Patenting Biotechnology Inventions Author: Dr. Kalyan C. Kankanala1IntroductionBiotechnology has the potential to transform humanity provided humanity wishes to betransformed.2 It promises better drugs, medical treatment tailored to the individual patientsbiological make-up, new crops and new industrial processes. Biotechnology companies spendhundreds of millions of dollars and sometimes decades to develop a product.3 Patents provide theneeded assurance for investors to risk the capital necessary in the long development process, so thatinvestment 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 researchoutput 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 itsresearch and investment intensive nature. However, the application of patent system tobiotechnology as a field has been fraught with uncertainty and ambiguity because of the nature ofthe field.Unique nature of BiotechnologyOne of the most unique features of biotechnology is its diversity. Biotechnology as a field hasnumber of sub fields. Though there is a common line running through all of them, each sub field hascharacteristics and features which are different from the others that a broad set of general rulescannot be framed for biotechnology as a whole. For example, genomics is different from tissueculture in characteristics, applications, processes and products and even in tissue culture; planttissue culture has different characteristics when compared to animal tissue culture. Figure 3.1provides an example of the diverse sub-fields that fall under the scope of biotechnology. As thefield is growing and evolving at a rapid pace, the list is a non-exhaustive one.1 Email: firstname.lastname@example.org, Blog: www.sinapseblog.com1Climbing 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) BIOPROC1.2. (2) HYBRIDO MA AND3. MONOCLON4.5. (1) CELL6.7. (2) RECOMBI8.9. (3) CLONING b)10.11. (4) GENOMIC12.13. (5) MICROAR14.15. (6) DNA16. Figure 3.1 – Examples of sub-fields in BiotechnologySource : 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 todevise or establish patent principles or rules for biotechnology as a whole and therefore, theapplication 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 religiousissues. Most issues in biotechnology, from patenting of genes or genetically modified crops topatenting 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 policyframers have been skeptical in applying the patent regime to promote a field that has the potential ofdisturbing ethics and values that have been built into the society.Furthermore, there has always been fear among people that biotechnology research might result inenvironment 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 ledto promulgation of safety guidelines for biotech research.4In addition to the aforesaid issues, the meaning of the term biotechnology has since long been veryvague and ambiguous. It has been attributed different meanings based on context, place, etc.The World Intellectual Property Organization (WIPO) defines biotechnology as any technologyusing living entities, in particular animals, plants, or microorganisms, or causing change in them."5The United States Office of Technology Assessment has defined Biotechnology as "any techniquethat uses living organisms or substances from those organisms to make or modify a product, toimprove plants or animals, or to develop microorganisms for specific uses."6The Organisation for Economic Co-operation and Development (OECD) has definedbiotechnology 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.7On review of the afore-mentioned definitions, it can be observed that each of the definitions havedifferent meaning and scope when compared to the others. While the WIPO definition is very broadand covers any technology that uses living organisms, the definition of Office of Technology isnarrower as it is limited to only techniques using living organisms to make or modify products andto improve plants or animals. On the other hand, the OECD definition has a different scope whencompared to other definitions because it defines the scope of biotechnology to include techniquesusing living organisms for production of knowledge, goods or services, which is an economic viewof the field. Due to differences in the meaning attributed by different organisations or groups, thescope 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 MatterUSATo be patentable subject matter in USA, an invention should be a process, machine, manufacture orcomposition of matter or any improvement thereof.8 There are three judicially created exclusions topatentable subject matter in USA. They are Laws of nature, physical phenomena, and abstract4 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 CONTEMPORARYISSUES IN LAW, MEDICINE AND ETHICS 237, 238 (Sheila A. M. McLean ed., 1996) (citing Committee of Expertson Biotechnology Inventions and Industrial Property, Second Session (Geneva, Feb. 3-7, 1986), reported inINDUSTRIAL PROPERTY, June 1986, at 251, 256.6 Jasemine Chambers, Patent Eligibility of Biotechnological Inventions in the United States, Europe, and Japan: HowMuch Patent Policy is Public Policy?, 34 Geo. Wash. Intl 