When India issued a compulsory licence for the anticancer drug Nexavar (sorafenib) in 2012 — meaning that cheaper copies could be made without the permission of the patent owner — the eyes of the world were drawn to the Indian patent system. This move has been followed by the rejection or revocation of several patents that protect anticancer and other drugs which have patent protection in many other countries (TABLE 1). Does this indicate that the patent system in India is weak, or rather that it is well placed to weed out weak patents at an early stage?

Paul Herrling, Chair of the Novartis Institute for Tropical Diseases, Basel, Switzerland, believes that the recent rejection and revocation of patents in India is “short- sighted” and will deter investment and innovation in the country. “India has become a challenging market for innovator companies to do business in. The country needs to put an ecosystem in place that encourages innovation if it hopes to attract research and development investment by both the global and local pharmaceutical industry,” he says.

But although the recent flurry of activity has knocked down patents that protect high-profile drugs, such activity may not be as common as often perceived. “No doubt, India’s intellectual property tribunal has liquidated more patents than its counterparts in other parts of the world, but a dispassionate look at the overall patent numbers will indicate that the situation is not as grim as is made out to be,” says Shamnad Basheer, a professor

in intellectual property law at the National University of Juridical Sciences, Kolkata, India. He notes that only a minor percentage — less than 2% — of the total number of pharmaceutical patent applications have been challenged. With increasing partnerships between global drug-makers and Indian generics companies, this percentage could dip even further in the coming years, he notes.

Several patents were rejected or overturned because of fairly standard reasons, including obviousness and lack of inventive step (TABLE 1). For example, Roche’s hepatitis C drug Pegasys (pegylated interferon alfa-2a) was deemed obvious because it was thought that a person could make use of the known facts that interferon could be used to treat hepatitis C and that pegylation of proteins could improve their efficacy. The patent on Pfizer’s Sutent (sunitinib malate) was found to lack an inventive step because there were insufficient differences in the chemical structure of sunitinib malate compared with other compounds claimed in the three earlier patents (although this decision is under appeal).

As well as the usual need for inventions to be non-obvious and inventive, India has an aspect of patent law — known as Section 3d — that sets a higher threshold for the issuance of patents compared with other countries. In particular, India bars patent protection for inventions that are a new form of a known substance — for example, new salts, isomers or polymorphs — that have not been shown

to result in increased efficacy of the drug. A prime example of a drug that fell at this hurdle is Novartis’ Glivec (imatinib mesylate), the patent on which was overturned in April of this year. Here, the Indian Supreme Court held that although the β-crystalline form of imatinib mesylate had increased bioavailability, this did not constitute any enhanced “therapeutic efficacy” over a previously known form of imatinib (imatinib free-base) that was already known to have anticancer properties.

“In my opinion, Section 3d of the Indian patent regime definitely strengthens India’s patent ecosystem,” says Prity Khastgir, a biotech and pharma patent attorney at Tech Corp Legal, New Delhi, India. “By invalidating weak patents and preventing extended periods of patent protection it prevents an undue monopoly on blockbuster drugs by multinational pharma giants.”

This aspect may seem like a big difference between India and other countries, but according to Bhaven Sampat, an associate professor in the Department of Health Policy and Management at Columbia University, USA, it is the timing of patent validity challenges that is a key difference between India and elsewhere. “India has a system to target weak patents on important drugs before they issue. In the United States these patents are instead targeted after drug approval, through costly litigation. It is important to recognize that both systems are functionally quite similar.”

When the Supreme Court invalidated the Glivec patent, it said that increased efficacy should be interpreted as “increased therapeutic efficacy”, but fell short on explicitly clarifying what studies were required to demonstrate this. “In particular, the court ducked the issue of whether a reduction in toxicity would count as

PATENT WATCH

India’s patent ecosystem — encouraging strong patents or discouraging innovation?

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‘increased efficacy,’” notes Basheer (who was an amicus curiae before the Court in this dispute), “and so lost an opportunity to fully clarify the scope and ambit of Section 3d.”

“I strongly feel that the [Indian] patent office should provide better clarity and define terms such as ‘increased therapeutic efficacy’ by giving proper examples and an in-depth analysis,” says Khastgir. Herrling also thinks there should be more clarity within the Indian patent regime. “The law needs to be predictable and courts need to hear cases far more quickly for there to be meaningful outcomes,” he says.

