Paper No. ______
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`Filed: January 15, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`
`ROSELLINI SCIENTIFIC, LLC
`
`PETITIONER
`
`V.
`
`GRÜNENTHAL GMBH
`
`PATENT OWNER
`
`___________________
`
`CASE NO.: IPR2016-00471
`PATENT NO. 7,994,364
`FILED: DECEMBER 10, 2009
`ISSUED: AUGUST 9, 2011
`INVENTORS: ANDREAS FISCHER, ET AL.
`
`TITLE: CRYSTALLINE FORMS OF (-)-(1R,2R)-3-(3-DIMETHYLAMINO-1-
`ETHYL-2-METHYLPROPYL)-PHENOL HYDROCHLORIDE
`___________________
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 7,994,364
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`Patent No. 7,994,364
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`TABLE OF CONTENTS
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`I.
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`Introduction ........................................................................................................ 1
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`II. Grounds for Standing (37 C.F.R. § 42.104(a)) .................................................. 1
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`III. Mandatory Notices (37 C.F.R. § 42.8) ............................................................... 1
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`A.
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`B.
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`C.
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`Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1)) .................................. 1
`
`Related Judicial and Administrative Matters (37 C.F.R. §
`42.8(b)(2)) ............................................................................................. 2
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`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)) and
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 2
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`IV. Payment of Fees (37 C.F.R. § 42.15(a) and § 42.103) ...................................... 2
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`V.
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`Identification of Challenge ................................................................................. 3
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`A. Overview of U.S. Patent No. 7,994,364 ................................................ 3
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`1.
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`2.
`
`3.
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`The ’364 Patent Specification ..................................................... 3
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`The ’364 Claims .......................................................................... 7
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`Prosecution History of the ’364 Patent and European
`Counterpart ................................................................................ 10
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`B.
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`C.
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`Claim Construction of Challenged Claims ......................................... 12
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`Statement of Precise Relief Requested for Each Claim
`Challenged ........................................................................................... 13
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`1.
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`2.
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`Claims for Which Review is Requested ................................... 13
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`Statutory Grounds of Challenge ............................................... 14
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`D. Overview of the State of the Art and Prior Art References ................ 14
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`1.
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`EP 475 (Ex. 1006, Ex. 1007, Ex. 1008) .................................... 14
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`Patent No. 7,994,364
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`2.
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`Bartholomaeus (Ex. 1009, 1010, 1011) .................................... 16
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`E.
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`Level of Ordinary Skill in the Art ....................................................... 17
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`VI. Detailed Explanation of the Challenge ............................................................ 17
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`A. Ground 1: EP 475 anticipates claims 1–4 and 24–27 of U.S.
`Patent No. 7,994,364 under 35 U.S.C. § 102(b). ................................ 17
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`1.
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`EP 475 anticipates independent claims 1 and 25. ..................... 17
`
`(a) EP 475 Example 25 discloses a procedure for
`making tapentadol HCl ................................................... 18
`
`2.
`
`EP 475’s Example 25 procedure for making
`tapentadol HCl inherently produces Form A,
`anticipating the ’364 Patent ...................................................... 22
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`(a) Methods and results from performing Example
`25 of EP 475 ................................................................... 22
`
`(b) An analysis of XRPD patterns demonstrates
`that following EP 475 procedures—including
`Example 25—produces both Forms A and B of
`tapentadol HCl ................................................................ 33
`
`(c) Melting Point .................................................................. 38
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`(d) Claim 25 .......................................................................... 40
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`3.
`
`EP 475 anticipates dependent claims 2–4. ................................ 41
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`(a) Claim 2 ............................................................................ 41
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`(b) Claim 3 ............................................................................ 42
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`(c) Claim 4 ............................................................................ 44
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`EP 475 anticipates dependent claims 24 and 26. ...................... 46
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`EP 475 anticipates independent claim 27. ................................ 48
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`4.
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`5.
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`Patent No. 7,994,364
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`B. Ground 2: Bartholomaeus anticipates claims 1–4 and 24–27
`of U.S. Patent No. 7,994,364 under 35 U.S.C. § 102(b). .................... 50
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`1.
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`2.
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`3.
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`4.
