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`Filed on behalf of L’Oréal USA, Inc.
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`By: Michelle E. O’Brien
`Timothy J. Murphy
`Joanna Cohn
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`The Marbury Law Group, PLLC
`11800 Sunrise Valley Drive
`15th Floor
`Reston, VA 20191
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`Tel: (703) 391-2900
`Fax: (703) 391-2901
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`
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`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 6,423,327
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`Mail Stop PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`Table of Contents
`I. Mandatory Notices (37 C.F.R. §42.8(a)(1)) ........................................................ 8
`
`II. Grounds for Standing (37 C.F.R. §42.104(a)) ...................................................10
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`III.
`
`Identification of Challenge (37 C.F.R. §42.104(b)) .......................................10
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`A. Citation of Prior Art ........................................................................................10
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`B. Statutory Grounds for Challenge and Non-Redundancy................................11
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`IV. The ‘327 Patent ...............................................................................................12
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`A. Technical Background .................................................................................13
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`B. Specification of the ‘327 Patent ..................................................................14
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`V. Level of Ordinary Skill in the Art .....................................................................25
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`VI. Claim Construction .........................................................................................25
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`VII. Grounds of Rejection ......................................................................................39
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`A. GROUND 1: Claims 1, 3, 5-7, and 9 are unpatentable under 35 U.S.C.
`§102(b) over DE‘107 ............................................................................................40
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`a. Claim 1 ........................................................................................................44
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`b. Claim 3 ........................................................................................................51
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`c. Claims 5-6 ...................................................................................................52
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`d. Claim 7 ........................................................................................................53
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`e. Claim 9 ........................................................................................................53
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`B. GROUND 2: Claims 1, 3-7, and 9 are unpatentable under 35 U.S.C. §103
`over DE‘107 ..........................................................................................................57
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`C. GROUND 3: Claims 1-7 and 9 are unpatentable under 35 U.S.C. §103 over
`the JP’153/DE’107 combination ...........................................................................60
`
`a. Claim 1 ........................................................................................................62
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`b. Claim 2 ........................................................................................................69
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`c. Claims 3-4 ...................................................................................................70
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`d. Claims 5-6 ...................................................................................................71
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`e. Claim 7 ........................................................................................................72
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`f. Claim 9 ........................................................................................................73
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`VIII. CONCLUSION ..............................................................................................78
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`Cases
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`TABLE OF AUTHORITIES
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`Advance Transformer Co. v. Levinson, 837 F.2d 1081(Fed.Cir.1988) ...................27
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`Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342 (Fed. Cir. 1999) ........... 42, 43, 50
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`Biogen Idec, Inc. v. GlaxoSmithKline LLC, 713 F.3d 1090 (Fed.Cir.2013) ...........27
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`Cont’l Can Co. v. Monsanto Co.,948 F.2d 1264 (Fed.Cir.1991) ............................55
`
`Graham v. John Deere Co., 383 U.S. 1 (1966) .......................................................40
`
`Hockerson-Halberstadt, Inc. v. Avia Grp. Int’l, Inc.,
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`222 F.3d 951 (Fed. Cir. 2000) .............................................................27
`
`In re Aller, 220 F.2d 454 (C.C.P.A. 1955) ...................................................... passim
`
`In re Antonie, 559 F.2d 618 (C.C.P.A. 1977) .................................................. passim
`
`In re Arkley, 455 F.2d 586 (C.C.P.A. 1972) .................................................... passim
`
`In re King, 801 F.2d 1324 (Fed. Cir. 1986) .............................................................42
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`In re O’Farrell, 853 F.2d 894 (Fed.Cir.1988) .........................................................66
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`In re Wertheim, 541 F.2d 257 (C.C.P.A. 1976) .......................................................58
