Annual Meeting of American Intellectual Property Law Association (AIPLA), 2011

1. Annual Meeting of American Intellectual Property Law Association (AIPLA), 2011 May 13, 2011 San Francisco Rajashree Sharma Partner-Corporate Law Group New Delhi, India

2. Roadmap • Introduction • Evolution of Indian Patents Act • Biotechnology & Scope of Patent Law in India • A summary overviewon biotechnology patenting activity in India • Biotechnology Patent Prosecution: Guidelines & Basic Considerations • Patentability of Biological Material (s) • Patentability of Micro-organism (s) • Patent law and Conservation of Biological Diversity (CBD) • Patent law and Traditional Knowledge • Biotech patent jurisprudence in India • Conclusion

3. 1. Introduction Biotechnology is a culmination of human intervention and natural processes Ever since a genetically engineered micro-organism was granted patent, the field of biotechnology gained enormous significance Evolution of patent law on biotechnology dates back to seventh century Global adoption of the patent system started in Venice as the first patent law was enacted in 1494 The requirements enshrined in the Venetian Statute such as utility, novelty and non-obviousness are still the basis of modern patent law around the world Cont….

4. Introduction Under the patent regime around the world the significance of biotechnology and its inventions are recognized and protected The TRIPS-level patent protection isan incentive mechanism to enhance biotechnology innovation in India Patent protection on novel biotechnology products can be obtained by prosecuting the patent applications in an articulate manner The trend of filing biotechnological patents in India has a steady growth 2007-08-2774 2008-09 -1884 2009-10-2700

5. 2. Evolution of Indian Patents Act • British rulers enacted the first ever patent law in India-the Act VI of 1856 based on the British patent law of 1852 • Consolidated Indian Patents and Designs Act, 1911 was enactedafter several modifications in 1859, 1872 and 1888. • The Patents Act 1970 was enacted highlighting universally accepted requirements of patentability such as novelty, inventive step and industrial application. • The Indian Patents Act, 1970. The patents granted under the Act are operative in the whole of India. Patents Act, 1970 Patents Rules, 2003 1999 Amended in 2002 2005 2005 (product) 2006

6. 3. Biotechnology & Scope of Patent Law in India • Indian patent practice and jurisprudence with respect to the patenting of biological materials are relatively new and thus not so well settled and/or uniform. • The Indian Patents Act, 1970 as in force, does not describe, in an inclusive manner, what is patentable under biotechnology discipline. Rather, Section 3 includes a list of inventions considered not patentable. • Additional hurdles like mandatory disclosure of biological material, prior approval from the Biodiversity Board and access & benefit issues under the Indian Patent regime exist. Cont…..

7. Biotechnology & Scope of Patent Law in India • Apart from TRIPS consisting criteria, Indian patent law has a long list of exceptions to patentability • e.g., frivolous, simple combination of known elements; • methods for curative & prophylactic treatments; traditional knowledge considered as not patentable • New requirement: not found in TRIPS - New use of a known substance considered non-patentable. Salts, Esters, ethers, Polymorphs, Metabolites, Pure form, Particle size, Isomers, mixtures of isomers, complexes, composition, derivatives too are considered non-patentable ‘unless they differ significantly in properties with regard to efficacy’ or if they ‘do not result in theenhancement of known efficacy of the substance’ • New requirement: not found in TRIPS - mere admixture – e.g., root-nodule bacteria of leguminous plants, use in combination does not improve natural functioning • non disclosure of origin and source of biomaterial - widens the scope of grounds for opposition and revocation