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 Compositionsof matter or manufactures.The exclusion most relevant for biotech inventions is Laws of nature exclusion. US Courts haveconsistently held that s per the exclusion anything that naturally exists or is a product of nature isnot patentable. The question relating to patentability of micro-organisms first came before the USSupreme Court in Funk Bros. Seed Co. v. Kalo Inoculant Co.10The case involved an inventionrelating to a mixed culture of Rhizobium bacteria capable of simultaneously inoculating the seeds ofplants belonging to several cross-inoculation groups.11 The court in this case held that the mereaggregation of species fell short of invention within the meaning of the patent statute because thecombination of species produced no new bacteria and no change in the six species of bacteria.12 Asthere was no change in the species, the court stated that qualities of the non-inhibitive strains werethe work of nature and therefore not patentable subject matter.13Later, the US Supreme Court in Diamond v. Chakrabarty, a landmark biotech case, held thateverything under the sun made by man is patentable.14 The case related to patentability of agenetically modified pseudomonas bacterium capable of degrading oil spills and a process by whichfour different plasmids, capable of degrading four different oil components, could be transferred toand maintained stably in a single Pseudomonas bacterium.15 The patent application relating to thebacterium was rejected on the ground that the bacterium was a product of nature and that it is aliving organism.16On appeal, the US Supreme Court held that the invention is patentable because it is a new bacteriumwith markedly different characteristics from any found in nature. The Supreme court further statedthat the test for determining whether an invention falls within the scope of Product of nature iswhether the invention in question involves a hand of man. If yes, the invention is not product ofnature 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 differentplasmids into it, the court held that it was not naturally existing and therefore patentable.17 It alsostated that living organisms were not excluded from the scope of patentable subject matter inUSA.18After the Chakrabarty’s decision, expounded the product of nature doctrine, patents have beengranted to various multi-cellular organisms. Patents were granted to polyploid oysters, geneticallymodified mice, rabbits and so on. Furthermore, patents have also been held patentable.19Furthermore, in USA, gene sequences, gene therapies and so on have also been held to bepatentable subject matter.9 Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980).10 333 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 Intl, Inc., 534 U.S. 124 (2001).
Though the scope of patentable subject matter is very broad in USA, human beings are notconsidered to be patentable subject matter. A patent application filed by Dr. Stuart Newman of NewYork Medical College covering fusion of embryonic human and animal cells to create chimeras formedical research was rejected by USPTO and such rejection was approved by the Court.20EuropeThe 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 ofexcluded inventions.21 According to Article 52 of EPC, any invention irrespective of the technologyto which it belongs can be considered as patentable subject matter so long as it is new, inventiveand has an industrial applicability and does not fall within the list of excluded inventions providedin Article 53 of the EPC.22Along with inventions contrary to public order or morality, the list of exclusions also includeplant and animal varieties, essential biological processes for the production of plants and animalsand methods of treatment. The EU Biotechnology Directive passed in 1998 clarified the scopeof patentability of biotech inventions to a large extent.23 Though the directive is not binding onthe European Patent Office, the implementing regulations have been modified to make the EUDirective on Biotechnology as a supplementary source for interpreting patentability of biotechinventions under the EPC.24As per Article 53 (b) of EPC, plant and animal varieties and essential biological processes for theproduction of plants and animals are not patentable subject matter but micro-organisms arepatentable.25 Rule 27b of the Implementing regulations of EPC provides that plants or animalsare patentable if the technical feasibility of the invention is not confined to a particular plant oranimal variety.26 In the light of the said rule, genetically modified animals and plants have beenheld 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 beeninserted using recombinant technology, the Technical Board of Appeals stated that if a geneticmodification can be applied to more than one variety then the invention is patentable subjectmatter as it falls outside the scope of exclusion of plant variety. 27In 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 patentable20 No Patent On Embryonic Human-Animal Chimera, 24 Biotechlr 290 (June, 2005).21 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,  E.P.O.R. 123.
