UNITED STATES PATENT AND TRADEMARK OFFICE
`________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________
`
`APOTEX INC., APOTEX CORP., APOTEX PHARMACEUTICALS
`HOLDINGS INC., and APOTEX HOLDINGS, INC.,
`Petitioners,
`
`v.
`
`OSI PHARMACEUTICALS, INC.,
`Patent Owner.
`________________
`
`U.S. Patent No. 6,900,221
`Issue Date: May 31, 2005
`Title of Patent: Stable Polymorph on N-(3-ethylphenyl)-6,7-bis(2methoxyethoxy)-
`4-quinazolinamine hydrochloride, Methods of Production,
`and Pharmaceutical uses thereof
`________________
`
`Case No.: T.B.D.
`________________
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 6,900,221 UNDER
`35 U.S.C. §§ 311-319 AND 37 C.F.R. § 42
`
`
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`TABLE OF CONTENTS
`TABLE OF CONTENTS ............................................................................................ i
`LIST OF EXHIBITS ................................................................................................. iv
`I.
`INTRODUCTION ........................................................................................... 1
`II. MANDANTORY NOTICES .......................................................................... 1
`A.
`Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) .................................... 2
`B. Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) .............................. 2
`C.
`Identification of Counsel (37 C.F.R. § 42.8(b)(3)) ............................... 2
`D.
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 3
`III. CLAIMS FOR WHICH REVIEW IS REQUESTED
`(37 C.F.R. § 42.104(b)(1)) ............................................................................... 3
`IV. GROUNDS FOR STANDING AND PROCEDURAL
`STATEMENT (37 C.F.R. § 42.104(a)) ........................................................... 3
`IDENTIFICATION OF CHALLENGE AND STATEMENT
`OF THE PRECISE RELIEF REQUESTED ................................................... 3
`VI. THRESHOLD REQUIREMENT FOR INTER PARTES
`REVIEW .......................................................................................................... 4
`VII. STATEMENT OF REASONS FOR THE RELIEF
`REQUESTED .................................................................................................. 4
`A. Overview of the ’221 Patent .................................................................. 5
`B.
`Relevant Prosecution History of the ’221 Patent and
`Reasons for Allowance of the Challenged Claims ................................ 7
`Priority Date of the Challenged Claims ................................................ 9
`Prior Litigation Involving the ’221 Patent .......................................... 10
`Level of Ordinary Skill in the Art ....................................................... 12
`Claim Construction (37 C.F.R. § 42.104(b)(3)) .................................. 13
`
`C.
`D.
`E.
`F.
`
`V.
`
`i
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`G.
`
`Patents and Printed Publications Relied Upon
`(37 C.F.R. § 42.104(b)(2)) .................................................................. 13
`1.
`Schnur (Ex. 1009) ..................................................................... 13
`2.
`Gibbs (Ex. 1010) ....................................................................... 17
`3.
`OSI’s 10-K (Ex. 1011) .............................................................. 18
`4. Wakeling (Ex. 1013) ................................................................. 19
`5. Moscatello (Ex. 1014) ............................................................... 21
`H. Unpatentability of the Challenged Claims
`(37 C.F.R. § 42.104(b)(4)) .................................................................. 22
`1.
`Ground I: Claims 44-46 and 53 are Unpatentable
`Under 35 U.S.C. § 103(a) (pre-AIA) as Obvious
`over Schnur in View of Gibbs or OSI’s 10-K ........................... 22
`a)
`The Prior Art Teaches or Suggests Each
`Element of Independent Claim 44 and
`Dependent Claim 53 ....................................................... 23
`The Prior Art Teaches of Suggests Each
`Element of Dependent Claim 45 .................................... 30
`The Prior Art Teaches or Suggests Each
`Element of Dependent Claim 46 .................................... 31
`The Rationale to Combine Schnur with
`Gibbs or OSI’s 10-K ....................................................... 33
`Ground II: Claim 47 is Unpatentable under
`35 U.S.C. § 103(a) (pre-AIA) as Obvious Over
`Schnur in View of Gibbs or Wakeling, Further in
`View of Moscatello ................................................................... 35
`a)
`Schnur in View of Gibbs or Wakeling Teach
`or Suggest That Erlotinib Was One of a
`Class of Compounds Having Similar
`Properties ........................................................................ 36
`
`2.