8. 4. A summary overview on biotechnology patenting activity in India • Mostly foreign application, howeverconsiderable increase in Indian applications • To translate the discovery into a patentable subject matter, the discovered component must be substantially changed through human intervention into a form in which it does not occur in nature, or employed in a process resulting into technical advancement and/or economic significance • Inventions filed for grant of patent recombinant DNA molecule, recombinant vaccine, monoclonal antibodies, recombinant therapeutic molecules, diagnostic kits, recombinant vectors, Isolated Nucleic acid encoding a gene, Method of preparation of recombinant hormones, DNA related inventions such as preparing plasmids, vectors etc, bioleaching, biotransformation, biological treatment of waste, gene and somatic cell therapy, pluripotent stem cells derived from regenerative tissue, recombinant microbes expressing chimeric HIV protein, regulation of cell mediated immune response, recombinant interleukin IL-18 inhibitors, plastid transformation vectors, Waste water and sewage treatment using microorganism, conjugate vaccine against cholera and tetanus, peptide based immunotherapy for atherosclerosis, mixed cell gene therapy, bone regeneration by gene therapy and treatment of flower.

9. I. Non-Patentable Inventions • Ordre public and morality exception - Section 3 (b)- . 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. • Discovery of living things or non living substances in nature - Section 3 (c) • Plants and animals in whole or any parts thereof other than micro-organisms but including seeds, varieties and species - Section 3 (j) • Essentially biological processes for the production or propagation of plants and animals– Section 3 (j) • Any Process for the medicinal, surgical, curative, prophylactic, diagnostic or therapeutic or other treatment of human beings or animals to render them free of disease or to increase their economic value or that of their products – Section 3(i) • New use or new property of known substance – Section 3(d) • Methods of agriculture or horticulture – Section 3(h) • Traditional knowledge – Section 3(p)

10. II. Patentable Inventions • Modified Microorganism and process therefor. • Isolated nucleic acids encoding gene, first time isolation of a molecule; novel peptides, peptide analogs, proteins, vaccines, antibodies, Primers, and cDNA • Recombinant: DNA, RNA, Amino Acids, antibodies,  oligonucleotides, primers, and genes, and Process therefor; • DNA related inventions such as preparing plasmids, vectors etc.; • Composition/formulation thereof. • Bioprobes, Biosensors • Diagnostic/Equipment kits, Research Tools • Cell lines-A cell line is patentable if artificially produced • Hybridoma technology: patents are also allowed on hybridoma technology, but not on protoplastfusion (on ethical issues). • Expressed sequence tags (ESTs), can be patented if it has a use, such as if it works as a probe Cont…..

11. II. Patentable Inventions • Methods of enzyme Purification. • Environment cleaning using biological materials such as solid or liquid waste (industrial/domestic) treatment, water treatment, mitigation of air pollution, bio-remediation. • Treatment of plants. • Process for preparing product using modified or known organism (extraction, fermentation etc.) • Biological material such as rDNA, plasmids are patentable provided they are produced by substantive human intervention • Processes for producing chemical and biological substances using microorganisms including lower plants and animals are patentable

12. 5. Biotechnology Patent prosecution: Guidelines & Basic Considerations • No formal bio-guidance with regard to biotechnological patent application • Some reference in Manual of Patent Practice and Procedure (MPPP) is there however inadequate • No mention of gene or DNA in the Patents Act 1970. • The biological material such as recombinant DNA, plasmids and processes of manufacturing thereof are patentable provided they are produced by substantive human intervention • Gene sequences, DNA sequences without having disclosed their functions are not patentable for lack of inventive step and industrial application. • 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 Cont……..

13. 5. Biotechnology Patent prosecution: Guidelines & Basic Considerations • During prosecution, the establishment of the biological function of a biotech invention, it is preferable to include biological experimental data / efficacy data – both in vitro as well as in vivo to support the efficacy of a claimed invention over the prior art • The specific sequence IDs of the genetic material being claimed must have been described sufficiently in the accompanying description so as to enable a person skilled in the art to identify and work upon such material (submission of SEQ ID in electronic as well as in paper form is also mandatory). Insufficient disclosure as well as enablement objections could be raised. • Additionally, the reference to more than one SEQ IDs requires establishing unequivocally that more than one sequence of IDs is so correlated with another that they constitute a single inventive concept. Cont……

