PTAB

IPR2020-01072

Sun Pharmaceutical Industries Ltd v. Merck Sharp & Dohme Corp

Log In

1. Case Identification

2. Patent Overview

  • Title: Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
  • Brief Description: The ’708 patent is directed to a dihydrogenphosphate salt of sitagliptin, specifically the compound 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine. The salt is described as a potent inhibitor of dipeptidyl peptidase-IV (DP-IV) for the treatment of type 2 diabetes.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-3, 17, 19, and 21-23 under §102 over WO '498

  • Prior Art Relied Upon: WO '498 (International Publication No. WO 03/004498).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that WO ’498, which the ’708 patent admits is prior art, anticipates the challenged claims. WO ’498 discloses the base compound sitagliptin (specifically the (R)-configuration in Example 7) and claims the compound along with its “pharmaceutically acceptable salts.” The reference provides a specific list of “[p]articularly preferred” acid salts that includes “phosphoric” acid. Petitioner contended that the disclosure of the sitagliptin base compound combined with a specific, finite list of preferred salt-formers that includes phosphoric acid constitutes an express disclosure of sitagliptin phosphate. Because WO '498 also teaches that the disclosed compounds may exist as stereoisomers, it anticipates claim 3 directed to the (S)-configuration. The reference further discloses pharmaceutical compositions (anticipating claim 17), methods of treating type 2 diabetes (anticipating claim 19), and processes for salt formation analogous to those in claims 21-23.

Ground 2: Anticipation of Claims 1-3, 17, 19, and 21-23 under §102 over the '871 Patent

  • Prior Art Relied Upon: The ’871 patent (Patent 6,699,871).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued the ’871 patent is prior art under 35 U.S.C. §102(e) as it was filed by different inventors before the invention date of the ’708 patent. The specification of the ’871 patent is identical in all material respects to WO ’498. The ’871 patent claims (R)-sitagliptin “or a pharmaceutically acceptable salt thereof” in its claim 17. Similar to WO ’498, its specification teaches that phosphoric acid is a “[p]articularly preferred” salt for the class of compounds that includes sitagliptin. Therefore, for the same reasons articulated for WO ’498, Petitioner asserted that the ’871 patent anticipates claims 1-3, 17, 19, and 21-23 by disclosing the specific combination of sitagliptin and the phosphate salt, along with its therapeutic uses and methods of preparation.

Ground 3: Obviousness of Claims 1-3, 17, 19, and 21-23 under §103 over WO '498 and Bastin

  • Prior Art Relied Upon: WO '498 (International Publication No. WO 03/004498) and Bastin (a 2000 journal article on salt selection procedures).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner argued that WO ’498 discloses sitagliptin as a weakly basic compound and exemplifies it as a hydrochloride salt. Bastin provides a general framework for salt selection and optimization for new chemical entities. Bastin specifically teaches that for weakly basic drugs, salts of inorganic acids like hydrochloride, sulfate, or phosphate are commonly considered to enhance properties such as aqueous solubility.
    • Motivation to Combine: A person of ordinary skill in the art (POSA), starting with the sitagliptin disclosed in WO ’498, would have been motivated to optimize its salt form for pharmaceutical development. Bastin provides the well-established rationale and toolkit for this routine optimization. A POSA would have looked to common, well-characterized salts, such as the inorganic acid salts listed in Bastin, to improve upon or find alternatives to the exemplified hydrochloride salt in WO '498, which can have disadvantages (e.g., high acidity, corrosion). The overlapping lists of preferred salts in WO '498 and common salts in Bastin would have directed a POSA to consider phosphate as a prime candidate.
    • Expectation of Success: A POSA would have had a reasonable expectation of success in forming the phosphate salt of sitagliptin. The formation of simple acid-base salts was highly predictable, and both references identified phosphate as a suitable and preferred option. The selection was from a small, finite list of known, predictable salt-formers, making it an "obvious to try" scenario with a high likelihood of success.

  • Additional Grounds: Petitioner asserted additional obviousness challenges, including that claims 3, 17, 19, and 21-23 are obvious over WO '498 alone, and that claim 4 (crystalline monohydrate) is obvious over WO '498 and Bastin in view of Brittain (a 1999 publication on pharmaceutical hydrates).

4. Arguments Regarding Discretionary Denial

  • Petitioner argued the Board should not exercise its discretion to deny institution under §325(d) because the Examiner never raised any prior art rejections during the prosecution of the ’708 patent. Therefore, the arguments and art presented in the petition are not cumulative of those previously considered by the USPTO.
  • Regarding denial under §314(a) based on co-pending district court litigation, Petitioner argued that the litigation was in its early stages. Petitioner contended it had not gained an unfair tactical advantage and that denying institution would not simplify issues for the district court or conserve resources, making denial under the Fintiv factors inappropriate.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-4, 17, 19, and 21-23 of Patent 7,326,708 as unpatentable.