UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
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`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`
`
`_______________
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`IPR2015-01490; Patent 7,754,702 B2
`____________________________________________________________
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`CORRECTED MOTION TO AMEND
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`4826-6801-0288.1
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`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`PHARMACOSMOS A/S,
`Petitioner,
`
`v.
`
`LUITPOLD PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`
`
`
`_______________
`
`IPR2015-01490; Patent 7,754,702 B2
`____________________________________________________________
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`CORRECTED MOTION TO AMEND
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`4826-6801-0288.1
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`IPR2015-01490
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`TABLE OF CONTENTS
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`I.
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`STATEMENT OF RELIEF REQUESTED .................................................... 1
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`A. Grounds 1, 4, or 5 .................................................................................. 1
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`B.
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`C.
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`Ground 3 ................................................................................................ 1
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`Ground 2 ................................................................................................ 2
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`II.
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`AMENDMENTS ............................................................................................. 2
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`A.
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`B.
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`Claim Listing ......................................................................................... 3
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`Nature and Scope of Amendments ........................................................ 5
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`1.
`
`2.
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`Substitute Claims ........................................................................ 5
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`Canceled Claims ......................................................................... 7
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`III.
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`PATENTABILITY OF THE AMENDED CLAIMS ...................................... 9
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`A.
`
`Person of Ordinary Skill in the Art (“POSITA”) .................................. 9
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`B. Written Support ................................................................................... 10
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`C.
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`Prior Art ............................................................................................... 12
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`1.
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`2.
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`3.
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`4.
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`5.
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`6.
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`Geisser ....................................................................................... 14
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`van Zyl-Smit, Funk, and Other Polymaltose Related Art ......... 14
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`Groman and Other Ferumoxytol Related Art ........................... 16
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`Kudasheva ................................................................................. 17
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`Vance......................................................................................... 17
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`Restless Leg Syndrome Related Art ......................................... 18
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`7. Marchasin and Other Dextran Related Art ............................... 19
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`8.
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`9.
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`Other Art of Record .................................................................. 20
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`Combinations of the Above Cited Art ...................................... 21
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`IV. CONCLUSION .............................................................................................. 21
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`TABLE OF AUTHORITIES
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`CASES
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`In re Abbott Diabetes Care Inc., 696 F.3d 1142 (Fed. Cir. 2012) ........................... 19
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`In re Johnson, 558 F.2d 1008 (CCPA 1977) ........................................................... 11
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`Masterimage 3D, Inc. v. RealD, Inc., IPR2015-00040 (PTAB July 15, 2015) ....... 12
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`Nike v Adidas AG, No. 2014-1719 (Fed. Cir. February 11, 2016). ......................... 13
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`Pharmacosmos A/S v. Luitpold Pharmaceuticals Inc., IPR 2015-01493 (PTAB
`January 8, 2016; February 26, 2016) .................................................................. 17
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`Pharmacosmos A/S v. Luitpold Pharmaceuticals Inc., IPR 2015-01495 (PTAB
`January 8, 2016) ............................................................................................. 4, 16
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`Santarus, Inc. v. Par Pharmaceutical, Inc. 694 F. 3d 1344 (Fed. Cir. 2012) ......... 11
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`STATUTES
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`35 § U.S.C. 112 .......................................................................................................... 8
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`35 U.S.C. § 316(d) ............................................................................................ 1, 3, 5
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`37 C.F.R. § 1.321(a) ................................................................................................... 2
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`37 C.F.R. § 42.121 ................................................................................ 1, 2, 3, 5, 6, 7
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`37 C.F.R. § 42.20(c) ................................................................................................. 13
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`37 C.F.R. § 42.22(a)(2) .............................................................................................. 1
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`EXHIBITS RELIED UPON
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`Exhibit No.