`
`ii
`
`b)
`
`c)
`
`d)
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`3.
`
`c)
`
`b) Moscatello Provides a Reasonable
`Expectation That Erlotinib, Like Other
`Compounds Described by Schnur and
`Wakeling or Gibbs, Would Treat Tumors
`That Express EGFRvIII .................................................. 37
`Rationale to Combine Schnur and Gibbs or
`Wakeling with Moscatello .............................................. 39
`Ground III: In the Alternative, Claims 44-47 and
`53 are Unpatentable Under 35 U.S.C. § 102(b)
`(pre-AIA) as Anticipated by Schnur ......................................... 44
`VIII. PETITIONER PRESENTS NEW GROUNDS OF
`UNPATENTABILITY .................................................................................. 46
`IX. THE ASSERTED GROUNDS ARE NON-CUMULATIVE
`AND NON-REDUNDANT ........................................................................... 46
`CONCLUSION .............................................................................................. 47
`X.
`XI. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND
`42.103 ............................................................................................................ 47
`XII. WORD COUNT CERTIFICATION UNDER 37 C.F.R. §§
`42.24(A) ........................................................................................................ 47
`APPENDIX A – Claim Chart: Ground I (Obviousness of Claims 44-46 and 53
`Over Schnur in View of Gibbs or OSI’s 10-K)
`APPENDIX B – Claim Chart: Ground II (Obviousness of Claim 47
`Over Schnur in View of Gibbs or Wakeling, and Moscatello)
`APPENDIX C – Claim Chart: Ground III (Anticipation of Claims 44-47 and 53
`By Schnur If Priority is Accorded to the ’907 Application)
`
`
`
`
`
`iii
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`Petitioners’
`Ex. No.
`1001
`
`1002
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`1008
`1009
`
`1010
`
`1011
`
`1012
`1013
`
`1014
`
`EXHIBIT LIST (37 C.F.R. § 42.63(e))
`
`Description
`U.S. Patent No. 6,900,221, titled “Stable Polymorph on N-(3-
`ethylphenyl)-6,7-bis(2methoxyethoxy)-4-S hydrochloride,
`Methods of Production, and Pharmaceutical uses thereof,” issued
`May 31, 2005
`Declaration of Giuseppe Giaccone, M.D., Ph.D.
`Excerpt from Prosecution History of U.S. Patent No. 6,900,221,
`Amendment dated June 19, 2002
`Excerpt from Prosecution History of U.S. Patent No. 6,900,221,
`Office Action dated August 30, 2002
`Excerpt from Prosecution History of U.S. Patent No. 6,900,221,
`Amendment dated February 28, 2003
`Excerpt from Prosecution History of U.S. Patent No. 6,900,221,
`Notice of Allowance dated June 18, 2003
`Provisional Appl. No. 60/164,907, filed November 11, 1999
`Provisional Appl. No. 60/193,191, filed March 30, 2000
`U.S. Patent No. 5,747,498, titled “Alkynyl and Azido-Substituted
`4-Anilinoquinazolines,” issued May 5, 1998
`J.B. Gibbs, “Anticancer drug targets: growth factors and growth
`factor signaling,” The Journal of Clinical Investigation 105(1):9-
`13 (Jan. 2000)
`Annual Report pursuant to Section 13 or 15(d) of the Securities
`Exchange Act of 1934 for the Fiscal Year Ended September 30,
`1998 Commission File Number 0-15190 OSI Pharmaceuticals,
`Inc.
