pat e n t s
Pharmaceutical and biotech product patents in India: doldrums or blissfulness? Pritom Chowdhury, Siraj A Khan, Prafulla Dutta & Jagadish Mahanta
npg
© 2014 Nature America, Inc. All rights reserved.
Confusion reigns over pharmaceutical and biotech-related patents in India owing to uncertain application of patent law and pressure from generics.
P
atent rights were first introduced in India in 1856 and were formalized by the Patent and Design Act in 1911 (ref. 1). The passage of the Patent Act of 1970 (ref. 2) repealed all previous legislation; however, it excluded pharmaceuticals and agrochemical products from patent eligibility. India then amended its patent law in 2005 (ref. 3) to comply with the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs)4, with the exception of certain exclusions from patentability available to the member states within their territories5. In conformity with this provision, Indian patent law instituted Section 3(d), which implies that a mere discovery of a new form of a known substance cannot be patented unless it is significantly more efficacious3. Moreover, patents are given only for inventions and not for discoveries. The absence of a marked distinction between patentable invention and unpatentable discovery gives rise to great problems; and the requirement of an inventive step blocks the circumstances where patents are sought for inventions that vary from existing ones by minor modifications. This hurdle of meeting the condition of an inventive step and/or non-obviousness means that only inventions that take a substantial intellectual leap will be granted patents in India. In 1991, the Indian government began reforms intended to stabilize the economy and open up the country’s market to international trade and investment6. This change and enforcement of the TRIPs agreement led to an
Pritom Chowdhury, Siraj A. Khan, Prafulla Dutta & Jagadish Mahanta are in the arbovirology group, Regional Medical Research Centre, Northeast Region (ICMR), Assam, India. e-mail: [email protected]
increase in patent applications (Table 1). India in India after the adoption of the new patis now recognized as a hub for R&D activi- ent regime the year before. In another case, ties, particularly in the pharma and biotech the Supreme Court of India revoked a patent industries7. After gaining a foothold on the held by Sugen (now Pfizer) for its drug Sutent global scene with its manufacturing of reverse- (sunitinib), citing the absence of any inventive engineered generic drugs and active phar- step9. Cipla, a generics giant, produces a much maceutical ingredients, it is now seeking cheaper generic version of Sutent. Roche’s antito become a major cancer drug Tarceva, player in outsourced a polymorph B verclinical research As recent court decisions make sion of erlotinib, as well as contract apparent, the current landscape was rejected on the manufacturing and basis of Section 3(d) research7. There are for patenting by multinationals (ref. 10). In another decision, Novartis 119 manufacturing in India is bleak. challenged a Section facilities in India 3(d) rejection for a approved by the US Food and Drug Administration, more than patent on its anticancer drug Glivec11, constiin any other country outside the United tuting a beta crystalline form of imatinib. The States. However, generating generic drugs has court ruled that the pharmacological properresulted in the systematic weakening of pat- ties of the beta crystalline form of imatinib ent rights for pharmaceutical products in India mesylate are equally possessed by imatinib and the exodus of several international phar- in free base form or its salt, thus questioning maceutical research companies. In reaction, the enhanced efficacy of Glivec. By contrast, remaining research companies have attempted Novartis already holds patents on the active to secure patent rights for their inventions in ingredient in Glivec in Japan (expires in 2014), spite of the likelihood that their validity will the US (expires in 2015) and Europe (expires be attacked on Section 3(d) grounds. This in 2016). has created confusion over product patents in In India, these scenarios have given rise to a India. This issue must be addressed as soon as situation that may negatively affect innovation possible to balance various players’ needs and in the long run, but some believe that the curmaintain an environment conducive for R&D rent law protects public health and stipulates investment in the pharma and biotech sectors. a higher threshold of inventiveness. Pharmaceutical patents As recent court decisions make apparent, the current landscape for patenting by multinationals in India is bleak. Roche’s patent on the hepatitis C drug Pegasys, which contains PEGylated interferon, was revoked by India’s Intellectual Property Appellate Board (IPAB)8—a noteworthy judgment because in 2006 it was the first product patent granted
nature biotechnology volume 32 NUMBER 2 FEBRUARY 2014
Issues with gene patenting Biotech is a research-intensive industry, and securing patents for its products is particularly challenging where there is uncertainty about the eligibility of materials that may already exist in nature and requirements for novelty and an inventive step. The Indian Patent Office’s guidelines with regard to biotech patents are inconsistent and grossly inadequate. The words gene 133
patents
Table 1 Increasing trend of patent applications in India from the year 2004–2011 Year
2005–2006
2006–2007
2007–2008
2008–2009
Filed
17,466
24,505
28,940
35,218
36,812
34,287
39,400
Examined
14,813
11,569
14,119
11,751
10,296
6,069
11,208
1,911
4,320
7,539
15,316
16,061
6,168
7,509
NA
NA
NA
NA
NA
NA
12,851
Granted Disposal of request for examination
2004–2005
2009–2010
2010–2011
npg
© 2014 Nature America, Inc. All rights reserved.