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`Description
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`1001
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`1002
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`1003
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`1004
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`1005
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`1006
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`1007
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`1009
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`1011
`1014
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`1017
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`1026
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`1031
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`1034
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`1047
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`1049
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`2005
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`2012
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`2013
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`U.S. Patent No. 7,754,702 (“the ’702 patent”)
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`WO 2004/037865 (“Geisser”)
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`WO 2004/037865 (English translation) (“Geisser”)
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`U.S. Publication No. 2003/0232084 (“Groman”)
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`Declaration of Dr. Robert Linhardt
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`van Zyl-Smit et al. Nephron 92:316-323 (2002) (“van Zyl-Smit”)
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`Prosecution History of the ’702 patent
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`U.S. Publication No. 2004/0180849 (“Helenek”)
`
`Spinowitz et al. Kidney Int’l 68:1801-1807(2005) (“Spinowitz”)
`U.S. Patent No. 7,612,109
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`U.S. Patent No. 6,599,498 (“the ’498 patent”)
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`Funk et al. Hyperfine Interactions 136:73-95(2001) (“Funk”)
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`U.S. Patent No. 3,100,202 (“Mueller”)
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`U.S. Patent No. 5,541,158 (“Vance”)
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`Marchasin et al. Blood 23(3):354-358(1964) (“Marchasin”)
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`Geisser et al. Areneim. Forsch./Drug Res. 41(II)(12):1439-1452
`(1992) (“Geisser paper”)
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`Prosecution History of the ’549 patent
`
`Fishbane, Am. J. Kidney Dis. 41(5 Suppl):18-26 (2003) (“Fishbane”)
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`Cisar et al. J. Exp. Med. 142(1):435-459 (1975) (“Cisar”)
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`2036
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`2037
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`2038
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`2039
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`2040
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`2041
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`2042
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`2043
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`2044
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`2045
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`2046
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`2047
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`2048
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`2049
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`2050
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`2051
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`2052
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`2054
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`2055
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`Fielding et al. British Medical Journal 279-283 (1961) (“Fielding”)
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`Kabat et al. J. Immunol. 70:514-531(1953) (“Kabat”)
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`WO 1997/011711 (“Lawrence PCT”)
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`U.S. Patent No. 6,960,571 to Helenek (“the ’571 patent”)
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`Landry et al. Am. J. Nephrol. 25(4):400-410 (2005) (“Landry”)
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`Beshara et al. Br J Haematol. 120(5):853-9 (2003). (“Beshara”)
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`Haines et al. Internal Med. Journal 39: 252-255 (2009) (“Haines”)
`
`Newnham et al. Internal Med. Journal 36(10): 672-674 (2006)
`(“Newnham”)
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`Andersson Br Med J. 2(5247):275-279 (1961). (“Andersson”)
`
`Bailie et al. Neprol. Dial. Transplant 20:1443-1449 (2005) (“Bailie”)
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`NKF-KDOQI (2000) (“Eschbach”)
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`MacDougall Neprol. Dial. Transpland 15(Ed. Comments):1743-1745
`(2000) (“MacDougall”)
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`Kudasheva et al. J. Inorganic Biochem. 98:1757-1769 (2004)
`(“Kudasheva”)
`
`Van Wyck et al. J. Am Soc Nephrol 15: S91-92, S107-S111
`(2004)(“Van Wyck”)
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`U.S. Publication No. 2008/0234226
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`Sipe et al. Brain Iron Metabolism and Neurodegenerative Disorders
`24(2-3):188-196 (2002) (“Sipe”)
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`Sofic et al. J. Neural Transm. 74: 199-205 (1988) (“Sofic”)
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`U.S. Patent No. 5,624, 668 (“Lawrence”)
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`Hamstra et al. JAMA 243:1726-1731(1980) (“Hamstra”)
`v
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`Curriculum Vitae of Dr. Adriana Manzi
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`Declaration of Dr. Adriana Manzi
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`U.S. Provisional Application 60/757,119 (“the ’119 Application”)
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`2057
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`2080
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`2083
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`I.
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`STATEMENT OF RELIEF REQUESTED
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`Patent Owner Luitpold Pharmaceuticals, Inc. contingently moves under 37
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`C.F.R. § 42.121 to amend the claims of U.S. Patent 7,754,702 (“the ’702 patent”) .
