Gliptins Global Competition, Will Impact India Too II

Drug Name	WO Publication No.	Mail-box Application No.	Status
Sitagliptin	WO03004498	26/CHENP/2004	Patent Granted
Vildagliptin	WO0034241	IN/PCT/2001/779/CHE	Patent Granted
Saxagliptin	WO2001068603	IN/PCT/2002/01154/MUM	Patent Granted
Denagliptin	WO2003002531	1536/KOLNP/2003	Not Known
Melogliptin	WO2005033099	1039/MUM/2003	Pending

Sitagliptin

Starting with Merck’s Sitagliptin, “first-in-class” drug to reach to market and approved by the US Food & Drug Administration (FDA). Earlier referred as MK-0431, Sitagliptin is broadly covered within the markush chemical structure described in WO03004498 and corresponding Indian Patent No. 209816 issued to Merck & Co. against the mail-box application no. 26/CHENP/2004. Marketed as Januvia, Sitagliptin recorded $ 668 million in worldwide sales in 2007 and is projected reaching $2 billion in annual worldwide sales by 2011. Abstract of Sitagliptin mail-box application reads as –

The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

Vildagliptin

Although Novartis’s Vildagliptin (earlier referred as LAF 237) was competing in parallel with Merck’s Sitagliptin, but later left out in race due to the US FDA concern and subsequent requests for additional safety data. Lately, Vildagliptin got approval by European health authorities and is marketed under the brand name Galvus. Vildagliptin is broadly covered within the markush chemical structure described in WO0034241 and corresponding Indian Patent No. 212815 against the mail-box application no. IN/PCT/2001/779/CHE claiming priority from US provisional application dated December 10, 1998. The abstract of Vildagliptin mail-box application reads as –

This invention relates to compound of formula (IA) or (IB) wherein R' represents hydroxy, C1-C7alkoxy, C1-Cg-alkanoyloxy, or Rs~N-CO-O-, where ~ and Rs independently are C1-C7alkyl or phenyl which is unsubstituted or substituted by a substituent selected from C1-C7 alkyl, C1-C7alkoxy, halogen and trifluoromethyl and where ~ additionally is hydrogen; or ~ and Rs together represent C3-Csalkylene; and R" represents hydrogen; or R' and R" independently represent C1-C7alkyl; in free form or in form of a pharmaceutically acceptable acid addition salt.

Saxagliptin

Bristol-Myer is likely to submit an NDA for Saxagliptin this year with the US FDA, making Saxagliptin possibly the third DPP IV inhibitor to gain market approval. Earlier referred as BMS-477118, Saxagliptin is broadly covered within the markush chemical structure described in WO2001068603 and corresponding Indian Patent No. 206543 issued to Bristol-Myer Squibb against the mail-box application no. IN/PCT/2002/01154/MUM claiming priority from US provisional application dated March 10, 2000. The abstract of Saxagliptin mail-box application reads as –

Dipeptidyl peptidase IV (DP 4) inhibiting compounds are provided having the formula (I) where x is 0 or I and y is 0 or 1 (provided that x = I when y = 0 and x =0 when y = 1); n is 0 or 1; X is H or CN; and wherein R1, R2, R3 and R4 are as described herein. A method is also provided for treating diabetes and related diseases, especially Type 11 diabetes, and other diseases as set out herein, employing such DP4 inhibitor or a combination of such DP4 inhibitor and one or more of another antidiabetic agent such as metformin, glyburide, troglitazone, pioglitazone, rosiglitazone and/or insulin and/or one or more of a hypolipidemic agent and/or anti-obesity agent and/or other therapeutic agent.

Denagliptin

Glaxo suspended the phase III studies for Denagliptin (earlier code name GW823093) due to toxicity problems, which is broadly covered within the markush chemical structure described in WO2003002531 and corresponding mail-box application no. 1536/KOLNP/2003 claiming priority from US provisional application dated June 27, 2001. The abstract of Denagliptin mail-box application reads as –

The present invention relates to novel compounds of formula (I): , their use for inhibiting serine proteases, such as dipeptidyl peptidases, such as dipeptidyl peptidase IV (DPP-IV) and to methods for their production and their therapeutic utility.

Melogliptin

Glenmark’s Melogliptin (earlier referred as GRC 8200) is currently in phase II studies, which is broadly covered within the markush chemical structure described in WO2005033099 and corresponding mail-box application no. 1039/MUM/2003 filed on October 03, 2003. The abstract of Melogliptin mail-box application reads as –

The present invention relates to novel dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), and their analogs, isomers, pharmaceutical compositions and therapeutic uses, methods of making the same.