plant and animal varieties, essential biological processes for the production of plants and animals and methods of treatment. The EU Biotechnology Directive passed in 1998 clarified the scope of patentability of biotech inventions to a large extent.23 Though the directive is not binding on the European Patent Office, the implementing regulations have been modified to make the EU Directive on Biotechnology as a supplementary source for interpreting patentability of biotech inventions under the EPC.24

As per Article 53 (b) of EPC, plant and animal varieties and essential biological processes for the production of plants and animals are not patentable subject matter but micro-organisms are patentable.25 Rule 27b of the Implementing regulations of EPC provides that plants or animals are patentable if the technical feasibility of the invention is not confined to a particular plant or animal variety.26 In the light of the said rule, genetically modified animals and plants have been held to be patentable as they fall outside the scope of animal or plant variety. In the Novartis case relating to patentability of transgenic plants into which DNA had been inserted using recombinant technology, the Technical Board of Appeals stated that if a genetic modification can be applied to more than one variety then the invention is patentable subject matter as it falls outside the scope of exclusion of plant variety. 27

In the Oncomouse case, the Technical Board of Appeals held that a genetically altered mouse, which involved inserting an activated oncogene to develop cancer in the mouse was patentable
20 21

No Patent On Embryonic Human-Animal Chimera, 24 Biotechlr 290 (June, 2005). Article 52, European Patent Convention. 22 Article 52, European Patent Convention 1973 as amended in 2000. 23 Council Directive 98/44/EC of 6 July 1998 on the legal protection of biotechnology inventions. 24 Rule 26 of the Implementing Regulations to the Convention on the grant of European Patents of 5 October 1973 as last amended by Decision of the Administrative Council of the European Patent Organisation of 7 December, 2006. 25 Article 53(b), European Patent Convention 1973 amended in 2000. 26 Rule 27 b of the Implementing Regulations to the Convention on the Grant of European Patents of 5 October 1973 as last amended by Decision of the Administrative Council of the European Patent Organisation of 7 December, 2006. 27 Novartis/Transgenic Plant, Technical Board of Appeal 3.3.4, [1999] E.P.O.R. 123.

subject matter.28 In the light of Oncomouse case, non human multicellular organisms including rodents and mammals can be considered to be patentable subject matter in Europe.

Gene sequences have also been held to be patentable subject matter in Europe. As per the implementing regulations, biological material, which is isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature, is patentable.29 Rule 29 (2) specifically mentions that gene sequences are patentable.30It provides that though the sequence or partial sequence of a gene, cannot constitute a patentable invention, an element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element. Human beings or parts of human beings are not patentable subject matter in Europe.

India The scope of eligible subjects is very broad in India. Any product or process irrespective of the technology is patentable subject matter in India.31 However, the Act provides a long list of inventions that are excluded from patentable subject matter, which includes biotechnology inventions.32 Discovery of any living thing occurring in nature is not patentable subject matter in India.33 Prohibited biotech subjects further include plant and animals in whole or any part thereof including seeds; varieties, species and essentially biological processes for production or propagation of plants and animals.34 However, microorganisms and microbiological processes are patentable subject matter.35 Genetically modified multicellular organisms including plants, animals, human beings and their parts are excluded from patentability in India. Gene sequences and DNA sequences having disclosed functions are considered patentable in India. However, human beings and embryonic stem cells are not patentable. Furthermore, methods of medical treatment are also prohibited from patentability in India.36

Utility/Industrial Applicability

USA
28 29

Decision T 19/90. Rule 27 (a) Implementing Regulations to the Convention on the Grant of European Patents of 5 October 1973 as last amended by Decision of the Administrative Council of the European Patent Organisation of 7th December, 2006. 30 Id. 31 Section 2(j), Indian Patent Act, 1970 as amended in 1999, 2002 and 2005) or process, machine, manufacture, composition of matter or improvements as in USA. (35 USC Section 101 (2005). 32 Section 3, Indian Patent Act, 1970 as amended in 1999, 2002 and 2005. 33 Section 3(c), Indian Patent Act, 1970 as amended in 1999, 2002 and 2005. 34 Section 3(j), Indian Patent Act, 1970 as amended in 1999, 2002 and 2005. 35 Id. 36 Section 3(i), Indian Patent Act, 1970 as amended in 1999, 2002 and 2005.