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`In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990) ......................................................58
`
`Ineos USA LLC v. Berry Plastics Corp., 783 F.3d 865 (Fed. Cir. 2015) ......... 49, 50
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`KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) ............................ 40, 57, 62, 66
`
`LSI Corp. and Avago Tech. U.S., Inc. v. Reg. of the Univ. of Minn.,
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`
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`IPR2017-01068, Paper 19 at 10 (P.T.A.B. Dec. 19, 2017) ................... 9
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`Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157 (Fed.Cir.2006) ....................... 66, 67
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`Modine Mfg. Co. v. United States ITC, 75 F.3d 1545 (Fed. Cir. 1996) ..................37
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`Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007) ....................................67
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`Phillips v. AWH Corp., 415 F.3d 1303 (Fed.Cir.2005). ..........................................26
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`Spansion, Inc. v. ITC, 629 F.3d 1331 (Fed.Cir.2010) ..............................................40
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`Tempo Lighting, Inc. v. Tivoli, LLC, 742 F.3d 973 (Fed.Cir.2014) ........................26
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`U.S. Patent No. 6,423,327
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`Titanium Metals Corp. v. Banner, 778 F.2d 775 (Fed. Cir. 1985) ............. 42, 65, 71
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`Statutes
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`35 U.S.C. §102 .........................................................................................................39
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`35 U.S.C. §102(a) ....................................................................................................16
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`35 U.S.C. §102(b) ............................................................................................ passim
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`35 U.S.C. §102(e) ....................................................................................................16
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`35 U.S.C. §103 ................................................................................................. passim
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`35 U.S.C. §103(a) ............................................................................................. 16, 18
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`35 U.S.C. §112 .................................................................................................. 37, 39
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`Rules
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`37 C.F.R. §42.10(a) .................................................................................................... 8
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`37 C.F.R. §42.10(b) ................................................................................................... 8
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`37 C.F.R. §42.104(a) ................................................................................................10
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`37 C.F.R. §42.104(b) ...............................................................................................10
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`37 C.F.R. §42.8(a)(1) ................................................................................................. 7
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`37 C.F.R. §42.8(b)(3) ................................................................................................. 8
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`37 C.F.R. §1.132 …………………………………………………………………19
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`EXHIBIT LIST
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`
`Exhibit No.
`
`Description
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`1001
`
`U.S. Patent No. 6,423,327 to Dobson et al.
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`1002
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`U.S. Patent No. 6,645,513 to Dobson et al.
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`1003
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`German Published Unexamined Application No. DE 19545107
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`1004
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`Certified Translation of DE 19545107 with Affidavit attesting
`to accuracy under 37 CFR 42.63(b)
`
`1005
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`Japanese Unexamined Publication JP-H-09-157153
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`1006
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`Certified Translation of JP-H-09-157153 with Affidavit
`attesting to accuracy under 37 CFR 42.63(b)
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`1007
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`U.S. Patent No. 5,091,182 to Ong et al.
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`1008
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`RESERVED
`
`1009
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`File History of U.S. Patent No. 6,423,327
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`1010
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`Declaration of R. Randall Wickett, Ph.D.
`
`1011
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`Declaration of S. Jamal Mustafa, Ph.D.
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`1012
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`PCT Publication WO1996014822A1 Porter et al.
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`1013
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`U.S. Patent No. 6,316,012 to N’Guyen et al.
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`1014
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`1015
`
`1016
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`Kathryn M. Neurath et al., AMP-Dependent Protein Kinase
`Alpha 2 Isoform Promotes Hypoxia-Induced VEGF Expression
`in Human Glioblastoma, 53 Glia 733, 733–743 (2006).
`
`Geoffrey Burnstock et al., Purinergic Signaling in Healthy and
`Diseased Skin, 132 J. Invest. Dermatol 526, 526–546 (2012).
`
`Robert J. Scheuplein, Permeability of the Skin: A Review of
`Major Concepts and Some New Developments, 67 J.
`INVESTIGATIVE DERMATOL. 672, 672-76 (1976).
