IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`IN RE: SITAGLIPTIN PATENT LITIGATION
`
`MDL No. 19-2902-RGA
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`Plaintiff,
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`v.
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`Defendants.
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`Plaintiff,
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`MERCK SHARP & DOHME CORP.,
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`ALVOGEN PINE BROOK LLC F/K/A
`ALVOGEN PINE BROOK, INC., ALVOGEN
`MALTA OPERATIONS LTD.,
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`MERCK SHARP & DOHME CORP.,
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`ANCHEN PHARMACEUTICALS, INC.
`and PAR PHARMACEUTICAL, INC.,
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`MERCK SHARP & DOHME CORP.,
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`SANDOZ, INC.,
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`v.
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`v.
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`Defendants.
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`Plaintiff,
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`Defendant.
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`C.A. No. 19-310-RGA
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`C.A. No. 19-311-RGA
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`C.A. No. 19-312-RGA
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`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 1
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`

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`Plaintiff,
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`
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`v.
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`Defendants.
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`Plaintiff,
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`MERCK SHARP & DOHME CORP.,
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`APOTEX INC., and APOTEX CORP.,
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`MERCK SHARP & DOHME CORP.,
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`ZYDUS PHARMACEUTICALS (USA) INC.
`and CADILA HEALTHCARE LTD.,
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`MERCK SHARP & DOHME CORP.,
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`MACLEODS PHARMACEUTICALS
`LIMITED, and MACLEODS PHARMA USA,
`INC.,
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`v.
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`v.
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`Defendants.
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`Plaintiff,
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`Defendants.
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`C.A. No. 19-313-RGA
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`C.A. No. 19-314-RGA
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`C.A. No. 19-316-RGA
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`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 2
`
`

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`Plaintiff,
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`
`
`v.
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`Defendants.
`
`Plaintiff,
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`MERCK SHARP & DOHME CORP.,
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`WATSON LABORATORIES, INC., and TEVA
`PHARMACEUTICALS USA, INC.,
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`MERCK SHARP & DOHME CORP.,
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`TEVA PHARMACEUTICALS USA, INC.,
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`MERCK SHARP & DOHME CORP.,
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`SUN PHARMACEUTICAL
`INDUSTRIES LTD.,
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`v.
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`v.
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`Defendant.
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`Plaintiff,
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`Defendants.
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`C.A. No. 19-317-RGA
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`C.A. No. 19-318-RGA
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`C.A. No. 19-319-RGA
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`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 3
`
`

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`Plaintiff,
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`v.
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`Defendants.
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`Plaintiff,
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`MERCK SHARP & DOHME CORP.,
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`TORRENT PHARMACEUTICALS LIMITED,
`and TORRENT PHARMA INC.,
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`MERCK SHARP & DOHME CORP.,
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`WOCKHARDT BIO AG, and WOCKHARDT
`USA LLC,
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`MERCK SHARP & DOHME CORP.,
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`LUPIN LIMITED, and LUPIN
`PHARMACEUTICALS, INC.,
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`v.
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`Plaintiff,
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`Defendants.
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`C.A. No. 19-320-RGA
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`C.A. No. 19-321-RGA
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`C.A. No. 19-347-RGA
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`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 4
`
`

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`MERCK SHARP & DOHME CORP.,
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`TORRENT PHARMACEUTICALS LIMITED,
`and TORRENT PHARMA INC.,
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`MERCK SHARP & DOHME CORP.,
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`MYLAN PHARMACEUTICALS INC.,
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`v.
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`Plaintiff,
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`v.
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`Defendants.
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`Plaintiff,
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`Defendants.
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`C.A. No. 19-872-RGA
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`C.A. No. 19-1489-RGA
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`DEFENDANTS’ INITIAL INVALIDITY CONTENTIONS
`
`Under the Court’s Scheduling Order (D.I. 18) and ¶ 4(d) of the District of Delaware’s
`
`Default Standard for Discovery, Including Discovery of Electronically Stored Information
`
`(“ESI”), Defendants Alvogen Pine Brook LLC f/k/a Alvogen Pine Brook, Inc. and Alvogen
`
`Malta Operations Ltd. (collectively “Alvogen”), Anchen Pharmaceuticals, Inc. and Par
`
`Pharmaceutical, Inc. (collectively, “Anchen”), Sandoz, Inc. (“Sandoz”), Apotex Inc. and Apotex
`
`Corp. (collectively, “Apotex”), Zydus Pharmaceuticals (USA) Inc. and Cadila Healthcare Ltd.
`
`(collectively, “Zydus”), Macleods Pharmaceuticals Limited and Macleods Pharma USA, Inc.
`
`(collectively, “Macleods”), Teva Pharmaceuticals USA, Inc. (“Teva”), Watson Laboratories, Inc.
`
`and Teva Pharmaceuticals USA, Inc. (collectively, “Watson”), Sun Pharmaceutical Industries
`
`Ltd. (“Sun”), Torrent Pharmaceuticals Limited and Torrent Pharma Inc. (collectively, “Torrent”),
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 5
`
`