14. 5. Biotechnology Patent prosecution: Guidelines & Basic Considerations A. Types of Objections Raised under First Examination report • Objections relating to non compliance of criteria for patentability such as lack of novelty and/or obviousness; community/folklore knowledge available, non-sufficient disclosure; non-compliance of Biological Diversity Act requirements; lack of functional aspects and information required under Section 8 of the Act B. Few Examples of Objections Raised Generally • Claims do not sufficiently define the invention; • Distinguishing features as compared to prior art given are not clear; • Disclosure is insufficient; • SEQ should be filed in electronic form; • Claims fall under section 3(i); • Claims fall under section 3(j). • Obtaining permission from NBA • Disclosure of deposition of biological material used in the invention • Invention that falls under 2(1)(j) • Use claims (generally not considered, need skilful wording). Cont..

15. 5. Biotechnology Patent prosecution: Guidelines & Basic Considerations C. Some examples of allowed claims in biotech inventions Novel Modified Microorganism:-The present invention relates to a modified microorganism comprising a mutation that disrupts the expression of the nucleotide sequence defined herein as SEQ ID No. 15.It also relates to bacterial genes and proteins, and their uses. More particularly, it relates to their use in therapy, for immunization and in screening for drugs. Nucleic Acid Molecule:-A nucleic acid molecule comprising a sequence of nucleotides that encodes an HPV31 L1 protein as set forth in SEQ ID No. 4, the nucleic acid comprising sequence of nucleotides as set forth in SEQ ID NO: 2 or SEQ ID NO. 3 wherein the sequence being codon-optimized for high level expression in a yeast (P-237941) Cell Line:-A method of producing human oral cancer cell line which comprises ………. 15

16. 5. Biotechnology Patent prosecution: Guidelines & Basic Considerations D. Some examples of rejected claims in biotech inventions Claims related to Methods for identifying tumors that are responsive to treatment with anti-ErbB2antibodies. After determination that the patient suffers from cancer (such as, Castration- Resistant Prostate Cancer-CRPC or ovarian cancer) that is positive for HER2 phosphorylation, the patient will receive a loading dose of 840 mg of rhuMAb 2C4 on day 1 of cycle 1 (first 21-day treatment period), followed by 420 mg on day 1 of each subsequent 21-day cycle, as continuous intravenous infusion. Applicant submitted that improvement lies in new amounts of rhuMAb (420 and 840 mg) The controller refused the application under section 3(d) (new use of known substance) as being dosage and 3(i) method of treatment that the said MAb are already known as described in the description. 16

17. 6. Patentability of Biological Material (s) (Disclosure and Enablement Requirements) Section 10(4) of the Patents Act, 1970 (as in force) • If the invention mentions a new biologicalmaterial in the specification and such material is not availableto public, the applicant has to deposit said biological materialin the International Depository Authority recognizedunder Budapest Treaty before filing of the application. • DEPOSITORY NO. • SEQ • Functional aspects of biologics for ex. application / use of biologics Source of material (in case generic material is not used)* • Geographical origin (in case generic material is not used)* • CBD compliance [prior approval of NBA is necessary for applying for patent and for material transfer (* The disclosure is mandatory only if any specific material imparting the specific property is required to work the invention. In case the material such as proteins/peptides/amino acids prepared synthetically can substitute the live material to work the invention, appropriate statements may be incorporated in the specification.)