subject matter.28 In the light of Oncomouse case, non human multicellular organisms includingrodents 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 theimplementing regulations, biological material, which is isolated from its natural environment orproduced by means of a technical process even if it previously occurred in nature, is patentable.29Rule 29 (2) specifically mentions that gene sequences are patentable.30It provides that though thesequence or partial sequence of a gene, cannot constitute a patentable invention, an elementisolated from the human body or otherwise produced by means of a technical process, includingthe sequence or partial sequence of a gene, may constitute a patentable invention, even if thestructure of that element is identical to that of a natural element. Human beings or parts of humanbeings are not patentable subject matter in Europe.IndiaThe scope of eligible subjects is very broad in India. Any product or process irrespective of thetechnology is patentable subject matter in India.31 However, the Act provides a long list ofinventions that are excluded from patentable subject matter, which includes biotechnologyinventions.32Discovery of any living thing occurring in nature is not patentable subject matter in India.33Prohibited biotech subjects further include plant and animals in whole or any part thereof includingseeds; varieties, species and essentially biological processes for production or propagation of plantsand animals.34 However, microorganisms and microbiological processes are patentable subjectmatter.35 Genetically modified multicellular organisms including plants, animals, human beings andtheir 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 ofmedical treatment are also prohibited from patentability in India.36Utility/Industrial ApplicabilityUSA28 Decision T 19/90.29 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 beenheightened for biotechnology inventions due to lack of maturity of the field.Considering the unique nature of gene based inventions more particularly Expressed SequenceTags, commonly known as ESTs, USPTO revised its utility examination guidelines for patentexaminers in 1999. The guidelines were later amended in 2001.37As per the guidelines, an invention should establish specific, substantial and credible utility fromthe point of view of a person with ordinary skill in the art. Although, all the three conditions mustbe cumulatively satisfied for qualifying the utility requirement, the most important condition forbiotech inventions is establishment of specific utility. Specific utility necessarily means a usespecific to the claimed subject matter rather than a general utility. The guideline defines specificutility as a practical utility having real world use38.Any invention that requires further research to ascertain its practical utility was considered to be notuseful because it lacked specific utility.39In 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 encodedby the claimed ESTs had no known functions, they were considered to be not useful.41 It inferredthat 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 tosatisfy the utility requirement. General uses of the invention will not be accepted for purposes ofutility and specific uses must be shown.EuropeAccording to Article 57 of the EPC, it is sufficient that the invention is capable of being industriallyproduced in order to fulfill the industrial application requirement.42 The ascertainment of industrialapplicability for biotechnology inventions is challenging because the field is filled with ambiguities.According to the Implementing regulations, partial and complete gene sequences are considered tobe patentable under the EPC. However, Rule 29 (3) of the Implementing regulation explicitly posesa requirement that the industrial application of a sequence or a partial sequence of a gene must bedisclosed in the patent application.43 Moreover, the preamble of the directive specifically mentionsthat a mere DNA sequence without indication of a function does not contain any technicalinformation and is therefore not a patentable invention.44 Thus, it can be concluded that biotechinventions and specifically gene sequences are patentable under the EPC only if the function of theinvention is explicitly mentioned in the application and with respect to gene sequences, theprotection is limited to the function thus mentioned.37 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. 137242 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 lastamended by Decision of the Administrative Council of the European Patent Organisation of 7th December, 2006.44 Preamble 23 Directive
In the Max Planck decision, which related to a Brain Derived Phosphatase, the board stated thatindustrial applicability could be satisfied only if a "practical" application of the invention wasdisclosed. 45 The Board inferred in the case that a vague and speculative indication of possibleobjectives that might or might not be achievable by carrying out further research with the tooldescribed in the patent application was not sufficient for fulfillment of the requirement of industrialapplicability.46 To summarize, biotechnology inventions can satisfy industrial applicabilityrequirement only if they have known uses, which are practical and specifically mentioned in thepatent application.IndiaIn India, for an invention to be industrially applicable, it is necessary to prove that the invention canbe made, Can be used in at least one field of activity and Can be reproduced with the samecharacteristics as many times as necessary.47 Since, no specific mention with regard to industrialapplicability of biotechnology patents have been provided for in the act, it is reasonable to apply thegeneral industrial applicability standards to biotechnology