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`Bartholomaeus anticipates independent claims 1 and
`25. .............................................................................................. 50
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`Bartholomaeus anticipates dependent claims 2–4. ................... 55
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`Bartholomaeus anticipates dependent claims 24 and
`26. .............................................................................................. 57
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`Bartholomaeus anticipates independent claim 27. ................... 59
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`VII. Conclusion ........................................................................................................ 59
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`Cases 
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`Patent No. 7,994,364
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`TABLE OF AUTHORITIES
`
`Atlas Powder Co. v. IRECO Inc.,
`190 F.3d 1342 (Fed. Cir. 1999) ............................................................. passim
`
`Bonito Boats, Inc. v. Thunder Craft Boats, Inc.,
`489 U.S. 141 (1989)....................................................................................... 48
`
`Bristol-Myers Squibb Co. v. Mylan Pharms. Inc.,
`No. 09-651, 2013 U.S. Dist. LEXIS 188207 (D. Del. Sept. 30,
`2013) .............................................................................................................. 17
`
`Callaway Golf Co. v. Acushnet Co.,
`576 F.3d 1331 (Fed. Cir. 2009) ..................................................................... 51
`
`Ex Parte Reddy,
`Appeal 2009-001215, 2010 Pat. App. LEXIS 13975 (Pat. App.
`Mar. 31, 2010) ........................................................................................ 38, 39
`
`Greenliant Sys., Inc. v. Xicor LLC,
`692 F.3d 1261 (Fed. Cir. 2012) .............................................................. 48, 58
`
`In re Am. Acad. of Sci. Tech. Ctr.,
`367 F.3d 1359 (Fed. Cir. 2004) ..................................................................... 13
`
`In re Graves,
`69 F.3d 1147 (Fed. Cir. 1995) ....................................................................... 53
`
`In re LeGrice,
`301 F.2d 929 (CCPA 1962) ........................................................................... 54
`
`In re Thorpe,
`777 F.2d 695 (Fed. Cir. 1985) ................................................................ 48, 58
`
`Schering Corp. v. Geneva Pharms., Inc.,
`339 F.3d 1373 (Fed. Cir. 2003) .............................................................. 36, 54
`
`SmithKline Beecham Corp. v. Apotex Corp.,
`403 F.3d 1331 (Fed. Cir. 2005) .................................................. 33, 34, 36, 38
`
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`Patent No. 7,994,364
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`SmithKline Beecham Corp.,
`439 F.3d 1312 (Fed. Cir. 2006) ..................................................................... 48
`
`Statutes
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`35 U.S.C. § 102 (b) .......................................................................................... passim
`
`35 U.S.C. § 102(a) ................................................................................................... 14
`
`35 U.S.C. § 103 ........................................................................................................ 14
`
`35 U.S.C. § 112 ........................................................................................................ 11
`
`35 U.S.C. § 311 ........................................................................................................ 14
`
`Other Authorities
`
`J. Glusker & K. Trueblood, Crystal Structure Analysis: A Primer 232
`(Oxford University Press 1985) ..................................................................... 47
`
`Korsch Tablet Press, http://www.labx.com/product/korsch-tablet-press ................ 55
`
`Regulations
`
`37 C.F.R. § 42.100(b) .............................................................................................. 13
`
`37 C.F.R. § 42.103 ..................................................................................................... 2
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`37 C.F.R. § 42.103(a) ................................................................................................. 2
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`37 C.F.R. § 42.15(a) ................................................................................................... 2
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`37 C.F.R. § 42.8(b)(1) ................................................................................................ 1
`
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 2
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`37 C.F.R. § 42.8(b)(4) ................................................................................................ 2
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`Patent No. 7,994,364
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`TABLE OF EXHIBITS
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`
`
`Description
`Exhibit No.
`Exhibit 1001 U.S. Patent No. 7,994,364 to Andreas Fische et al., filed on Dec.
