The speculation seemed to have come to an end on June 26 2009 when the Intellectual Property Appellate Board (IPAB) gave its decision on the Novartis patent application directed to the beta crystalline version of imatinib mesylate (Gleevec), refusing the patent application. Novartis then filed a special leave petition (SLP) before the Supreme Court, which has issued notice to the respondents in the matter (Union of India and others) to decide the issue of maintainability.

The facts of the Novartis pre-grant oppositions are well known and this article is only an attempt to summarise the issues and the propositions of law that have been discussed in the judgment.

By way of background, Novartis AG, a Swiss pharmaceutical company, applied for patent number 1602/MAS/1998 claiming Swiss priority of July 18 1997 for an invention directed to a "beta crystalline form of imatinib mesylate". Cancer Patient Aid Association (CPAA), NATCO Pharma, CIPLA Ltd, Ranbaxy and Hetero Drugs filed pre-grant oppositions to the grant of patent on the application under section 25(1) of the Indian Patents Act.

The Assistant Controller of Patents in the pre-grant proceedings issued five distinct orders in January 2006 refusing the grant of a patent. Aggrieved by the orders, novartis filed writ petitions before the High Court of Madras which were later converted into appeals. Some of the main issues that were discussed in the judgment are discussed below.

On the reliability of experts affidavit

The IPAB observed that where experiments have not been conducted by the experts themselves, the reliability of the affidavit of such experts cannot be discredited. It is sufficient if the deponent (expert) supervises the experiments through a technical team of experts who are supposed to carry out the experiments under his supervision and guidance, based on which the group leader comes to a conclusion.

At another level, the IPAB also discussed the reliability of affidavit of employees. The IPAB held that if the affiants are employees, they generally tend to lose their impartiality when making averments and thus reduce their evidentiary value.

Disclosure requirement

With regard to the disclosure of prior art under Section 10(4) of the Indian Patents Act in the patent specification, the IPAB did recognise that under the law (Section 10(4)), disclosure of prior art is not mandatory but held that despite there not being any specific provision under the Indian law, the relevant prior art including the closest one ought to be disclosed in the patent specification and the applicant cannot be considered to have discharged its duty or obligation unless the prior art is disclosed so that the invention can be sufficiently distinguished over the prior art.

Comparative studies with regard to Section 3(d)

As the invention was directed to a novel beta crystalline form of imatinib mesylate, the unique provision of Section 3(d) of the Indian Patents Act was attracted. This section requires the applicant to establish in a case where the invention is directed to a new form of a known substance that there is an enhancement of the known efficacy of that substance over the known substance.

The IPAB held that properties of imatinib and imatinib mesylate (salt) could not be equated and the experimental evidence shown for imatinib vis-à-vis its beta form of salt could not be adopted for comparison between data for imatinib mesylate and beta form of imatinib mesylate.

Disclosure of bioavailability/efficacy data

The IPAB during the proceedings concluded that imatinib mesylate will be considered as being the "known substance" for the purpose of Section 3(d). The applicant will therefore have to cross the Section 3(d) hurdle by establishing that the new form of imatinib mesylate is significantly different in properties from the known form with regard to efficacy. The issue before the IPAB was therefore to ascertain whether the patent specification complies with Section 10 particularly with regard to bioavailability/efficacy data or is it sufficient that this requirement can be considered as being met if the data which was not originally disclosed in the specification can be provided in the form of affidavits/evidence. The IPAB also considered the allowability of an amendment under Section 59 to meet the sufficiency requirement with regard to Section 3(d) with a view to incorporate new data that was not originally disclosed. The IPAB held that the law is very clear in this respect and any subsequent discovery that was otherwise not known to the applicant at the time of filing cannot be cured by filing an amendment. Such a request for amendment would be entertained only if the original patent specification did disclose or provide the information and for that reason the patentability of the invention would be established based upon the original disclosure and no new matter can therefore be added subsequently.

Definition of efficacy

In the judgment, the meaning and scope of the expression "efficacy" was discussed. The IPAB held that efficacy as understood and held by the Madras Court in pharmacology is understood as meaning "therapeutic effect" in healing a disease or having a good effect on the body. The IPAB went to the extent to hold that thermo dynamic stability, hydroscopity, better flow properties etc, are properties that help in only maintaining the presentability of the drug/medicine and have no relationship with the curing or healing effect.

Is bioavailability the same as therapeutic efficacy?

The IPAB held that in pharmacology, therapeutic efficacy and bioavailability are generally not the same to the extent that the definition of efficacy states that therapeutic effect is independent of potency (that is, bioavailability).

Priority date

The IPAB has ruled that Switzerland has to be considered as the convention country under the changed patent law of 2005 (Section 133) and is entitled to get the priority date of July 18 1997. They reasoned that when the examination report on patentability is based on the amended patent law effective from January 1 2005, then why would the convention priority date have to be decided according to the old or unamended law? Reliance in this regard was placed on of Agouron Pharmaceuticals Inc v Controller of Patents in the High Court at Calcutta (special Jurisdiction, Original side) (AID No 2 of 2001) in which the Honourable S K Mukherjee observed: "It is well settled that the appellate Court is entitled to take into consideration any change in law and give proper relief on that basis."