Source: Annual report of the office of the Controller General of Patents, Designs, Trademarks and Geographical Indication. NA, not available.
or DNA do not appear anywhere in the Indian Patent Act, nor is there any special directive issued by the Indian government for according legal protection to biotech-related inventions. Indian patent law provides no distinction between products of nature and products modified or isolated from nature. By contrast, isolated genes or other products of nature with proven efficient function by human intervention are patentable in the United States. Recently, the patents on two human genes associated with breast and ovarian cancer (BRCA1 and BRCA2) were reinstated12. An analysis of the US and UK case laws shows the balancing attempt made by the judiciary in protecting biotech inventions. In one such case, Genentech vs. The Wellcome Foundation13, a patent was granted to Genentech for tissue plasminogen activator. The patent application was challenged on the basis of obviousness to the persons skilled in the art. The appellate court concluded that the traditional concept of obviousness from the perspective of a hypothetical addressee is unsuitable in the field of biotech, where much technological complexity is involved. The Indian Patent Act, on the other hand, lists exclusions by which plants or animals, in whole or any part thereof, other than microorganisms, cannot be patented. It did not, however, define what constitutes a microorganism. In Dimminaco A.G. vs. Controller of Patents, Designs & others14, the court ruled that there is no statutory bar to patenting living processes for products that involve an inventive step. But this is the major hurdle faced by biotech inventions, where very often, inventions that vary in minute details from those already patented are the subject of patent protection claims. Indian patent law has yet to articulate a distinction between a gene from nature and a gene modified with human intervention.
134
The effects of patenting decisions There is a growing disparity between, on one side, patient advocacy groups and others that favor reducing drug prices and increasing the availability of generics, and, on the other side, R&D-based pharmas and biotechs that say such actions will stifle innovation, shift R&D investment away from India to more favorable destinations and may lead to a dearth in funding for disease research. All this, if patent protection cannot be guaranteed. The interpretation of Section 3(d) remains a gray area and is a topic of much debate. However, the principal issue in the case against patents being pursued by nongovernmental organizations and civil society is that of drug pricing. Patented drugs cost much more than the same generic drugs developed afterwards. Therefore, there is a need for a cohesive policy to be formulated, by both R&D-based pharma companies and policymakers, so that innovative pharma is rewarded, and at the same time prices are controlled for the Indian population. One option is a compulsory licensing model, wherein the innovator companies get a royalty or sizable profits while allowing generic companies to provide drugs at an affordable rate. In a wider aspect, globally, India is a major supplier of HIV/AIDS generic drugs, accounting for almost 85% of the market in subSaharan Africa15. But with debate on whether generic drugs are truly the equivalent of their branded counterparts16, stringent regulatory measures and a clear policy should be framed, which will assist in the country’s efforts toward global patent harmonization. India has a vast store of traditional knowledge of medicinal plants and natural remedies; such resources could be used to produce medicines to spur pharma and biotech R&D. Though such an accomplishment will not happen overnight, steps must be initiated now.