`10, 2009, and issued on Aug. 9, 2011 (the “’364 Patent”)
`Exhibit 1002 Relevant Excerpts of U.S. Patent No. 7,994,364 Prosecution
`History (“’364 prosecution history”)
`Exhibit 1003 EP1799633 A2 Bibliographic Data (“EP 633 Data”)
`Exhibit 1004 Grünenthal GmbH Apr. 18, 2008 Reply to EPO Communication
`Re: Patent App. No. 05 770 026.2 (“Apr. 18 EPO
`Communication”)
`Exhibit 1005 EPO Nov. 14, 2007 Communication to Grünenthal GmbH Re:
`Patent App. No. 05 770 026.2 (“Nov. 14 EPO Communication”)
`Exhibit 1006 Certified English Translation of European Patent No. EP 0 693
`475 A1 (“EP 475”)
`Exhibit 1007 European Patent No. EP 0 693 475 A1, by Dr. Helmut Bushmann
`et al., to Grünenthal GmbH, issued Jan. 24, 1996 (“German EP
`475”)
`Exhibit 1008 Translator Certification for EP 0 693 475 A1 (“EP 475
`Certification”)
`Exhibit 1009 Certified English Translation of International Patent App. No. WO
`03/035053 A1 (“Bartholomaeus”)
`International Patent App. No. WO 03/035053 A1, by Johannes
`Bartholomӓus and Iris Ziegler, published May 1, 2003 (“German
`WO 053”)
`Exhibit 1011 Translator Certification for International Patent App. No. WO
`03/035053 A1 (“WO 053 Certification”)
`Exhibit 1012 Expert Declaration of William Edward Mayo, Ph.D. (“Mayo
`Declaration”)
`Exhibit 1013 CV of William Edward Mayo, Ph.D. (“Mayo CV”)
`Exhibit 1014 Expert Declaration of Ron Bihovsky, Ph.D. (“Bihovsky
`Declaration”)
`Exhibit 1015 CV of Ron Bihovsky, Ph.D. (“Bihovsky CV”)
`
`Exhibit 1010
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`Patent No. 7,994,364
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`Exhibit 1020
`
`Description
`Exhibit No.
`Exhibit 1016 U.S. Patent No. RE39,593 E to Helmut Bushman et al., filed Jun.
`17, 2003, and issued Apr. 24, 2007 (“Bushmann 593”)
`Exhibit 1017 U.S. Patent No. 6,248,737 to Helmut Bushmann et al., issued Jun.
`19, 2001 (“Bushmann 737”)
`Exhibit 1018 U.S. Patent No. 6,344,558 to Helmut Bushmann et al., issued Feb.
`5, 2002 (“Bushmann 558”)
`Exhibit 1019 Plaintiffs’ Opening Claim Construction Brief, Janssen Pharms.,
`Inc. et al. v. Actavis Elizabeth LLC et al., 2-13-cv-04507 (D. NJ),
`D.I. No. 141 (“Janssen Claim Construction Brief”)
`July 15, 2015 Orange Book: Approved Drug Products with
`Therapeutic Equivalence Evaluations listing for Nucynta (“Orange
`Book”)
`Exhibit 1021 “X-ray Diffraction”, the United States Pharmacopeia <941>, USP
`38/NF33, (2015) p. 10/10 (“USP 38”)
`Exhibit 1022 European Patent No. EP 1 612 203 B1, by Dr. Andreas Fischer et
`al., to Grünenthal GmbH, issued Jan. 8, 2007 (“EP 203”)
`Exhibit 1023 H.P. Klug & L.E. Alexander, “X-Ray Diffraction Procedures”, 2nd
`Ed., Wiley, Chapter 7, pp 505-531 (“Klug”)
`Exhibit 1024 D. Krawitz, “Introduction to Diffraction in Materials Science and
`Engineering”, Wiley (2001), Ch. 8, pp 215-234 (“Krawitz 1”)
`Exhibit 1025 F.H. Chung & D.K. Smith, “Industrial Applications of X-Ray
`Diffraction”, Dekker, (2000), p21 (“Chung”)
`Exhibit 1026 V. K. Pecharsky & P.Y. Zavalij, “Fundamentals of Powder
`Diffraction and Structural Characterization of Materials”, 2nd Ed.,
`Springer (2009) pp. 380-382 (“Pecharsky 1”)
`Exhibit 1027 “Phase Identification by X-ray Powder Diffraction Evaluation of
`Various Techniques,” J.D. Hanawalt, Advances in X-ray Analysis,
`1976, 20:63 – 73 (“Hanawalt”)
`Exhibit 1028 “A Hanawalt Type Phase Identification Procedure for a
`Minicomputer,” Robert L. Snyder, Advances in X-ray Analysis,
`1980, 24:83 – 90 (“Snyder”)
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`Patent No. 7,994,364
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`Description
`Exhibit No.
`Exhibit 1029 “Phase Identification Using Whole-Patterns Matching,” D. K.