`

`Wockhardt Bio AG and Wockhardt USA LLC (collectively, “Wockhardt”), Lupin Limited and
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`Lupin Pharmaceuticals, Inc. (collectively, “Lupin”), and Mylan Pharmaceuticals Inc. (“Mylan”)
`
`(all collectively, “Defendants”) hereby provide their Initial Invalidity Contentions with respect to
`
`the asserted claims of U.S. Patent No. 7,326,708 (“the ’708 patent”) and U.S. Patent No.
`
`8,414,921 (“the ’921 patent”) (collectively, “the Patents-in-Suit”) to Plaintiff Merck Sharp &
`
`Dohme Corp. (“Merck”).
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 6
`
`

`

`TABLE OF CONTENTS
`
`
`
`
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`General Statements ............................................................................................................. 1
`
`Identification of Prior Art ................................................................................................... 5
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`
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`Patent/Publication References ................................................................................ 6
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`Prior Art Patents and Published Patent Applications .................................. 7
`
`Prior Art Publications ................................................................................. 8
`
`Earliest Effective Filing Date of the Patents-In-Suit ............................................ 11
`
`
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`The ’708 Patent ......................................................................................... 11
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`The ’921 Patent ......................................................................................... 12
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`Scope and Content of the Prior Art ....................................................................... 12
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`WO ’498.................................................................................................... 13
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`The ’871 patent ......................................................................................... 17
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`The ’563 publication ................................................................................. 17
`
`Stahl .......................................................................................................... 18
`
`Bastin ........................................................................................................ 20
`
`Bighley ...................................................................................................... 23
`
`Tong .......................................................................................................... 24
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`Shankar ..................................................................................................... 24
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`Berge ......................................................................................................... 25
`
`Gould......................................................................................................... 26
`
`Brittain 1999 ............................................................................................. 28
`
`Ohannesian ................................................................................................ 29
`
` Morris ........................................................................................................ 30
`
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`Brittain 2002 ............................................................................................. 32
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`Byrn........................................................................................................... 33
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 7
`
`

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`Physician’s Desk Reference 55th Edition .................................................. 34
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`Herman 2004 ............................................................................................. 34
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`Herman 2005 ............................................................................................. 35
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`Brazg ......................................................................................................... 35
`
`Kim 2004 .................................................................................................. 36
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`The ’509 publication ................................................................................. 37
`
`The ’578 publication ................................................................................. 37
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`The ’922 publication ................................................................................. 38
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`The ’844 publication ................................................................................. 40
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` WO ’355.................................................................................................... 40
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`The ’862 patent ......................................................................................... 41
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`The ’451 patent ......................................................................................... 42
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`The ’146 patent ......................................................................................... 43
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`Remington ................................................................................................. 44
`
`2003 Handbook ......................................................................................... 44
`
`The ’275 patent ......................................................................................... 45
`
`The ’859 patent ......................................................................................... 47
`
` WO ’808.................................................................................................... 48
`
` WO ’501.................................................................................................... 48
`
`
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`The ’797 publication ................................................................................. 49
`
`Solomons................................................................................................... 51
`
`Aulton ....................................................................................................... 51
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`
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`Basis for Invalidity ............................................................................................................ 51
`
`
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`The ’708 Patent ..................................................................................................... 51
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`
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`Claims 1-23 Are Anticipated by the ’871 Patent ...................................... 51
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 8
`
`