inventions. As biotechnology inventionscan be made and used in an industry and can be reproduced as many times as required, they wouldsatisfy the Industrial Applicability requirement in India. The guidelines for examiningbiotechnology inventions in the Manual of Patent Practice provide that gene sequences and DNAsequences whose functions are not disclosed do not satisfy the Industrial Applicability requirement.NoveltyUSAThe novelty requirement in USA has been lowered to a certain extent in order to accommodatepatent grants to biotechnology inventions. Courts have held that isolated and purified genesequences were novel even if they are identical to the sequences in nature. It has been held thatisolation and purification of a naturally existing gene sequence lends novelty to the sequence. Mostcases with respect to novelty of biotechnology inventions in USA relate to conception and reductionof a gene sequence to practice.In Amgen v. Chugai48, one of the most important novelty cases, the court stated that a gene was achemical compound, albeit a complex one and is therefore patentable. The Court then pointed outthat it was well established in US law that conception of a chemical compound required that theinventor was able to define it so as to distinguish it from other materials, and to describe how toobtain it.49 The court further said that conception of a generalized approach for screening a DNAlibrary that may be used to identify and clone the Erythropoetin (Epo) gene of unknown constitutionwas not conception of a "purified and isolated DNA sequence" encoding human EPO.50 Abiotechnology invention for purposes of novelty is said to be conceived only if it is reduced topractice.Europe45 Max Planck/BDP1 Phosphatase, Legal Board of Appeal 3.3.8 , E.P.O.R. 14, (2004).46 Id.47 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 PatentOffice. The Implementing regulations to EPC provide that biological material which is isolatedfrom its natural environment or produced by means of a technical process even if it previouslyoccurred in nature, is patentable. The regulations specifically provide that an element isolated fromthe human body or otherwise produced by means of a technical process, including the sequence orpartial sequence of a gene, may constitute a patentable invention, even if the structure of thatelement is identical to that of a natural element. As per the regulations, a gene sequence isolatedfrom nature would be considered to be novel in the light of what exists in nature even if its structureis same as the one existing in nature.51The principle was applied by the board in the Relaxin Decision.52 The Relaxin case dealt with aprocess for obtaining H2-relaxin, the DNA encoding it, their chemical structure and use of theprotein. The Board pointed out in the case that isolation of a gene of a known protein for the firsttime through conventional methods would make the gene sequence novel. 53 The Board furtherstated that natural existence of genes would not anticipate their isolation, as the isolated genescontaining only the coding regions were different from their natural counterparts. It can be inferredfrom the case that just like in USA, the threshold for novelty determination for biotechnologyinvention is relatively low and an isolated gene sequence with slight difference from the prior artcan be considered as novel.IndiaThe Patents Act does not have any explicit provisions with respect to novelty of biotechnologyinventions. Since most biotechnology inventions are products of nature inherently present in livingorganisms, they could be construed as discoveries and not patentable. However, the Manual ofpatent practice and procedure provides that biological material such as recombinant DNA, Plasmidsand processes of manufacturing thereof are patentable provided they are produced by substantivehuman intervention. As there are no decided cases on the subject, the interpretation of the Manualis being used to analyze novelty of biotechnology inventions. Several patents have been granted forisolated gene sequences in India and such sequences have been considered to be novel by the patentoffice in the light of their natural counterparts.Non obviousness/Inventive StepUSAThe Non-obviousness standards required for biotechnology inventions have been interpreted bycourts to be different from the generally accepted principles. In Hybritech v. Monoclonal54, a caseinvolving a patent over "Immunometric Assays Using Monoclonal Antibodies", the court held thepatent non-obvious despite the existence of twenty prior art references because the prior art as awhole did not make the invention obvious at the time the invention was made. Though somereferences seemed to anticipate the invention, the Court pointed out that they were made after thedate of conception of the invention, thus taking them out of the scope of prior art. The court in thiscase reiterated the importance of secondary indicia by determining the sandwich assays usingmonoclonal antibodies to be nonobviousn because of the commercial success, unexpectedadvantages 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 542.54 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 beinvalid based on obviousness along with other claims. The Federal Circuit held the patentnonobvious by reasoning that it might have been feasible, perhaps obvious to try, to successfullyprobe a human gDNA library with a monkey cDNA probe but it does not indicate that the genecould have been identified and isolated with a reasonable likelihood of success. Neither the DNAnucleotide sequence of the human Epo gene nor its exact degree of homology with the monkey Epogene was known at the time the claimed invention was made. According to the court, though theidea of using the monkey gene to probe for a