Patent watch | Nature Reviews Drug Discovery

You have full access to this article via your institution. Download PDF GLIVEC PATENT DENIED IN INDIA The Intellectual Property Appellate Board of India has rejected Novartis' patent

application for the anticancer drug Glivec (the β-crystalline form of imatinib mesylate) because it has not shown an increase in efficacy compared with similar compounds. In January 2006,

the patent application for Glivec was first rejected by the Indian patent office, which considered Glivec to be a new form of a known substance. Indian patent law differs from that in most

other countries in that, for pharmaceutical products to be patented, as well as being novel and containing an 'inventive step' in their creation (that is, being non-obvious), new

forms of known compounds must overcome the additional hurdle of showing increased efficacy. For example, different salts, polymorphs or isomers of known substances are not patentable —

because they are considered to be the same substance — unless they “differ significantly in properties with regard to efficacy”. This clause was designed to prevent a practice known as

'evergreening', whereby the lifespan of patent protection for a drug is extended by the patenting of incremental modifications to the drug. This increased efficacy bar is thought

by some to be set too high (see _Nature Rev. Drug Discov._ 6, 180–180; 2007), because scientific discovery often advances in small, but important, stages. Indeed, in a separate case,

Novartis had challenged this aspect of Indian patent law under the World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), but the court

had deferred a decision, saying that it had no jurisdiction over WTO rules. The β-crystalline form of imatinib mesylate shows a 30% increase in bioavailability compared with other forms of

imatinib, which makes the compound more suitable for formulation and preparation into a pharmaceutical product. Novartis asserted that, in this case, bioavailability and efficacy are one and

the same, and so the definition of efficacy was central to this case. Although the Board said that Glivec was novel, embodied an inventive step and was not the same as imatinib because it

had “advantageous properties”, they decided that efficacy is different from an advantageous property of a drug. Efficacy was defined as “therapeutic healing in disease or having good effect

on the body”. It was stated that “imatinib mesylate and its β-crystalline form are therapeutically the same substance, and the β-crystalline form of imatinib mesylate and imatinib are the

same substance with regard to efficacy”. Moreover, “imatinib mesylate is a known substance”. So, for Glivec to be patented, it would have to show significantly greater efficacy than imatinib

mesylate in treating cancer. However, 'significant' was not defined; in the Board's opinion, it may vary from case to case. Moreover, there was no discussion as to which

models — for example, cellular or animal assays, or clinical trials — would be acceptable to show an increase in therapeutic efficacy. Overall, it therefore seems that this elevated standard

of inventive step means that a drug can be patentable in other areas of the world — more than 30 countries in the case of Glivec — but might not be granted a patent in India. EU REPORT ON

ANTICOMPETITIVE PATENT PRACTICES The European Union (EU) Commission has published its report of an inquiry into possible anticompetitive conditions within the pharmaceutical industry (see

_Nature Rev. Drug Discov._ 7, 194; 2008), which aimed to improve patient “access to safe, innovative and affordable medicines”. The main findings of the report are that it takes too long for

generics to reach the market, that there has been a decline in the number of innovative medicines reaching the market and that there is an urgent need for an EU patent and EU patent

litigation system (currently, patents must be litigated in individual countries of the EU). The report identified several patent-related practices that might be contributing to these

findings, using 'quotations' from inspections of innovator companies as evidence. One practice was the generation of “patent clusters” for one product; that is, the attempt by a

company to obtain as many patents as possible — some of which are “not very strong” — for a single drug, with the aim of delaying or blocking market entry of generics. Another strategy

identified was “defensive patenting”, whereby a company holds patents for the sole purpose of excluding or limiting the freedom of competitors, without the company pursuing “innovative

efforts”. The Commission says that it is now going to scrutinize the sector more closely and, where appropriate, prosecute for violation of competition laws. EU COMMISSION REPORT:

http://ec.europa.eu/competition/sectors/pharmaceuticals/inquiry/index.html PATENT ADVISORS Daniel M. Becker: Dechert, Mountain View, CA, USA. Luke Kempton: Wragge & Co., London, UK.

Leslie Meyer-Leon: Bromberg & Sunstein, Boston, MA, USA. George W. Schlich: Schlich & Co., London, UK. John A. Tessensohn: Shusaku Yamamoto, Osaka, Japan. Philip Webber: Frank B.

Dehn & Co., London, UK. PHOSPHOINOSITIDE 3-KINASE INHIBITORS The phosphoinositide 3-kinases (PI3Ks) transduce signals from growth factors and cytokines, through the generation of

phospholipids, to downstream effectors such as the AKT–mTOR (mammalian target of rapamycin) pathway. As such, PI3Ks have regulatory roles in cell survival, proliferation and differentiation.

In their Review on page 627, Liu and colleagues discuss recent progress in understanding the PI3K pathway and highlight opportunities and challenges associated with targeting this pathway

in cancer. In Table 1, we summarize international patent applications filed in the past 9 months related to PI3K inhibitors. Data were kindly researched by Irene Catania at Thomson Reuters

using the Derwent World Patents Index. Authors * Charlotte Harrison View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Harrison, C. Patent watch. _Nat Rev Drug Discov_ 8, 606–607 (2009). https://doi.org/10.1038/nrd2963 Download citation * Issue Date: August

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