`
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`6
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`1017
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`1018
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`1019
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`1020
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`1021
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`Karen A. Holbrook & George F. Odland, Regional Differences
`in the Thickness (Cell Layers) of the Human Stratum Corneum:
`An Ultrastructural Analysis , 62 J. Investigative Dermatol. 415,
`415-22 (1974).
`
`C. Lotte et al., In vivo relationship between transepidermal
`water loss and percutaneous penetration of some organic
`compounds in man: effect of anatomic site, 279 Arch Dermatol
`Res 351, 351-6 (1987).
`
`H. Koizumi et al., Adenosine Deaminase in Human Epidermis
`from Healthy and Psoriatic Subjects, 275 Arch Dermatol Res
`310, 310-14 (1983).
`
`P. Singh & M.S. Roberts, Skin Permeability and Local Tissue
`Concentrations of Nonsteroidal Anti-Inflammatory Drugs after
`Topical Application, 268 J. Pharmacol. Exp. Ther 144, 144-51
`(1994).
`
`Gary L. Grove et al., Use of nonintrusive tests to monitor age-
`associated changes in human skin, 32 J. Soc. Cosmet. Chem.
`15, 15-26 (1981).
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`L’Oréal USA, Inc. (“Petitioner”) petitions for inter partes review of claims
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`1-7 and 9 of U.S. Patent No. 6,423,327 to Dobson, Jr. et al., entitled
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`“TREATMENT OF SKIN WITH ADENOSINE OR ADENOSINE ANALOG”
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`(“the ‘327 patent,” Ex. 1001).
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`I. Mandatory Notices (37 C.F.R. §42.8(a)(1))
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`REAL PARTY IN INTEREST
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`The real parties-in-interest are L’Oréal USA, Inc. and L’Oréal S.A.
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`RELATED MATTERS
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`The ‘327 patent, entitled “Treatment of Skin with Adenosine or Adenosine
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`Analog,” issued on July 23, 2002, from U.S. Patent Application No. 09/672,348
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`(“the ‘348 application”), filed September 28, 2000, which was a continuation of
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`U.S. Patent Application No. 09/179,006 (“the ‘006 application”), filed October 26,
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`1998.1 (Ex. 1001, cover page.)
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`
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`A petition for inter partes review is being filed concurrently herewith
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`
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`1 Petitioner does not concede that any claim of the ‘327 patent is entitled to priority
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`to the ‘006 application, and reserves the right to challenge priority; however, for
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`purposes of this Petition, Petitioner will refer to the earliest possible priority date
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`of the ‘327 patent as October 26, 1998.
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`challenging claims 1-7 and 9 of U.S. Patent No. 6,645,513 (“the ‘513 patent,” Ex.
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`1002), which claims priority to both the ‘348 and ‘006 applications.
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`
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`University of Massachusetts Medical School and Carmel Laboratories, LLC
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`v. L’Oréal S.A. and L’Oréal USA, Inc., Case 1:17-cv-00868, filed on June 30,
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`2017, in United States District Court for the District of Delaware, includes a
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`complaint for patent infringement of the ‘327 patent (“Delaware suit”).
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`LEAD AND BACKUP COUNSEL
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`Pursuant to 37 C.F.R. §42.8(b)(3) and 37 C.F.R. §42.10(a), Petitioner
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`appoints Michelle E. O’Brien (Reg. No. 46,203) as its lead counsel, and Timothy
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`J. Murphy (Reg. No. 62,585) and Joanna Cohn (Reg. No. 68,010) as its back-up
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`counsel. Pursuant to 37 C.F.R. §42.10(b), a power of attorney is being filed with
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`this designation of counsel.