18. 7. Patentability of Micro-organism (s) • Microbiological inventions include new products, processes, uses and compositions involving biological materials • Inventions cover methods to isolate and obtain new organisms, improve their character, modify them and find their new and improved uses. • New micro-organisms isolated for the first time from the natural surrounding can only be patented if they differ in character from the known micro-organisms and find a new or improved use or function. Claims to micro-organisms have been allowed on the grounds that they are the products of micro-biological processes • In the Dimminaco AG vs. Controller of Patents, theCalcutta High Court held in 2002 that a patent on a micro-organism is valid. The court ruled that the Act did not preclude a living end product from being patented. As a result, a large number of patents have been granted to microorganisms since then

19. 8. Patent law and Conservation of Biological Diversity ABS Issues & Biotechnology Patents • Mandatory disclosure in patent application of source and geographical origin of biological material and traditional knowledge used in invention(S.10(4)(d) of Indian Patents Act, 2005 • Amended Patents Act also provides for pre-grant opposition and revocation of granted patents of grounds of non-disclosure or wrongful disclosure of source or geographical origin of biological resources and traditional knowledge (S.25(1) & S.64) • NBA’s prior approval is required before seeking patent based on biological material and TK obtained from India Sec 6(1). • Gate - keeping in accessing biological resources • ABS provisions in Biodiversity Act, 2002. Several guidelines have come up from time to time w.r.t. ABS.

20. 9. Patent law and Traditional Knowledge • Section 3(p) excludes from patentability “an invention which, in effect, is traditional knowledge or which is an aggregation or duplication of known properties of traditionally known component or components.” • disclosure requirements mandate inclusion of the source and geographical origin of biological material used in the claimed invention, and interested parties may oppose or petition to revoke an Indian patent on the ground that the invention claimed therein is anticipated “having regard to the knowledge, oral or otherwise, available within any local or indigenous community in India or elsewhere . . . • Access to its the online database contains translations of manuscripts and textbooks in five languagesTraditional Knowledge Digital Library (TKDL),that contains translations of manuscripts and the online database textbooks in five languages Cont……

21. Patent law and Traditional Knowledge • Prior art & enablement • The TKDL allows examiners to compare patent applications with existing traditional knowledge • New patent applications need to demonstrate significant improvements and inventiveness compared to prior art in their field. If the medical use of an herb is a traditional practice, and thereby public knowledge, it is considered prior art under regulations. • The patent applicant may still be granted a patent on a new method for industrial-scale production of the active ingredient of the herb, for example, if this process is new and inventive example-jeevani, a medicine based on the traditional medicinal knowledge, an extract of arogyappacha plant [Trichopus zeylanicus]

22. 10. A. Biotech patent jurisprudence in India- • Dimminaco AG v Controller of Patents and Designs • Dimminaco AG filed a process patent application for a vaccine for infectious bursitis in poultry. It claimed a lyophilized microorganism • Application rejected on the grounds: the vaccine involved processing of certain microbial substances; this was only a natural process devoid of any manufacturing activities • On appeal, the Calcutta high court considered the dictionary meaning of “manufacture” and “substance” and reversed the decision passed by the controller. • The Court held that law does not bar processes where the end-product is living cont…

23. 10. A. Biotech patent jurisprudence in India Dimminaco AG v Controller of Patents and Designs • No statutory bar to accept a manner of manufacture as patentable even if the end product contains a living organism. • One of the common test is vendibility test (In other words the product should be a commercial entity) • The MPPP states that a “living entity of artificial origin such as micro-organism, or vaccines are considered patentable • This landmark judgment opens up new opportunities for obtaining patents related to live microorganisms subject to fulfilling basic criteria for patenting cont…..

24. Biotech patent jurisprudence in India B.Speaking Roses International Inc. vs. Controller-General of Patents And Anr. • Speaking Roses international Inc., had on September 19, 2002, applied for a patent for “providing an image on an Organic Product, being flowers” • The first ground of rejection was that the application was in contravention of Section 3(j) of the Patents Act, 1970. As per sub-clause (j), such exclusion extends to “Plants and animals in whole or any part thereof other than micro-organisms but including seeds, varieties and species and essentially biological processes for production or propagation of plants and animals. • The court held that the patent sought was not for any flowers or organic products, but for providing an Image on an organic product. Hence it was not a plant that was being sought to be patented. • Image was to be created by a mechanical process and not a biological one. Therefore, the claim did not fall within the scope of the aforesaid Section3(j).