`Smith, et al., Advances in X-ray Analysis, 1993, 36:287 – 299
`(“Smith”)
`Exhibit 1030 B.D. Cullity, “Elements of X-ray Diffraction”, 2nd Ed, Addison
`Wesley, (1978), p.402 (“Cullity”)
`Exhibit 1031 C. Suryanarayana & M.G. Norton, “X-Ray Diffraction – A
`Practical Approach”, Plenum, (1998), p. 240 (“Suryanarayana”)
`Exhibit 1032 “A Plug-in Program to Perform Hanawalt or Fink Search-Indexing
`Using Organics Entries in the ICDD PDF-4/Organics 2003
`Database,” J. Faber, et al., Advances in X-ray Analysis, 2004,
`47:166 – 173 (“Faber”)
`Exhibit 1033 V. K. Pecharsky & P.Y. Zavalij, “Fundamentals of Powder
`Diffraction and Structural Characterization of Materials”, 2nd Ed.,
`Springer (2009) p 385 (“Pecharsky 2”)
`Exhibit 1034 H.G. Brittain, Ed. “Polymorphism in Pharmaceutical Solids”,
`Marcel Dekker, 1999, p. 236 (“Brittain”)
`Exhibit 1035 “A Criterion for Rating Powder Diffraction Patterns and
`Evaluating the Reliability of Powder Pattern Indexing,” Gordon S.
`Smith and Robert L. Snyder, J. Appl. Cryst., 1979, 12:60 – 65
`(“Smith”)
`Exhibit 1036 D. Krawitz, “Introduction to Diffraction in Materials Science and
`Engineering”, Wiley (2001), Ch. 8, pp 269-277 (“Krawitz 2”)
`Exhibit 1037 V. K. Pecharsky & P.Y. Zavalij, “Fundamentals of Powder
`Diffraction and Structural Characterization of Materials”, 2nd Ed.,
`Springer (2009) pp. 524-545 (“Pecharsky 3”)
`Exhibit 1038 R.E. Dinnebier & S.J.L. Billinge, “Powder Diffraction – Theory
`and Practice”, RSC Publishing, 2008, pp. 266-281 (“Dinnebier 1”)
`Exhibit 1039 “Unit-Cell Refinement from Powder Diffraction Scans,” G.S.
`Pawley, J. Appl. Cryst., 1981, 14:357 – 361 (“Pawley”)
`Exhibit 1040 R.E. Dinnebier & S.J.L. Billinge, “Powder Diffraction – Theory
`and Practice”, RSC Publishing, 2008, pp. 153 -159 (“Dinnebier
`2”)
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`I.
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`Patent No. 7,994,364
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`INTRODUCTION
`Petitioner Rosellini Scientific, LLC, requests an Inter Partes Review
`
`(“IPR”) of claims 1–4 and 24–27 (collectively, the “Challenged Claims”) of U.S.
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`Patent No. 7,994,364 (the “’364 Patent”) (Ex. 1001) in accordance with 35 U.S.C.
`
`§§ 311–19 and 37 C.F.R. §§ 42.100 et seq.
`
`II. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A))
`Pursuant to 37 C.F.R. § 42.104(a), Petitioner certifies that the ’364 Patent is
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`available for IPR and that Petitioner is not barred or estopped from requesting IPR
`
`challenging the claims of the ’364 Patent on the grounds identified in this Petition.
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`III. MANDATORY NOTICES (37 C.F.R. § 42.8)
`A. Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1))
`Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner certifies that Rosellini
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`Scientific, LLC (“Rosellini”) and nXn Partners, LLC (“nXnP”) are the real parties
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`in interest (collectively, “RPI”). The RPI hereby certify the following information:
`
`other than Rosellini and nXnP, no other person or entity (including any investor,
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`limited partner, or member or any other person) has authority to direct or control
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`(i) the timing of, filing of, content of, or any decisions or other activities relating to
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`this Petition or (ii) any timing, future filings, content of, or any decisions or other
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`activities relating to the future proceedings related to this Petition. All of the costs
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`associated with this Petition have been or will be borne by Rosellini or nXnP.