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`SERVICE INFORMATION:
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`Petitioner provides the following service information for designated counsel:
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`The Marbury Law Group, PLLC
`11800 Sunrise Valley Drive
`15th Floor
`Reston, VA 20191
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`Tel: (703) 391-2900
`Fax: (703) 391-2901
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`Petitioner consents to electronic service by email to the email addresses:
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`mobrien@marburylaw.com;
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`tjmurphy@marburylaw.com;
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`jcohn@marburylaw.com; and
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`327IPR@marburylaw.com.
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`II. Grounds for Standing (37 C.F.R. §42.104(a))
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`Petitioner certifies that the ‘327 patent is available for inter partes review
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`and that Petitioner is not barred or estopped from requesting an inter partes review
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`challenging the claims on the grounds identified in this Petition.
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`
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`Furthermore, although Petitioner does not concede that PO is entitled to
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`sovereign immunity, PO waived any possible claim of sovereign immunity in this
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`proceeding by asserting the ‘327 patent against Petitioner in the Delaware suit.
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`See, e.g., LSI Corp. and Avago Tech. U.S., Inc. v. Reg. of the Univ. of Minn.,
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`IPR2017-01068, Paper 19 at 10 (P.T.A.B. December 19, 2017).
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`III.
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`Identification of Challenge (37 C.F.R. §42.104(b))
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`A. Citation of Prior Art
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`
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`Petitioner cites the following prior art references:
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`• German Published Unexamined Application No. DE 198459107
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`(“DE‘107,” Ex. 1003, with reference herein to Ex. 1004 (certified
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`translation)) is prior art under at least 35 U.S.C. §102(b) because it
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`published on June 5, 1997, more than 1 year before the earliest
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`possible priority date of the ‘327 patent.
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`• Japanese Unexamined Publication JP-H-09-157153 (“JP’153,” Ex.
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`1005, with reference herein to Ex. 1006 (certified translation)) is prior
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`art under at least 35 U.S.C. §102(b) because it published on June 17,
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`1997, more than 1 year before the earliest possible priority date of the
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`‘327 patent. JP’153 was not considered by the Examiner who
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`examined the ‘327 patent.
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`• U.S. Patent No. 5,091,182 to Ong (“Ong,” Ex. 1007) is prior art
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`under at least 35 U.S.C. §102(b) because it issued on February 25,
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`1992, more than 1 year before the earliest possible priority date of the
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`‘327 patent. Ong was not considered by the Examiner who examined
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`the ‘327 patent.
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`B. Statutory Grounds for Challenge and Non-Redundancy
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`Petitioner requests review of claims 1-7 and 9 of the ‘327 patent on the
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`following grounds:
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`• GROUND 1: Claims 1, 3-7, and 9 are unpatentable under 35 U.S.C.
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`§102(b) as anticipated by DE‘107 (Ex. 1003, 1004).
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`• GROUND 2: Claims 1, 3-7, and 9 are unpatentable under 35 U.S.C.
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`Petition for Inter Partes Review of
`U.S. Patent No. 6,423,327
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`§103 as obvious over DE‘107 (Ex. 1003, 1004).
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`• GROUND 3: Claims 1-7 and 9 are unpatentable under 35 U.S.C.
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`§103 as obvious over JP’153 (Ex. 1005, 1006) and DE‘107 (Ex. 1003,
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`1004).
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`The grounds are not redundant because they are based on different statutory
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`bases and different prior art references. In addition, JP ‘153 was not considered by
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`the Examiner during prosecution of the ‘327 patent, and the ‘327 patent was
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`improperly allowed over DE’107 based on a misapplication of the law regarding
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`inherency. Accordingly, all Grounds should be instituted.
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`IV. The ‘327 Patent
`
`The ‘327 patent relates to “[m]ethods for enhancing the condition of non-
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`diseased skin by application of compositions containing adenosine2 [to the
`
`skin]….” (Ex. 1001, Abstract.)