`Declaration of Laurence S. Lese, Esq.
`A.E. Wakeling et al., “Specific inhibition of epidermal growth
`factor receptor tyrosine kinase by 4-anilinoquinazolines,” Breast
`Cancer Research and Treatment 38:67-73 (1996)
`D.K. Moscatello et al., “Constitutive Activation of
`Phosphatidylinositol 3-Kinase by a Naturally Occurring Mutant
`Epidermal Growth Factor Receptor,” The Journal of Biological
`Chemistry 273(1): 200-206 (January 1998)
`
`iv
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`V.A. Pollack et al., “Inhibition of Epidermal Growth Factor
`Receptor-Associated Tyrosine Phosphorylation in Human
`Carcinomas with CP-358,774: Dynamics of Receptor Inhibition
`In Situ and Antitumor Effects in Athymic Mice,” The Journal of
`Pharmacology and Experimental Therapeutics 291(2):739-748
`(1999)
`J.D. Moyer et al., “Induction of Apoptosis and Cell Cycle Arrest
`by CP-358,774, an Inhibitor of Epidermal Growth Factor Receptor
`Tyrosine Kinase,” Cancer Research 57:4838-48 (1997)
`V. Rusch et al., “The Epidermal Growth Factor Receptor and its
`Ligands as Therapeutic Targets in Human Tumors,” Cytokine &
`Growth Factor Reviews 7(2):133-141 (1996) (“Rusch”).
`T. Cerny, “Expression of epidermal growth factor receptor (EGF-
`R) in human lung tumours,” British Journal of Cancer 54:265-69
`(1986)
`B.R. Voldborg et al., “Epidermal growth factor receptor (EGFR)
`and EGFR mutations, function and possible role in clinical trials,”
`Annals of Oncology 8:1197-1206 (1997)
`M. Lee et al., “Epidermal Growth Factor Receptor Monoclonal
`Antibodies Inhibit the Growth of Lung Cancer Cell Lines,”
`Journal of the National Cancer Institute Monographs (13):117-
`123 (1992)
`H. Masui et al., “Growth Inhibition of Human Tumor Cells in
`Athymic Mice by Anti-Epidermal Growth Factor Receptor
`Monoclonal Antibodies,” Cancer Research 44:1002-7 (1984)
`I.E. Garcia de Palazzo et al., “Expression of Mutated Epidermal
`Growth Factor Receptor by Non-Small Cell Lung Carcinomas,”
`Cancer Research 53:3217-20 (1993)
`C.J. Wikstrand, “Cell Surface Localization and Density of the
`Tumor-associated Variant of the Epidermal Growth Factor
`Receptor, EGFRvIII,” Cancer Research 57:4130-40 (1997)
`D. Veale et al., “The relationship of quantitative epidermal growth
`factor receptor expression in non-small cell cancer to long term
`survival,” British Journal of Cancer 68:162-65 (1993)
`M. Haeder et al., “Epidermal Growth Factor Receptor Expression
`in Human Lung Cancer Cell Lines,” Cancer Research 48:1132-36
`(1988)
`D. Veale et al., “Epidermal growth factor receptors in non-small
`cell lung cancer,” British Journal of Cancer 55:513-16 (1987)
`
`v
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`1027
`
`1028
`
`
`
`I. Linnoila, “Pathology of Non-Small Cell Lung Cancer. New
`Diagnostic Approaches,” Hematol Oncol Clin North Am.
`4(6):1027-51 (1990)
`OSI Pharmaceuticals, Inc., Pfizer, Inc., and Genentech Inc. v.
`Mylan Pharmaceuticals Inc., Civil Action No. 09-cv-185-SLR (D.
`Del.), Slip Op. dated May 1, 2012
`
`
`
`
`vi
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`TABLE OF AUTHORITIES
`
`Cases
`Impax Labs., Inc. v. Aventis Pharma Inc., 468 F.3d 1366, 1383 (Fed.