homologous human gene might have been obvious totry, but the realization of that idea was not obvious. Finally, the court stated that hindsight is not ajustifiable basis on which to find that ultimate achievement of a long sought and difficult scientificgoal was obvious.In In re Deuel56, a case involving an invention relating to isolated and purified DNA and cDNAmolecules encoding heparin-binding growth factors, the Federal Circuit held the invention nonobvious despite Bohlen and Maniatis references disclosing a group of protein growth factors and ageneral gene cloning method. The issue raised in this case was whether the combination of a priorart reference teaching a method of gene cloning, together with a reference disclosing a partial aminoacid sequence of a protein, would render DNA and cDNA molecules encoding the protein primafacie obvious. The court held that the subject matter of the invention could not be conceived basedon the teachings in the references because, until the claimed molecules were actually isolated andpurified, it would have been highly unlikely for one of ordinary skill in the art to contemplate theclaimed 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 CellActivation Inducing Ligand also referred to as NAIL which plays a major role in activation ofthe Natural Killer cells that are instrumental in fighting tumors and viruses.58 The patentoffice stated that the claimed amino acid sequence was obvious in light of combination of twoprior art references namely Valiante’s patent bearing the U.S. Patent No. 5,688,690 whichdiscloses a receptor protein called p38 receptor which the board found was essentially thesame protein as NAIL and the Laboratory Manual on Cloning authored by Joseph Sambrookwhich provided information with regard to conventional techniques to isolate and sequenceany gene. The federal circuit affirmed the Board’s decision stating that in light of the specificteachings of Sambrook and Valiante, artisans in this field had every motivation to seek andevery 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 andwas held to be obvious.Due to lack of maturity in the field, the non-obviousness requirement in USA was lower forbiotechnology inventions when compared to other inventions. The reasonable expectation ofsuccess was considered to be lower and anything obvious to try was generally considerednon-obviousns. However, the differing decisions in Deuel and Kubin cases, which havesimilar facts indicates that the non-obviousness standards are also not applied uniformly.Europe55 Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200 (Fed Cir. 1991)56 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 In re Kubin, 561 F.3d 1351 (2009).58 Id at 1353.
Tests for Determination of inventive step of biotechnology inventions have been ambiguousdue to uncertainty in the field. The European Patent Office and Boards have been striving toframe clear guidelines for determining inventive step of biotechnology inventions. In theRelaxin 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 byconventional means, but providing to the public for the first time a product whose existencewas previously unknown, the claimed invention must be regarded as inventive irrespective ofthe methods used to prepare the product.60The non-obviousness determination is always done from the point of view of a person withordinary skill in the art. The knowledge of the person skilled in the art in case of biotechinventions had been aptly discussed in R. v. Genentech61, a case concerned with interferon-gamma and the DNA sequence coding for it. In this case the Board stated that Skilled personin the art must be considered as that of a team of the appropriate specialists, who know all thedifficulties still to be expected when considering cloning a new gene. The board also inferredthat a skilled person must be assumed to lack the inventive imagination to solve problems forwhich there do not exist already routine methods of solution, the appropriate comparisonbeing not with a team but with a highly skilled technician carrying out a project where theinitial instructions received were already adequate to tell the technician how to overcome anyproblems likely to arise.62Also in R. v. Chiron63 decision, which dealt with inventive step of a DNA moleculecomprising 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 theknowledge of the person skilled in the art while determining obviousness. In this decision theboard stated that an invention would lack inventive step even if the prior art reference lackscomplete description, provided the reference can be supplemented by information available toa person with ordinary skill in the art. As per the Board, reasonable likelihood of success canmake an invention obvious and showing low expectation of success can rebut it. The Boardpointed 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 suchas 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 successand expert testimony are considered. The standards of non-obviousness are higher in Europewhen compared to USA and it is therefore comparatively difficult to satisfy this requirementin Europe.IndiaDue to dearth of case law, the approach to inventive step with regard to biotechnologyinventions in India is not clear. As per the Manual, it can be safely concluded that isolatedgene sequences and protein sequences will be considered to have an inventive step in the lightof their naturally existing counter parts. Furthermore, the economic significance requirementis relatively easy to prove for biotechnology inventions due to their various applications indrugs 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,  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],  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],  E.P.O.R. 48.