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`Patent No. 7,994,364
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`B. Related Judicial and Administrative Matters (37 C.F.R. § 42.8(b)(2))
`Pursuant to 37 C.F.R. § 42.8(b)(2), Petitioner states that the ’364 Patent has
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`been the subject of the following lawsuits: Janssen Pharms., Inc. et al. v. Actavis
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`Elizabeth LLC et al., D. NJ.-2-13-cv-04507 (filed Jul. 25, 2013); Janssen Pharms.,
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`Inc. et al. v. Sandoz Inc. et al., D. NJ.-2-13-cv-06929 (filed Nov. 14, 2013);
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`Janssen Pharms., Inc. et al. v. Roxane Labs., Inc., D. Nev.-3-13-cv-00639 (filed
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`Nov. 15, 2013); Janssen Pharms., Inc. et al. v. Alkem Labs. Ltd., D. NJ.-2-13-cv-
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`07803 (filed Dec. 23, 2013); Janssen Pharms., Inc. et al. v. Roxane Labs., Inc., D.
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`NJ.-2-14-cv-03941 (filed Jun. 19, 2014); and Janssen Pharms., Inc. et al. v.
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`Watson Labs., Inc., D. NJ.-2-14-cv-04617 (filed Jul. 23, 2014).
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`C.
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`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)) and Service
`Information (37 C.F.R. § 42.8(b)(4))
`
`Lead counsel is Sarah E. Spires, Reg. No. 61,501,
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`sspires@skiermontderby.com. Back-up counsel are Dr. Parvathi Kota, Reg. No.
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`65,122, pkota@skiermontderby.com; and Paul J. Skiermont (pro hac vice
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`requested), pskiermont@skiermontderby.com—all of Skiermont Derby LLP, 2200
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`Ross Ave. Ste. 4800W, Dallas, Texas 75201, P: 214-978-6600/F: 214-978-6601.
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`Petitioner consents to electronic service.
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`IV. PAYMENT OF FEES (37 C.F.R. § 42.15(A) AND § 42.103)
`The required fees are submitted herewith in accordance with 37 C.F.R.
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`§§ 42.103(a) and 42.15(a). If any additional fees are due during this proceeding,
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`the Office is authorized to charge such fees to Deposit Account No. 506293. Any
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`overpayment or refund of fees may also be deposited in this Deposit Account.
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`V.
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`IDENTIFICATION OF CHALLENGE
`A. Overview of U.S. Patent No. 7,994,364
`The ’364 Patent is titled “Crystalline Forms of (-)-(1R,2R)-3-(3-
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`Dimethylamino-1-Ethyl-2-Methylpropyl)-Phenol Hydrochloride.” (Ex. 1001 at
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`Front Cover.) The underlying application, U.S. Patent App. No. 12/634,777 (the
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`“’777 Application”) was filed on Dec. 10, 2009. The ’777 Application is a
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`continuation of U.S. Patent App. No. 12/274,747, filed on Nov. 20, 2008 (now
`
`abandoned), which is a continuation of U.S. Patent App. No. 11/646,232, filed on
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`Dec. 28, 2006 (now abandoned), which is a continuation of Application No.
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`PCT/EP2005/006884, filed on Jun. 27, 2005. (Id.) The ’777 Application claims
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`priority back to E.P. Patent App. No. 04015091, filed on Jun. 28, 2004. (Id.)
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`The ’364 Patent Specification
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`1.
`The ’364 Patent claims the crystalline Form A of (−)-(1R,2R)-3-(3-
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`dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (“tapentadol HCl”),
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`pharmaceutical compositions containing Form A, methods of producing Form A
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`compounds, and methods of treating conditions by administering the compound,
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`including methods for the treatment of pain. (Id. at Abstract.) The ’364 Patent
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`acknowledges that “U.S. Pat. Nos. 6,248,737 and 6,344,558 as well as European
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`Patent EP 693 475 B1 (“EP 475”) disclose the substance and the synthesis of (−)-
`3
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`(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride in
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`example 25.” (Id. at 1:46–49.)1 However, the ’364 Patent purports to disclose “a
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`new form (Form A) of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-
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`phenol hydrochloride which is different from the form already known (Form B)
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`obtained by the procedure described in example 25 of U.S. Pat. No. 6,248,737 and
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`U.S. Pat. No. 6,344,558 as well as EP 693 475 B1.” (Id. at 1:58–63.)
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`According to the ’364 Patent, “[t]he new crystalline Form A of (−)-(1R,2R)-
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`3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride can be
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`identified by X-ray powder diffraction. The X-ray diffraction (“XRPD”) pattern is
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`shown in FIG. 1 [copied below] with the peak listing showing in Table 1 [also
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`copied below].” (Id. at 2:14–18.)