Utility requirement assesses the usefulness of an invention. The standards of utility have been heightened for biotechnology inventions due to lack of maturity of the field. Considering the unique nature of gene based inventions more particularly Expressed Sequence Tags, commonly known as ESTs, USPTO revised its utility examination guidelines for patent examiners in 1999. The guidelines were later amended in 2001.37 As per the guidelines, an invention should establish specific, substantial and credible utility from the point of view of a person with ordinary skill in the art. Although, all the three conditions must be cumulatively satisfied for qualifying the utility requirement, the most important condition for biotech inventions is establishment of specific utility. Specific utility necessarily means a use specific to the claimed subject matter rather than a general utility. The guideline defines specific utility as a practical utility having real world use38. Any invention that requires further research to ascertain its practical utility was considered to be not useful because it lacked specific utility.39 In re Fisher, the inventor claimed several uses of the ESTs including its use as a molecular marker, primer and so on among other general uses. 40 The court in this case stated that since genes encoded by the claimed ESTs had no known functions, they were considered to be not useful.41 It inferred that utility should be directed to a particular disease or aspect and cannot be very general. To summarize, a biotech invention must satisfy substantial, credible and specific utility in order to satisfy the utility requirement. General uses of the invention will not be accepted for purposes of utility and specific uses must be shown.

Europe According to Article 57 of the EPC, it is sufficient that the invention is capable of being industrially produced in order to fulfill the industrial application requirement.42 The ascertainment of industrial applicability for biotechnology inventions is challenging because the field is filled with ambiguities. According to the Implementing regulations, partial and complete gene sequences are considered to be patentable under the EPC. However, Rule 29 (3) of the Implementing regulation explicitly poses a requirement that the industrial application of a sequence or a partial sequence of a gene must be disclosed in the patent application.43 Moreover, the preamble of the directive specifically mentions that a mere DNA sequence without indication of a function does not contain any technical information and is therefore not a patentable invention.44 Thus, it can be concluded that biotech inventions and specifically gene sequences are patentable under the EPC only if the function of the invention is explicitly mentioned in the application and with respect to gene sequences, the protection is limited to the function thus mentioned.

Revised Interim Utility Guidelines, 64 FR 71440, Dec.21, 1999; 1231 O.G.136(2000);and correction at 65 FR 3425, Jan.21, 2000;1231 O.G. 67 (2000). 38 Definition, Chapter III Asserted Specific Utility, Guidelines for Examination of Applications for Compliance with the Utility Requirement (1995). 39 Id. 40 In re Fisher, 421 F.3d 1365 (C.A.Fed.,2005). 41 Id. 1372 42 Article 57, European Patent Convention 1973 as amended in 2000. 43 Rule 29 (3) Implementing Regulations to the Convention on the Grant of European Patents of 5 October 1973 as last amended by Decision of the Administrative Council of the European Patent Organisation of 7th December, 2006. 44 Preamble 23 Directive

37

In the Max Planck decision, which related to a Brain Derived Phosphatase, the board stated that industrial applicability could be satisfied only if a "practical" application of the invention was disclosed. 45 The Board inferred in the case that a vague and speculative indication of possible objectives that might or might not be achievable by carrying out further research with the tool described in the patent application was not sufficient for fulfillment of the requirement of industrial applicability.46 To summarize, biotechnology inventions can satisfy industrial applicability requirement only if they have known uses, which are practical and specifically mentioned in the patent application. India In India, for an invention to be industrially applicable, it is necessary to prove that the invention can be made, Can be used in at least one field of activity and Can be reproduced with the same characteristics as many times as necessary.47 Since, no specific mention with regard to industrial applicability of biotechnology patents have been provided for in the act, it is reasonable to apply the general industrial applicability standards to biotechnology inventions. As biotechnology inventions can be made and used in an industry and can be reproduced as many times as required, they would satisfy the Industrial Applicability requirement in India. The guidelines for examining biotechnology inventions in the Manual of Patent Practice provide that gene sequences and DNA sequences whose functions are not disclosed do not satisfy the Industrial Applicability requirement.

