Tuesday, January 05, 2010

Is Section 3 (d) Jeopardizing Innovation?

Section 3(d) is a great piece of legal provision, carefully drafted to negate patent protection for trivial and obvious improvements, in general, made to already known pharmaceutical/chemical substances. Notably, wording of section 3(d) is not open-ended but clearly conditional which leaves room for patent protection for incremental innovations. In fact, any patent application that is rejected u/s section 3(d) must strictly fall within the condition laid down by the section 3(d). However, the application of the section 3(d) by the Indian Patent Office, and more particularly by the Indian Judiciary raised serious questions about the understanding and spirit of section 3(d). In this post, I will try to raise certain points that often puzzled me about the way section 3(d) is interpreted and applied by the Indian Patent Office and Indian Judiciary. I will sincerely welcome and appreciate comments by the readers which help to clarify and add value to the points made in the post.
In Novartis infamous Glivec case, the Madras High Court opined that the efficacy under section 3(d) need to be construed as “therapeutic” efficacy only. Strictly adhering to the Madras High Court opinion, improved efficacy does not include any enhancement in pharmacological parameters (such as bioavailability, toxicity, increased self-life, stability and so on). This mean any physical or chemical improvement made to a known drug substance cannot qualify for patent protection unless and until they do not result into enhanced therapeutic efficacy. Let us consider the Imatinib case. Novartis applied patent application for beta-crystalline form of Imatinib Mesylate which was denied by the IPO and later by the Madras High Court suggesting that improved bioavailability do not account to enhanced therapeutic efficacy.

Suppose if Novartis wanted to have a patent protection for beta-crystalline form of Imatinib Mesylate then what data they need to provide to the IPO in light of the Madras High Court decision? Simple! Novartis need to provide clinical data to prove that beta-crystalline form of Imatinib Mesylate is therapeutically enhanced in treating chronic myelogenous leukemia (CML) when compared to known Imatinib Mesylate substance. In other words, Novartis need to prove that beta-crystalline form is better than known substance not in terms of bioavailability or any other pharmacological parameters but in terms of therapeutic treatment activity (may be something like improving inhibition activity towards tyrosine kinase enzymes). Now the first point that come to my mind is that whether a polymorph or a salt of a known drug substance can improve therapeutic treatment activity, that is, mechanism of drug action of the known drug substance or they are used for improving pharmacological parameters of the know drug substances? I may be wrong in my understanding on this issue but surely would love to hear comments from readers and the industry experts. Whether the Madras High Court opinion of restricting efficacy only to therapeutic efficacy jeopardizes innovation?


  1. Shrikant Kulkarni2:19 PM

    Welcome back, Good article.

  2. Chitra Iyer5:50 PM

    Dear Varun,

    Thanks for raising several thought provoking questions.

    Based on my understanding of the drug discovery process, pharmacological parameters such as ADME characteristics, and other factors such as solubility and permeability as important as therapeutic efficacy. Another important factor is safety which is equally if not more important than efficacy.
    In other words if you had an extremely potent drug which did not have good solubility properties and therefore had to be given in high doses which in turn increased the toxicity- we are actually achieving very less.

    Similarly an extremely potent drug may have less half life and therefore does not stay in the body long enough to show the best activity. In such cases modifying the drug to improve its half life would be very desirable.

    In my experience the best drugs need not be the most potent molecule , but the molecule having reasonable potency and also having the so called good drug like properties so that the over all package makes it a good / safe drug.
    Therefore, in the Novartis case, if the High Court opined that, the efficacy under section 3(d) need to be construed as “therapeutic” efficacy only , then we need to take series look at interpretation of section 3d.
    I would love to hear what our fellow readers have to say about this.

  3. Dear varun

    1. I distinctly remember (which I must have read in one of those IPHealth website year 2007ish newsletters) that about 30 % enhancement is activity is required. The API in question didnot qualify. I will have to dig up my IPHealth saved information to be sure. Expect some feed back from readers.

    2. Polymorph will lose the identity once in solution and hence its interaction with the relevant biosurface will be identical to the 'earlier ' polyporph.

    3. Salt will have same fate. Once into the system ( faster or slower) it will have same effect as the freebase or free acid which is therapeutically acive molecule .

    4. Ms. Chitra Iyer has made very valid points about safety and toxicity. These factors sholuld be considered during the polymorph or salt like patent granting. Patent system cannot operate in vacuum , away from medicinal realities especially when taxpayers are supporters of the system and benefactors (or victims)of the monopolised products. Their protection should be interlinked.

    5. Toxicity profile may be influenced by structural changes and hence the corresponding congeners will not fall into Polymorph catagory. Salts may open up some avenues :
    a. how tight is the salt pair ?
    b. when the non-API species in the Saltpair undergoes randomisation with other species in the surrounding micro-sphere at the biosurface , what are the changed parameters in Newer salt Vs earlier patented salt . etc

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