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`1 The ’364 Patent explains that “the 1R,2R configuration as shown in the drawing
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`of the structure in example 25 is correct although the configuration is reported as
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`(-)-(1R,2S) in U.S. Pat. No. 6,248,737 and (-)-(1S,2S) in U.S. Pat. No. 6,344,558
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`as well as in EP 693 475 B1.” (Ex. 1001 at 1:50–54.)
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`Patent No. 7,994,364
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`Fig. 1: XRPD pattern of Form A
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`17.0
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`22.0
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`210
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`32.0
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`37.0
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`42 n
`."
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`47.n1'l'hm
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`"2 n
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`..
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`12.0
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`7.0
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`.E'
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`3 "
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`a
`3%
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`(Ex. 1001 at Fig. 1.)
`(Ex. 1001 at Fig. 1.)
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`Patent No. 7,994,364
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`(Ex. 1001 at Table 1 (emphasis added).)
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`The ’364 Patent explains:
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`To discriminate crystalline Form A of (−)-(1R,2R)-3-(3-
`dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride from
`Form B it is more advantageous to look at the unique peaks in the X-
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`Patent No. 7,994,364
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`ray diffraction diagram, i.e. e.g. the lines with sufficient intensity at 2-
`theta values, where Form B does not show lines with significant
`intensity. Such characteristic X-ray lines (2-theta values) for Form A
`in a powder diffraction pattern when measured using Cu Kα radiation
`at ambient temperature are: 15.1±0.2, 16.0±0.2, 18.9±0.2, 20.4±0.2,
`22.5±0.2, 27.3±0.2, 29.3±0.2 and 30.4±0.2 [highlighted in Table 1,
`above].
`(Id. at 2:27–36.) The ’364 Patent claims at least this “crystalline Form A of (-)-
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`(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methulpropyl)-phenol hydrochloride”
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`displaying the above “X-ray lines (2-theta values) for Form A” in each of the
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`Challenged Claims, as shown below. (See 18:66–19:19, 20:36–22:13.)
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`
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`Additionally, the ’364 Patent allegedly provides procedures for obtaining
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`tapentadol HCl’s Form A—found in Examples 1–6, as well as for obtaining
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`tapentadol HCl’s Form B—found in Examples 7–9. Of note, Example 7 purports to
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`obtain Form B by following Example 25 of EP 475—the anticipatory prior art
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`reference relied upon in Ground 1, and discussed in more detail below.
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`The ’364 Claims
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`2.
`The ’364 Patent’s Challenged Claims include 3 independent claims and 5
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`dependent claims. Claim 1 is representative and is reproduced below.
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`A crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-
`methulpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-
`theta values) in a powder diffraction pattern when measured using Cu
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`Patent No. 7,994,364
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`Kα radiation at 15.1±0.2, 16.0±0.2, 18.9±0.2, 20.4±0.2, 22.5±0.2,
`27.3±0.2, 29.3±0.2 and 30.4±0.2.
`(Ex. 1001 at 18:66–19:4.)
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`Claim 2 depends from claim 1 and adds the limitation that Form A exhibits
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`“at least X-ray lines (2-theta values) in a powder diffraction pattern when
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`measured using Cu Kα radiation at 14.5±0.2, 18.2±0.2, 20.4±0.2, 21.7±0.2 and
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`22.5±0.2. (Id. at 19:7–10.)
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`Claim 3 depends from claim 1 and adds the limitation that Form A exhibits
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`“an X-ray pattern (2-theta values) in a powder diffraction pattern when measured
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`using Cu Kα radiation essentially the same as that provided in FIG. 1” (copied
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`below). (Id. at 19:13–15.)
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`Claim 4 depends from claim 1 and adds the limitation that the Form A
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`crystal has a monoclinic form. (Id. at 19:18–19.)
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`Claim 24 depends from claim 1 and is a “product by process” claim that
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`adds the limitation that Form A is
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`produced by the process of:
`dissolving (−) (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-
`methylpropyl)-phenol hydrochloride of Form B in acetonitrile
`together with active carbon,
`heating the solution to the boiling point,
`removing the active carbon by filtering,
`stirring the solution at a temperature below 40ºC.,
`removing part of the solvent residue by filtering and removing part of
`the solvent,
`leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-
`phenol hydrochloride of Form A to crystalize,
`redissolving the resulting crystals in acetonitrile,
`removing insoluble residue by filtering and removing part of the
`solvent, and
`leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-
`phenol hydrochloride of Form A to crystalize.