Novelty USA The novelty requirement in USA has been lowered to a certain extent in order to accommodate patent grants to biotechnology inventions. Courts have held that isolated and purified gene sequences were novel even if they are identical to the sequences in nature. It has been held that isolation and purification of a naturally existing gene sequence lends novelty to the sequence. Most cases with respect to novelty of biotechnology inventions in USA relate to conception and reduction of a gene sequence to practice. In Amgen v. Chugai48, one of the most important novelty cases, the court stated that a gene was a chemical compound, albeit a complex one and is therefore patentable. The Court then pointed out that it was well established in US law that conception of a chemical compound required that the inventor was able to define it so as to distinguish it from other materials, and to describe how to obtain it.49 The court further said that conception of a generalized approach for screening a DNA library that may be used to identify and clone the Erythropoetin (Epo) gene of unknown constitution was not conception of a "purified and isolated DNA sequence" encoding human EPO.50 A biotechnology invention for purposes of novelty is said to be conceived only if it is reduced to practice. Europe

45

Max Planck/BDP1 Phosphatase, Legal Board of Appeal 3.3.8 ,[2006] E.P.O.R. 14, (2004).

46 47

Id. Page 13, Para 2.4, Chapter II, Manual of Patent Practice and Procedures 2005. 48 Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200 (C.A.Fed. (Mass.),1991). 49 Id. at 1206. 50 Id. at 1207.

Novelty of biotechnology inventions has been the subject of uncertainty at the European Patent Office. The Implementing regulations to EPC provide that biological material which is isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature, is patentable. The regulations specifically provide that an element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element. As per the regulations, a gene sequence isolated from nature would be considered to be novel in the light of what exists in nature even if its structure is same as the one existing in nature.51 The principle was applied by the board in the Relaxin Decision.52 The Relaxin case dealt with a process for obtaining H2-relaxin, the DNA encoding it, their chemical structure and use of the protein. The Board pointed out in the case that isolation of a gene of a known protein for the first time through conventional methods would make the gene sequence novel. 53 The Board further stated that natural existence of genes would not anticipate their isolation, as the isolated genes containing only the coding regions were different from their natural counterparts. It can be inferred from the case that just like in USA, the threshold for novelty determination for biotechnology invention is relatively low and an isolated gene sequence with slight difference from the prior art can be considered as novel. India The Patents Act does not have any explicit provisions with respect to novelty of biotechnology inventions. Since most biotechnology inventions are products of nature inherently present in living organisms, they could be construed as discoveries and not patentable. However, the Manual of patent practice and procedure provides that biological material such as recombinant DNA, Plasmids and processes of manufacturing thereof are patentable provided they are produced by substantive human intervention. As there are no decided cases on the subject, the interpretation of the Manual is being used to analyze novelty of biotechnology inventions. Several patents have been granted for isolated gene sequences in India and such sequences have been considered to be novel by the patent office in the light of their natural counterparts. Non obviousness/Inventive Step USA The Non-obviousness standards required for biotechnology inventions have been interpreted by courts to be different from the generally accepted principles. In Hybritech v. Monoclonal54, a case involving a patent over "Immunometric Assays Using Monoclonal Antibodies", the court held the patent non-obvious despite the existence of twenty prior art references because the prior art as a whole did not make the invention obvious at the time the invention was made. Though some references seemed to anticipate the invention, the Court pointed out that they were made after the date of conception of the invention, thus taking them out of the scope of prior art. The court in this case reiterated the importance of secondary indicia by determining the sandwich assays using monoclonal antibodies to be nonobviousn because of the commercial success, unexpected advantages and praise from experts of the diagnostic kits made by Hybritech.