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`A. Grounds 1, 4, or 5
`If issued claim 1 is found unpatentable based on Grounds 1 or 4, Luitpold
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`requests cancelling claim 1 and replacing it with substitute claim 58. See 37
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`C.F.R. § 42.22(a)(2)(ii); 35 U.S.C. § 316(d). If issued claims 2, 3, 10-13, 23, 25,
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`27, and 41-43 are found unpatentable on Ground 1, Luitpold requests cancelling
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`these claims and replacing them with proposed substitute claims 59-64 and 67-72,
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`as noted in the claim listing below.
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`If issued claims 14 and 15 are found unpatentable on Ground 4, Luipold
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`requests cancelling these claims and replacing them with proposed substitute
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`claims 65 and 66, as noted in the claim listing below.
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`If issued claim 1 or claim 30 is found unpatentable on Ground 5, Luitpold
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`requests cancelling these claims and replacing claim 1 with claim 58, which
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`incorporates the limitations of claim 30.
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`B. Ground 3
`If issued claim 17 or issued claim 47 is found unpatentable based on Ground
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`3, Luitpold requests cancelling the claim deemed unpatentable and replacing it
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`with the corresponding proposed substitute claim: claim 74 for claim 17 and claim
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`73 for claim 47. Id.
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`C. Ground 2
`If issued claim 1 or issued claim 28 is found unpatentable based on Ground
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`2, the Board is requested to cancel claim 28 and accept a statutory disclaimer of
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`claim 29, which depends from claim 28 but is not challenged in this proceeding.
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`Id.; 37 C.F.R. § 1.321(a). Upon occurrence of this contingency and grant of the
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`Motion to Amend by the Board, Patent Owner will complete the disclaimer
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`provided below in Appendix C. Luitpold understood the Board’s guidance during
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`the conference call of March 9, 2016, to permit such a contingent disclaimer.
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`II. AMENDMENTS
`Patent Owner provides a complete listing of proposed amendments with a
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`correlation of the substitute claims to the issued claims. No more than one
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`substitute claim is proposed for each canceled claim. 37 C.F.R. § 42.121(a)(3).
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`Indeed, there is only one proposed substitute independent claim and there are fewer
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`proposed substitute dependent claims compared to the instituted claims. The
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`proposed substitute claims are not broader than the issued claims. 35 U.S.C. §
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`316(d)(3); 37 C.F.R. § 42.121. A listing of the claim amendments is found in
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`Appendix A, labeled “Claims Listing.” For the Board’s convenience, and as
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`authorized in Paper 22, Patent Owner also provides family-tree graphics showing
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`the relationship of the claims, one graphic for the issued claims, another showing
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`both the issued and cancelled claims, and yet another one for the proposed
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`substitute claims.
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`A. Claim Listing
`Proposed substitute claim 58 is reproduced below.
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`58.
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`(Substitute for claim 1, if found unpatentable) A method of treating a
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`disease, disorder, or condition characterized by iron deficiency or dysfunctional
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`iron metabolism resulting in reduced bioavailability of dietary iron, comprising
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`administering to a subject in need thereof an iron carbohydrate complex in a
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`single dosage unit of at least about 0.6 grams of elemental iron;
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`wherein
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`the iron carbohydrate complex is selected from the group consisting of
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`an iron carboxymaltose complex, an iron mannitol complex, an iron
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`polymaltose complex, an iron gluconate complex, and an iron sorbitol
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`complex; and
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`the iron carbohydrate complex has a substantially non-immunogenic
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`carbohydrate component and substantially no cross reactivity with anti-dextran
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`antibodies
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`wherein said disease, disorder or condition is not Restless Leg Syndrome,
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`and
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`wherein the iron carbohydrate complex comprises an iron core with a mean
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`iron core size of no greater than about 9 nm.
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`No new issues of construction are raised by the amendment to substitute
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`claim 58.
