PTAB

IPR2020-00040

Mylan Pharmaceuticals Inc v. Merck Sharp & Dohme Corp

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1. Case Identification

2. Patent Overview

  • Title: Phosphoric acid salt of a dipeptidyl peptidase-IV inhibitor
  • Brief Description: The ’708 patent is directed to the dihydrogenphosphate salt of sitagliptin, specifically claiming the compound, its stereoisomers, a crystalline monohydrate form, and methods of use. Sitagliptin is a dipeptidyl peptidase-IV (DP-IV) inhibitor used for the treatment of type 2 diabetes.

3. Grounds for Unpatentability

Ground 1: Anticipation over WO '498 - Claims 1-3, 17, 19, and 21-23 are anticipated by WO '498.

  • Prior Art Relied Upon: Edmonson (International Publication No. WO 03/004498) ("WO '498").
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that WO '498 anticipates all limitations of the challenged claims. The ’708 patent specification itself admits that WO '498 discloses the base compound sitagliptin and its "pharmaceutically acceptable salts." Petitioner contended that WO '498 further discloses two closed lists: a primary list of 33 compounds that includes (R)-sitagliptin, and a secondary list of eight "particularly preferred" salts that explicitly names "phosphoric" acid. Petitioner asserted that the combination of these two lists discloses (R)-sitagliptin phosphate, anticipating claims 1 and 2. For claim 3, Petitioner argued that WO '498's teaching that "all of the possible optical isomers...are included within the ambit of this invention" anticipates the (S)-configuration. For dependent claims 17 (composition), 19 (method of treatment), and 21-23 (process), Petitioner mapped each element to corresponding disclosures in WO '498 regarding pharmaceutical compositions, therapeutic utility for diabetes, and analogous salt-formation processes.

Ground 2: Obviousness of the Phosphate Salt over WO '498 and Bastin - Claims 1-3, 17, 19, and 21-23 are obvious over WO '498 in view of Bastin.

  • Prior Art Relied Upon: WO '498 and Bastin (a 2000 journal article on salt selection).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that WO '498 discloses the base compound (R)-sitagliptin and exemplifies its hydrochloride salt. The primary difference between the prior art and the claims is the specific use of a phosphate anion instead of a chloride anion.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA), starting with the sitagliptin disclosed in WO '498, would be motivated to optimize its salt form for pharmaceutical use. A POSA would consult a general reference on salt selection, such as Bastin. Bastin teaches that for "weakly basic drug substances" (like sitagliptin, which has an amine group), salts of inorganic acids like hydrochloride or phosphate are standard options to consider. Because both WO '498 (listing "phosphoric" as preferred) and Bastin (listing "phosphate" as a common choice) identify the phosphate salt as a suitable candidate, a POSA would be motivated to substitute the exemplified hydrochloride salt with the phosphate salt.
    • Expectation of Success: The combined teachings provided a finite and identified set of predictable solutions for salt formation. Since both references point to phosphate as a conventional and preferred choice for a basic compound like sitagliptin, a POSA would have had a reasonable expectation of success in forming a stable and effective sitagliptin phosphate salt through routine experimentation.

Ground 3: Obviousness of the Crystalline Monohydrate over WO '498 and Brittain - Claim 4 is obvious over WO '498 and Brittain.

  • Prior Art Relied Upon: WO '498 and Brittain (a 1999 publication on polymorphism).

  • Core Argument for this Ground:

    • Prior Art Mapping: Petitioner's argument presupposed that (R)-sitagliptin phosphate (the salt of claim 2) was rendered anticipated or obvious by other grounds. Claim 4 further limits this salt to being a "crystalline monohydrate."
    • Motivation to Combine: A POSA would be motivated to investigate the solid-state forms of (R)-sitagliptin phosphate. WO '498 explicitly discloses that its compounds "may also be in the form of hydrates." To understand which hydrate form is likely, a POSA would turn to the general knowledge in the field, as articulated in Brittain. Brittain teaches that monohydrates are the "most frequently encountered" form of crystalline hydrates for pharmaceutical actives, representing an "expected trend."
    • Expectation of Success: Given WO '498's suggestion that hydrates may form and Brittain's teaching that monohydrates are the most common and expected form, a POSA would have had a reasonable expectation of success in preparing and identifying the crystalline monohydrate of (R)-sitagliptin phosphate.

  • Additional Grounds: Petitioner asserted additional grounds including anticipation of claims 1-3, 17, 19, and 21-23 over Patent 6,699,871 (which shares a specification with WO '498), and obviousness of certain claims over WO '498 alone or in further combination with Bastin and Brittain.

4. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Board should not exercise its discretion to deny institution under 35 U.S.C. §325(d) or §314(a).
  • Regarding §325(d), Petitioner asserted that its arguments were not cumulative because the Examiner never raised any prior art rejections during the prosecution of the ’708 patent.
  • Regarding §314(a) and related district court litigation, Petitioner argued that the corresponding litigation was in its "infant stages" and that Petitioner had not gained any tactical advantage, making denial inappropriate.

5. Relief Requested

  • Petitioner requests institution of an inter partes review (IPR) and cancellation of claims 1-4, 17, 19, and 21-23 of the ’708 patent as unpatentable.