51

Rule 23c(a) and Rule 23e(2)- Patentable biotechnological inventions, PART II – Implementing regulations to Part II of the Convention. 52 Howard Florey/Relaxin (Oppositions by Fraktion der Grunen Im Europaischen Parlament; Lannoye), Opposition Division, 8 December 1994, (1995) E.P.O.R. 541. 53 Id. at 542.
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Hybritech, Inc.,v..Monoclonal Antibodies, 802 F.2d 1367 (Fed. Cir. 1986).

In Amgen v. Chugai55, a patent for DNA sequences encoding erythropoetin (Epo) was claimed to be invalid based on obviousness along with other claims. The Federal Circuit held the patent nonobvious by reasoning that it might have been feasible, perhaps obvious to try, to successfully probe a human gDNA library with a monkey cDNA probe but it does not indicate that the gene could have been identified and isolated with a reasonable likelihood of success. Neither the DNA nucleotide sequence of the human Epo gene nor its exact degree of homology with the monkey Epo gene was known at the time the claimed invention was made. According to the court, though the idea of using the monkey gene to probe for a homologous human gene might have been obvious to try, but the realization of that idea was not obvious. Finally, the court stated that hindsight is not a justifiable basis on which to find that ultimate achievement of a long sought and difficult scientific goal was obvious. In 'In re Deuel56', a case involving an invention relating to isolated and purified DNA and cDNA molecules encoding heparin-binding growth factors, the Federal Circuit held the invention non obvious despite Bohlen and Maniatis references disclosing a group of protein growth factors and a general gene cloning method. The issue raised in this case was whether the combination of a prior art reference teaching a method of gene cloning, together with a reference disclosing a partial amino acid sequence of a protein, would render DNA and cDNA molecules encoding the protein prima facie obvious. The court held that the subject matter of the invention could not be conceived based on the teachings in the references because, until the claimed molecules were actually isolated and purified, it would have been highly unlikely for one of ordinary skill in the art to contemplate the claimed invention. The court further stated that 'What cannot be conceived cannot be obvious.' In In re Kubin’s57 case, the invention dealt with an amino acid sequence of Natural Killer Cell Activation Inducing Ligand also referred to as NAIL which plays a major role in activation of the Natural Killer cells that are instrumental in fighting tumors and viruses.58 The patent office stated that the claimed amino acid sequence was obvious in light of combination of two prior art references namely Valiante’s patent bearing the U.S. Patent No. 5,688,690 which discloses a receptor protein called p38 receptor which the board found was essentially the same protein as NAIL and the Laboratory Manual on Cloning authored by Joseph Sambrook which provided information with regard to conventional techniques to isolate and sequence any gene. The federal circuit affirmed the Board’s decision stating that in light of the specific teachings of Sambrook and Valiante, artisans in this field had every motivation to seek and every reasonable expectation of success in achieving the sequence of the claimed invention. As per the Court, the claimed invention was reasonably expected in light of the prior art and was held to be obvious.

Due to lack of maturity in the field, the non-obviousness requirement in USA was lower for biotechnology inventions when compared to other inventions. The reasonable expectation of success was considered to be lower and anything obvious to try was generally considered non-obviousns. However, the differing decisions in Deuel and Kubin cases, which have similar facts indicates that the non-obviousness standards are also not applied uniformly. Europe
55 56

Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200 (Fed Cir. 1991) IN RE THOMAS F. DEUEL, YUE-SHENG LI, NED R. SIEGEL and PETER G. MILNER, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed Cir. 1995).
57 58

In re Kubin, 561 F.3d 1351 (2009). Id at 1353.

