Patent for cancer cure formulae (Novartis – Glivec)

Cancer Cure – Exorbitant Not Affordable – Because of Monopoly[Patent] in the Market – Delay Due to Dark Days in the past Without Proper Patent Laws in India to Hook – Public Good Wins over the Monopoly

Excerpt from : Novartis AG And Ors. Vs. Union of India And Ors [Dated: April 1, 2013] [Court:Supreme]

A landmark judgement rendered by justice AFTAB ALAM; RANJANA PRAKASH DESAI, JJ. Supreme Court of India wherein various aspects of social/legal issues are dealt with, in detail.

Because the judgement is very huge running around 200 paragraphs, Here I would like to share brief excerpts from the judgement on various points very elaborately discussed in the course of arguments for easy reference.
Hope this would benefit public at large and professionals in particular and the Law students alike.

[This brief is dedicated to my daughter who is pursuing Law in Christ University,Bangalore]

What are the rights conferred on the owner of the patent?

Rights Conferred

[ Article 28 of TRIPS Agreement]

1. A patent shall confer on its owner the following exclusive rights:
(a) where the subject matter of a patent is a product, to prevent third parties not having the owner’s consent from the acts of: making, using, offering for sale, selling, or importing [This right, like all other rights conferred under this Agreement in respect of the use, sale, importation or other distribution of goods, is subject to the provisions of Article 6.] for these purposes that product;
(b) where the subject matter of a patent is a process, to prevent third parties not having the owner’s consent from the act of using the process, and from the acts of: using, offering for sale, selling, or importing for these purposes at least the product obtained directly by that process.

QUESTION BEFORE THE COURT IN THE PRESENT APPEAL
Whether the appellant is entitled to get the patent for the beta crystalline form of a chemical compound called Imatinib Mesylate which is a therapeutic drug for chronic myeloid leukemia and certain kinds of tumours and is marketed under the names “Glivec” or “Gleevec”.

BRIEF NOTE: 23. As this Court now proceeds to decide the case on merits, it needs to be noted that after notice was issued in the SLPs filed by Novartis AG, all the five parties who had filed pre-grant oppositions before the Controller (hereinafter referred to as the Objectors) filed their respective counter-affidavits. Two of the Objectors, namely NATCO Pharma Ltd. and M/s Cancer Patients Aid Association, additionally filed Special Leave Petition, challenging the findings recorded by the IPAB in favour of Novartis AG. Leave to appeal has also been granted in all those SLPs, and hence, all the issues are open before this Court and this Court is deciding the case unbound by any findings of the authority or the tribunal below.

Why the delay in the proceedings?
That the application was made at the time when there was a different patent regime. After the application was made and before it was taken up for consideration, a number of amendments were introduced in the Indian Patents Act, 1970, which brought about fundamental changes in the patent law of the country.

What is the “mail-box” procedure?
12. In 1997, when the appellant filed its application for patent, the law in India with regard to product patent was in a transitional stage and the appellant’s application lay dormant under an arrangement called “the mailbox procedure”. Before the application for patent was taken up for consideration, the appellant made an application (Application No.EMR/01/2002) on March 27, 2002, for grant of exclusive marketing rights (EMR) for the subject product under section 24A of the Act, which was at that time on the statute book and which now stands deleted. The Patent Office granted EMR to the appellant by order dated November 10, 2003.
The appellant’s application for patent was taken out of the “mailbox” for consideration only after amendments were made in the Patents Act, with effect from January 1, 2005.

What the Appellant Claims?
Para 8.. In the application it claimed that the invented product, the beta crystal form of Imatinib Mesylate, has (i) more beneficial flow properties: (ii) better as it “stores better and is easier to process”; has “better processability of the methanesulfonic acid addition salt of a compound of formula I”, and has a “further advantage for processing and storing”.

Who are the opposers/objectors?
The patent application had attracted five (5) pre-grant oppositions [The oppositions were made by
M/s. Cancer Patients Aid Association (Respondent No. 4),
NATCO Pharma Ltd. (Respondent No. 5),
CIPLA Ltd. (Respondent No. 6),
Ranbaxy Laboratories Ltd. (Respondent No. 7),
Hetro Drugs Ltd. (Respondent No. 8).]