Novelty/anticipation: extent of disclosure

The IPAB held that to establish a case of anticipation there has to be a clear and unmistakable enabling disclosure in the prior art for a person skilled in the art to prepare the subject compound from the prior art disclosure.

The IPAB identified guidelines culled from different decided cases on anticipation as reported in the book, Patent Law by P Narayanan (4th edition, pages 380-381):

For a document to anticipate a claim it must contain clear and unmistakable directions to the claimed invention or there must be evidence that carrying out what was suggested in the document inevitably resulted in the claimed invention. The clear and unmistakable direction must amount to an enabling disclosure. To consider whether carrying out such instructions as might be found in the prior document would inevitably result in the claimed invention, the Court must have regard especially in the field of high technology, to expert evidence as to the effect of carrying out the instructions [Quantel v Spaceward 1990 RPC 83] ... the information given in the prior document must be sufficient to enable the instructed reader at once to perceive and understand and be able practically to apply the discovery without the necessity of making further experiments.

Non-obviousness

The Zimmerman Patent (or the 1993 patent) names different N-phenyl -2- pyrimidineamine derivatives including imatinib and various acid addition salts thereof, which include mesylate also though this is not separately named and identified. The IPAB held on the ground of obviousness that an uninventive man has no magic formula to choose mesylate from the big list of salts given in the 1993 patent. IPAB further ruled that though a working example for preparing a salt has been given in the 1993 patent it is not possible for a person skilled in the art to prepare imatinib mesylate from imatinib by a conventional process as suggested in the 1993 patent. As no possibility of polymorphism, which is not a general phenomenon of a salt, can be predicted from that salt from any prior document, it is not possible for an uninventive man to discover the same and to reach to the beta crystal form of imatinib mesylate, or to find its advantageous properties or to find a suitable process for its preparation or make a solid pharmaceutical composition containing the crystal form.

In essence, the IPAB held that there has to be sufficient disclosure in the prior art such as working examples and motivation for an uninventive man to discover and reach the beta form of imatinib mesylate or find its advantageous properties.

Selection patents

The IPAB recognized the principle of selection patents even when there is no reference to them as such in the Indian patent law (the Act). The IPAB established these guidelines as the minimum requirements of a selection patent:

• Whether there is any statement in the specification where the nature of the invention concerns some kind of selection.
• Whether the selection is from a class of substances, which is already generally known.
• Whether the selected substance is new.
• Whether the selection is a result of any research by human intervention and ingenuity opposed to mere verifications.
• Whether the selection is unexpected or unpredictable.
• Whether the selected substance possesses any unexpected and advantageous property.

Applying this test to the Novartis case, the board found out that the statement in the specification that "it has now been surprisingly found that a crystal form may under certain conditions be found in the methane sulfonate salt of this compound which is described hereinafter as ß-crystal form, and which has very advantageous properties", is a primary ground for selection, which was met.

Section 3(d) of the Patent Act

The IPAB held that while the claim covering the beta crystalline (BC) version of IM (Imatinib Mesylate) is both novel and inventive, it fails the test under section 3(d), which requires a demonstration of "significantly enhanced efficacy". The IPAB held that the only kind of efficacy that would satisfy section 3(d) is therapeutic efficacy as discussed above.

The IPAB noted that although the product claim covering the beta crystalline version of imatinib mesylate was not patentable, the process for manufacturing the beta crystalline version could be patentable.

The IPAB also noted that any patent granted over Gleevec is likely to cause "public disorder". It elucidates this by stating that since Gleevec costs Rs120,000 ($2,500) a month per patient, it is far too expensive for the common man. Therefore any patent granted to support such a high monopoly price would be against public order and can be denied a patent under Section 3(b).

Greater insight expected

The Board has looked into several aspects of the Indian Patents Act from disclosure requirement to anticipation, from obviousness to Section 3(d) and public interest. However, the fate of the SLP filed by Novartis before the Supreme Court will over the next few months give greater clarity and insight on these aspects of the Indian patent system.

Archana Shanker

Archana Shanker completed her law degree in 1991, at the Campus Law Centre after graduating in science from Delhi University. She did her postgraduate diploma in bioinformatics (2005), and later specialised in pharmaceutical regulatory approvals from Hamdard University. She has been practising both as an advocate and a patent attorney and is a senior partner of Anand and Anand. She handles complex patent litigation issues before various judicial and quasi judicial forums in India such as the High Court and the Indian Patent Appellate Board (IPAB), and specialises in providing services including drafting patent applications for filing in India and overseas, infringement opinion and validity analysis and feasibility studies to handling patent prosecution and oppositions from the filing stage through to presenting cases at hearings before the Patent Office. With a total experience of 18 years in patents, Archana's strength lies in her ability to quickly conceptualise the broad picture and provide innovative solutions and strategies to complex issues. She has dealt with a diverse set of inventions covering computer-based applications, biotechnology-related technologies, nanotechnology-based inventions as well as new organic and pharmaceutical compounds. She is the author of several articles on patents in publications such as Managing Intellectual Property, Getting the Deal Through and MIP's Life Science Focus and has spoken extensively at national and international forums. She is a member of APAA, AIPPI and FICPI, and was formerly on the committees of APAA (India Chapter).

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