Conclusions There should be no doubt that pharma and biotech products are patentable in India. However, with the conflicting interests of the R&D-driven multinationals and Indian generic companies and inconsistent application of the patent law, the actual scope of protection for product patents is uncertain. India must revise its patent law and policies, harmonize with international standards and deal with the domestic issue of drug pricing. AUTHOR CONTRIBUTIONS All authors contributed to the present work substantially. P.C. conceived the study, collected the data and drafted the manuscript. S.A.K., P.D. and J.M. critically edited the manuscript and suggested incorporation of essential contents. COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. 1. The Indian Patent and Design Act (1911). 2. The Indian Patent Act (1970). 3. The Patent (Amendment) Act. The Gazette of India (2005). http://ipindia.nic.in/ipr/patent/patent_2005.pdf 4. Mehta, P.S. Schweizerisches Jahrbuch für Entwicklungspolitik 17, 97–106 (1998). 5. Declaration on the TRIPs agreement and public health. WT/MIN(01)/DEC/2. Adopted on 14th November 2001. http://www.wto.org/english/thewto_e/minist_e/ min01_e/mindecl_trips_e.htm 6. Sharma, C.K. Economic Reforms (Routledge, UK; 2011). 7. Bajpai, V. ISRN Public Health (2013). http://dx.doi. org/10.1155/2013/167059 8. Indian Intellectual Property Appellate Board directive, recital 250/2012. 9. Sugen, Inc. USA and Pharmacia and Upjohn Co, USA v. Cipla Ltd. Case No. 00785 (2012). 10. F. Hoffmann-La Roche v. Cipla Ltd. Case No. 89 (2008). 11. Novartis AG v. Union of India & others Case No. 2728 (2013). 12. Association for Molecular Pathology v. Myriad Genetics Case No. 11–725 (2013). 13. Genentech v. Wellcome Foundation RPC 147 (1989). 14. Dimminaco A.G. v. Controller of Patents & Designs and others Case No.1 (2002) 15. Chien, C.V. PLoS ONE 2, e278 (2007). 16. Wainberg, M.A. N. Engl. J. Med. 352, 747–750 (2005).
volume 32 NUMBER 2 FEBRUARY 2014 nature biotechnology
Pharmaceutical and biotech product patents in India: doldrums or blissfulness? Pritom Chowdhury, Siraj A Khan, Prafulla Dutta & Jagadish Mahanta
npg
© 2014 Nature America, Inc. All rights reserved.
Confusion reigns over pharmaceutical and biotech-related patents in India owing to uncertain application of patent law and pressure from generics.
P
atent rights were first introduced in India in 1856 and were formalized by the Patent and Design Act in 1911 (ref. 1). The passage of the Patent Act of 1970 (ref. 2) repealed all previous legislation; however, it excluded pharmaceuticals and agrochemical products from patent eligibility. India then amended its patent law in 2005 (ref. 3) to comply with the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs)4, with the exception of certain exclusions from patentability available to the member states within their territories5. In conformity with this provision, Indian patent law instituted Section 3(d), which implies that a mere discovery of a new form of a known substance cannot be patented unless it is significantly more efficacious3. Moreover, patents are given only for inventions and not for discoveries. The absence of a marked distinction between patentable invention and unpatentable discovery gives rise to great problems; and the requirement of an inventive step blocks the circumstances where patents are sought for inventions that vary from existing ones by minor modifications. This hurdle of meeting the condition of an inventive step and/or non-obviousness means that only inventions that take a substantial intellectual leap will be granted patents in India. In 1991, the Indian government began reforms intended to stabilize the economy and open up the country’s market to international trade and investment6. This change and enforcement of the TRIPs agreement led to an
Pritom Chowdhury, Siraj A. Khan, Prafulla Dutta & Jagadish Mahanta are in the arbovirology group, Regional Medical Research Centre, Northeast Region (ICMR), Assam, India. e-mail: [email protected]
increase in patent applications (Table 1). India in India after the adoption of the new patis now recognized as a hub for R&D activi- ent regime the year before. In another case, ties, particularly in the pharma and biotech the Supreme Court of India revoked a patent industries7. After gaining a foothold on the held by Sugen (now Pfizer) for its drug Sutent global scene with its manufacturing of reverse- (sunitinib), citing the absence of any inventive engineered generic drugs and active phar- step9. Cipla, a generics giant, produces a much maceutical ingredients, it is now seeking cheaper generic version of Sutent. Roche’s antito become a major cancer drug Tarceva, player in outsourced a polymorph B verclinical research As recent court decisions make sion of erlotinib, as well as contract apparent, the current landscape was rejected on the manufacturing and