Novartis vs India and Section 3(d) of Patent Act 1970

1. Novartis claims that huge efforts in terms of R&D work are involved in the "invention" of imatinib mesylate (a derivative) from imatinib (a base) and hence it deserves to be given a patent on imatinib mesylate for 20 years. Since Section3(d) precludes the granting of a patent on a derivative, which comes under "mere discovery of a new from of a known substance", it should be struck down, as per the contention of Novartis. But this argument is not fair.  

1. Novartis claims that huge efforts in terms of R&D work are involved in the "invention" of imatinib mesylate (a derivative) from imatinib (a base) and hence it deserves to be given a patent on imatinib mesylate for 20 years. Since Section3(d) precludes the granting of a patent on a derivative, which comes under "mere discovery of a new from of a known substance", it should be struck down, as per the contention of Novartis. But this argument is not fair. R & D work is definitely involved in synthesizing a number of derivatives from a base drug, in doing screening and animal toxicity studies on chosen derivatives and in finding their bioequivalence or enhanced efficacy in animals and in human beings. Nobody can question the point that time, effort, money and   intelligence are being spent on the development of derivatives or dosage forms which are more efficacious that the drug (new chemical entity, NCE) which is first found. This is a struggle for improvement of the existing situation and it goes on perennially.

            But all this effort is much lesser than the effort involved in the invention of an NCE. On an average it takes 10 to 12 years to get an NCE into the market (after its invention) and billions of dollars. Teams led by stalwarts in the field of drug research which are multidisciplinary in their composition, spend years in designing molecules, synthesizing them or extracting them or producing them in other ways. The inputs that go into the development of an NCE are at least 100 times, may be a1000 times more than the inputs that go into the development of a derivative. So when an NCE is developed the inventor should definitely be rewarded with a patent and the opportunity to manufacture it for 20 years.

            But when a derivative or a new dosage form is developed it is a much lesser affair and it need not be, it should not be equated with an invention; it should not be given a patent and there is definitely no need to give manufacturing rights for 20 years. To encourage this type of invention the Govt. may think of incorporating in the Patent Act 1970, provisions for exclusive marketing rights (EMRs) for a limited period. But development of a derivative or a new dosage form should not be equated with an invention.

2.         The development of a new dosage form involves skills which are taught in the subject of Pharmaceutical Technology and it is an established subject which is all the while developing because of extensive research in multiple directions. The development of a derivative involves skills which are taught in the subjects of Pharmaceutical Chemistry and Synthetic Chemistry and Computer Aided Drug Design. This development is also facilitated greatly by the greater understanding of Molecular biology and Drug-Receptor interaction. The receptors necessary to be acted upon in the case of different diseases have been discovered and the molecules which have the right chemical structure required to attach to those receptors are being designed and synthesized.

All these subjects are the tools that help in the development of a new derivative or dosage form. They also help in the development of an NCE, but the NCE has to go through clinical trials and establish its quality, efficacy and safety as per ICH guidelines. When it comes to a new derivative or a new dosage form, since the quality, safety and efficacy have already been established, only bioequivalence has to be proved.

The development of a derivative or a new dosage form requires definite skills, but it is not shooting into darkness, it is a project that takes a limited amount of time. So development of a derivative involves subject skills, but an invention requires higher levels of inventive skills. The two cannot be equated.

3. The European countries are in an unhappy position where they have to grant patents on seemingly insignificant improvements over existing technologies.

In Europe, in 1980's the list of a drug's properties eligible for patenting was relatively limited. They included

• Primary uses
• Process and intermediates
• Bulk forms
• Simple formulations
• Composition of matter

During the 1990, the list grew to include patents on

• Expansive number of uses
• Methods of treatments
• Mechanism of action
• Packaging
• Delivery profiles
• Dosing regimen
• Dosing range
• Dosing route
• Combinations
• Screening methods
• Chemistry methods
• Biological target
• Field of use

            Indeed, it is frivolous to seek a patent based on dosing regimen or dosing route or combination. Many of these which are in the list of 13 are "obvious" to the "person skilled in the art" and they should not become eligibility criteria for patents.

            India should not allow itself to be thrust into this type of a situation. Clear distinction should be there between "invention" and "further development of an invention".

• 4. The development which accrues into a drug therapy by way of development of dosage regimen, or dosage form etc. will automatically increase its therapeutic usage by doctors; hence gets better revenues and that should suffice as an incentive to the developers. They should not attempt to block competition by generics. Let the invention get patent protection. Let a clear "clinically significant" improvement in the NCE itself be granted EMR for a fixed period such as one year. Or let there be some other agreement by which companies which develop inventions benefit. Let the simple improvements by means of changes in dosage form or dosage regimen or dosing route buy their own laurels in the open market; if it is a better form it will fetch better revenues.

• 5. The Division Bench of Madras High Court which has been hearing the writ petition from the Swiss pharmaceutical major Novartis AG, challenging rejection of its patent application for beta crystalline form of imatinib mesylate posed a query to the senior counsel of the firm, Mr. Soli Sorabjee;

"Whether or not would there be "absolute bar" for grant of patents for chemical derivates if section 3(d) of the Amended Patents Act, 1970, were to go, as pleaded by the petitioner".

Mr. Justice R.Balasubramanian and Mr.Prabha Sridevan, also raised a point whether vesting some discretion with the authority would be objectionable.

Presenting his arguments Mr.Sorabjee said that the statute framed by the legislature on this subject should contain guidelines which would help in the authority not acting arbitrarily. The present Section 3(d) vested with the authority unfettered powers, which might result in questionable decisions by the authority concerned. The section incorporated terms like "significantly" and "efficacy" which were not defined and were nebulous and vague.

If Section 3(d) goes, then simple derivatives, and combinations can get patents. In March 2006 the Indian Network for people living with HIV/AIDS (INP+) filed an opposition to the patent claim for a fixed-dose combination of zidovudine and lamivudine filed by Galxo Sunithkline (GSK). INP+ based its opposition on Section 3(d) of the patent law, as the patent claim in question was not for a new invention but simply for the combination of two existing drugs. Similar oppositions on AIDS medicine patent applications have followed as most of the patent claims are for known pharmaceutical substances such as polymorphs, salts, and combinations. Soon after its patent was opposed in India, GSK announced the withdrawal of all its patents and patent applications for the fixed-dose combination of zidovudine and lamivudine.

So Section 3(d) is simply essential to (1) distinguish between "inventions" and "further developments" (2) prevent patenting of "obvious to person skilled in the art" level developments (3) prevent frivolous patent applications and to (4) instill a sense of "responsibility" in the companies before they apply for a patent.

The word "significant" and "efficacy" are sufficiently discussed and explained in pharmaceutical literature. ICH guidelines very clearly explain when a pharmaceutical can be considered as effective. All that the patenting authorities have to do is to take the advice of expert committees in relevant fields to take decisions pertaining to terms such as "significant" and "efficacy". The Act cannot be expected to explain such terms.

6.         The giant MNCs that are almost ruling the world today have grown out of the society. Their money, both for R & D and for other purposes is coming form the society. If, the society were to observe a "boycott" where would they be? It is true that they are manufacturing pharmaceuticals, which are life saving. But they should not forget that, they are able to survive and flourish because the society is buying their medicines; if it were not so, they would have to close business and go home.

            So they should think with compassion and contribute to the society by the simple mechanism of ignoring this hunt for patents for all "small" developments.