Tests for Determination of inventive step of biotechnology inventions have been ambiguous due to uncertainty in the field. The European Patent Office and Boards have been striving to frame clear guidelines for determining inventive step of biotechnology inventions. In the Relaxin case59 which dealt with a process for obtaining H2-relaxin and the DNA encoding it, the Board pointed out that as the proprietor was not preparing a known substance by conventional means, but providing to the public for the first time a product whose existence was previously unknown, the claimed invention must be regarded as inventive irrespective of the methods used to prepare the product.60 The non-obviousness determination is always done from the point of view of a person with ordinary skill in the art. The knowledge of the person skilled in the art in case of biotech inventions had been aptly discussed in R. v. Genentech61, a case concerned with interferongamma and the DNA sequence coding for it. In this case the Board stated that Skilled person in the art must be considered as that of a team of the appropriate specialists, who know all the difficulties still to be expected when considering cloning a new gene. The board also inferred that a skilled person must be assumed to lack the inventive imagination to solve problems for which there do not exist already routine methods of solution, the appropriate comparison being not with a team but with a highly skilled technician carrying out a project where the initial instructions received were already adequate to tell the technician how to overcome any problems likely to arise.62 Also in R. v. Chiron63 decision, which dealt with inventive step of a DNA molecule comprising a specified nucleotide sequence encoding insulin-like growth factor II (IGF-II), the court inferred that lack of sufficient information in prior art can be supplemented by the knowledge of the person skilled in the art while determining obviousness. In this decision the board stated that an invention would lack inventive step even if the prior art reference lacks complete description, provided the reference can be supplemented by information available to a person with ordinary skill in the art. As per the Board, reasonable likelihood of success can make an invention obvious and showing low expectation of success can rebut it. The Board pointed out that reasonable likelihood of success can be proved by prior art information, experiments, expert testimony and so on. While determining inventive step of biotechnology inventions under EPC various factors such as obviousness in the light of combination of prior art to a person with ordinary skill in the art, reasonable expectation of success and secondary considerations such as commercial success and expert testimony are considered. The standards of non-obviousness are higher in Europe when compared to USA and it is therefore comparatively difficult to satisfy this requirement in Europe. India Due to dearth of case law, the approach to inventive step with regard to biotechnology inventions in India is not clear. As per the Manual, it can be safely concluded that isolated gene sequences and protein sequences will be considered to have an inventive step in the light of their naturally existing counter parts. Furthermore, the economic significance requirement is relatively easy to prove for biotechnology inventions due to their various applications in drugs and diagnostics sector. Principles such as reasonable expectation of success,
59

Howard Florey/Relaxin(Oppositions by Fraktion der Grunen Im Europaischen Parlament; Lannoye), Opposition Division, 8 December 1994, [1995] E.P.O.R. 541. 60 Id. at 548. 61 R. v. Genentech/HIF-Gamma, Technical Board of Appeal 3.3.2, July 20, 1993 [FN1], [2003] E.P.O.R. 12. 62 Id. 63 R. v. Chiron/IGF-II, T475/93,Technical Board of Appeal 3.3.4, July 17, 1997 [FN1], [2003] E.P.O.R. 48.

predictability of the field and so on are applied to determine inventive step in India as well and would be applied to biotechnology inventions. However, as it stands now the law does not indicate any differing standards for biotechnology inventions when compared to other inventions. Enablement and Written Description The Courts and Patent Offices have set different standards of written description and enablement requirements for biotech inventions when compared with other inventions due to their unique nature. Considering the uncertainties in the field, patent offices generally insist on detailed description of the invention with research data and examples. Enablement is commonly not assessed through supplementation of prior art unless specific reference is made in the written description. The written description and enablement requirements may be satisfied by deposit of biological materials or submission of sequence listings in case of genetic inventions. USA Unlike in Europe and India, USA considers written description and enablement as two different requirements. The US Courts have laid down differing standards for written description and enablement requirements. The standards are generally higher when compared to other inventions and require specificity, reduction to practice, examples and experimental data. A short note on a few cases explaining the differing standards adopted for biotech applications have been provided hereunder. In Amgen v. Chugai64 , a case relating to an infringement of a patent over DNA sequences encoding Erythropoietin, the court stated that generic claims to genetic sequences could be valid where they were of a scope appropriate to the invention disclosed by an applicant.65 The court further stated that claims in a patent application have to be adequately supported by the written description and stating a few gene analogs would not support a claim over all gene analogs of a protein. In another case, Fiers v. Revel,66 a case relating to patent applications for DNA coding for human fibroblast beta-interferon, the court pointed out that claiming all DNA's that achieve a result without defining what means would do so was not in compliance with the description requirement and that it was an attempt to preempt the future before it had arrived. 67 In Regents of the University of California v. Eli Lilly & Co68, a case relating to recombinant plasmids and microorganisms that produce human insulin, the court held that the claim of the patent directed to recombinant prokaryotic microorganism modified to encode human insulin was invalid, because patent specification did not fulfil statutory written description requirement.69 The court in this case inferred that description of DNA sequences by function without pointing out the structure or physical characteristics would not be sufficient to satisfy the written description requirement. It also laid down that disclosure of structure of a few species in a genus would not be sufficient to support a claim of the entire genus unless substantial features of the genus and substantial common physical characteristics were described.