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`Claims 1-23 Are Anticipated by WO ’498 ............................................... 64
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`Claims 1-23 Are Anticipated by the ’563 Publication .............................. 75
`
`Claims 1-20 and 24 Are Invalid for Obviousness-Type Double
`Patenting ................................................................................................... 86
`
`Claims 1-24 Are Obvious Over WO ’498 or the ’563 Publication
`in View of the General Knowledge in the Art, Including Bastin,
`Berge, Stahl, Gould, Ohannesian, Bighley, Tong, Shankar,
`Solomons, the PDR, Byrn, Brittain 1999, and/or Brittain 2002 ............... 98
`
`No Objective Indicia of Non-Obviousness ............................................. 111
`
`Claims 1-23 Are Invalid Under 35 U.S.C. § 102(f) ................................ 114
`
`Claims 1-3, 17, 19, and 21-23 Are Invalid for Lack of Written
`Description and Enablement ................................................................... 115
`
`Claims 4-16, 18, 20, and 24 Are Invalid for Failure to Comply with
`35 U.S.C. § 112, paragraph 4 and/or Indefinite ...................................... 117
`
`
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`The ’921 Patent ................................................................................................... 119
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`The Asserted Claims of the ’921 Patent are Obvious Over WO
`’498, the Prior Art Regarding Formulations Containing Metformin,
`and the General Knowledge in the Art ................................................... 119
`
`The Asserted Claims of the ’921 Patent are Obvious Over Herman
`2005 and/or Brazg in View of the ’509 Publication and/or the ’578
`Publication, the Prior Art Regarding Formulations Containing
`Metformin, and the General Knowledge in the Art ................................ 143
`
`The Asserted Claims of the ’921 Patent are Obvious over the ’509
`Publication and/or the ’578 Publication in View of Herman 2004,
`the Prior Art Regarding Formulations Containing Metformin, and
`the General Knowledge in the Art .......................................................... 165
`
`No Objective Indicia on Non-Obviousness ............................................ 188
`
`Claims 1, 3-22, 24, and 26 Are Invalid Under §112, Second
`Paragraph ................................................................................................ 190
`
`APPENDIX A ............................................................................................................................. 198
`
`APPENDIX B ............................................................................................................................. 224
`
`APPENDIX C ............................................................................................................................. 242
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 9
`
`

`

`APPENDIX D ............................................................................................................................. 273
`
`APPENDIX E ............................................................................................................................. 304
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 10
`
`

`

`inherency; suggestion, teaching, or motivation to combine; reasonable expectation of success;
`
`common knowledge, the prior art as a whole, or the nature of problems; and/or responding to
`
`Plaintiff’s assertion, if any, of differences between the claimed inventions and prior art and/or
`
`objective indicia of non-obviousness. Defendants’ experts may also rely on additional
`
`references, not identified below, when providing background information or a tutorial to the
`
`Court at trial or any other hearing; or in responding to any responsive contentions by Plaintiff
`
`regarding nonenablement of prior art or objective indicia of non-obviousness, or for any other
`
`purpose.
`
`
`
`Prior Art Patents and Published Patent Applications
`
`The following prior art patent references, alone or in combination, including with
`
`references and citations listed in Appendices A and E, anticipate and/or render obvious one or
`
`more of the asserted claims of the Patents-in-Suit.
`
`
`
`Patent No. /
`Application No.
`
`Identifier
`
`Named
`Inventor(s)
`
`Date Issued/
`Published
`
`Produced as
`
`1.
`
`PCT Publication
`No. WO 03/004498
`
`WO ’498
`
`Edmondson et al.
`
`Jan. 16, 2003
`
`2.
`
`U.S. Patent
`No. 6,699,871
`
`3.
`
`4.
`
`5.
`
`6.
`
`U.S. Patent Appl.
`Pub. No.
`2003/0100563
`U.S. Patent Appl.
`Pub. No.
`2003/0153509
`U.S. Patent Appl.
`Pub. No.
`2003/0166578
`U.S. Patent Appl.
`Pub. No.
`2005/0051922
`
`’871 patent
`
`Edmondson et al. Mar. 2, 2004
`
`’563 publication Edmondson et al. May 29, 2003
`
`’509 publication Bachovchin et al.
`
`’578 publication Arch et al.
`
`’922 publication Nangia et al.
`
`August 14,
`2003
`
`September 4,
`2003
`
`March 10,
`2005
`
`DEFS-
`JANUMET_00000785
`-853
`DEFS-
`JANUMET_00000743
`-765
`DEFS-
`JANUMET_00000601
`-626
`DEFS-
`JANUMET_00000627
`-659
`DEFS-
`JANUMET_00000660
`-666
`DEFS-
`JANUMET_00000680
`-689
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 11
`
`