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`Claim 1 recites “[a] method for enhancing the condition of unbroken skin of
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`a mammal by reducing one or more of wrinkling, roughness, dryness, or laxity of
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`the skin, without increasing dermal cell proliferation, the method comprising
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`2 The ‘327 specification discusses both adenosine and adenosine analogs
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`throughout; however, since adenosine analogues were canceled from the claims,
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`Petitioner’s discussion will focus only on adenosine.
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`topically applying to the skin a composition comprising a concentration of
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`adenosine in an amount effective to enhance the condition of the skin without
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`increasing dermal cell proliferation, wherein the adenosine concentration applied
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`to the dermal cells is 10−4 M to 10−7 M.” (Ex. 1001, 10:19-27.)
`
`A. Technical Background
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`As was well known prior to and in 1998, human skin is comprised of many
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`layers, including outer, epidermal layers, which cover inner layers, including the
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`dermis. (Ex. 1001, 1:19-25; Ex. 1010, ¶31-32.) As the ‘327 patent explains, skin
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`has “a surface layer, known as the epidermis, and a deeper connective tissue layer,
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`known as the dermis.” (Ex. 1001, 1:19-25.) Further, the “dermis is composed of a
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`variety of cell types, including fibroblasts.” (Id.) Thus, the dermis, made up of
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`different types of dermal cells including dermal fibroblast cells, is covered by the
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`outer layer, the epidermis, made up of different types of epidermal cells. (Ex.
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`1010, ¶30.)
`
`It was also well known prior to 1998 that human skin changes with age and
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`exposure to environmental agents such as ultraviolet radiation and atmospheric
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`pollutants. (Ex. 1001, 1:26-28; Ex. 1004, 1:11-34; Ex. 1006, 2:7-28; Ex. 1012,
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`1:13-16; Ex. 1013, 1:16-24; Ex. 1010, ¶34.) Indeed, age, ultraviolet radiation, and
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`pollution have long been understood to damage the skin and contribute to an
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`increase in the appearance of wrinkles and a decrease in the skin’s brightness and
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`Petition for Inter Partes Review of
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`smoothness. (Ex. 1004, 1:11-34; Ex. 1006, p. 2, ll. 7-28; Ex. 1012, 1:13-16; Ex.
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`1013, 1:16-23; Ex. 1010, ¶34.) It was, therefore, known well before the ‘327
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`patent’s earliest priority date to treat skin that had such damage by topically
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`applying cosmetic compositions comprising various compounds and chemicals,
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`such as antioxidants, to the outer, epidermal layer of the skin. (Ex. 1006, 2:29-35
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`and Abstract; Ex. 1012, 1:14-3:14; Ex. 1013, 1:55-59 and Abstract; Ex. 1010,
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`¶37,58.)
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`Adenosine is a nucleoside that occurs naturally in all human cells, and is
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`relevant to many biochemical processes in the human body. (Ex. 1010, ¶14.) Prior
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`to 1998, adenosine was known to have antioxidant properties. (Ex. 1013, 1:32-35;
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`Ex. 1011, ¶38.) Likewise, adenosine was known prior to 1998 to be useful in
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`cosmetic compositions for treating skin dryness and wrinkling, such as that caused
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`by aging, ultraviolet radiation, and pollution. (Ex. 1004, 1:1-34; Ex. 1006, 2:7-28;
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`Ex. 1013, 1:16-23.)
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`B. Specification of the ‘327 Patent
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`The ‘327 patent states that “adenosine stimulates DNA synthesis, increases
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`protein synthesis, and increases cell size in cultures of human skin fibroblasts,”
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`which effects the ‘327 patent asserts permit the use of adenosine in the disclosed
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`“methods and compositions for enhancing the condition of skin.” (Ex. 1001, 1:37–
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`41.) According to the ‘327 patent, “the invention provides a method for enhancing
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`the condition of non-diseased skin of a mammal, e.g., a human” utilizing the
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`aforementioned effects of adenosine, by “topically applying a therapeutically
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`effective amount of a composition including adenosine…to non-diseased skin of
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`the mammal.” (Id., 1:42–47.) Finally, the ‘327 patent states that the methods
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`include “topically administering a composition including a therapeutically
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`effective amount of adenosine...to a region of skin of the mammal containing the
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`dermal cell,” and that “the adenosine…does not cause proliferation of the dermal
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`cell.” (Id., 1:56-60, 1:63-67, 2:3-8.)
