Tuesday, April 2, 2013

Novartis Decision: Is Beta Crystalline Form of Imatinib Mesylate the same as Glivec?

In my last two posts, I have blogged on the Novartis decision of the Supreme Court. Most of us have been using Glivec and Beta Crystalline form of Imatinib Mesylate interchangeably. Here’s Para 193 of the Supreme Court’s finding on the issue:

193. Coming back to the case of the appellant, there is yet another angle to the matter. 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, 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.”

Now let’s examine the basis for this finding. The Supreme Court seems to have proceeded under the assumption that Novartis was obliged under law to mention the ‘beta-crystalline (BC)” form on its package, failing which, according to the Court, it was fair to assume that Imatinib Mesylate was being sold under the EMR granted for the BC form.

Before assuming thus and arriving at an adverse finding, it would have helped to undertake the following: 

1.  Branding of drugs is governed by Section 9 of the Drugs and Cosmetics Act, 1940 read with the manner of labeling prescribed under Rules 96 and 97 of the Drugs and Cosmetics Rules, 1945. Assuming that the Court deemed it relevant to address the issue of branding in a proceeding for grant of a patent, there appears to be no such discussion on the relevant provisions of the law. Unless these Drug Rules and their interpretation by Courts mandate mentioning the polymorphic form of the drug as part of the packaging, the patent applicant need not mention “beta crystalline form” as part of its package. 

2.  It would have also helped to understand the labelling practices prescribed by Indian Pharmacopoeia or the official pharmacopoeias in order to form an informed opinion on the facts of the case. 

3.  Tests could have been undertaken to check if what was being sold under the name of Glivec was Imatinib Mesylate or its BC form.

There is no discussion in the decision on the above aspects of the issue, and the Hon’ble Court seems to have proceeded on the basis of the packaging. Also, the packaging relied upon by the Hon'ble Court does not seem to state that its contents are the subject-matter of the impugned patent application.

I request better-informed readers to share with us their inputs to understand the issue better. 


  1. Anyway they failed to place on record any research data supporting their argument of increased bio availability of 30%. Had they placed on record any evidence in the form of research data, the question of examination would have come up. The beta crystalline form of Imatinib Mesylate, failed to qualify the test of Section 3(d) of the Act without contest on technical grounds. However, I am unable to understand as why in this 112 page judgment, history of Patent Act has been discussed at length.

    1. I too do not have slightest clue about the reasons for the length of the judgment. In fact, the discussion on the merits of the case could have been concluded in less than half the number of pages.

  2. You are right Sai. There is no statutory or regulatory obligation to specify the chemical form (which type of crystal) on the pack. In my opinion, imatinib mesylate (Gleevec) for which the FDA approval was received in 2001 is nothing but beta-form of imatinib mesylate. The USFDA access data clearly says that imatinib mesylate exists in crystalline form (http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021588s035lbl.pdf) and the beta form is more active than the alpha form. Thus, the commercial interest form was the beta form with which all the data was generated and subsequently submitted at the FDA. This is why, imatinib was held as the nearest entity and not imatinib mesylate per se. Since there was no known efficacy of imatinib free base, it was not possible to show efficacy. Hence, bioavailability studies were done. Why Novartis did not assert that Gleevec indeed is the beta form, is a question that has bothered me too as the only answer that i can think of leads me to the evergreening angle. The Court's statement "It is beyond doubt that what was marketed then was Imatinib Mesylate and not the subject product, Imatinib Mesylate in beta crystal form" - what is the basis for this strong conclusion, i have no clue. Just because the packs did not mention it is the beta form, does not prove that it is not beta form. The Court further states that the comparison should have been with imatinib mesylate (non-crystalline) form rather than imatinib. But if one goes by the FDA data, imatinib mesylate exists in a crystalline form and not non-crystalline. So, how did Court arrive at this finding is puzzling to me. Or is it that i am missing something here?


    1. Deepa I just looked at the document you linked to, and while it does say that "Imatinib mesylate is a white to off-white to brownish or yellowish tinged crystalline powder" but it does not say anything about the beta or alpha forms -- where exactly do you see that? thanks!