`

`8.
`
`PCT Publication
`No. WO 03/045355
`
`WO ’355
`
`9.
`
`U.S. Patent No.
`6,099,862
`
`’862 patent
`
`10.
`
`U.S. Patent No.
`6,117,451
`
`’451 patent
`
`11.
`
`U.S. Patent No.
`6,303,146
`
`12. PCT Publication
`No. WO
`2001/97808
`13. U U.S. Patent No.
`6,284,275
`
`’146 patent
`
`WO ’808
`
`’275 patent
`
`14. U.S. Patent No.
`6,099,859
`
`’859 patent
`
`WO ’501
`
`15. PCT Publication
`No. WO
`1999/38501
`16. U.S. Patent Appl.
`Pub. No.
`2004/0014797
`
`Tosetti et al.
`
`June 5, 2003
`
`Chen et al.
`
`Kumar
`
`August 8,
`2000
`
`September 12,
`2000
`
`Bonhomme et al.
`
`October 16,
`2001
`
`Arch et al.
`
`Chen et al.
`
`Cheng et al.
`
`DEFS-
`JANUMET_00000673
`-679
`DEFS-
`JANUMET_00000854
`-883
`DEFS-
`JANUMET_00000705
`-713
`DEFS-
`JANUMET_00000714
`-722
`DEFS-
`JANUMET_00000733
`-742
`Dec. 27, 2001 DEFS-
`JANUMET_00000766
`-784
`Sept. 4, 2001 DEFS-
`JANUMET_00000723
`-732
`Aug. 8, 2000 DEFS-
`JANUMET_00000690
`-704
`Bachovchin et al. May 8, 1999 DEFS-
`JANUMET_00000884
`-955
`Jan. 22, 2004 DEFS-
`JANUMET_00000667
`-672
`
`
`
`Patent No. /
`Application No.
`
`7.
`
`U.S. Patent Appl.
`Pub. No.
`2004/0213844
`
`Identifier
`
`Named
`Inventor(s)
`
`Date Issued/
`Published
`
`Produced as
`
`’844 publication Massironi
`
`October 28,
`2004
`
`’797 publication Moinet et al.
`
`
`
`Prior Art Publications
`
`The following prior art publications, alone or in combination, including with references
`
`and citations listed in Appendices A and E, render obvious one or more of the asserted claims of
`
`the Patents-in-Suit.
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 12
`
`