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`According to the ‘327 patent, “a ‘therapeutically effective amount’ of
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`adenosine…means an amount that enhances the skin when applied to the skin.”
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`(Id., 2:38-40.) Specifically, the ‘327 patent states that “[t]he therapeutically
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`effective amount of adenosine used in the above-described methods is preferably
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`10-3 M to 10-7 M, more preferably 10-3 M to 10-6 M, and most preferably about 10-4
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`M.” (Id., 2:13–16.) These molar ranges correspond to weight percents of
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`preferably 0.000265% to 0.00000265%, more preferably 0.000265% to
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`0.0000265%, and most preferably about 0.00265%.3 (Ex. 1010, ¶30.)
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`Finally, the ‘327 patent defines the phrase “enhancement of skin condition”
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`
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`3 The claimed range of 10-4 M to 10-7 M corresponds to 0.00265% to
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`0.00000265%. (Ex. 1010, ¶30.)
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`as bringing about “a noticeable decrease in the amount of wrinkling, roughness,
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`dryness, laxity, shallowness, or pigmentary mottling in skin.” (Ex. 1001, 2:35-37.)
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`C. Prosecution of the ‘327 Patent
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`1. Overview
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`The ‘348 application, which ultimately issued as the ‘327 patent, was filed
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`on September 28, 2000, with original claims 1-53, and a preliminary amendment
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`canceling claims 2-53 and adding priority information to the specification. (Ex.
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`1009, at 6–47.) This left claim 1 as the sole, pending claim, which read:
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`1. A method for enhancing the condition of non-diseased skin of
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`a mammal, comprising topically applying a therapeutically
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`effective amount of a composition comprising adenosine or an
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`adenosine agonist to non-diseased skin of said mammal.
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`(Id., at 30.) The ‘348 application, which claimed priority to the ‘006 application,
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`was filed in lieu of responding to an Office Action issued in the ‘006 application,
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`finally rejecting all claims.
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`On April 20, 2001, the Examiner issued a non-final Office Action in which
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`claim 1 was rejected under 35 U.S.C. §102(e) as anticipated by U.S. Patent Nos.
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`5,998,423 (“Manneth”) and 5,932,558 (“Cronstein”), as well as under 35 U.S.C.
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`§102(a) as anticipated by U.S. Patent No. 5,770,582 (“von Borstel”). (Id. at 53-
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`54.) Claim 1 was also rejected under 35 U.S.C. §103(a) as unpatentable over each
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`of Manneth, Cronstein and von Borstel. (Id. at 54-55.).
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`In response, claim 1 was canceled and new claims 54-79 were added,
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`including new claim 54 directed to a “method for increasing DNA synthesis,” new
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`claim 63 directed to a “method for increasing protein synthesis,” and new claim 70,
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`which would ultimately be further amended and issue as claim 1 of the ‘327 patent,
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`which read:
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`70. A method for enhancing the condition of unbroken skin of a
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`mammal by reducing one or more of wrinkling, roughness,
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`dryness, or laxity of the skin, without increasing dermal cell
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`proliferation the method comprising topically applying to the
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`skin a composition comprising a concentration of adenosine in
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`an amount effective to enhance the condition of the skin
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`without increasing dermal cell proliferation.