WHAT THE OBJECTORS SAYS?
PARA 65.  all the counsel representing the Union of India and the different Objectors unanimously took the stand that the TRIPS Agreement has sufficient flexibility (vide Articles 7, 8 and 27), which was further reaffirmed by the Doha Declaration (in paragraphs 4 to 6), to enable the member States to control the patent rights in a manner as to avoid any adverse impact on public-health. It was contended on behalf of the Union of India and the Objectors that the TRIPS Agreement coupled with the Doha Declaration leaves it open to the member States to adjust their respective patent systems by regulating the grant of patents and to set up higher standards for patent protection for pharmaceutical and agricultural chemical products. The Union of India and all the Objectors maintained that the patent law in India, as it stands to-day after major changes were brought about in the Patents Act, 1970 in 2005, is fully TRIPS compliant. But they insisted that the Indian law must be judged and interpreted on its own terms, and not on the basis of standards of patentability prescribed in some countries of the western world.

BREIF ABOUT THE TRIPS AGREEMENT
60. The Agreement (vide. Part V: Article 64) provides for a mechanism for resolution of disputes between the members of the WTO. In case of a dispute, a panel of specially appointed trade experts interprets the provisions of the Agreement and issues a report. The panel’s decision may be subjected to appeal before the WTO Appellate Body. If a party to the decision fails to abide by a decision, the other party can impose trade sanctions on the member in breach, upon authorization by the Dispute Settlement Body. The dispute resolution mechanism in the TRIPS is strong and effective as was proved in the case of India herself.

What the The Assistant Controller of Patents and Designs held?
14. The Assistant Controller of Patents and Designs heard all the parties on December 15, 2005, as provided under rule 55 of the Patent Rules, 2003, and rejected the appellant’s application for grant of patent to the subject product by 5 (five) separate, though similar, orders passed on January 25, 2006 on the 5 (five) opposition petitions. The Assistant Controller held that the invention claimed by the appellant was anticipated by prior publication, i.e., the Zimmermann patent; that the invention claimed by the appellant was obvious to a person skilled in the art in view of the disclosure provided in the Zimmermann patent specifications; and further that the patentability of the alleged invention was disallowed by section 3(d) of the Act;

Views regarding benevolent free distribution programme discussed
Para 19..We are fully conscious of the Appellant’s benevolent GIPAP program for free distribution of GLEEVEC to certain cancer patients. But as per information furnished in its written counter-argument by R 3 that when the Appellant was holding the right as EMR on GLEEVEC it used to charge Rs.1,20,000/- per month for a required dose of the drug from a cancer patient, not disputed by the Appellant, which in our view is too unaffordable to the poor cancer patients in India. Thus, we also observe that a grant of product patent on this application can create a havoc to the lives of poor people and their families affected with the cancer for which this drug is effective. This will have disastrous effect on the society as well. Considering all the circumstances of the appeals before us, we observe that the Appellant’s alleged invention won’t be worthy of a reward of any product patent on the basis of its impugned application for not only for not satisfying the requirement of section 3(d) of the Act, but also for its possible disastrous consequences on such grant as stated above, which also is being attracted by the provisions of section 3(b) of the Act which prohibits grant of patent on inventions, exploitation of which could create public disorder among other things (Sic .) We, therefore, uphold the decision of R 8 on section 3(d) of the Act to the extent that product patent cannot be made available to the Appellant”
20. Though agreeing with the Assistant Controller that no product patent for the subject patent could be allowed in favour of the appellant, the IPAB held that the appellant could not be denied the process patent for preparation of Imatinib Mesylate in beta crystal form. The IPAB ordered accordingly.

JUSTICE AYYANGAR’S CONTRIBUTION IN THE DEVELOPMENT OF PATENT LAW:
PARA 36. Justice Ayyangar examined the nature of the patent right and considered the arguments advanced as justifications/rationalizations for grant of patents. He described the patent law, in his report, as an instrument for managing the political economy of the country. He observed:
“It would not be an exaggeration to say that the industrial progress of a country is considerably stimulated or retarded by its patent system according as to whether the system is suited to it or not.” (p. 9, para 16)

He also quoted from Michel [Michel on Principal National Patent Systems, Vol. I, P.15] with approval as under:
“* * * Patent systems are not created in the interest of the inventor but in the interest of national economy. The rules and regulations of the patent systems are not governed by civil or common law but by political economy.”
Para 37..Patent systems are not created in the interest of the inventor but in the interest of national economy. The rules and regulations of the patent systems are not governed by civil or common law but by political economy.” “the Indian Patent system has failed in its main purpose, namely, to stimulate invention among Indians and to encourage the development and exploitation of new inventions for industrial purposes in the country so as to secure the benefits thereof to the largest section of the public.” (Interim Report, p. 165).
[Patents Enquiry Committee I) report and the Ayyangar Committee’s report are important milestones in the development of the patent law in the country].