`

`Reference
`
`Identifier
`
`Date
`Published
`
`
`
`1.
`
`2.
`
`Handbook of Pharmaceutical Salts:
`Properties, Selection, and Use
`(P. Heinrich Stahl & Camille G.
`Wermuth eds., 2002)
`
`Bastin, R.J. et al., Salt Selection and
`Optimisation Procedures for
`Pharmaceutical New Chemical Entities,
`4 Organic Process Research & Dev.,
`427-35 (2000)
`
`Stahl
`
`2002
`
`Bastin
`
`2000
`
`Bighley
`
`1996
`
`Tong
`
`1998
`
`Shankar
`
`1994
`
`3.
`
`Bighley, L.D. et al., Encyclopedia of
`Pharmaceutical Technology, Vol. 13
`453-99 (James Swarbrick & James C.
`Boylan eds., 1996)
`
`4.
`
`Tong, Wei-Qin (Tony) et al., In Situ Salt
`Screening—A Useful Technique for
`Discovery Support and Preformulation
`Studies, 3(2) Pharm. Dev. and Tech.
`215-23 (1998)
`
`5.
`
`Shankar, R.M., et al., Selection of
`Appropriate Salt Form(s) for New Drug
`Candidates, 11(10) Pharm. Res., S-236
`(1994)
`
`6.
`
`Berge, S.M., et al., Pharmaceutical
`Salts, 66(1) J. Pharm. Scis. 1-19 (1977)
`
`Berge
`
`1977
`
`7.
`
`Gould, P.L., Salt Selection for Basic
`Drugs, 33 Int’l J. Pharmaceutics 201-
`217 (1986)
`
`Gould
`
`1986
`
`8.
`
`Polymorphism in Pharmaceutical Solids
`(Harry G. Brittain ed., 1999)
`
`Brittain 1999
`
`1999
`
`9.
`
`Handbook of Pharmaceutical Analysis
`(Lena Ohannesian & Anthony J. Streeter
`eds., 2002)
`
`10.
`
`Morris, K.R., et al., An Integrated
`Approach to the Selection of Optimal
`Salt Form For a New Drug Candidate,
`105 Int’l J. Pharmaceutics 209-17
`(1994)
`
`Ohannesian
`
`2001
`
`Morris
`
`1994
`
`Produced as
`
`DEFS-
`JANUMET_00000363-
`591
`
`DEFS-
`JANUMET_00000044-
`52
`
`DEFS-
`JANUMET_00000072-
`120
`
`DEFS-
`JANUMET_00000592-
`600
`
`DEFS-
`JANUMET_00000318-
`320
`
`DEFS-
`JANUMET_00000053-
`71
`
`DEFS-
`JANUMET_00000252-
`270
`
`DEFS-
`JANUMET_00000121-
`227
`DEFS-
`JANUMET_00000295-
`301
`
`DEFS-
`JANUMET_00000286-
`294
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 13
`
`

`

`
`
`11.
`
`Reference
`
`Identifier
`
`Date
`Published
`
`Brittain, Harry, Encyclopedia of
`Pharmaceutical Technology 2239-2249
`(James Swarbrick & James C. Boylan
`eds., 2002)
`
`Brittain 2002
`
`2002
`
`12.
`
`Byrn, Stephen, Pharmaceutical Solids:
`A Strategic Approach to Regulatory
`Considerations, 12(7) Pharm. Research.
`945-54 (1995)
`
`Byrn
`
`1995
`
`13. Physicians’ Desk Reference (55th ed.)
`
`PDR
`
`2001
`
`14.
`
`Herman, Gary et al., The DP-IV
`Inhibitor MK-0431 Enhances Active
`GLP-1 and Reduces Glucose Following
`an OGTT in Type 2 Diabetics, 64th
`Annual Meeting Scientific Sessions of
`the American Diabetes Association
`(June 2004)
`
`15.
`
`Herman, Gary et al., Co-Administration
`of MK-0431 and Metformin in Patients
`with Type 2 Diabetes Does Not Alter the
`Pharmacokinetics of MK-0431 or
`Metformin, 65th Annual Meeting
`Scientific Sessions of the American
`Diabetes Association (June 2005)
`
`16.
`
`Ronald Brazg et al., Effect of Adding
`MK-0431 to On-Going Metformin
`Therapy in Type 2 Diabetic Patients
`Who Have Inadequate Glycemic Control
`on Metformin, 65th Annual Meeting
`Scientific Sessions of the American
`Diabetes Association (June 2005)
`
`Herman 2004
`
`2004
`
`Herman 2005
`
`2005
`
`Brazg
`
`2005
`
`Produced as
`
`DEFS-
`JANUMET_00000228-
`241
`
`DEFS-
`JANUMET_00000242-
`251
`
`DEFS-
`JANUMET_00000001-
`13
`DEFS-
`JANUMET_00000271-
`272
`
`DEFS-
`JANUMET_00000273-
`274
`
`DEFS-
`JANUMET_00000961
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 14
`
`