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`(Ex. 1009, at 62.) It was argued that the cited references did not disclose the
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`elements recited in the new claims, and that “[t]he invention is based on the
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`discovery that adenosine stimulates DNA synthesis, increases protein synthesis,
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`and increases cell size in cultures of human dermal cells, such as fibroblasts, all
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`without increasing cell proliferation.” (Id. at 63.) Further, it was argued that “in
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`these methods, the adenosine…[is] applied to the cells or topically to the skin to
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`increase the cell size, and the function and abundance of products produced by the
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`dermal cells, such as fibroblasts, e.g., by increasing DNA synthesis and/or protein
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`synthesis.” (Id.) Finally, it was argued that Cronstein’s teaching to treat open
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`wounds such as burns would necessarily require application to broken skin, which
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`PO asserted was different from the claim 70’s recited method of enhancing
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`unbroken skin. (Id. at 67.)
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`On October 10, 2001, the Examiner issued a final Office Action rejecting
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`new claims 70, 74-76 and 78 under 35 U.S.C. §102(b) as anticipated by DE‘107
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`(Ex. 1003, 1004), and claims 70 and 76 under 35 U.S.C. §102(b) as anticipated by
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`Hartzshtark et al. in Experentia (1985) (“Hartzshtark”). (Ex. 1009, at 73-74.) The
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`final Office Action also rejected claims 70 and 72-78 under 35 U.S.C. §103(a) as
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`unpatentable over DE‘107 and/or Hartzshtark, claim 71 under 35 U.S.C. §103(a) as
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`unpatentable over DE‘107, Hartzshtark, and U.S. Patent No. 5,618,544 (“Brown”),
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`and claims 78-79 under 35 U.S.C. §103(a) as unpatentable over DE‘107,
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`Hartzshtark, and U.S. Patent No. 5,785,978. (Ex. 1009, at 74-77.)
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`Regarding DE‘107, which discloses the use of adenosine in cosmetic
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`compositions at a concentration as low as 0.001% (3.8 x 10-5 M) for treating skin
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`damage associated with aging, the Examiner stated:
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`[DE‘107] discloses a cosmetic and dermatological preparation
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`containing adenosine for the treatment of natural, chemical
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`induced or UV-induced skin aging and its sequelae. While
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`[DE‘107] states that adenosine stimulates cell proliferation,
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`[DE‘107] does not state that adenosine increases cell
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`proliferation. … Accordingly, the method of [DE‘107], which
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`employs adenosine as claimed, also reduces one or more
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`conditions such as dryness, wrinkles, etc.
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`(Id. at 74 (emphasis original)). Regarding Hartzshtark, which discloses the
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`application of adenosine to the skin at concentrations of both 0.1% and 0.033%,
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`the Examiner stated that the reference:
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`discloses that application of adenosine [to the skin]…reduced
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`the degree of skin indentation, which is an indication of a
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`firmer and younger skin.
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`(Id.) In other words, the Examiner pointed out that both DE‘107 and Hartzshtark
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`disclose exactly what was claimed, i.e. a method of reducing wrinkles in the skin
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`by topical application of adenosine thereto.
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`In response, claims 54-69 were canceled and independent claim 70 was
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`amended to recite a specific concentration of adenosine: “wherein the adenosine
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`concentration applied to the dermal cells is 10-4 M to 10-7 M.” (Id. at 82, 88.) In an
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`attempt to distinguish over DE‘107, it was argued that the reference “must be
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`mistaken in that adenosine was not likely actually administered at this low
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`concentration,” and a Declaration Under 37 C.F.R. §1.132 (“Declaration”) was
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`submitted addressing this point. (See Section C.2, infra.)
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`With regard to the anticipation and obviousness rejections over Hartzshtark,
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`it was argued that the newly-added concentration range of 10-4 M to 10-7 M of
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`adenosine in claim 70 distinguished Hartzshtark’s disclosures of compositions
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`containing 0.1% (3.8 x 10-3 M) and 0.033% (1.27 x 10-3 M) adenosine, as greater
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`than, and therefore outside, the claimed range:
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`The proposed amended claims would recite a maximum
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`concentration of adenosine of 10-4 M.
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` . . . .