`(Id. at 19:38–55.)
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`Independent claim 25 requires “A solid pharmaceutical composition
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`comprising, as an active ingredient,” the crystalline Form A of claim 1, “and at
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`least one suitable additive or auxiliary substance.” (Id. at 19:56–63.)
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`Claim 26 depends from claim 25 and adds the limitation that Form A is
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`produced by the process of:
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`Patent No. 7,994,364
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`dissolving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-
`phenol hydrochloride of Form B in acetonitrile together with active
`carbon,
`heating the solution to the boiling point,
`removing the active carbon by filtering,
`stirring the solution at a temperature below 40º C.,
`removing insoluble residue by filtering and removing part of the
`solvent, and
`leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-
`phenol hydrochloride of Form A to crystalize, and
`at least one suitable additive or auxiliary substance.
`(Id. at 19:67–22:4.)
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`Independent claim 27 requires “A method of treating or inhibiting pain or
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`urinary incontinence, said method comprising the step of administering a
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`pharmaceutically effective amount of “the crystalline Form A of claim 1 “to a
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`subject in need thereof.” (Id. at 22:5–13.)
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`Prosecution History of the ’364 Patent and European Counterpart
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`3.
`The ’777 Application that led to the ’364 Patent received light treatment
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`during prosecution. The only claims to ever receive a rejection were as-filed claims
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`26 and 27. (Ex. 1002 at 502.) For these two claims, the Examiner stated that the
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`2 All page citations to the File History—Ex. 1002—are to the exhibit’s Bates
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`number. For all other exhibits, page citations are to the internal page numbering of
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`the exhibit.
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`Patent No. 7,994,364
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`pending 35 U.S.C. § 112 rejection could “be removed by adding the word ‘solid’ in
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`front of the word ‘pharmaceutical.’” (Id. at 51–53.) The applicant therefore
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`amended claims 26 and 27 according to the Examiner’s suggestion. (Id. at 58–64.)
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`Additionally, the applicant submitted an IDS containing information about
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`“four clinical trials of a crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-
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`ethyl-2-methylpropyl)-phenol hydrochloride (CG5503) [that] were conducted in
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`the United States through contract research organizations from 2001 to January
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`2003.” (Id. at 64.) The applicant explained that “[a]t the time of these clinical
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`trials, the crystalline material used to prepare the pharmaceutical dosage forms for
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`these clinical trials was not tested to determine which crystalline form it was.” (Id.
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`at 54.) The applicant went on to state that, “[a]lthough tests have shown that even
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`when the crystalline form B, produced as disclosed in US patent no. 6,248,737, is
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`subjected to tableting, it retains its form B crystalline structure and does not
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`convert to the crystalline form A….” (Id. at 65 (emphasis added).) Additionally,
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`the applicant remarked that “[e]xtreme stress tests of crystalline form B alone (i.e.,
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`in the absence of any other tablet ingredients) for extended durations of 60 seconds
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`have yielded mixtures of crystalline forms B and A, but under normal tableting
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`conditions, no conversion to crystalline form A can be detected.” (Id. at 65.)
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`Importantly, these statements were made without any provocation from the
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`Examiner, and without providing any data to support their veracity.
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`Patent No. 7,994,364
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`In direct contrast to the applicant’s statements above, during prosecution of
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`the ’364 Patent’s European counterpart—the ’777 Application—the European
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`applicant (and owner of the ’364 Patent)—Grünenthal GmbH (“Grünenthal”)—
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`stated that “[t]he crystalline form B disclosed in D1 [EP 475] has the disadvantage
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`that under the influence of pressure (which occurs e.g. in the manufacturing
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`process for the drug tablet) polymorph B (crystalline form of D1 [EP 475]) is
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`transformed in a mixture of the crystalline forms A and B.” (Ex. 1004 at 1
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`(emphasis added); see Ex. 1003 at 1 (“Also published as: … US799364”).)