`

`
`
`Reference
`
`Identifier
`
`Date
`Published
`
`Produced as
`
`DEFS-
`JANUMET_00000275-
`285
`
`DEFS-
`JANUMET_00000302-
`317
`
`DEFS-
`JANUMET_00000014-
`16
`
`DEFS-
`JANUMET_00000321-
`362
`
`DEFS-
`JANUMET_00000956-
`960
`
`17.
`
`Kim, Dooseop et al., (2R)-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: A
`Potent, Orally Active Dipeptidyl
`Peptidase IV Inhibitor for the Treatment
`of Type 2 Diabetes, 48 J. Med. Chem.
`141-51 (December 13, 2004)
`
`18.
`
`Remington: The Science and Practice of
`Pharmacy (Gennaro ed., 20th ed. 2000)
`858-71
`
`Kim 2004
`
`2004
`
`Remington
`
`2000
`
`19.
`
`The Handbook of Pharmaceutical
`Excipients (Rowe ed., 4th ed. 2000)
`568-69
`
`2003
`Handbook
`
`2003
`
`20.
`
`Organic Chemistry, Ch. 3: An
`Introduction to Organic Reactions: Acid
`and Bases, (Solomons ed., 6th ed. 1996)
`
`Solomons
`
`1996
`
`21.
`
`Pharmaceutics: The Science of Dosage
`Form Design, (M.E. Aulton ed., 2nd ed.
`2002)
`
`Aulton
`
`2002
`
`
`
`
`
`Earliest Effective Filing Date of the Patents-In-Suit
`
`Discovery is ongoing and Defendants have not yet had the opportunity to engage in full
`
`discovery regarding the conception and reduction to practice of each of the asserted claims of the
`
`Patents-in-Suit. Defendants therefore reserve the right to (i) challenge any date(s) of conception
`
`or reduction to practice asserted by Merck; and (ii) identify additional prior art.
`
`
`
`The ’708 Patent
`
`The ’708 patent issued on February 5, 2008, from U.S. Appl. No. 10/874,992, filed on
`
`June 23, 2004, which claims priority benefit to U.S. Provisional Appl. No. 60/482,161, filed on
`
`June 24, 2003. As such, the earliest possible effective filing date of the ’708 patent with respect
`
`to prior art under pre-AIA 35 U.S.C. § 102(b) is June 24, 2003. Defendants do not concede,
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 15
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`

`

`however, that the ’708 patent is entitled to an earliest effective filing date of June 24, 2003,
`
`rather it is not entitled to any earlier date.
`
`
`
`The ’921 Patent
`
`The ’921 patent issued on April 9, 2013, from U.S. Appl. No. 12/085,722, filed on May
`
`29, 2008, which is the United States National Stage Entry of International Patent Appl. No.
`
`PCT/US2006/047380, filed on December 12, 2006, which claims priority benefit to U.S.
`
`Provisional Appl. No. 60/750,954, filed on December 16, 2005. As such, the earliest possible
`
`effective filing date of the ’921 patent with respect to prior art under pre-AIA 35 U.S.C. § 102(b)
`
`is December 16, 2005. Defendants do not concede, however, that the ’921 patent is entitled to an
`
`earliest effective filing date of December 16, 2005, rather it is not entitled to any earlier date.
`
`
`
`Scope and Content of the Prior Art
`
`
`
`The scope and content of the prior art includes the patents and publications submitted by
`
`Plaintiff during the prosecution of the Patents-in-Suit and the documents produced in conjunction
`
`with service of these contentions identified at DEFS-JANUMET_00000001 - DEFS-
`
`JANUMET_00000961. See In re Rouffet, 149 F.3d 1350, 1357 (Fed. Cir. 1998) (“[The law]
`
`presumes that all prior art references in the field of the invention are available to this
`
`hypothetical skilled artisan.”); Custom Accessories, Inc. v. Jeffrey-Allan Indus., 807 F.2d 955,
`
`962 (Fed. Cir. 1986) (“The person of ordinary skill is a hypothetical person who is presumed to
`
`be aware of all the pertinent prior art.”); Abbott Labs. v. Andrx Pharm., Inc., 452 F.3d 1331,
`
`1336 (Fed. Cir. 2006) (stating that a person of ordinary skill possesses the “understandings and
`
`knowledge reflected in the prior art”); Randall Mfg. v. Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013)
`
`(“the knowledge of [a POSA] is part of the store of public knowledge that must be consulted
`
`when considering whether a claimed invention would have been obvious”).
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 16
`
`