PRODUCT PATENT OR PROCESS PATENT?
42. Coming next to the patents for inventions relating to food and medicine, Justice Ayyangar pointed out that barring the US, there was hardly any country that allowed unrestricted grant of patents in respect of articles of food and medicines, or as to the licensing and working of patents in this class. In none of the countries of Europe were patents granted for product claims for articles of food or medicine, and in a few (Denmark for articles of food; and Italy, under the law of 1957, for medicinal products) even claims for processes for producing them were non- patentable. He explained that the reason for this state of law is stated is necessary in order that important articles of daily use such as medicine or food, which are vital to the health of the community, should be made available to everyone at reasonable prices and that no monopoly should be granted in respect of such articles. It is considered that the refusal of product patents would enlarge the area of competition and thus result in the production of these articles in sufficient quantity and at the lowest possible cost to the public.

POSITION OF INDIA IN INTERNATIONAL PHARMACEUTICAL INDUSTRY
Para 58..“Because of the rapid growth and structural transformation in the last three decades or so, India now occupies an important position in the international pharmaceutical industry India has received worldwide recognition as a low cost producer of high quality bulk drugs and formulations. India produces about 350 bulk drugs ranging from simple pain killers to sophisticated antibiotics and complex cardiac products. Most of the bulk drugs are produced from basic stages, involving complex multi-stage synthesis, fermentation and extractions. For more than 25 bulk drugs, India accounts for more than 50 per cent of the international trade. India is a major force to reckon with in the western markets for such drugs as ibuprofen, The law relating to patents is contained in the Patents Act, 1970 which came into force on the 20th April, 1972. The Act was last amended in March, 1999 to meet India’s obligations under the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) which forms part of the Agreement establishing the World Trade Organisation (WTO).

Development of technological capability in India, coupled with the need for integrating the intellectual property system with international practices and intellectual property regimes, requires that the Act be modified into a modern, harmonised and user-friendly legislation to adequately protect national and public interests while simultaneously meeting India’s international obligations under the TRIPS Agreement which are to be fulfilled by 31st December, 1999.

WHAT DOES SECTION 3(d) OF THE PATENT ACT WHICH HAS BEARING ON THE DECISION OF THE CASE SAYS?
PARA 17-18:
.. “Since India is having a requirement of higher standard of inventive step by introducing the amended section 3(d) of the Act, what is patentable in other countries will not be patentable in India. As we see, the object of amended section 3(d) of the Act is nothing but a requirement of higher standard of inventive step in the law particularly for the drug/pharmaceutical substances.”

18. The IPAB also referred to the judgment of the Madras High Court, dismissing the appellant’s writ petitions challenging the constitutional validity of section 3(d) where the High Court had observed:
“We have borne in mind the object which the amending Act wanted to achieve namely, to prevent evergreening; to provide easy access to the citizens of the country to life saving drugs and to discharge their constitutional obligation of providing good health care to its citizens.”

PARA 95. After the amendment with effect from Jan 1, 2005, section 3(d) stands as under: –
“Section 3. What are not inventions.- The following are not inventions within the meaning of this Act,-
(d) the mere discovery of a new form of a known substance which does not result in the 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.
Explanation.-For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.”
PARA 103. We are clearly of the view that the importance of the amendment made in section 3(d), that is, the addition of the opening words in the substantive provision and the insertion of explanation to the substantive provision, cannot be under-estimated. It is seen above that, in course of the Parliamentary debates, the amendment in section 3(d) was the only provision cited by the Government to allay the fears of the Opposition members concerning the abuses to which a product patent in medicines may be vulnerable. We have, therefore, no doubt that the amendment/addition made in section 3(d) is meant especially to deal with chemical substances, and more particularly pharmaceutical products. The amended portion of section 3(d) clearly sets up a second tier of qualifying standards for chemical substances/pharmaceutical products in order to leave the door open for true and genuine inventions but, at the same time, to check any attempt at repetitive patenting or extension of the patent term on spurious grounds.

WHAT IS EVERGREENING?
Evergreening” is a term used to label practices that have developed in certain jurisdictions wherein a trifling change is made to an existing product, and claimed as a new invention. The coverage/protection afforded by the alleged new invention is then used to extend the patentee’s exclusive rights over the product, preventing competition.[PARA 100]

THE TECHNICAL ASPECT OF THE PRODUCT [GLEEVEC- A CANCER CURE] PATENT IS DISCUSSED THREADBARE IN PARA 108 TO 157:
108. The subject product admittedly emerges from the Zimmermann patent. Hence, in order to test the correctness of the claim made on behalf of the appellant, that the subject product is brought into being through inventive research, we need to examine in some detail the Zimmermann patent and certain developments that took place on that basis.
157. In light of the discussions made above, we firmly reject the appellant’s case that Imatinib Mesylate is a new product and the outcome of an invention beyond the Zimmermann patent. We hold and find that Imatinib Mesylate is a known substance from the Zimmermann patent itself. Not only is Imatinib Mesylate known as a substance in the Zimmermann patent, but its pharmacological properties are also known in the Zimmermann patent and in the article published in the Cancer Research journal referred to above. The consequential finding, therefore, is that Imatinib Mesylate does not qualify the test of “invention” as laid down in section 2(1)(j) and section 2(1)(ja) of the Patents Act, 1970.

