Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.

FOR PETITIONER: Jitendra Malik Alissa Pacchioli Heike Radeke Christopher West Lance Soderstrom KATTEN MUCHIN ROSEMAN LLP Russell W. Faegenburg Tedd W.Van Buskirk Michael H. Teschner LERNER, DAVID, LITTENBERG, KRUMHOLZ & MENTLIK, LLP Jovial Wong WINSTON & STRAWN LLP

FOR PATENT OWNER: Stanley E. Fisher Jessamyn S. Berniker Shaun P. Mahaffy Anthony H. Sheh WILLIAMS & CONNOLLY LLP

Before SHERIDAN K. SNEDDEN, ROBERT A. POLLOCK, and TIMOTHY G. MAJORS, Administrative Patent Judges.

JUDGMENT FINAL WRITTEN DECISION DETERMINING NO CHALLENGED CLAIMS UNPATENTABLE 35 U.S.C.§ 318(A) DENYING PATENT OWNER'S MOTION TO EXCLUDE 37 C.F.R. § 42.64

MAJORS, ADMINISTRATIVE PATENT JUDGE

I. INTRODUCTION

Mylan Pharmaceuticals Inc. ("Petitioner" or "Mylan"), ^[2] on October 30, 2019, filed a Petition to institute inter partes review of claims 1-4, 17, 19, and 21-23 of U.S. Patent No. 7, 326, 708 B2 (Ex. 1001, "the '708 patent"). Paper 1 ("Pet." or "Petition"). On May 12, 2020, based on the preliminary record, we instituted inter partes review of the challenged claims on all asserted grounds. Paper 21 ("Inst. Dec.").

After institution, Patent Owner Merck Sharp & Dohme Corp. ("Patent Owner" or "Merck") filed a Response. Paper 41 ("POResp."). Petitioner filed a Reply. Paper 65 ("Reply"). Patent Owner filed a Sur-reply. Paper 74 ("Sur-reply"). Also before us is Patent Owner's Motion to Exclude (see Papers 81, 85). We held an oral hearing on February 11, 2021, and the transcript is on file. Paper 90 ("Tr.").

As a brief overview, the claims here relate to a compound called "sitagliptin" and, specifically, to particular dihydrogenphosphate ("DHP") salt forms of it that have a 1-to-l ratio, or stoichiometry, between the relevant phosphate anion and the corresponding sitagliptin cation. Pet. 1-2; POResp. 1 (discussing "1:1 sitagliptin DHP"); Ex. 1001, 244-65, 15:64-16:15 (claim 1). Sitagliptin is among a class of compounds known as dipeptidyl peptidase-IV inhibitors, which can inhibit an enzyme implicated in the etiology of non-insulin dependent diabetes mellitus (i.e., Type 2 diabetes). Id. at 1:3-36. Indeed, Merck developed and sells its drug product, Januvia, which is indicated for treatment of Type 2 diabetes and includes a 1:1 sitagliptin DHP salt. PO Resp. 1, 25-26; Ex. 2003 ¶ 2.^[3]

The dispute in this case focuses, in large part, on whether an earlier-filed international patent application, which Merck also owns, expressly or inherently discloses the 1:1 sitagliptin DHP salt claimed in the '708 patent.^[4]At institution, and despite our determination that this prior art included no explicit disclosure of a phosphate salt of sitagliptin having the 1:1 stoichiometry, we nevertheless instituted trial based, inter alia, on testimony from Petitioner's expert that sitagliptin can only be mono-protonated and reacting sitagliptin with phosphoric acid forms the 1:1 DHP salt "every time" and is, thus, inherent. Inst. Dec. 52-53 (noting preliminary record "suggest[s] the 1:1 salt is the necessary byproduct of contacting phosphoric acid and sitagliptin"). Because it is undisputed that the prior art does not expressly disclose the specific 1:1 DHP salt of sitagliptin, ^[5] and the evidence through trial now shows that sitagliptin can form phosphate salts in non-1:1 ratios without necessarily forming the 1:1 salt (i.e., no inherency), Merck argues that Petitioner's anticipation challenge fails. PO Resp. 6-19.

If anticipation fails, Petitioner is left with obviousness. But, in Merck's telling, the obviousness challenge fares no better because Merck's inventors reduced to practice the subject matter of almost all the challenged claims before the key prior art published, thus disqualifying that art as a § 102(a) reference; and, even if that art still qualifies under § 102(e), Merck's common ownership of the art eliminates it from the obviousness analysis under § 103(c)(1).^[6] PO Resp. 22-28. For the two dependent claims for which Merck does not argue an earlier reduction to practice, Merck contends those claims are not obvious because, among other things, that claimed subject matter was highly unpredictable and Petitioner failed to show a reason why it would have been made by an ordinarily skilled person with a reasonable expectation of success. Id. at 38-59.

We address in detail the parties' arguments on anticipation and obviousness in the sections below. On this trial record, however, we find Petitioner has failed to show by a preponderance of the evidence that claims 1-4, 17, 19, and 21-21 are unpatentable. Petitioner has, thus, not met its burden and proved unpatentability of the challenged claims. 35 U.S.C. § 316(e). Our reasoning is detailed in Section II below.