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`In addition to excluding “iron polymaltose complex” and “iron polyglucose
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`sorbitol carboxymethyl ether,” the claims should be construed to exclude iron
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`dextran – a species explicitly disparaged by the specification. Ex. 1001, col. 1:38-
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`54; Ex. 2080, ¶¶61-62, 67. In IPR2015-01495 (relating to US Patent 8,895,612
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`issuing from a continuation of the ’702 patent), the Board agreed to this
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`construction, noting that, in the context of the entire disclosure, the term “iron
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`polyisomaltose” would not be understood by one of ordinary skill in the art to
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`include an “iron dextran.” Pharmacosmos A/S v. Luitpold Pharmaceuticals Inc.,
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`IPR2015-01495, Paper 11, pp. 12-14 (PTAB January 8, 2016).
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`During prosecution of another continuation of the ’702 patent (that is, during
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`prosecution of the application that matured into the ’549 patent) the distinction
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`between “dextran” and “polyisomaltose” was clarified in response to the
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`Examiner’s rejection of the claims over art relating to an iron dextran complex:
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`dextran refers to a branched molecule whereas polyisomaltose refers to a linear
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`molecule. Ex. 2005, pp. 60-77.
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`B. Nature and Scope of Amendments
`The proposed substitute claims are not broader than the issued claims and
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`are responsive to the instituted grounds or are otherwise permitted. 35 U.S.C. §
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`316(d)(3); 37 C.F.R. § 42.121.
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`Substitute Claims
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`1.
`Contingent on a finding of unpatentability on Grounds 1, 4, or 5, Luitpold
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`requests that claims 1-3, 10-15, 23, 25, 27, and 41-43 be replaced with claims 58-
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`72. Further, contingent on finding unpatentability on one or more of these grounds
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`and a finding of unpatentability on Ground 2 for claim 17 or claim 47, Luitpold
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`requests the claim found unpatentable be replaced with claim 74 or claim 73,
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`respectively.
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`Substitute claim 58 narrows claim 1 by deleting a single species – “iron
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`polymaltose complex” – from the Markush grouping of iron carbohydrate
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`complexes in the issued claim and adding the limitation of claim 30 “wherein the
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`iron carbohydrate complex comprises an iron core with a mean iron core size of no
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`greater than about 9 nm.” Thus, substitute claim 58 narrows the scope of claim 1
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`by no longer covering the method as it relates to the administration of an iron
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`polymaltose complex.1 Additionally, claim 58 further narrows the scope of the
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`substitute claims by limiting the mean iron core size of the iron carbohydrate
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`complex to no greater than about 9 nm.
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`This amendment (proposing claim 58) is responsive to Grounds 4 and 5 –
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`anticipation over van Zyl-Smit and obviousness over van Zyl-Smit and Funk. 37
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`C.F.R. § 42.121(a)(2)(i); Decision Granting Institution, Paper 11, pp. 16-18. van
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`Zyl-Smit is cited for anticipation based on its alleged teaching of high dose
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`administration of an iron polymaltose complex. Petition, pp. 52-54; Decision
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`Granting Institution, Paper 11, pp. 16-18. Funk is likewise characterized by
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`Petitioner to relate to iron polymaltose complexes. Petition, p. 55; Decision
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`Granting Institution, Paper 11, p. 18. Thus, deletion of the species relating to van
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`Zyl-Smit and Funk responds to these grounds of unpatentability.
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`This amendment is also responsive to Grounds 1 and 3 – anticipation over
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`Geisser and obviousness over Geisser and Groman – by adding a limitation
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`1 The Board confirmed that “deleting members of a Markush group would
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`be considered a narrowing amendment.” Order of March 11, 2016, Paper 22, p. 4.
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`relating to iron core size not taught by Geisser. Ex. 2080, ¶87. 37 C.F.R. §
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`42.121(a)(2)(i); Decision Granting Institution, Paper 11, pp. 6, 14-15.
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`Substitute claims 59-74, based on claims 1-3, 10-15, 17, 23, 25, 27, 41-43,
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`and 47 depend directly or indirectly from substitute claim 58, just as the issued
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`claims depend directly or indirectly from claim 1. Thus, for the same reasons,
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`these amendments are both narrowing in scope and responsive to instituted
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`grounds.
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`Canceled Claims
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`2.
`Contingent on a finding of unpatentability on Ground 2, claim 28 is
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`canceled, consistent with Petitioner’s assertion that it improperly depends from
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`claim 1. For the same reason, claim 29 is disclaimed, as it depends from claim 28.