The Zimmermann patent
Jürg Zimmermann invented a number of derivatives of N-phenyl-2-……………..[para 5]
The Zimmermann patent is a patent for “Pyrimidine Derivatives and Processes for the Preparation thereof”.
124. From the above passage from the judgment, it is evident that, according to the Board of Patent Appeals, the Zimmermann patent teaches any person skilled in the art how to use Imatinib, a compound of formula I, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition for treating tumours or in a method of treating warm-blooded animals suffering from a tumoral disease. However, the Board of Patent Appeals held that the teaching in the Zimmermann patent did not go beyond Imatinib Mesylate and did not extend to beta crystalline form of Imatinib Mesylate, which represented a manipulative step [Not an “inventive step”! A “manipulative step” may or may not be an “inventive step”, which is the requirement under Indian law.] in a method of treating tumor disease in a patient.
131. In the face of the materials referred to above, we are completely unable to see how Imatinib Mesylate can be said to be a new product, having come into being through an “invention” that has a feature that involves technical advance over the existing knowledge and that would make the invention not obvious to a person skilled in the art. Imatinib Mesylate is all there in the Zimmermann patent. It is a known substance from the Zimmermann patent.

WHAT IS EFFICACY? -SECTION3(d)
Para 177. The portion added in section 3(d) by the 2005 amendment reads as under:
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 [is not inventions within the meaning of the Act].

Para 180. What is “efficacy”?
Efficacy means [The New Oxford Dictionary of English, Edition 1998.] “the ability to produce a desired or intended result”. Hence, the test of efficacy in the context of section 3(d) would be different, depending upon the result the product under consideration is desired or intended to produce. In other words, the test of efficacy would depend upon the function, utility or the purpose of the product under consideration. Therefore, in the case of a medicine that claims to cure a disease, the test of efficacy can only be “therapeutic efficacy”. The question then arises, what would be the parameter of therapeutic efficacy and what are the advantages and benefits that may be taken into account for determining the enhancement of therapeutic efficacy? With regard to the genesis of section 3(d), and more particularly the circumstances in which section 3(d) was amended to make it even more constrictive than before, we have no doubt that the “therapeutic efficacy” of a medicine must be judged strictly and narrowly. Our inference that the test of enhanced efficacy in case of chemical substances, especially medicine, should receive a narrow and strict interpretation is based not only on external factors but there are sufficient internal evidence that leads to the same view. It may be noted that the text added to section 3(d) by the 2005 amendment lays down the condition of “enhancement of the known efficacy”. Further, the explanation requires the derivative to “differ significantly in properties with regard to efficacy”. What is evident, therefore, is that not all advantageous or beneficial properties are relevant, but only such properties that directly relate to efficacy, which in case of medicine, as seen above, is its therapeutic efficacy.

Conclusion:
Para 193.  It is seen above that in the US the drug Gleevec came to the market in 2001. It is beyond doubt that what was marketed then was Imatinib Mesylate and not the subject product, Imatinib Mesylate in beta crystal form. It is also seen above that even while the appellant’s application for grant of patent lay in the “mailbox” awaiting amendments in the law of patent in India, the appellant was granted Exclusive Marketing Rights on November 10, 2003, following which Gleevec was marketed in India as well.
On its package [A copy of the package is enclosed at the end of the judgment as appendix III.], the drug was described as “Imatinib Mesylate Tablets 100 mg” and it was further stated that “each film coated tablet contains:
100 mg Imatinib (as Mesylate)”. On the package there is no reference at all to Imatinib Mesylate in beta crystalline form. What appears, therefore, is that what was sold as Gleevec was Imatinib Mesylate and not the subject product, the beta crystalline form of Imatinib Mesylate.
194. If that be so, then the case of the appellant appears in rather poor light and the claim for patent for beta crystalline form of Imatinib Mesylate would only appear as an attempt to obtain patent for Imatinib Mesylate, which would otherwise not be permissible in this country.

195. In view of the findings that the patent product, the beta crystalline form of Imatinib Mesylate, fails in both the tests of invention and patentability as provided under clauses (j), (ja) of section 2(1) and section 3(d) respectively, the appeals filed by Novartis AG fail and are dismissed with cost. The other two appeals are allowed.

Leave a Reply

Your email address will not be published. Required fields are marked *