64

Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200 (C.A.Fed. (Mass.),1991). Id. 66 Fiers v. Revel, 984 F.2d 1164 (C.A.Fed.,1993). 67 Id. 68 Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, (C.A.Fed. (Ind.),1997). 69 Id. at 1569.
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The USPTO passed the revised guidelines for written description in 2001, which are largely in conformity with case law. 70 The guidelines explain how biotechnology inventions such as genes, ESTs, antisense, ORFs, etc., would be considered for purposes of written description. Before 1990, Gene sequence data was being submitted in different formats by different applicants due to absence of a standard format recommended by the USPTO. To resolve the inconvenience caused during examination of gene based invention due to the lack of uniformity with regard to submission of gene sequence data the Office amended its regulations to establish a standardized format for descriptions of nucleotide and amino acid sequence data.71 Europe The threshold for disclosure and enablement requirement in Europe is much higher for biotechnology inventions when compared to other technologies. Assessment of the sufficiency of a disclosure depends on the correlation of the facts of the case to certain general parameters such as the character of the technical field, the average amount of effort necessary to put into practice a certain written disclosure in that technical field, the time when the disclosure was presented to the public and the corresponding general knowledge and the amount of reliable technical details disclosed in a document.72 In the Weyershaeuser Case that dealt with microbiologically produced reticulated cellulose the board stated that the disclosure should be sufficiently clear such that it can be enabled by a person skilled in the art without undue burden on that person.73 Further, in R. v. Massachusetts Institute of Technology decision, 74the board stated that in case of gene based inventions, the requirement of trial and error to carry out the invention would make the disclosure non-enabling. To work biotechnology inventions involves several molecular biology techniques and requires extensive experimentations for standardization of experiments. Also, the time taken for successful completion of an invention would depend on the level of skill of the technician performing the experiment. Thus, in many cases, several attempts may be required to complete an enabled invention. This issue has been addressed in R v. Genentech case, which related to sufficiency of disclosure in a patent concerning amino acid sequence and DNA sequences of interferon-gamma.75 In this case the Board stated that a patent application relating to a gene would be enabling even if the experimentation required is burdensome, so long as undue experimentation is not required. It further stated that deposit of biological materials is not compulsory as long as an application can be enabled based on written description.

Later, in the Biogen Decision the Board laid down that disclosure can rely on functional characteristics in case of genetic inventions.76 This decision reduced the burden of patent disclosure for biotechnology inventions. To summarize, the written description and enablement requirement for biotechnology inventions must satisfy higher standards than other inventions with a few exceptions. While deposit of biological materials can supplement a
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USPTO Guidelines and Training Materials on Written Description, Federal Register /Vol. 66, No. 4/Friday, January 5, 2001. 71 Manual of Patent Examining Procedure, 2420 The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures - the Sequence Rules. 72 Dr. Kalyan C. Kanakanala, Genetic Patent Law and Strategy (1stedition 2007), pp 123-124. 73 Eyershaeuser/Cellulose, Technical Board of Appeal 3.3.4, [2001] E.P.O.R. 35. 74 R. v. Massachusetts Institute Of Technology/Biopolymers, Technical Board of Appeal 3.3.4, [2003] E.P.O.R. 16. 75 R. v. Genentech/HIF-Gamma, Technical Board of Appeal 3.3.2, [2003] E.P.O.R. 12. 76 Biogen/Recombinant Dna(Oppositions by Hoffmann la Roche; Upjohn; Boehringer Ingelheim Zentrale; Bender; Cetus; Hoechst; Boehringer Mannheim, Technical Board of Appeal 3.3.2, [1990] E.P.O.R. 190.