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`Petitioner asserts that these claims improperly depend on issued claim 1, as
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`the “iron polyglucose sorbitol carboxymethyl ether complex” does not fit within
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`the category of “iron sorbitol complex” listed in this claim. Petition, p. 12-13, 39.
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`Further, Petitioner’s expert Dr. Linhardt notes that “iron polyglucose sorbitol
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`carboxymethyl ether would not fall within any of the categories of iron
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`carbohydrate complexes listed in claim 1.” Ex. 1005, ¶14. Petitioner notes that the
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`alleged anticipating species disclosed in Groman – ferumoxytol – is an iron
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`polyglucose sorbitol carboxymethyl ether. Petition, p. 39.
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`Patent Owner and its expert agree with the conclusions of Petitioner and
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`Petitioner’s expert: the species disclosed in Groman and claimed in issued claims
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`28 and 29 does not fall within the scope of issued claim 1. Ex. 2080, ¶¶ 27-31.
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`Cancelation of claim 28 and disclaimer of claim 29 amounts to acknowledgement
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`by the Patent Owner that the claims are improperly dependent.
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`This amendment is responsive to Ground 2 – anticipation over Groman.
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`Groman is cited as anticipating art based on its teaching of an iron polyglucose
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`sorbitol carboxymethyl ether. Petition, p. 39. Cancelation of issued claim 28 (and
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`disclaimer of claim 29) and acknowledgement of the improper dependency
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`confirms that iron polyglucose sorbitol carboxymethyl ether does not fall within
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`the scope of issued claim 1. Thus, issued claim 1 could not be anticipated by
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`Groman since it did not cover this species to begin with.
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`The proposed substitute claims have the effect of disavowing coverage of
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`two species – an iron polymaltose complex (by removal from the claims) and an
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`iron polyglucose sorbitol carboxymethyl ether (by clarification that this was never
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`within the scope of the claims to begin with) – from the scope of the independent
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`claim. Moreover the substitute claims add an additional limitation of a mean iron
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`core size no greater than about 9 nm.
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`III. PATENTABILITY OF THE AMENDED CLAIMS
`The proposed substitute claims comply with the requirements of § 112 (pre-
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`AIA) and are patentable over the prior art. As an initial matter, the only “added
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`feature” or limitation in the amended claims was previously present in issued claim
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`30, which Petitioner challenged as obvious over van Zyl-Smit and Funk. The
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`additional amendments (i.e., deletion of “iron polymaltose complex,” cancellation
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`of claim 28, and disclaimer of claim 29) do not affirmatively add limitations but
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`rather (1) exclude a species from the claims and (2) acknowledge that another
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`species was never within the scope of the claims to begin with.
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`Person of Ordinary Skill in the Art (“POSITA”)
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`A.
`A person of ordinary skill in the art (“POSITA”) is a person with an
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`undergraduate degree in chemistry or biochemistry with relevant academic or
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`industrial experience in the area of carbohydrates and their metal complexes. More
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`specifically, since the claims are directed to a method of administration, relevant
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`academic or industrial experience should pertain to the production of biologics for
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`pharmaceutical use or the administration of such compounds in the context of their
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`pharmaceutical use. Ex. 2080, ¶¶ 15-17. Luitpold’s expert Dr. Manzi is well
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`qualified to opine on the understanding of a POSITA. Ex. 2057.
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`B. Written Support
`The Board notes that Patent Owner should demonstrate written support for
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`the claims “as a whole” in the specification. Order of March 11, 2016, Paper 22, p.
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`4.
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`Substitute claims 58-74 find support in both the January 6, 2006 priority
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`application U.S. Application Serial No. 60/757,119 (Ex. 2083, “the ’119
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`application”) and the specification as originally filed (Ex. 1007, p. 282-333), which
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`also incorporates the ’119 specification by reference (Ex. 1007, p. 282, ¶ [0001]).
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`No new matter is added. Based on the disclosure of the ’119 application, one of
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`ordinary skill would understand the inventors had possession of the subject matter
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`of substitute claims 58-74 in January 2006. Ex. 2080, ¶58.
