Pharmaceutical polymorphs and patent strategy

(This article is a summary of the issues discussed in Duncan’s 21 May 2008 presentation at the Generic Medicine Industry Association conference in Sydney Australia.)

The Glivec battle in India

Novartis’s ongoing stoush with the Madras High Court in India created quite a stir on the world stage late last year. It concerns the patentability of the Beta crystalline form of Imatinib, the active pharmaceutical ingredient in the blockbuster drug Glivec (Gleevec). (For those who are unaware, polymorphs are the various crystal forms of a material.)

The case derives from substantial changes to the Indian Patent Act made in 2005 and focuses on section 3(d) which bars from patentability certain types of patents which have traditionally been quite useful to innovator companies. The section reads:

‘The following are not inventions within the meaning of this Act,

‘the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant.’

The case is currently mired in side issues about the constitutionality of the section and the proper composition of the Appeals Board which was to hear the appeal from the original patent office decision. Please read our August 2007 article for further background on the case.

International ramifications

One of the allegations that has been made by Novartis is that India’s section 3(d) does not comply with TRIPS. The contrary argument (much propounded by Shamnad Basheer over at SpicyIP) is that it does, as it is merely an obviousness standard that member states are free to define in a manner consistent with their national policy.

The controversy has become even more acute since a number of other Asian countries have apparently foreshadowed that they will enact provisions similar to India’s 3(d). These include the Philippines, Maldives, Pakistan, Sri Lanka, Vietnam, Indonesia, Malaysia and Bangladesh.

So how are things looking in other jurisdictions?

A mixed bag…

United Kingdom criticises ‘try on’ patents

On 9 May 2008, the UK Court of Appeal handed down its decision in the Perindopril (Coversyl) beta polymorph patent case. In essence, the patent was held to be obvious in light of a prior patent owned by the innovator (Servier) which disclosed an almost identical process to that required to form the beta polymorph.

The Judges were quite critical of the use of this patent to attempt to extend the monopoly period – saying that it was “invalid, and very plainly so’ and ‘It is the sort of patent which can give the patent system a bad name.’

Filing the beta polymorph patent was not the only thing that Servier has done to reinforce their IP position for the drug – they acquired to groups of synthetic process patents from Lupin in April and then October 2007 to add to their portfolio.

Australia – perindopril opposition dismissed, but what does it mean?

The same patent was the subject of an Opposition in Australia which was dismissed on 11 April this year. This doesn’t mean that the Australian Patent Office thinks such patents are automatically valid, only that the grounds on which the opposition was run – that the amendment itself was bad – were insufficient.

United States – Detrol application by Hetero…

The issue of polymorph patentability is yet to be litigated at the CAFC, but the USPTO seems to still be content to issue polymorph patent claims. The latest that I am aware of is Hetero’s tolterodine tartrate (Detrol) polymorph patent application – US 20050131067, which has been allowed with a claim 1 that reads:

  1. A crystalline tolterodine tartrate form 1, characterized by an x-ray powder diffraction spectrum having peaks expressed as 2 theta at about 11.9, 13.6, 14.2, 15.9, 16.9, 18.4, 18.8, 20.4, 22.0, 23.9, 25.4, 26.3 and 29.8 degrees.

Whether a District court, or the CAFC would uphold such a claim is a different matter altogether, particularly in light of the greater invalidity risk created by the US Supreme Court in the KSR v Teleflex decision on 30 April 2007. (KSR basically made it easier to invalidate patents on the ground of obviousness.)

Strategic options

For innovators, each of these cases obviously serves as a roadmap as to what you can expect in these respective jurisdictions. Careful attention to developments, and proactive steps will obviously be crucial. You may, for example decide that it is worthwhile to seek amendments well before the time when you are currently expecting generic competition, and you will certainly need to reconsider the drafting and prosecution strategy for these patents.

Generic companies will obviously take heart from some of these developments. However, you should not assume that just because a polymorph patent has been invalidated in one jurisdiction that another will in the same jurisdiction, or that even the equivalent patent will be invalidated in a different jurisdiction. Instead, focus on understanding the underlying rationale for invalidation and deeply analyse the ways that this can be used in the jurisdictions of interest to you.

In the Australian context (for this conference)…

As I wrote in my August 2007 article in IAM Magazine, even at the best of times, Australia is a difficult place to invalidate a patent based on obviousness. As mentioned in the article, this is due to the very narrow prior art base on which obviousness is tested there. Consequently, the mere fact that a particular patent has been invalidated in another country based on obviousness does not mean that this will automatically happen in any other country, and least of all in Australia. You will need to take a very careful look at the prior art used and whether it can be fitted into the narrow category of relevant prior art under the Australian test.

On the innovator side of the equation, I would be considering co-filing an Innovation patent (which is even harder to invalidate) which will at least provide 8 years of stronger protection.

One Comment on “Pharmaceutical polymorphs and patent strategy

  1. Section 3(d) is aimed at forbidding evergreening of the patents. US patentability jurisprudence envisages patenting anything under the sun. However, such criteria for patentability is leading to evergreening of the patents and hence monopoly of the patent system. Section 3d is one such provision which prevents the same. K.M.Senthil Kumar

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