`

`Exemplary claim charts identifying prior art references, describing the scope and content
`
`of the prior art and demonstrating that each and every element of each of the asserted claims of
`
`the Patents-in-Suit was known in the art, are provided in Appendices A and E, which is attached
`
`hereto. Defendants reserve their right to rely on additional prior art references to establish the
`
`scope and content of the prior art as discovery proceeds in this case. In addition, Defendants
`
`provide below preliminary discussions of disclosures of certain art identified in Appendices A
`
`and E. Such preliminary discussions are exemplary and are not intended to be limiting or to
`
`exhaustively identify each relevant disclosure of each reference.
`
` WO ’498
`
`WO ’498 was filed as International Patent Appl. No. PCT/US2002/021349 on July 5,
`
`2002 and names Scott D. Edmondson, Michael H. Fisher, Dooseop Kim, Malcolm Maccoss,
`
`Emma R. Parmee, Ann E. Weber, and Jinyou Xu as inventors. None of the individuals identified
`
`as inventors on the face of WO ’498 overlap with the individuals identified as inventors on the
`
`face of the ’708 patent. WO ’498 therefore is by another. WO ’498 designates the United States
`
`and was published in English on January 16, 2003 under Article 21(2) of the Patent Cooperation
`
`Treaty. WO ’498 further claims priority to the ’474 application, filed July 6, 2001. As
`
`demonstrated in the tables in Appendix C, the disclosures of the ’474 application provide
`
`sufficient support under pre-AIA 35 U.S.C. § 112, ¶ 1 for each of the published claims of
`
`WO ’498. As such, WO ’498 is prior art to the ’708 patent under pre-AIA 35 U.S.C. § 102(a) as
`
`of its January 16, 2003 publication date and under pre-AIA 35 U.S.C. § 102(e) as of the July 6,
`
`2001 filing date of the ’474 application. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1380 (Fed.
`
`Cir. 2017) (citing Dynamic Drinkware, 800 F.3d at 1378) (holding that a provisional application
`
`must provide support under § 112, ¶ 1 for the claims in a published patent application for the
`
`Merk Sharp & Dohme Corp. Exhibit 2008
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`IPR2020-00040
`Page 17
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`

`

`published patent application to be prior art as of the provisional application’s filing date).
`
`WO ’498 further qualifies as prior art to the ’921 patent under pre-AIA 35 U.S.C. § 102(b).
`
`WO ’498 discloses “compounds which are inhibitors of the dipeptidyl peptidase-IV
`
`enzyme (‘DP-IV inhibitors’).” See WO ’498, Abstract. WO ’498 teaches that an “embodiment
`
`of the present invention includes compounds of the formula Ia . . . and pharmaceutically
`
`acceptable salts and individual diastereomers thereof.” Formula Ia is reproduced below:
`
`Id. at 5:14-19.
`
`
`
`WO ’498 also discloses that “[a]nother embodiment of the present invention includes
`
`compounds of the formula Ib . . . and pharmaceutically acceptable salts and individual
`
`diastereomers thereof.” Formula Ib is reproduced below:
`
`Id. at 5:21-25.
`
`
`
`And WO ’498 discloses that “[a]nother embodiment of the present invention includes
`
`compounds of the formula Ic . . . and pharmaceutically acceptable salts and individual
`
`diastereomers thereof.” Formula Ic is reproduced below:
`
`Merk Sharp & Dohme Corp. Exhibit 2008
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`Page 18
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`