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`After the applicant’s amendment to claims 26 and 27, the Examiner issued a
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`Notice of Allowance. (Ex. 1002 at 76–79.) With authorization from a telephone
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`interview, the Examiner further amended (1) claim 5 to require that “during the
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`process the temperature is kept below + 40 ºC,” (2) claim 25 to require dependency
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`from claim 1, and (3) claim 27 to require dependency from claim 26. (Id. at 77–
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`78.)
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`B. Claim Construction of Challenged Claims
`A claim subject to IPR receives the “broadest reasonable construction in
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`light of the specification of the patent in which it appears.” 37 C.F.R. § 42.100(b);
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`see In re Cuozzo Speed Techs., LLC, 778 F.3d 1271, 1279 (Fed. Cir. 2015). In
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`applying such a standard, the broadest reasonable construction of claim language is
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`not one that permits any reading, but instead is one that must be made “in light of
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`Patent No. 7,994,364
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`the specification as it would be interpreted by one of ordinary skill in the art.” In re
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`Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004) (citation
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`omitted).
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`Unless otherwise noted, Petitioner accepts, for purposes of this IPR only,
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`that the claim terms of the ’364 Patent are presumed to take on the ordinary and
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`customary meaning that they would have to one of ordinary skill in the art.
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`(Ex. 1012 ¶ 29.) However, Petitioner notes that neither the claim terms nor the
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`specification of the ’364 Patent makes any mention of the purity of the crystalline
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`compound recited in claims 1–4 or 24–27. (See generally, Ex. 1001.) Thus,
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`Petitioner notes that no particular level of purity should be attributed to the
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`crystalline compound recited in claims 1–4 or 24–27. See Ex Parte Reddy, 2010
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`Pat. App. LEXIS 13975, at *9–10 (Pat. App. Mar. 31, 2010) (“The claims do not
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`require a specific amount of crystalline compound or purity of the compound. If
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`the solids or crystals of [the prior art] have even a small portion of the claimed
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`compound in the product, the product is anticipated.”). (Ex. 1012 ¶ 30.)
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`C.
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`Statement of Precise Relief Requested for Each Claim Challenged
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`Claims for Which Review is Requested
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`1.
`Petitioner requests IPR under 35 U.S.C. § 311 of claims 1–4 and 24–27 of
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`the ’364 Patent, and cancellation of these 8 claims as unpatentable.
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`Patent No. 7,994,364
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`Statutory Grounds of Challenge
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`2.
`Petitioner requests IPR of claims 1–4 and 24–27 of the ’364 Patent in view
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`of the following references, each of which is prior art to the ’364 Patent under Pre-
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`AIA 35 U.S.C. §§ 102(a) or (b) or 103. The Examiner did not rely on any of the
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`prior art listed in the following chart as the basis of any rejection in any Office
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`Action. (See generally, Ex. 1002.) Claims 1–4 and 24–27 are unpatentable under
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`35 U.S.C. § 102(b):
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`Ground Proposed Rejections for the ’364 Patent
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`1
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`Claims 1–4 and 24–27 are anticipated under 35
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`Exhibit
`Number(s)
`1006, 1007, 1008
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`U.S.C. § 102(b) by European Patent No. 693 475
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`B1 (Ex. 1006, “EP 475”).
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`2
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`Claims 1–4 and 24–27 are anticipated under 35
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`1009, 1010, 1011
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`U.S.C. § 102(b) by International Patent
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`Publication No. WO 09/035053 (Ex. 1009,
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`“Bartholomaeus”).
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`D. Overview of the State of the Art and Prior Art References
`1.
`EP 475 (Exs. 1006, 1007, 1008)
`In early 1994, scientists at the assignee of the ’364 Patent—Grünenthal—
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`allegedly first synthesized the pain killer tapentadol HCl. (Ex. 1019 at 7.)
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`Grünenthal first described tapentadol HCl, also known as (−)-(1R,2R)-3-(3-
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`Patent No. 7,994,364
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`dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, in German Patent
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`App. No. DE 4426245, which was filed on July 23, 1994. This application served
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`as a basis for priority for EP 475, which issued on January 24, 1996, to
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`Grünenthal.3 ) Grünenthal then repeated the EP 475 disclosure in the various EP
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`475 counterparts, which included U.S. Pat. Nos. 6,248,737 and 6,344,558. (See
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`Ex. 1017; Ex. 1018.)
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`Along with other teachings, EP 475 discloses the synthesis of tapentadol
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`HCl in Example 25, as shown