Friday, November 04, 2011

Glivec patent dispute: the case so far
Part II

Round Two: Madras High Court
Continuing from our earlier post where we discussed rejection of beta-crystalline imatinib mesylate application by the Madras Patent Office under S. 3 (d), we will now focus on round two where Novartis approached the Madras High Court challenging constitutional validity of S. 3 (d). Before we discuss the judgment, a quick reading of S. 3 (d) –

mere discovery of a new form of a known substance which does not result in increased efficacy of that substance or the mere discovery of any new property or new use for a known substance or the mere use of a known process, machine or apparatus unless such 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.”

The Patent Office rejection particularly involved the underlined portion of S. 3 (d) which Novartis in its appeal argued is vague, arbitrary and unconstitutional. Novartis also argued that S. 3 (d) is non-complaint with the TRIPS Agreement. The appeal was filed with the Madras High Court and was dismissed in August 2007.

TRIPS Compatibility
On TRIPS issue, the Madras High Court refused to address the question and categorically cited lack of jurisdiction to decide the validity of S. 3 (d) being in violation of Article 27 of TRIPS Agreement and further noted that the proper forum to bring this issue would be the WTO’s Dispute Settlement Body (DSB).

Constitutional Validity
On Constitutional validity issue, Novartis argued violation of Article 14 of the Constitution of India on the ground of vagueness, arbitrariness and conferring un-canalised powers on the Patent Office. During hearing, Novartis counsel particularly stressed upon that:

(1)   in the absence of proper guidelines as how to establish the enhancement of known efficacy of a known substance, the Patent Office is vested with arbitrary discretionary power to decide the enhancement efficacy.
(2)   in the absence of proper explanation and guidelines to the expression   “enhancement of the known efficacy” and “differ significantly in properties with regard to efficacy”, these expressions stand ambiguous.

Opposing counsels, however, defended use of general expressions and argued that the Legislature left these expressions for the Patent Office to apply mind and decide whether the invented drug is within or outside S. 3 (d) and further added that any fixed formula would be unwise and humanely impossible. 

The Madras High Court found none of Novartis arguments persuasive and hold S. 3 (d) not in violation of Article 14 of the Constitution of India. The High Court categorically relied upon (1) Medicinal Dictionary, and (2) Parliamentary debate to come to a decision over Novartis arguments.

While addressing Novartis argument that S. 3 (d) stands vague and ambiguous, the Court look into Dorland’s Medical Dictionary for the meaning of the expression “efficacy” in the field of Pharmacology which defines it as the ability of a drug to product the desired therapeutic effect” where efficacy is independent of the potency of the drug. The court further noted the dictionary meaning of “therapeutic” which defines it “healing of disease – having a good effect on the body.” Taking both “efficacy” and “therapeutic” definitions into account, the Court came with the observation that the patent applicant is expected to show “how effective the new discovery would be in healing a disease/having a good effect on the body?

The Court further limited applicability of the Explanation provided under S. 3 (d) to discoveries made in the pharmacology field. The Court particularly found that the Explanation creates a deeming fiction of derivatives of a known substance are deemed to be the same substance unless they differ significantly in properties with regard to efficacy. 

The Court finally came with the observation that S. 3 (d) along with the Explanation prescribes a test “to decide whether the discovery is an invention or not is that the Patent applicant should show the discovery has resulted in the enhancement of the known efficacy of that substance and if the discovery is nothing other than the derivative of a known substance, then, it must be shown that the properties in the derivatives differ significantly with regard to efficacy.

In the course of addressing issue of vagueness and ambiguity, the Court surprisingly pointed that Novartis, being a pharmaceutical giant, “cannot plead that they do not know what is meant by enhancement of a known efficacy and they cannot show that the derivatives differ significantly in properties with regard to efficacy.

The Court while addressing Novartis second argument that the Patent Office is vested with arbitrary discretionary power to decide the enhancement efficacy looked into Parliamentary debate for the Legislative object and purpose of enacting S. 3 (d). The Court observed that S. 3 (d) was included “to achieve namely, to prevent evergreening; to provide easy access to the citizens of this country to life saving drugs and to discharge their Constitutional obligation of providing good health care to it's citizens.” 

The High Court also relied upon the Supreme Court precedents recognizing that Legislature is permissible to lay down broad policy and delegate powers of rule making to the statutory authority to implement the policy, particularly in areas of specialized knowledge, where the Legislature lacks and knowledge and expertise to frame detailed rules.

