India rejects patents for Pfizer’s Caduet, GSK’s rosiglitazone salt

Torrent opposed Pfizer’s Caduet claims.

The Delhi Patent Office has rejected a patent application from Pfizer Inc seeking protection for its Caduet pills. Caduet is a therapeutic combination of amlodipine and atorvastatin.

The Indian Patent Office’s decision favours Torrent Pharma Ltd of Ahmedabad, Gujarat which had filed a Pre-grant Opposition against granting patent for Caduet.

Torrent in its petition argued that since Cuduet is combination two known medicines, the product is not eligible for a new patent under the sections of Indian Patent (Amendment) Act 2005.

Torrent also argued that Pfizer cannot claim a patent for Caduet under the ground of ‘Not an invention/not patentable” under section 3(d) & 3(e) of the Patent Act 2005, as well.

And the Delhi Patent Office rejected the application on grounds of (1) lack of inventive step under section 25 (1) (e), (2) not patentable under section 25(1)(f),(3) insufficiency of description under section 25(1)(g) and section 3(d) (lack of enhanced efficacy) and 3(e) (lack of synergy).

While rejecting a patent for Pfizer’s Caduet, the Indian Patent Office (IPO) noted that the “composition/combination essentially comprising amlodipine or its pharmaceutically acceptable salt (amlodipine besylate) and atorvastatin or its pharmaceutically acceptable salt (hemi calcium salt of atorvastatin). A composition vide section 3(d) cannot be patented unless any significant therapeutic efficacy over the parent substance is shown.”

Caduet is an admixture of amlodinpine and atorvastatin salts.Amlodipine besylate performs its usual function i.e. acting as a calcium channel blockers and atorvastatin lowering of lipid level. So, the Caduet combination did not result in any enhanced additive effect because not a single example in.

Besides, Pfizer did not provide any data to prove the additional benefits of the synergistic combination, Caduet.

In addition, Pfizer’s assertion in the filing application that the amlodipine was “approved and used for treating hypertension and atorvastatin was approved and used for treating hyperlipidemia does not mean that they were both prescribed in combination,” the IPO decision observed.

Caduet is marketed by Pfizer and has US Patent No. 6,455,574 listed with Orange Book.

In 2007 Pfizer successfully blocked Indian drug major Ranbaxy’s claim for a generic version of Caduet, when a US district court decided that Ranbaxy cannot launch its generic until at least 2010.

Again, in 2008 Pfizer Inc lodged a declaratory judgment suit claiming that Ranbaxy’s proposed generic would infringe two patents related to atorvastatin, in a move that could stop Ranbaxy Laboratories Ltd from marketing a generic version of the Caduet until 2016. Pfizer filed its complaint in the US District Court for the District of Delaware, seeking a judgment that Ranbaxy’s copycat Caduet would infringe two patents Pfizer says are valid through July 16, 2016. The suit sought injunctive relief barring Ranbaxy from making, selling or importing its generic until those patents expire.

Patent office refuses GSK’s claim on rosiglitazone ethane sulphonate

Similarly, GlaxoSmithKline has been denied a patent for rosiglitazone salt -an anti-diabetic drug by the Indian Patent Office.

The Delhi Patent Office has rejected the patent application no. 295/DELNP/2003 for ethane sulphonate salt of rosiglitazone.

While rejecting GSK’s patent claim for ethane sulphonate salt of rosiglitazone, IPO said Glaxo failed to establish that ethanesulphonate salt of rosiglitazone  is better in terms of the efficacy with respect of the rosiglitazone.

Though Glaxo provided four supporting Annexures in their written submissions but the Delhi Patent Office do not found them supporting the application efficacy with respect to the known rosiglitazone.

GSK in its application dated 30.12.2008 claimed that ethane sulphonate salt of rosiglitazone, a derivative of the parent compound rosiglitazone, has good stability, aqueous solubility and bulk flow properties.

However, IPO stated in its decision that: :The applicants could not establish that the compound as claimed in the instant Patent Application is better in terms of the efficacy with respect to the parent compound as known in prior art, hence in lack of the efficacy the instant Patent Application can not be allowed. Accordingly the instant Patent Application No. 00295/DELNP/2003 is refused.”

Rosiglitazone risks heart diseases

Rosiglitazone is a thiazolidinedione class of drugs. It is marketed under the brand name Avandia and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Annual sales peaked at approx $2.5bn in 2006. Patent expires 2012.

A meta-analysis reported in May 2007 that the use of rosiglitazone was associated with a 43% more risk of heart attacks and an even higher risk of death from all cardiovascular diseases (64% more likely).

Following this, the US FDA issued an alert on May 21, 2007. On July 30, 2007 an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of myocardial ischemic events (including heart attacks) than a placebo, but data from several long term, prospective clinical trials showed than when rosiglitazone was compared to metformin, or sulfonylurea, there was no difference in the risk of heart attack. This data, coupled with the meta-analysis, prompted the FDA to state that the data on the association between rosiglitazone and myocardial ischemia were inconclusive.

US sales of rosiglitazone (Avandia) has been declining ever since: $2.2 billion in 2006. Sales in 2Q 2007 down 22% compared to 2006 and ultimately reaching to  million in the fourth quarter of 2007.