Not all patents that have been challenged have been overturned. Recently, one patent that protects GlaxoSmithKline’s Tykerb (lapatinib), which claims bicyclic heteroaromatic compounds and their hydrochloride salts, was upheld as non-obvious. However, an additional patent that claimed new ditosylate salts of these compounds, which had superior moisture sorption properties, failed the Section 3d hurdle because this improved property did not result in greater therapeutic efficacy.

Does the inability to obtain such patents really harm innovation? “I am sceptical as to whether the ability to get a secondary patent in a low-income country currently matters for global innovation incentives,” says Sampat, “although this could change if they generate a larger share of global pharmaceutical revenues.”

However, there might be situations in which a secondary patent could be useful. “An interesting hybrid case is for incremental innovations that make a drug more useful in a low-income country; for example, a heat-stable version of an HIV drug,” says Sampat. “If these incremental improvements were costly to achieve, it is more plausible that secondary patents in India would matter for multinational firms’ innovation incentives.”

Patent invalidity opens the door for generics companies to step in and make their version of the drugs. But given that a growing number of important therapies are biologics, which are difficult to copy, entry of biosimilars to the Indian market might not be rapid. Since 2012, any generics company that applies to market a biosimilar in India must follow guidelines (“Guidelines on Similar Biologics:

Regulatory Requirements for Marketing Authorization in India”), which mirror those issued by the European Medicines Agency.

However, Basheer notes that India’s regulatory space is particularly murky: “Two parliamentary committee reports have severely indicted regulators for cosying up to drug makers and failing to protect the interests of patients.” He also highlights Roche’s recent decision to abandon its patents for its biologic Herceptin (trastuzumab; used for the treatment of breast cancer) in India. “If this recent incident is any indication, it appears that big pharma will pursue fewer drug patents in India. However, they are likely to shift the battleground to drug regulation and up the ante for generics, particularly biosimilars,” he concludes.

Charlotte Harrison

PATENT ADVISORS

Daniel M. Becker: Dechert, Mountain View, CA, USA.Luke Kempton: Wragge & Co., London, UK.Leslie Meyer-Leon: IP Legal Strategies, Boston, MA, USA.George W. Schlich: Schlich & Co., London, UK. John A. Tessensohn: Shusaku Yamamoto, Osaka, Japan.Philip Webber: Dehns, London, UK.

Table 1 | Recent patents that have been denied in India

Drug; generic name (company)

Main indications Date when patent was overturned or revoked

Reason and other comments

Nexavar; sorafenib (Bayer/Onyx)

Hepatocellular carcinoma

March 2012 •Compulsory licence issued because of high pricing and patent was not worked*

•Patent not held invalid (but patent validity is under challenge)•Decision: http://bit.ly/zETHCy

Sutent; sunitinib (Pfizer)

Renal cell carcinoma, gastrointestinal stromal tumour

October 2012 •Obviousness and lack of invention•Patent office reconsidering decision following a court order•Decision: http://bit.ly/17NCjit

Iressa; gefitinib (AstraZeneca)

Breast cancer, non- small cell lung cancer

November 2012 •Obvious •Decision: http://bit.ly/TqizYg

Pegasys; peginterferon alfa-2a (Roche)

Hepatitis C November 2012 •Obvious and cited high cost•Decision: http://bit.ly/Px0Hhj

Formoterol and mometasone aerosol suspension (free of carrier) (Merck)

Asthma (not known if product is marketed)

December 2012 •Lack of invention•Decision: http://bit.ly/13FWuOa

Glivec; imatinib (Novartis)

Leukaemia, soft tissue sarcoma

April 2013 •No increase in therapeutic efficacy •Lack of invention•Decision: http://bit.ly/14HQQMM

Herceptin; trastuzumab (Roche)

Breast cancer August 2013 •Patent application submitted incorrectly •New form of known substance•Roche abandoned patented product•Decision: http://bit.ly/15MZCFs

Tykerb; lapatinib (GlaxoSmithKline)

Breast cancer August 2013 •One patent valid (bicyclic heteroaromatic compounds)•Decision: http://bit.ly/1an041r•Different salt of these compounds invalid; new form of

known substance• Decision: http://bit.ly/1ezDpBx

Ganfort; bimatoprost and timolol (Allergan)

Glaucoma August 2013 •Lack of invention and obvious•Decision: http://bit.ly/15gLKXC

Combigan; brimonidine and timolol (Allergan)

Glaucoma August 2013 •Patent application submitted incorrectly •Decision: http://bit.ly/1ed6hSA

*Meaning that the product had not been manufactured in India.

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