Patent Circle Exclusive: Tarceva Patent Litigation Analysis II

Erlotinib is reported to be a derivative of gefitinib, and this argument likely to heat up in Tarceva patent litigation. Cipla certainly will contest the validity of the ‘203 patent under section 3(d) of the Act and possibly extend to post-grant opposition under clause (f) of section 25(2) of the Act. Considering lack of know-how in dealing such complex validity, Indian Courts surely have a tough task ahead, and need to be diligent and detailed in delivering judgment.

Quinazoline Family

Quinazoline is a compound made of fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. Gefitinib and Erlotinib belongs to a class of 4-anilinoquinazoline derivatives, an anilino (phenylamino) group attached at the 4-position of quinazoline. Over the years, compounds belonging to 4-anilinoquinazoline family are reported to be useful as an analgesic and anti-inflammatory agent and in the treatment of cancer.

Gefitinib is broadly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,457,105 (genus patent), and particularly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,770,599 (species patent). Both genus and species patents are issued to Zeneca and currently listed with the Orange Book. Erlotinib is broadly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,747,498 (the ‘498 patent). The markush 4-anilinoquinazoline structures are represented below –

Above markush structures have similar 4-anilinoquinazoline base structure, which in fact structurally resembling to anti-cancer markush 4-anilinoquinazolines disclosed in European Patent No. 0 520 722 (‘the 722 patent) issued to Imperial Chemical Industries (ICI) and markush 4-anilinoquinazolines disclosed in US Patent No. 4,464,375 (the ‘375 patent) issued to Sankyo having analgesic and anti-inflammatory properties.

According to the literature citation taken from the genus patent, none of the public disclosure (till that date) reported quinazoline derivative to have anti-cancer properties arising from receptor tyrosine kinase inhibitory properties, and most of the know quinazoline derivatives were reported to possess analgesic, anti-inflammatory, bronchodilator, hypotensive or anti-malarial properties, or tested for antiarrythmic properties. The application for genus patent was filed August 02, 1994 having foreign priority from British patent applications with earliest dated January 20, 1992. Doing some extra-research over the prior art literature, the ‘722 patent seems to be the first patent literature to report and mark a major breakthrough and discovery of new class of 4-anilinoquinazolines for cancer treatment. The ‘722 patent claims priority from British patent applications with earliest dated June 28, 1991. This, in fact, technically suggest that both Gefitinib and Erlotinib are chemical variations of markush 4-anilinoquinazolines disclosed in the ‘722 patent.

Following ICI discovery of new class of 4-anilinoquinazoline inhibitors, AstraZeneca invented first 4-anilinoquinazoline anti-cancer drug candidate Gefitinib, marketed as Iressa followed by Pfizer’s Erlotinib and Glaxo’s Lapatinib (marketed as Tykerb).

Is Erlotinib a derivative of Gefitinib? To be continue …