predictability of the field and so on are applied to determine inventive step in India as welland would be applied to biotechnology inventions. However, as it stands now the law does notindicate any differing standards for biotechnology inventions when compared to otherinventions.Enablement and Written DescriptionThe Courts and Patent Offices have set different standards of written description andenablement requirements for biotech inventions when compared with other inventions due totheir unique nature. Considering the uncertainties in the field, patent offices generally insiston detailed description of the invention with research data and examples. Enablement iscommonly not assessed through supplementation of prior art unless specific reference is madein the written description. The written description and enablement requirements may besatisfied by deposit of biological materials or submission of sequence listings in case ofgenetic inventions.USAUnlike in Europe and India, USA considers written description and enablement as twodifferent requirements. The US Courts have laid down differing standards for writtendescription and enablement requirements. The standards are generally higher when comparedto other inventions and require specificity, reduction to practice, examples and experimentaldata. A short note on a few cases explaining the differing standards adopted for biotechapplications have been provided hereunder.In Amgen v. Chugai64 , a case relating to an infringement of a patent over DNA sequencesencoding Erythropoietin, the court stated that generic claims to genetic sequences could bevalid where they were of a scope appropriate to the invention disclosed by an applicant.65 Thecourt further stated that claims in a patent application have to be adequately supported by thewritten description and stating a few gene analogs would not support a claim over all geneanalogs of a protein.In another case, Fiers v. Revel,66 a case relating to patent applications for DNA coding forhuman fibroblast beta-interferon, the court pointed out that claiming all DNAs that achieve aresult without defining what means would do so was not in compliance with the descriptionrequirement and that it was an attempt to preempt the future before it had arrived. 67 InRegents of the University of California v. Eli Lilly & Co68, a case relating to recombinantplasmids and microorganisms that produce human insulin, the court held that the claim of thepatent directed to recombinant prokaryotic microorganism modified to encode human insulinwas invalid, because patent specification did not fulfil statutory written descriptionrequirement.69 The court in this case inferred that description of DNA sequences by functionwithout pointing out the structure or physical characteristics would not be sufficient to satisfythe written description requirement. It also laid down that disclosure of structure of a fewspecies in a genus would not be sufficient to support a claim of the entire genus unlesssubstantial features of the genus and substantial common physical characteristics weredescribed.64 Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200 (C.A.Fed. (Mass.),1991).65 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.