`Cir. 2006) ............................................................................................................ 11
`Rassmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1325-26
`(Fed. Cir. 2005) ................................................................................................... 11
`Graham v. John Deere Co., 383 U.S. 1, 17 (1966) ................................................. 22
`In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986) ............................. 29
`Geo. M. Martin Co. v. Alliance Machine System Intern. LLC, 618 F.3d
`1294, 1302 (Fed. Cir. 2010) ................................................................................ 34
`Amgen Inc. v. Hoeschst Marion Roussel, Inc., 314 F.3d 1313, 1357
`(Fed. Cir. 2003) ................................................................................................... 34
`Statutes
`35 U.S.C. § 102 ............................................. 3, 5, 7, 11, 14, 17-19, 21, 23, 35, 44-46
`35 U.S.C. §103 ............................................................................... 3, 4, 23, 30-35, 46
`35 U.S.C. § 314(a) ..................................................................................................... 4
`35 U.S.C. § 119(e) ............................................................................................... 9, 10
`Other Authorities
`65 Fed. Reg. 54633 (Sept. 8, 2000) ..................................................................... 8, 27
`Regulations
`37 C.F.R. § 42.8(a)(1) ................................................................................................ 1
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 1
`37 C.F.R. § 42.10(b) .................................................................................................. 1
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 2
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 2
`
`vii
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`37 C.F.R. § 42.8(b)(4) ................................................................................................ 3
`37 C.F.R. § 42.104(b)(1) ............................................................................................ 3
`37 C.F.R. § 42.104(a) ................................................................................................. 3
`37 C.F.R. § 42.6(c) ..................................................................................................... 4
`37 C.F.R. § 42.104(b)(3) .......................................................................................... 13
`37 C.F.R. § 42.104(b)(2) .......................................................................................... 14
`37 C.F.R. § 42.104(b)(4) .......................................................................................... 22
`37 C.F.R. § 1.104(e) ............................................................................................. 8, 27
`37 C.F.R. § 42.15(a) ................................................................................................. 46
`37 C.F.R. § 42.103 ................................................................................................... 46
`37 C.F.R. § 42.24(a) ................................................................................................. 46
`
`
`
`
`viii
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`I.
`
`INTRODUCTION
`
`In accordance with 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-42.80 and
`
`42.100-42.123, Petitioners Apotex Inc., Apotex Corp., Apotex Pharmaceuticals
`
`Holdings Inc., and Apotex Holdings, Inc. (collectively “Apotex” or “Petitioners”)
`
`petition for Inter Partes Review of claims 44-47 and 53 of U.S. Patent No.
`
`6,900,221 to Norris, et al., titled “Stable Polymorph on N-(3-ethylphenyl)-6,7-
`
`bis(2methoxyethoxy)-4-quinazolinamine hydrochloride, Methods of Production,
`
`and Pharmaceutical uses thereof” (“the ’221 patent,” Ex. 1001). Concurrently
`
`filed herewith is a Power of Attorney pursuant to 37 C.F.R. § 42.10(b).
`
`This Petition demonstrates that there is a reasonable likelihood that
`
`Petitioners will prevail on at least one of the challenged claims, and therefore
`
`respectfully request that Inter Partes Review be instituted. Further, for the reasons
`
`set forth herein, and in the accompanying Exhibits, Petitioners respectfully submit
`
`that claims 44-47 and 53 of the ’221 patent should be canceled as unpatentable.
`
`II. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`A. Real Party-In-Interest (37 C.F.R. § 42.8(b)(1))
`Apotex Inc., Apotex Corp., Apotex Pharmaceuticals Holdings Inc., and
`
`Apotex Holdings, Inc. are the real parties-in-interest for Petitioners.