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`Substitute claim 58 recites a method of treating a disease, disorder, or
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`condition characterized by iron deficiency or dysfunctional iron metabolism,
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`comprising administering to a subject in need thereof an iron carbohydrate
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`complex in a single dosage unit of at least about 0.6 grams of elemental iron. This
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`same method is recited in original claim 1 of the ’119 application and described
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`throughout. Ex. 2083, p. 27, claim 1, p. 4, ¶ [0008], p. 6, ¶ [0019]; Ex. 1007, p.
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`193, ¶ [0008], p. 200, ¶ [0034].
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`The particular iron species recited in substitute claim 58 are recited in
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`original claim 21 and in the paragraphs describing exemplary iron carbohydrate
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`complexes in the ’119 application. Ex. 2083, p. 29, claim 21, pp. 12-13, ¶ [0042].
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`In the ’702 patent’s specification, as originally filed, these species are listed in an
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`original claim. Ex. 1007, p. 323, claim 1, p. 298, ¶ [0059].
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`Support for the iron carbohydrate specified in substitute claim 58 having a
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`non-immunogenic carbohydrate component is likewise found in the specification
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`of the ’119 application and the specification as originally filed. Ex. 2083, p. 13, ¶
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`[0043]; Ex. 1007, p. 323, claim 1, p. 298, ¶ [0060].
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`Support for the further limitation of substitute claim 58 carving out Restless
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`Leg Syndrome from the indications covered by the claims is found in the listing of
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`alternative disease indications in both the ’119 application and the specification as
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`originally filed. Ex. 2083, p. 12, ¶ [0041]; Ex. 1007, p. 284-285, ¶ [0010]; see,
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`e.g., Santarus, Inc. v. Par Pharmaceutical, Inc. 694 F.3d 1344, 1359-60 (Fed. Cir.
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`2012) (citing In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187 (CCPA 1977))
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`(Written support for a negative limitation can be found in a listing of alternatives.).
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`The added limitation of a mean iron core size no greater than about 9 nm in
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`substitute claim 58 is recited in the ’119 application as a characteristic of the iron
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`carbohydrate complexes disclosed therein that may make it “amenable to
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`administration at dosages far higher than contemplated by current administration
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`protocols.” Ex. 2083, p. 13, ¶ [0043]. The limitation is further contemplated as a
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`limitation on all the preceding claims, including claim 21, in claim 26 of the ’119
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`application. Ex. 2083, p. 30, claim 26. Similar support is found in the
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`specification as originally filed. Ex. 1007 , p. 286, ¶ [0016], , p. 298, ¶ [0060], p.
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`327, claim 33. Thus, this limitation is not disclosed in relation to a particular
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`embodiment but rather in relation to high dose administration of iron carbohydrate
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`complexes, as a whole.
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`Claims 59-74 add no further amendments to the claims other than changing
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`their dependency from issued claim 1 to substitute claim 58 and maintaining
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`subsequent dependency relationships. These claims likewise find support in the
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`applications as filed. See, e.g., Ex. 1007, pp. 324-330, claims 2-3, 10-15, 17, 26,
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`28, 30, 44-46, 50; Ex. 2083, pp. 27-32, claims 2-3, 10-13, 15, 22-24, 35-37, 39.
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`Thus, the substitute claims as a whole have clear written support in both the
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`priority document and the specification as filed.
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`Prior Art
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`C.
`As the moving party, Patent Owner has the burden of demonstrating
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`patentability of the substitute claims over the prior art. 37 C.F.R. § 42.20(c). The
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`scope of this prior art includes any “material art,” which as noted by the Board is
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`any art that addresses “the limitation added by the proposed substitute claim.”
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`Order of March 11, 2016, Paper 22, p. 2; Masterimage 3D, Inc. v. RealD, Inc.,
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`IPR2015-00040, Paper 42, pp. 1–3 (PTAB July 15, 2015).