The USPTO passed the revised guidelines for written description in 2001, which are largely inconformity with case law. 70 The guidelines explain how biotechnology inventions such asgenes, ESTs, antisense, ORFs, etc., would be considered for purposes of written description.Before 1990, Gene sequence data was being submitted in different formats by differentapplicants due to absence of a standard format recommended by the USPTO. To resolve theinconvenience caused during examination of gene based invention due to the lack ofuniformity with regard to submission of gene sequence data the Office amended itsregulations to establish a standardized format for descriptions of nucleotide and amino acidsequence data.71EuropeThe threshold for disclosure and enablement requirement in Europe is much higher forbiotechnology inventions when compared to other technologies. Assessment of thesufficiency of a disclosure depends on the correlation of the facts of the case to certain generalparameters such as the character of the technical field, the average amount of effort necessaryto put into practice a certain written disclosure in that technical field, the time when thedisclosure was presented to the public and the corresponding general knowledge and theamount of reliable technical details disclosed in a document.72 In the Weyershaeuser Case thatdealt with microbiologically produced reticulated cellulose the board stated that the disclosureshould be sufficiently clear such that it can be enabled by a person skilled in the art withoutundue burden on that person.73Further, in R. v. Massachusetts Institute of Technology decision, 74the board stated that incase of gene based inventions, the requirement of trial and error to carry out the inventionwould make the disclosure non-enabling. To work biotechnology inventions involves severalmolecular biology techniques and requires extensive experimentations for standardization ofexperiments. Also, the time taken for successful completion of an invention would depend onthe level of skill of the technician performing the experiment. Thus, in many cases, severalattempts may be required to complete an enabled invention. This issue has been addressed inR v. Genentech case, which related to sufficiency of disclosure in a patent concerning aminoacid sequence and DNA sequences of interferon-gamma.75 In this case the Board stated that apatent application relating to a gene would be enabling even if the experimentation required isburdensome, so long as undue experimentation is not required. It further stated that deposit ofbiological materials is not compulsory as long as an application can be enabled based onwritten description.Later, in the Biogen Decision the Board laid down that disclosure can rely on functionalcharacteristics in case of genetic inventions.76 This decision reduced the burden of patentdisclosure for biotechnology inventions. To summarize, the written description andenablement requirement for biotechnology inventions must satisfy higher standards than otherinventions with a few exceptions. While deposit of biological materials can supplement a70 USPTO Guidelines and Training Materials on Written Description, Federal Register /Vol. 66, No. 4/Friday, January5, 2001.71 Manual of Patent Examining Procedure, 2420 The Requirements for Patent Applications Containing NucleotideSequence 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,  E.P.O.R. 35.74 R. v. Massachusetts Institute Of Technology/Biopolymers, Technical Board of Appeal 3.3.4,  E.P.O.R. 16.75 R. v. Genentech/HIF-Gamma, Technical Board of Appeal 3.3.2,  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,  E.P.O.R. 190.
written description, it is not compulsory to deposit materials. Furthermore, disclosure ofbiotech inventions must be specific and broad disclosures are not sufficient.IndiaIn India, for biotechnology inventions, which describe biological material in the specification,the law provides for deposit of such biological materials at a recognized depository. Themanual of patent practice and procedure requires the invention to be described completely inthe specification to enable a person skilled in the art to be able to carry out the invention byreading the specification. 77 However, there are no cases in India that talk about differingwritten description or enablement standards for biotechnology inventions.MoralityMoral and ethical issues have since long been playing a very important role in defining the progressof biotechnology. Right from the recombinant DNA controversy, ethics and morals have eitherimpeded or slowed biotech progress. Issues surrounding ownership of genes and geneticallymodified humans, moral and identity dangers inherent in human cloning and genetic modificationof human beings, suffering to animals due to genetic intervention, potential hazards to environmentdue to genetic manipulation, ecological balance and other issues have been cited as serious issuesfor granting patents on biotechnology inventions. The involvement of moral and ethical issues inpatenting biotech inventions depends on the social, ideological, religious and economic conditionsin a country. Variances in the role of morals and ethics in determining patentability in differentcountries, which is dependant on social and ideological conditions gives rise to differences in thescope of patent protection.USAThe US patent statute does not contain any provisions relating to morals. Patentability analysis ofan invention in USA does not involve determination of morality as none of the patentabilityrequirements 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 forsubject matter relating to human beings as granting such patents would be against Amendment 13of the US Constitution, which prohibits slavery.78 Based on