25. Patent grant Procedure FILING OF APPLICATION PROVNL. / COMPLETE PUBLICATION OF APPLICATION Early publication on request REQUEST FOR EXAMINATION • WITHIN 48 MONTHS FROM filing date EXAMINATION-ISSUE OF FER 3rd Party Representation • ALL OBJECTIONS TO BE COMPLIED WITHIN 12 MONTHS GRANT OF PATENT OPPOSITION • WITHIN 12 MONTHS Decision of Controller Appeal Revocation/Amendment Appellate Board 25

26. 11. Conclusion • The patenting of biological material are relatively new to India. • Standardized practice has yet to be satisfactorily established with respect to patenting or non-patenting of biological inventions • If a claim of an invention is related to a novel and inventive and modified genetic material, wherein such genetic material is identified by its protein or amino acid sequences at least in the description and in the claims, such genetic material is capable of industrial application, then the Patent Office generally accepts such invention as patentable • Inventions are subject to the fulfillment of the relatively broad criteria. • Patenting of biological material in India is still decided on a case-by-case basis. cont…..

27. 11. Conclusion • India’s post-TRIPS patent laws include certain provisionstomake biotechnology patenting more attractive • The allowable claims disclosed in the preceding slide that the biotech patent can be obtained in diverse areas provided • To grant a patent the description/enablement requirements be complied with and prosecute articulately. • India being one of the bio-diversity rich countries, it would, thus, be prudent to reap the due benefits from its rich bio-resources with an enabling provision for patent protection in biotechnological innovations and inventions

28. THANK YOU FOR YOUR ATTENTION

29. Amendments of use & treatment claims HEPATITIS C VIRUS VACCINE PATENT NO. 218516 • 1. Original claims were 59. During prosecution we deleted certain claims and merged and amended Use/ treatment claims in to 1 claim and restricted the claims to 19 only. Further, with the help of omnibus claim we covered a novel nucleic acid and a pharmaceutical composition thereof substantially as described in the specification with reference to examples, drawings and sequence. • A nucleic acid as claimed in preceding claims and a pharmaceutical composition thereof is useful for treating or preventing HCV infected subjects. • Claims amended in appln. for vaccines for staphylococcal infection • 3. A pharmaceutical composition, comprising protein as claimed in previous claims in an effective amount in the range of 1 to 1000 µg preferably to 5 to 500 µg and more preferably 10 to 100 µg and pharmaceutically and physiologically acceptable carrier to be used as a vaccine in managing Staphylococcal infections. • 4. A vaccine comprising of protein of amino acid sequence of SEQ ID No: 3,4, or 5, a method for producing the same and the pharmaceutical composition thereof useful for managing staphylococci associated infections substantially such as herein described. 29

30. Response to the objection on biological material A VACCINE FOR STAPHYLOCOCCAL INFECTION PATENT NO. 232694 Objection In page 8 of the complete specification you have mentioned the accession number of the protein but have not mentioned the date anywhere as u/s 3 (p) and 10(4) (d) you have to mention the date of accession within the prescribe time and also mention with u have obtained permission from NBA for the material claimed. Response With regard to your fresh objection raised vide your mail dated February 20, 2009, we humbly wish to submit that according to Section 10 (d) (ii), the application shall be completed by depositing the material to an international depository authority if the applicant mentions a biological material in the specification which may not be described in such a way as to satisfy clause (a) and (b), and if such material is not available to the public. We feel that the protein should not be considered as biological material for depositing as such. Moreover, in view of the disclosure of SEQ, the requirement may be considered as complied with. 30

31. Table Depicting Some of the Biotech Patents Granted in India

32. Table Depicting Some of the Biotech Patents Granted in India

33. Table Depicting Some of the Biotech Patents Granted in India