written description, it is not compulsory to deposit materials. Furthermore, disclosure of biotech inventions must be specific and broad disclosures are not sufficient. India In India, for biotechnology inventions, which describe biological material in the specification, the law provides for deposit of such biological materials at a recognized depository. The manual of patent practice and procedure requires the invention to be described completely in the specification to enable a person skilled in the art to be able to carry out the invention by reading the specification. 77 However, there are no cases in India that talk about differing written description or enablement standards for biotechnology inventions. Morality Moral and ethical issues have since long been playing a very important role in defining the progress of biotechnology. Right from the recombinant DNA controversy, ethics and morals have either impeded or slowed biotech progress. Issues surrounding ownership of genes and genetically modified humans, moral and identity dangers inherent in human cloning and genetic modification of human beings, suffering to animals due to genetic intervention, potential hazards to environment due to genetic manipulation, ecological balance and other issues have been cited as serious issues for granting patents on biotechnology inventions. The involvement of moral and ethical issues in patenting biotech inventions depends on the social, ideological, religious and economic conditions in a country. Variances in the role of morals and ethics in determining patentability in different countries, which is dependant on social and ideological conditions gives rise to differences in the scope of patent protection. USA The US patent statute does not contain any provisions relating to morals. Patentability analysis of an invention in USA does not involve determination of morality as none of the patentability requirements deal with morality. Despite the fact that morality is not a part of patentability analysis, the USPTO has laid down in its guidelines for examiners that patents would not be granted for subject matter relating to human beings as granting such patents would be against Amendment 13 of the US Constitution, which prohibits slavery.78 Based on the guidelines, the patent application filed by Jeremy Refkin for a human-animal chimera was rejected. Europe Unlike the US Patent Law, the European Patent Convention provides provisions relating to morality for grant of patents. Article 53 of EPC provides that European patents shall not be granted in respect of inventions the publication or exploitation of which would be contrary to "ordre public" or morality, provided that the exploitation shall not be deemed to be so contrary merely because it is prohibited by law or regulation in some or all of the Contracting States.79 The EU Biotechnology Directive also lays sufficient emphasis on morality as a factor to be considered before granting patents in biotech inventions.
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2.6 Sufficiency of Disclosure, Manual of Patent Practice And Procedure, 2005. Slavery and Involuntary Servitude, 13th Amendment, The Constitution of United States of America (2006). 79 Article 53(a), Convention On The Grant Of European Patents (European Patent Convention) of 5 October 1973 text as amended by the act revising Article 63 EPC of 17 December 1991 and by decisions of the Administrative Council of the European Patent Organisation of 21 December 1978, 13 December 1994, 20 October 1995, 5 December 1996 and 10 December 1998.