the guidelines, the patent applicationfiled by Jeremy Refkin for a human-animal chimera was rejected.EuropeUnlike the US Patent Law, the European Patent Convention provides provisions relating to moralityfor grant of patents. Article 53 of EPC provides that European patents shall not be granted in respectof inventions the publication or exploitation of which would be contrary to "ordre public" ormorality, provided that the exploitation shall not be deemed to be so contrary merely because it isprohibited by law or regulation in some or all of the Contracting States.79 The EU BiotechnologyDirective also lays sufficient emphasis on morality as a factor to be considered before grantingpatents in biotech inventions.77 2.6 Sufficiency of Disclosure, Manual of Patent Practice And Procedure, 2005.78 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 decisionsinvolving biotechnology inventions. In the Harvard Mouse Case ,80 the invention relating to agenetically modified mouse was held patentable despite moral concerns. After reviewing themorality concerns, the Board held that the mouse was patentable though it is put through sufferingbecause the benefit to human beings outweighs the suffering of the animal. The Board in this casestated 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 forobtaining H2-relaxin and the DNA encoding it.82It was argued that the claimed invention was notpatentable under Article 53(a) as the patent required taking of the tissue from a pregnant woman. Itwas argued that it amounted to an immoral act, which was against human dignity because itinvolves making use of a female condition (pregnancy) in a technical process oriented towardsprofit.83It was also argued that the patenting of human genes such as that encoding H2-relaxinamounted to a form of modern slavery since it involved the dismemberment of women and theirpiecemeal sale to commercial enterprises throughout the world and that the patenting of humangenes means that human life was being patented, which was intrinsically immoral.84The Opposition Division rejected the arguments stating that there was no reason to perceive theisolation of mRMA from the tissue of pregnant woman as immoral because it was taken byconsent.85 As human tissue, blood, bone and so on have been the subject of isolation for medicalpurpose, the Opposition Division pointed out that such practice was accepted by the public.86 It thenpointed out that patents covering DNA encoding human H2-relaxin, or any other human gene donot confer on their proprietors any rights to individual human beings and therefore, no womanwould be affected in any way by the present invention and was free to live her life as she wishedand had exactly the same right to self-determination as she had before the patent was granted.87 Inaddition, the Opposition Division stated that the exploitation of the invention does not involvedismemberment and piecemeal sale of women because gene cloning could be done in unicellularorganisms and a woman was only required initially for isolating the tissue for which consent wastaken.88Finally, the Opposition Division pointed out that the allegation that human life was being patentedwas unfounded because DNA was not life, but a chemical substance, which carried geneticinformation and could be used as an intermediate in the production of proteins, which might bemedically useful.89 It further stated that the patenting of a single human gene had nothing to do withthe patenting of human life.90 In the light of its reasoning, the Opposition Division concluded thatthe 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 the80 Harvard/Onco-Mouse, Examining Division,  E.P.O.R. 4.81 Howard Florey/Relaxin(Oppositions by Fraktion der Grunen Im Europaischen Parlament; Lannoye), Opposition Division,  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.
Contracting States that patenting human genes such as that encoding H2-relaxin was immoral andtherefore could be patented.The cases elucidate that morality determination forms an integral part of patentability analysis withregard to biotechnology inventions. This provision has been invoked regularly by the EuropeanPatent Office while deciding upon patentability of such inventions. An invention will not be granteda 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 outweighsthe suffering caused to the animals. Potential unknown danger to society or environment will not befatal to patentability of an invention.IndiaSection 3(b) of the Indian Patent Act provides that an invention the primary or intended use orcommercial exploitation of which would be contrary to public order or morality or which causesserious prejudice to human, animal or plant life or health or to the environment is not patentable.91As 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 Procedureprovides that Any biological material and method of making the same which is capable of causingserious prejudice to human, animal or plant lives or health or to the environment including the useof those that would be contrary to public order and morality are not patentable. It further providesthat 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 arenot patentable as they are against public order and morality. The Indian Patent Law has strongprohibitions against patenting of biotechnology inventions based on morality and public order.SummaryIt 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 heightenedstandards, non-obviousness standards have generally been lowered to accommodate ambiguities inthe field. Morality plays an important role in determining patentability of biotech inventions. Therole of morality is higher in Europe and India when compared to USA.91 Section 3(b) of the Indian Patent Act, 1970 as amended in 1999, 2002 and 2005.