`

`Id. at 6:3-8.
`
`
`
`WO ’498 additionally teaches that “Formula Ia shows the preferred stereochemistry at the
`
`carbon atom that is attached to the amine group of the beta amino acid from which these
`
`compounds are prepared,” i.e., the (R)-stereoisomer, which is also shown in Formula Ib and
`
`Formula Ic. Id. at 9:4-6.
`
`WO ’498 also provides preferred substituents for Ar, X, R1, and R2. For instance,
`
`WO ’498 states that “[i]n the present invention it is more preferred that Ar is selected from the
`
`group consisting of: (1) phenyl[;] (2) 2-fluorophenyl[;] (3) 3,4-difluorophenyl[;] (4) 2,5-
`
`difluorophenyl[;] (5) 2,4,5-trifluorophenyl[;] (6) 2-fluoro-4-(trifluoromethyl)phenyl[;] and (7) 4-
`
`bromo-2,5-difluorophenyl.” Id. at 6:17-25. WO ’498 teaches that “X is selected from the group
`
`consisting of: (1) N, and (2) CR2.” Id. at 4:15-17. WO ’498 also discloses preferred
`
`substituents for R1, stating that “[i]n the present invention it is even more preferred that R1 is
`
`hydrogen or CF3.” Id. at 7:23-25. And WO ’498 states that for R2 “it is even more preferred that
`
`R2 is CF3 or CF2F3.” Id. at 8:15-16. As such, WO ’498 discloses, at most, 84 most preferred
`
`compounds of its invention, which includes sitagliptin.
`
`WO ’498 additionally teaches that “[w]hen the compound of the present invention is
`
`basic,” like sitagliptin, “salts may be prepared from pharmaceutically acceptable non-toxic acids,
`
`including inorganic and organic acids . . . . Particularly preferred are citric, hydrobromic,
`
`hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acids.” Id. at 10:8-15.
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 19
`
`

`

`Example 7 of WO ’498 discloses preparation of 7-[(3R)-3-amino-4-(2,4,5-
`
`trifluorophenyl)butanoyl]-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine
`
`hydrochloride, i.e., the hydrochloride salt of sitagliptin. The structure is reproduced below:
`
`
`
`Id. at 46:1-26. Example 7 further teaches obtaining the hydrochloride salt by combining
`
`sitagliptin with hydrogen chloride in methanol and stirring the mixture at ambient temperature
`
`for one hour. Id. at 46:20-24. WO ’498 also discloses obtaining hydrochloride salts of other
`
`molecules of its invention also by combining them with hydrogen chloride in methanol and
`
`stirring the mixture at ambient temperature. Id. at 38:17-21, 39:17-21, 40:17-21, 42:3-7, 43:22-
`
`26, 45:19-23.
`
`WO ’498 specifically claims pharmaceutically acceptable salts of sitagliptin in a Markush
`
`group of 32 other compounds. Id. at 54:17-60:5. And WO ’498 discloses that the salts of its
`
`invention can be formulated into pharmaceutical compositions with a pharmaceutically
`
`acceptable carrier. Id. at 12:10-12. WO ’498 further discloses that “[s]alts in the solid form may
`
`exist in more than one crystal structure, and may also be in the form of hydrates.” Id. at 9:32-34.
`
`WO ’498 also teaches that the salts of its invention, including sitagliptin, inhibit DP-IV with an
`
`IC50 of less than about 1 M and have utility in the treatment of type II diabetes. Id. at 13:5-9,
`
`21-30.
`
`Merk Sharp & Dohme Corp. Exhibit 2008
`Mylan Pharmaceuticals Inc. v. Merk Sharp & Dohme Corp.
`IPR2020-00040
`Page 20
`
`

`

`
`
`The ’871 patent
`
`The ’871 patent was filed as U.S. Patent Appl. No. 10/189,603 on July 5, 2002 and names
`
`Scott D. Edmondson, Michael H. Fisher, Dooseop Kim, Malcolm Maccoss, Emma R. Parmee,
`
`Ann E. Weber, and Jinyou Xu as inventors. None of the individuals identified as inventors on
`
`the face of the ’871 patent overlap with the individuals identified as inventors on the face of the
`
`’708 patent. The ’871 patent therefore is by another.
`
`The ’871 patent claims the benefit of priority to U.S. Appl. No. 60/303,474 (“the ’474
`
`application”), filed July 6, 2001. As demonstrated in the tables in Appendix B, the disclosures of
`
`the ’474 application provide sufficient support under pre-AIA 35 U.S.C. § 112, ¶ 1 for each of
`
`the issued claims of the ’871 p