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`The art of record – cited by Petitioner and made of record in the prosecution
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`of the ’702 patent – is addressed below. The proposed claims are patentable over
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`the prior art, including prior art identified by the Board in its institution decision
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`and other prior art known to Luitpold. See Nike v Adidas AG, ____ F.3d. ____,
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`No. 2014-1719, slip op. at 40 (Fed. Cir. February 11, 2016).
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`The art cited by Petitioner and the art otherwise made of record in the
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`prosecution of the ’702 patent is addressed below in relation to (1) whether the
`
`references relate to embodiments within the scope of the claims to anticipate the
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`claims and, (2) if not, whether the references present a teaching or suggestion that
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`may be combined with any one or more of the other references to render the claims
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`obvious. As explicitly addressed in subsection (9) below, in January 2006 there
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`was no motivation to combine the references.
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`The threshold for obviousness here is high, given that “[t]he prior art as of
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`January 2006 can be characterized by three primary themes: (1) high doses of any
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`iron carbohydrate complexes should generally not be administered due to
`
`uncertainty of their possible immunogenic reactions, (2) more specifically, iron
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`dextran complexes were to be administered with caution due to the risk of iron
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`dextran related immunogenic reactions, and (3) based on these findings with iron
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`dextran, understanding the rate of immunogenic reactions requires a cohort large
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`enough to reveal adverse reaction incidence rates.” Ex. 2080, ¶65.
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`1. Geisser
`Geisser (Ex. 1002, Ex. 1003 (English translation), and Ex. 1014 (English
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`language equivalent)) does not offer any explicit teaching that the carbohydrate
`
`component of its iron carbohydrate complex is substantially non-immunogenic;
`
`indeed, Geisser provides no examples of actual administration of its compound.
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`Further, Geisser is silent on properties of the iron in the iron carbohydrate complex
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`to which the method of production disclosed therein relates; there are no
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`physicochemical characterizations of the iron apart from the final iron
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`carbohydrate complex. Ex. 2080, ¶87. Thus, motivation to alter iron core size to
`
`contravene dosing conventions in the art (as identified by the ’702 patent) cannot
`
`be found in Geisser.
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`van Zyl-Smit, Funk, and Other Polymaltose Related Art
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`2.
`van Zyl-Smit (Ex. 1006), cited by Petitioner, relates to the administration of
`
`iron polymaltose – a species now specifically excluded from substitute claim 58.
`
`Further, van Zyl-Smit contrasts the properties of its iron polymaltose to the
`
`properties of other iron carbohydrates (iron sucrose and iron gluconate). Ex. 1006,
`
`p. 7. Thus, van Zyl-Smit offers no reasonable expectation that the doses or
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`4826-6801-0288.1
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`methodology disclosed therein are cross-applicable to other iron carbohydrate
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`complexes, such as the remaining species in the substitute claims. Ex. 2080, ¶82.
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`Like van Zyl-Smit, Funk (Ex. 1026), cited by Petitioner, relates to the
`
`comparison of chemical properties of two iron polymaltose species, iron dextran
`
`and iron sucrose. Ex. 1026, p. 2-3. None of these species fall within the scope of
`
`substitute claim 58. Further, Funk measures different properties for each of the
`
`species tested. See, e.g., Ex. 1026, p. 18. Thus, like with van Zyl-Smit, Funk
`
`offers no reasonable expectation that its disclosure is predictive of or relevant to
`
`any other iron carbohydrate complexes. Ex. 2080, ¶83.
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`Other art of record relating to iron polymaltose complexes such as Newnham
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`(Ex. 2043, accepted for publication after January 6, 2006, and, hence, not prior
`
`art), Haines (Ex. 2042, published after January 6, 2006, and, hence, not prior art),
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`and Beshara (Ex. 2041) disclose limitations on dosing and adverse reactions
`
`against iron polymaltose. Ex. 2080, ¶¶81, 84. Thus, these references neither teach
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`substantially non-immunogenic carbohydrate components nor address a species
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`listed in substitute claim 58. Ex. 2080, ¶80.
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`For at least these reasons, none of the art relating to iron polymaltose
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`complexes anticipates the substitute claims or offers teachings that may be
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`combined with any other reference discussed herein to render the substitute claims
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`obvious.