In short, the Madras High Court dismissed Novartis plea challenging constitutional validity and TRIPS compatibility of S. 3 (d). The decision, however, lacked meticulousness that could have resolved uncertainty and debate concerning S. 3 (d) as the Madras High Court missed important opportunity by taking an approach which was more to defend the provision rather acknowledging and resolving the issue. If mere theoretical use of medicinal dictionary could have resolved such complex issue then neither Novartis (pharmaceutical major) nor the Patent Office (specialized body) would have ever approached the High Court just to hear dictionary meaning of “efficacy”. The Patent Office could have easily discussed and conveyed mere dictionary meaning to Novartis in their Office library. The expression “efficacy” needed more scientific and technical explanation which is obviously beyond the expertise of the Patent Office, in fact, Office of Drug Controller General of India would be the appropriate body to decide the efficacy enhancement.

In its decision, the Madras High Court restricted efficacy in terms of therapeutic efficacy for new discoveries made in the pharmacology field but the decision lacked diligent insight to take into account inventions such as polymers, liposomes, peptides, lipids, releasing agents etc. which are therapeutically inactive but broadly falls in the area of pharmacology and are used to deliver and facilitate absorption of therapeutic active agents. Is the Court expecting such inventions per se to show enhancement in therapeutic efficacy or else they altogether do not qualify for patent protection in India? In fact, we have been prosecuting more than dozen patent applications that claim classes of polymers and compounds used to deliver and facilitate adsorption of therapeutic agents and surprisingly all these applications got rejection under S. 3 (d) as the Patent Office contended that claimed subject-matter lack increased efficacy.

Ironically contrary to the High Court theoretical observations that S. 3 (d) is not vague and arbitrary and having hindsight to help Patent Office adjudicate patents applications in the field of pharmacology, the Patent Office continue to use fairly irrational discretions in applying S. 3 (d) even where it is not required. The so-called specialized body not only lacked insight to basics of pharmaceutical science but even failed to differentiate therapeutic active inventions from therapeutic inactive inventions. As of now, the Patent Office has been treating both therapeutic active compounds and therapeutically inactive agents (such as biodegradable polymers used as carriers for therapeutic active agents) exactly the same and constantly been applying S. 3 (d) rejections.

Using “efficacy” yardstick for inventions that are not therapeutically active but still falls in the area of pharmacology is correct or erroneous, not only leave considerable ambiguity but also arbitrariness on the Patent Office in deciding the same. As a patent practitioner, it is often hard to process the fact that the Patent Office asked for “therapeutic efficacy” for therapeutically inactive inventions.

Let us now summarize what the High Court observed in its judgment.

(1)   S. 3 (d) not in violation of Article 14 of the Constitution of India.
(2)   Lack jurisdiction to decide issue of TRIPS compatibility.
(3)   Inclusion of S. 3 (d) to prevent ever-greening.
(4)   Expression “efficacy” not vague and ambiguous.
(5)   Explanation under S. 3 (d) limited to discoveries in the field of pharmacology.
(6)   Patent Applicant either needs to show how effective new discovery would be in healing a disease or how effective new discovery would be in having a good effect on the body.
In light of facts covered so far, the expression “efficacy” contemporarily needs to be in terms of “therapeutic efficacy” which as the High Court observed can be gauged by showing effectiveness in healing a disease or showing effectiveness in having a good effect on the body. Let us end this post by putting the Court observation into analytical perspective.

(1)   Whether a toxic drug provides healing or good effect on the body? Or in other words, does the threshold to make drug non-toxic qualify for therapeutic efficacy?
(2)   Whether an unstable drug provides good effect on the body? Or in other words, does the threshold to make drug formulation stable/increase self-life qualify for therapeutic efficacy?
(3)   Whether lack of bioavailability provides healing or good effect on the body? Or in other words, does the threshold to make drug bioavailable qualify for therapeutic efficacy?

However, one point that we found hard to digest was the High Court observation that inclusion of S. 3 (d) was to prevent ever-greening. Anyone with experience working in pharmaceutical industry can easily understand that “ever-greening” is more of a business strategy for product lifecycle management to extend protection beyond original compound/patent by protecting incremental and even possibly trivial innovations. It would be completely wrong to acknowledge that ever-greening is only and all about trivial innovations. Now if we consider the Legislature has intention to prevent ever-greening then that would mean to rule out any protection beyond original patent. In that case, S. 3 (d) not only disqualifies trivial innovations but also genuine incremental innovations. And if incremental innovations are not what the Legislature wanted to exclude from patent protection then the word “ever-greening” is inappropriately used.

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