Glivec patent dispute: the case so far Part I

The high-profile Glivec patent dispute in which Novartis challenged the Madras (Chennai) Patent Office decision of rejecting its patent application for beta-crystalline version of imatinib mesylate under vaguely interpreted S. 3 (d) is now been heard in the Supreme Court of India. The dispute has been in print media more for the wrong reasons and widely reported as controversial because of NGOs vociferous criticism of Novartis’s legal recourse but for patent practitioners the case has been of significant concern to see how judiciary meticulously approaches to interpret S. 3 (d), more particularly efficacy. Despite the case is been heard by the Supreme Court, there had been various news floating across the internet and print media arguing that win for Novartis could have a “devastating impact” on access of medicines in the developing world and would increase the drug pricing drastically. Also, the case has keenly been followed by pharmaceutical sector in India outcome of which could outline the future of Indian pharmaceutical industry. In short, the Glivec dispute brought multifaceted debates in India (even across the border) but in this post we will try focusing more on facts rather falling trap to ‘vested’ debates. 

First Round: Madras Patent Office

In 1993, Novartis filed a patent disclosure for revolutionary anti-cancer molecule imatinib which was first drug in the class of tyrosine kinase inhibitors to reach the market. In July 1997, Novartis filed another patent application disclosing methanesulfonic acid (mesylate) addition salt of imatinib in two distinct crystalline variants: alpha and beta. During studies, Novartis found beta-crystalline to be more stable, commercially viable variant to manufacture Glivec oral tablets. 

In 1995, India became a signatory member of the World Trade Organization (WTO) and agreed to grant patent protection for pharmaceutical products more as a compulsion under TRIPS agreement. India further being a developing country got 10-years transition period to implement patent protection for drug products but at the same time had obligation to accept patent application under “mail-box” provision. The “mail-box” provision paved way for global pharmaceutical companies to file patent application for their drug products in India. 

Imatinib been a pre-1995 disclosure was not eligible for patent protection in India. In July 1998, Novartis filed application 1602/MAS/98 for alpha and beta crystalline variants of imatinib mesylate which stayed in “mail-box” till 2005. In November 2003, the Controller granted first Exclusive Marketing Right (EMR) to Glivec for a period of 5 years. The EMR gave Novartis the right to exclusively sell and distribute the drug in India which Novartis attempted enforcing against the generic manufacturers by filing suits in the Madras and Delhi High Court. In January 2004, the Madras High Court granted Novartis an interim injunction restraining generic manufacturers from manufacturing, selling, distributing or exporting the generic drug. The injunction was later made absolute by Justice R. Balasubramanian. In August 2004, Novartis voluntarily filed divisional application 799/CHE/2004 for alpha crystalline variant. Later in December 2004, Justice Deshmukh of the Delhi High Court disagreed with the Madras High Court decision to allow injunction and refused to grant temporary injunction to Novartis.

In 2005, the patent act was amended and Novartis application for beta-crystalline variant came up for examination. The 2005 amendment also provides that EMRs would either be replaced by patents (if granted) or cancelled (if applications were rejected). Later in 2005, various representations for pre-grant oppositions were made by Cancer Patients Aid Association and generic manufacturers for beta-crystalline variant and the application was rejected by the Madras (Chennai) Patent Office on January 25, 2006 and subsequently cancelling the EMR. The rejection was primarily made on the grounds of:

• Lack of novelty/Anticipation
• Lack of inventive step
• Non-patentable subject matter u/s 3 (d)
• Wrong priority

In May 2006, Novartis filed writ petitions before the Madras High Court not only against the rejection order but also challenging the constitutional validity of S. 3 (d) which was later converted into appeals. In April 2007, the Central Government notified operationalisation of the Intellectual Property Appellate Board (IPAB) subsequent to which appeals got divided between the High Court and the IPAB, earlier judging the constitutional validity and later to decide the patentability of beta-crystalline imatinib mesylate. 

In March 2009, Novartis’s divisional application for alpha crystal variant of imatinib mesylate also got rejected by the Madras Patent Office following representations for pre-grant opposition made by generic manufacturers. The rejection was primarily made on the grounds of:

• Lack of inventive step
• Lack of utility
• Non-patentable subject matter u/s 3 (d)
• Insufficient disclosure

To this point, the whole Glivec patent dispute remained with and was decided by the Madras Patent Office which can briefly be summarize into following key points covered so far.