We also deny Patent Owner's Motion to Exclude. Infra Section III.

A. Related Patents and Proceedings

"[T]here are no related United States patents or pending applications" and "this is the first 1PR directed to the '708 patent." Pet. 7, 67.

Petitioner identifies several related cases before the courts including, without limitation: Merck Sharp & Dohme Corp. v. Mylan Pharm. Inc. et al., 1:19:-cv-00101 (N.D. W.Va.); Merck Sharp & Dohme Corp. v. Mylan Pharm. Inc. et al, 1:19-cv-01489 (D. Del); and Merck Sharp & Dohme Corp. v. Sandoz, Inc., 1:19-cv-00312 (D. Del). Pet. 6-7 (listing cases). Patent Owner states that it "filed Hatch-Waxman suits alleging infringement of the '708 patent, among others, against fourteen generic drug companies including Mylan, Teva, Apotex, Par, Sun, and Sandoz." Paper 10, 10. The litigation against the generic drug companies "has been consolidated for pretrial proceedings in a multidistrict litigation ('MDL')" before the district court in Delaware. Id. (identifying In re Sitagliptin Phosphate (708 & '921) Patent Litig, C. A. No. 19-md-2902-RGA (D. Del.)).

There are also related matters filed with the Board. After institution, other petitioners filed substantially identical petitions challenging claims of the '708 patent and requested joinder with Mylan in this proceeding. See IPR2020-01045 ("Teva" matter); IPR2020-01060 ("Dr. Reddy's" matter); IPR2020-01072 ("Sun" matter). We instituted trial in those other matters and joined the petitioners as parties here. IPR2020-00040, Papers 44-46. The Dr. Reddy's and Sun parties remain joined. The Teva parties (Teva Pharmaceuticals USA, Inc. and Watson Laboratories, Inc.) have settled with Merck and IPR2020-01045 is terminated. The Teva parties are no longer joined. IPR2020-00040, Paper 73, 2-3.

B. Asserted Grounds of Unpatentability

Petitioner asserts six grounds of unpatentability (Pet. 12) as set forth in the table below:

Claim(s) Challenged	35 U.S.C. §	Basis
1-3, 17, 19, 21-23	102(a), 102(e)(2)[7]	WO '498[8]
1-3, 17, 19, 21-23	102(e)(2)	'871 patent [9]
3, 17, 19, 21-23	103	WO '498
1-3, 17, 19, 21-23	103	WO '498, Bastin [10]
4	103	WO '498, Bastin, Brittain [11]
4	103	WO '498, Brittain

Petitioner relies on the Declaration of Mukund Chorghade, Ph.D. (Ex. 1002) and Dr. Chorghade's Reply Declaration (Ex. 1035), among other evidence.

Patent Owner relies on the Declaration of Allan S. Myerson, Ph.D. (Ex. 2101), the Declaration of Adam J. Matzger, Ph.D. (Ex. 2103), and testimony from several current or former Merck employees (including many of the '708 patent's eight named inventors), among other evidence. See, e.g., Exs. 2002 (VydraDecl), 2003 (WenslowDecl), 2004 (Ferlita Decl), 2005 (Diddle Decl), 2109 (Herman Decl), 2124 (Cypes Decl), 2127 (Hansen Decl), and 2140 (Shultz Decl).

C. The 708 Patent

The '708 patent is titled "PHOSPHORIC ACID SALT OF A DIPEPTIDYL PEPTIDASE-IV INHIBITOR." Ex. 1001, code (54). The '708 patent claims priority to non-provisional and provisional patent applications filed, respectively, on June 23, 2004, and June 24, 2003. Id. at codes (21), (22), (60). The patent issued February 5, 2008. Id. at code (45).

According to the '708 patent, "[t]he present invention relates to a particular salt of a dipeptidyl peptidase-IV inhibitor," and specifically, the dihydrogenphosphate ("DHP") salt of 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. Id. at 1:13-17. The chemical, 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, is also known as "sitagliptin." See Ex. 2003 ¶ 2; Pet. 1 n. 1.^[12] The structural formula for the DHP salt of sitagliptin is shown below as formula (I):

(Image Omitted)

Ex. 1001, 244-63. This formula reflects a salt with one phosphate anion associated with one sitagliptin amine cation (with a stereogenic carbon at *). Id. at 346-52 ("[T]he dihydrogenphosphate salt of the present invention is comprised of one molar equivalent of mono-protonated [sitagliptin] . . . and one molar equivalent of the dihydrogenphosphate (biphosphate) anion.").

The '708 patent states that this salt is "useful for the treatment and prevention of diseases and conditions for which an inhibitor of dipeptidyl peptidase-IV is indicated, in particular Type 2 diabetes." Id. at 1:19-22.

In a section related to background of the invention, the '708 patent identifies WO 03/004498 (i.e., WO '498), which is "assigned to Merck & Co." Id. at 149-50. The '708 patent states that WO '498 "describes a class of beta-amino tetrahydrotriazo1o[4, 3-a]pyrazines, which are potent inhibitors of DP-1V and therefore useful for the treatment of Type 2 diabetes." Id. at 1:50-52. According to the '708 patent, WO '498...