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`3. Groman and Other Ferumoxytol Related Art
`Groman (Ex. 1004), cited by Petitioner, relates to the administration of iron
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`polyglucose carboxymethyl ether (also known as carboxymethylated reduced
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`dextran or ferumoxytol) and a hydrogenated dextran.
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`Neither of these species is included within the scope of the claims – certainly
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`not upon the cancelation of claim 28 (and disclaimer of claim 29) and
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`acknowledgement of its improper dependency. That is, if Groman’s species were
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`regarded as within the scope of issued claim 1 on the basis of the dependency of
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`claims 28 and 29, cancelling and/or disclaiming the improperly dependent claims
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`prevents even that unwarranted basis. Moreover, Groman offers no indication that
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`its teachings can be extrapolated to any other iron carbohydrate complexes; thus,
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`combining the teachings of Groman with another iron carbohydrate species offers
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`no reasonable expectation of success. See, e.g., Pharmacosmos A/S v. Luitpold
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`Pharmaceuticals Inc., IPR 2015-01495, Paper 11, pp. 16-18 (PTAB January 8,
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`2016) (The Board found no motivation to combine Geisser (Ex. 1002) and Groman
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`(Ex. 1004), citing Patent Owner’s arguments regarding structural differences
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`between the respective iron carbohydrate complexes.); Ex. 2080, ¶¶74-77, 79.
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`Other art of record relating to ferumoxytol such as the ’498 patent (Ex.
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`1017) and Landry (Ex. 2036) is likewise not related to the species listed in
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`substitute claim 58. Ex. 2080, ¶¶ 74-79.
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`4. Kudasheva
`Kudasheva (Ex. 2044) relates to the characterization of iron complexes –
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`particularly iron sucrose and iron gluconate. Ex. 2080, ¶ 88.
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`Kudasheva identifies the iron core size of these iron carbohydrate complexes
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`to fall within the claimed range of no greater than about 9 nm. Ex. 2048, p. 1,
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`Abstract. However, Kudasheva does not teach administration of these iron
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`carbohydrate complexes or relate iron core size to dose. Ex. 2080, ¶88. Thus,
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`Kudasheva does not provide a motivation to “administer[] to a subject” iron
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`carbohydrate complexes with a mean iron core size in the claimed range, let alone
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`administration of these complexes at doses outside the low dose range taught in the
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`art as of January 6, 2006. See, e.g., Ex. 1006, p. 7; Ex. 2080, ¶¶ 58-65, 88.
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`Vance
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`5.
`Vance (Ex. 1034), cited by Petitioner, does not teach a single dosage unit of
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`0.6 g as required by substitute claim 58. Pharmacosmos A/S v. Luitpold
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`Pharmaceuticals Inc., IPR 2015-01493, Paper 11, pp. 9-10 (PTAB January 8,
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`2016); Paper 21, pp. 3-4 (PTAB February 26, 2016) (finding that Vance does not
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`teach that any amount of iron disclosed within the specified range– especially
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`amounts greater or equal to 600 mg –would have been considered suitable for
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`once-daily administration).
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`Further, Vance’s only examples relate to administration of “ferrous sulfate
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`tablets at approximately 300 milligrams 3 times each day (i.e., 900 mg per day).”
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`Ex. 1034, col. 6:24-27. Vance does not provide correspondence between the
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`dosing regimen and the particular iron species used or guidance on how to
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`optimize the titration parameters specified therein based on the iron complex used.
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`Thus, Vance offers no reasonable expectation that the dosage required by
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`substitute claim 58 could be administered in a manner such that its carbohydrate
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`component has a substantially non-immunogenic effect. Ex. 1034, col. 5:31-36;
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`Ex. 2080, ¶ 89. Thus, Vance does not provide motivation to administer a dose
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`outside the low dose range taught in the prior art.
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`Restless Leg Syndrome Related Art
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`6.
`US 6,960,571 (Ex. 2039) and its earlier publication, US 2004/0180849 (Ex.
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`1009, “Helenek”), relate to the use of iron carbohydrate species for Restless Leg
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`Synd
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