The European Patent Office has expounded the morality provision under Article 53 in its decisions involving biotechnology inventions. In the Harvard Mouse Case ,80 the invention relating to a genetically modified mouse was held patentable despite moral concerns. After reviewing the morality concerns, the Board held that the mouse was patentable though it is put through suffering because the benefit to human beings outweighs the suffering of the animal. The Board in this case stated that the utility of the mouse model for cancer treatment makes it moral and therefore, patentable. Another important case on morality is the Relaxin case. The Relaxin case81 related to a process for obtaining H2-relaxin and the DNA encoding it.82It was argued that the claimed invention was not patentable under Article 53(a) as the patent required taking of the tissue from a pregnant woman. It was argued that it amounted to an immoral act, which was against human dignity because it involves making use of a female condition (pregnancy) in a technical process oriented towards profit.83It was also argued that the patenting of human genes such as that encoding H2-relaxin amounted to a form of modern slavery since it involved the dismemberment of women and their piecemeal sale to commercial enterprises throughout the world and that the patenting of human genes means that human life was being patented, which was intrinsically immoral.84 The Opposition Division rejected the arguments stating that there was no reason to perceive the isolation of mRMA from the tissue of pregnant woman as immoral because it was taken by consent.85 As human tissue, blood, bone and so on have been the subject of isolation for medical purpose, the Opposition Division pointed out that such practice was accepted by the public.86 It then pointed out that patents covering DNA encoding human H2-relaxin, or any other human gene do not confer on their proprietors any rights to individual human beings and therefore, no woman would be affected in any way by the present invention and was free to live her life as she wished and had exactly the same right to self-determination as she had before the patent was granted.87 In addition, the Opposition Division stated that the exploitation of the invention does not involve dismemberment and piecemeal sale of women because gene cloning could be done in unicellular organisms and a woman was only required initially for isolating the tissue for which consent was taken.88 Finally, the Opposition Division pointed out that the allegation that human life was being patented was unfounded because DNA was not 'life', but a chemical substance, which carried genetic information and could be used as an intermediate in the production of proteins, which might be medically useful.89 It further stated that the patenting of a single human gene had nothing to do with the patenting of human life.90 In the light of its reasoning, the Opposition Division concluded that the invention was not against widely-accepted moral standards of behaviour by promoting slavery, the sale of women, and so on, nor was there a clear consensus among members of the public in the

Harvard/Onco-Mouse, Examining Division, [1990] E.P.O.R. 4. Howard Florey/Relaxin(Oppositions by Fraktion der Grunen Im Europaischen Parlament; Lannoye), Opposition Division, [1995] E.P.O.R. 541. 82 Id. 83 Id. at 549. 84 Id. 85 Id. at 550. 86 Id. 87 Id. at 551. 88 Id. 89 Id. 90 Id.
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Contracting States that patenting human genes such as that encoding H2-relaxin was immoral and therefore could be patented. The cases elucidate that morality determination forms an integral part of patentability analysis with regard to biotechnology inventions. This provision has been invoked regularly by the European Patent Office while deciding upon patentability of such inventions. An invention will not be granted a patent if evidence can be shown that it or its exploitation is against public order or morality. Patents will be granted over genetically modified animals only if the benefit to mankind outweighs the suffering caused to the animals. Potential unknown danger to society or environment will not be fatal to patentability of an invention.

India Section 3(b) of the Indian Patent Act provides that an invention the primary or intended use or commercial exploitation of which would be contrary to public order or morality or which causes serious prejudice to human, animal or plant life or health or to the environment is not patentable.91 As per the section an invention would not be patentable if it is immoral or against public order, harmful to human, animal or plant life or harmful to environment. The Manual of Patent Procedure provides that Any biological material and method of making the same which is capable of causing serious prejudice to human, animal or plant lives or health or to the environment including the use of those that would be contrary to public order and morality are not patentable. It further provides that the processes for cloning human beings or animals, processes for modifying the germ line, genetic identity of human beings or animals, uses of human or animal embryos for any purpose are not patentable as they are against public order and morality. The Indian Patent Law has strong prohibitions against patenting of biotechnology inventions based on morality and public order. Summary It can be seen from the review of patentability requirements for biotechnology inventions in USA, Europe and India that the requirements are applied differently when compared to other inventions. While some requirements like subject matter, utility and written description have heightened standards, non-obviousness standards have generally been lowered to accommodate ambiguities in the field. Morality plays an important role in determining patentability of biotech inventions. The role of morality is higher in Europe and India when compared to USA.

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Section 3(b) of the Indian Patent Act, 1970 as amended in 1999, 2002 and 2005.

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