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`Thus, there would have been no suggestion or motivation in
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`[Hartzshtark] for one of skill in this field to use a maximum
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`concentration of 10-4 M adenosine as recited in applicants’
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`claim 70.
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`(Id. at 85-86 (emphasis original); see also id. at 90.) In other words, the
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`concentrations of adenosine in Hartzshtark’s compositions were relied on to
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`distinguish the claimed method “wherein the adenosine concentration applied to
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`the dermal cells is 10-4 M to 10-7 M.”
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`A Notice of Allowance was mailed on March 21, 2002. (Id. at 116.) The
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`Examiner stated that while “the prior art of record teaches administering adenosine
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`to the skin for treating aging…the art of record utilizes concentrations much higher
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`than claimed and also require that the amounts of adenosine stimulate cell
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`proliferation for the treatment.” (Id. at 117.) Additionally, the Examiner indicated
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`that the results presented in the Declaration were persuasive: “applicants have
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`shown that using adenosine at the claimed concentrations [does] not result in
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`adverse affects but still provide skin conditioning effects.” (Id.)
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`However, as discussed in greater detail below, an improper legal standard
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`regarding inherency was applied regarding DE‘107, erroneously leading to
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`issuance of the ‘327 patent.
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`2. Improper Declaration
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`As noted, a Declaration was submitted in response to the final Office Action,
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`which appears to have been relied on by the Examiner in concluding that the
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`claims were patentable. (Id. at 117.) The Declaration purports to describe ex vivo
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`tests of cultured “skin fibroblast cells, which make up a significant portion of
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`dermal cells, from two different donors (an 84 year-old man and 30 year-old
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`female), with varying concentrations of adenosine (10-4 or 10-5 M).” (Id. at 82-83.)
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`It was argued that the Declaration demonstrated that the lowest concentration of
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`DE‘107, i.e. 0.001% which was within the claimed range and between the two
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`tested points of 10-4 M and 10-5 M, would not increase dermal fibroblast cell
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`proliferation. This was further alleged to demonstrate that DE‘107 “must be
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`mistaken in that adenosine was not likely actually administered at this low
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`concentration” and therefore DE‘107 “cannot be valid, and…does not disclose the
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`same invention as the proposed claims in the present application.” (Id. at 84; see
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`also id. at 90 where it was stated that testing at the two concentrations of adenosine
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`“had no significant effect on cell proliferation” of the dermal fibroblast cells, and
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`concluded that “lower concentrations of adenosine, e.g. 10-6 and 10-7 M, would
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`also not increase cell proliferation.”)
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`The Examiner’s reliance on these representations made by the applicant in
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`the ‘348 application was improper for at least the following reasons.
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`a. Declaration not commensurate in scope with claims
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`As an initial matter, the Declaration was improper because the Declaration
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`was not commensurate in scope with the claims.
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`First, the ex vivo testing in a dish, with cultured fibroblast cells taken from
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`the dermis of the subjects, did not use the claimed method of “topical” application
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`to “unbroken skin,” i.e. to the epidermal layer of the skin. (Ex. 1009, 89-91, 107-
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`111.)
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`Second, only one type of dermal cell was tested—dermal fibroblast cells—
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`despite the fact that the ‘327 patent teaches that the dermal layer of skin comprises
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`“a variety of cell types,” in addition to fibroblasts. (Ex. 1001, 1:24-25.) As such,
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`the Declaration cannot support a position that cell proliferation was demonstrated
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`not to occur in every type of dermal cell, and in fact there is no testimony to this
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`effect in the Declaration.
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`Third, no concentrations of adenosine were tested outside the claimed range
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`in order to establish any criticality for the range. (Ex. 1009, 89-91, 107-111.)
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`For at least these reasons, the Declaration was not commensurate in scope
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`with the claims, and should not have been relied on by the Examiner.
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`b. Declaration does not establish anything about whether DE’107’