1. Imatinib per se not patented in India.
2. Imatinib mesylate per se not patented in India.
3. Application for beta-crystalline variant of imatinib mesylate stand rejected.
4. Rejection order for beta-crystalline appealed before the Madras High Court.
5. Appeal against rejection order for beta-crystalline transferred to newly formed IPAB.
6. Application for alpha-crystalline variant of imatinib mesylate rejected.
7. Madras high court only to decide constitutional validity of S. 3 (d).
8. IPAB only to decide patentability of beta-crystal variant of imatinib mesylate.

To put it more simple, generic manufacturers are safe, in fact, are free to manufacture and sell tablets which may contain either of the following: imatinib free base, imatinib mesylate, or any other form of imatinib mesylate. In addition, following the patent office decision to reject patent applications for both alpha and beta crystalline variants, generic manufacturers are also free to use alpha crystalline variant but the only area of concern remains if generic manufacturers are using or intending to use beta-crystalline variant since the rejection order got appealed by Novartis.

Technically, none of generic manufacturers is barred from manufacturing and selling generic imatinib mesylate tablets; it is just the specific crystalline form, i.e. beta-crystalline variant which need attention as long as Novartis exhaust all its legal options. And even if Novartis wins the case, it would be a mere child’s play for competitively talented generic manufacturers to avoid using or designing-around beta-crystalline variant. In fact, inclusion of S. 3 (d) was advocated on the fact that inventing new polymorphic form involves no inventiveness (human ingenuity) and is mere more of a routine practice within the industry. So what’s the big deal if Novartis receive patent protection for specific beta-crystalline form of imatinib mesylate? In patent domain, such patent are considered extremely narrow patent.  

In light of facts covered so far, the argument that the win for Novartis would adversely impact the drug supply and pricing stands dubious, misleading, and motivated to malign spirit/nuances of patent system in India. In fact any generic manufacturer using imatinib mesylate other than beta-crystalline variant does not need to have even a slight concern about Novartis patent dispute.

An act to streamline, harmonize US patent law - II

Section 6

Inter partes review

Amends 35 USC § 311 to replace inter partes re-examination with “inter partes review” allowing third party to challenge validity or scope of an issued patent only on a ground that is permissible under 35 USC § 102 and 103. The review must be filed within nine months after grant or reissuance of patent or after the grant of termination of post-grant review. Prior art submissions are limited to patents and printed literature.

Post grant review

Enacts 35 USC § 321 to allow third party (petitioner) to institute a post-grant review for an issued patent. The review must be filed within nine months after grant or reissuance of patent. This reform will permit third party to challenge the validity or scope of patent based on any ground of patentability and prior art submission is not limited to patents and printed literature. Importantly, in the case of both post-grant review and inter partes review proceeding, the third party will be estopped from raising similar invalidity arguments in subsequent USPTO or the International Trade Commission (ITC) or litigation proceedings that were raised or reasonably could have been raised during the review.

This reform will now allow the US to have post-grant opposition procedure similar to Europe and India. Amendments made to section 6 will come in effect 1-year after the date of enactment, i.e. September 16, 2012 and will be applicable to any patent issued before or after the effective date.

Section 7

Patent Trial and Appeal Board

Amends 35 USC § 6 to existing Board of Patent Appeals and Interferences with newly formed “Patent trial and Appeal Board” to hear appeals and conduct derivation, inter partes review and post-grant review proceedings. The Patent Trial and Appeal Board will be having a panel of at least three members.

Appeal to Court of Appeals for the Federal Circuit

Amends 35 USC § 141 to permit either party to appeal the Patent Trial and Appeal Board adverse decision only to the US Court of Appeals for the Federal Circuit. 

Amendments made to section 7 will come in effect 1-year after the date of enactment, i.e. September 16, 2012 and will be applicable to proceedings commenced on or after the effective date.

Section 8

Preissuance submission by third parties

Amends 35 USC § 122 to permit third party to submit, for consideration and inclusion in the record of a patent application, any patent, published patent application, or other printed publication of potential relevance to the examination of the application, if such submission is made in writing within six months of publication of the application.

Amendments made to section 8 will come in effect 1-year after the date of enactment, i.e. September 16, 2012 and will be applicable to any patent application filed before or after the effective date.

Section 9

Venue

Amends 35 USC § 32, 145, 146, 154(b)(4)(A) and 293 to shift default venue from United States District Court of Columbia to “United States District Court for the Eastern District of Virginia.”

This amendment is in effect immediately and will apply to any civil action commenced on or after the effective date.

Section 10

Micro entity defined

Enacts 35 USC § 123 to include a new class of inventor “micro-entity” which has filed no more than four applications, and has gross income below a designated level without having transferred ownership interest in the application to an entity with gross income exceeding such limit. This provision is in effect immediately.