basis of Section 3(d) research7. There are for patenting by multinationals (ref. 10). In another decision, Novartis 119 manufacturing in India is bleak. challenged a Section facilities in India 3(d) rejection for a approved by the US Food and Drug Administration, more than patent on its anticancer drug Glivec11, constiin any other country outside the United tuting a beta crystalline form of imatinib. The States. However, generating generic drugs has court ruled that the pharmacological properresulted in the systematic weakening of pat- ties of the beta crystalline form of imatinib ent rights for pharmaceutical products in India mesylate are equally possessed by imatinib and the exodus of several international phar- in free base form or its salt, thus questioning maceutical research companies. In reaction, the enhanced efficacy of Glivec. By contrast, remaining research companies have attempted Novartis already holds patents on the active to secure patent rights for their inventions in ingredient in Glivec in Japan (expires in 2014), spite of the likelihood that their validity will the US (expires in 2015) and Europe (expires be attacked on Section 3(d) grounds. This in 2016). has created confusion over product patents in In India, these scenarios have given rise to a India. This issue must be addressed as soon as situation that may negatively affect innovation possible to balance various players’ needs and in the long run, but some believe that the curmaintain an environment conducive for R&D rent law protects public health and stipulates investment in the pharma and biotech sectors. a higher threshold of inventiveness. Pharmaceutical patents As recent court decisions make apparent, the current landscape for patenting by multinationals in India is bleak. Roche’s patent on the hepatitis C drug Pegasys, which contains PEGylated interferon, was revoked by India’s Intellectual Property Appellate Board (IPAB)8—a noteworthy judgment because in 2006 it was the first product patent granted
nature biotechnology volume 32 NUMBER 2 FEBRUARY 2014
Issues with gene patenting Biotech is a research-intensive industry, and securing patents for its products is particularly challenging where there is uncertainty about the eligibility of materials that may already exist in nature and requirements for novelty and an inventive step. The Indian Patent Office’s guidelines with regard to biotech patents are inconsistent and grossly inadequate. The words gene 133
patents
Table 1 Increasing trend of patent applications in India from the year 2004–2011 Year
2005–2006
2006–2007
2007–2008
2008–2009
Filed
17,466
24,505
28,940
35,218
36,812
34,287
39,400
Examined
14,813
11,569
14,119
11,751
10,296
6,069
11,208
1,911
4,320
7,539
15,316
16,061
6,168
7,509
NA
NA
NA
NA
NA
NA
12,851
Granted Disposal of request for examination
2004–2005
2009–2010
2010–2011
npg
© 2014 Nature America, Inc. All rights reserved.
Source: Annual report of the office of the Controller General of Patents, Designs, Trademarks and Geographical Indication. NA, not available.
or DNA do not appear anywhere in the Indian Patent Act, nor is there any special directive issued by the Indian government for according legal protection to biotech-related inventions. Indian patent law provides no distinction between products of nature and products modified or isolated from nature. By contrast, isolated genes or other products of nature with proven efficient function by human intervention are patentable in the United States. Recently, the patents on two human genes associated with breast and ovarian cancer (BRCA1 and BRCA2) were reinstated12. An analysis of the US and UK case laws shows the balancing attempt made by the judiciary in protecting biotech inventions. In one such case, Genentech vs. The Wellcome Foundation13, a patent was granted to Genentech for tissue plasminogen activator. The patent application was challenged on the basis of obviousness to the persons skilled in the art. The appellate court concluded that the traditional concept of obviousness from the perspective of a hypothetical addressee is unsuitable in the field of biotech, where much technological complexity is involved. The Indian Patent Act, on the other hand, lists exclusions by which plants or animals, in whole or any part thereof, other than microorganisms, cannot be patented. It did not, however, define what constitutes a microorganism. In Dimminaco A.G. vs. Controller of Patents, Designs & others14, the court ruled that there is no statutory bar to patenting living processes for products that involve an inventive step. But this is the major hurdle faced by biotech inventions, where very often, inventions that vary in minute details from those already patented are the subject of patent protection claims. Indian patent law has yet to articulate a distinction between a gene from nature and a gene modified with human intervention.
134
The effects of patenting decisions There is a growing disparity between, on one side, patient advocacy groups and others that favor reducing drug prices and increasing the availability of generics, and, on the other side, R&D-based pharmas and biotechs that say such actions will stifle innovation, shift R&D investment away from India to more favorable destinations and may lead to a dearth in funding for disease research. All this, if patent protection cannot be guaranteed. The interpretation of Section 3(d) remains a gray area and is a topic of much debate. However, the principal issue in the case against patents being pursued by nongovernmental organizations and civil society is that of drug pricing. Patented drugs cost much more than the same generic drugs developed afterwards. Therefore, there is a need for a cohesive policy to be formulated, by both R&D-based pharma companies and policymakers, so that innovative pharma is rewarded, and at the same time prices are controlled for the Indian population. One option is a compulsory licensing model, wherein the innovator companies get a royalty or sizable profits while allowing generic companies to provide drugs at an affordable rate. In a wider aspect, globally, India is a major supplier of HIV/AIDS generic drugs, accounting for almost 85% of the market in subSaharan Africa15. But with debate on whether generic drugs are truly the equivalent of their branded counterparts16, stringent regulatory measures and a clear policy should be framed, which will assist in the country’s efforts toward global patent harmonization. India has a vast store of traditional knowledge of medicinal plants and natural remedies; such resources could be used to produce medicines to spur pharma and biotech R&D. Though such an accomplishment will not happen overnight, steps must be initiated now.
Conclusions There should be no doubt that pharma and biotech products are patentable in India. However, with the conflicting interests of the R&D-driven multinationals and Indian generic companies and inconsistent application of the patent law, the actual scope of protection for product patents is uncertain. India must revise its patent law and policies, harmonize with international standards and deal with the domestic issue of drug pricing. AUTHOR CONTRIBUTIONS All authors contributed to the present work substantially. P.C. conceived the study, collected the data and drafted the manuscript. S.A.K., P.D. and J.M. critically edited the manuscript and suggested incorporation of essential contents. COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. 1. The Indian Patent and Design Act (1911). 2. The Indian Patent Act (1970). 3. The Patent (Amendment) Act. The Gazette of India (2005). http://ipindia.nic.in/ipr/patent/patent_2005.pdf 4. Mehta, P.S. Schweizerisches Jahrbuch für Entwicklungspolitik 17, 97–106 (1998). 5. Declaration on the TRIPs agreement and public health. WT/MIN(01)/DEC/2. Adopted on 14th November 2001. http://www.wto.org/english/thewto_e/minist_e/ min01_e/mindecl_trips_e.htm 6. Sharma, C.K. Economic Reforms (Routledge, UK; 2011). 7. Bajpai, V. ISRN Public Health (2013). http://dx.doi. org/10.1155/2013/167059 8. Indian Intellectual Property Appellate Board directive, recital 250/2012. 9. Sugen, Inc. USA and Pharmacia and Upjohn Co, USA v. Cipla Ltd. Case No. 00785 (2012). 10. F. Hoffmann-La Roche v. Cipla Ltd. Case No. 89 (2008). 11. Novartis AG v. Union of India & others Case No. 2728 (2013). 12. Association for Molecular Pathology v. Myriad Genetics Case No. 11–725 (2013). 13. Genentech v. Wellcome Foundation RPC 147 (1989). 14. Dimminaco A.G. v. Controller of Patents & Designs and others Case No.1 (2002) 15. Chien, C.V. PLoS ONE 2, e278 (2007). 16. Wainberg, M.A. N. Engl. J. Med. 352, 747–750 (2005).
volume 32 NUMBER 2 FEBRUARY 2014 nature biotechnology