`
`Apotex Inc. is an Ontario corporation organized under Canadian laws, and is
`
`wholly owned by Apotex Pharmaceuticals Holdings Inc., which itself is wholly
`
`1
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`owned by Apotex Holdings, Inc. Both Apotex Pharmaceuticals Holdings Inc. and
`
`Apotex Holdings, Inc. are Ontario corporations. Apotex Corp. is a Delaware
`
`corporation and is ultimately wholly owned by Apotex Holdings, Inc. None of
`
`Apotex Inc., Apotex Corp., Apotex Pharmaceuticals Holdings Inc., and Apotex
`
`Holdings, Inc. are publicly traded companies.
`
`According to U.S. Patent Office (“PTO”) records, the assignee of the ’221
`
`patent is OSI Pharmaceuticals, Inc. (Melville, NY) (“OSI” or “Patent Owner”).
`
`B. Notice of Related Matters (37 C.F.R. § 42.8(b)(2))
`The ’221 patent is presently at issue in the following patent infringement
`
`
`
`lawsuits:
`
`- OSI Pharmaceuticals, LLC and Genentech, Inc. v. Apotex Inc. and
`
`Apotex Corp., Civil Action No. 1:15-cv-00772-SLR (D. Del); and
`
`- Pfizer Inc., OSI Pharmaceuticals, LLC and Genentech, Inc. v.
`
`Breckenridge Pharmaceutical, Inc. and Natco Pharma Ltd., Civil Action
`
`No. 1:15-cv-01063-SLR (D. Del.).
`
`C.
`
`Identification of Counsel (37 C.F.R. § 42.8(b)(3))
`Lead Counsel
`Back-Up Counsel
`William Blake Coblentz
`Aaron S. Lukas, Ph.D.
`(Reg. No. 57,104)
`(Reg. No. 59,443)
`COZEN O’CONNOR
`COZEN O’CONNOR
`1200 19th Street, N.W.
`1200 19th Street, N.W.
`Washington, D.C. 20036
`Washington, D.C. 20036
`Telephone No.: 202-912-4837
`Telephone No.: 202-912-4823
`Fax. No.: 202-861-1905
`Fax. No.: 202-861-1905
`
`2
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`Email: wcoblentz@cozen.com
`
`
`Email: alukas@cozen.com
`
`D.
`Service Information (37 C.F.R. § 42.8(b)(4))
`Please direct all correspondence to lead counsel and back-up counsel at the
`
`
`
`contact information above. Petitioners consent to service by electronic mail at the
`
`email addresses set forth above.
`
`III. CLAIMS FOR WHICH REVIEW IS REQUESTED (37 C.F.R.
`§ 42.104(b)(1))
`Petitioner respectfully requests review of claims 44-47 and 53 of the ’221
`
`
`
`patent, and cancellation of those claims as unpatentable.
`
`IV. GROUNDS FOR STANDING AND PROCEDURAL STATEMENT
`(37 C.F.R. § 42.104(a))
`As required by 37 C.F.R. § 42.104(a), Petitioners certify that the ’221 patent
`
`
`
`is available for Inter Partes Review and that the Petitioners are not barred or
`
`estopped from requesting Inter Partes Review on the grounds identified in this
`
`Petition.
`
`V.
`
`IDENTIFICATION OF CHALLENGE AND STATEMENT OF THE
`PRECISE RELIEF REQUESTED
`Petitioners request inter partes review and cancellation of claims 44-47 and
`
`53 of the ’221 patent on one or more of the grounds under 35 U.S.C. §§ 102 and
`
`103 set forth herein. The ’221 patent is to be reviewed under pre-AIA §§ 102 and
`
`103. Petitioners’ detailed statement of the reasons for the relief requested is set
`
`forth below in the section titled “Statement of Reasons for Relief Requested.” In
`
`3
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`accordance with 37 C.F.R. § 42.6(c), copies of the exhibits are filed herewith. In
`
`addition, this Petition is accompanied by the Declaration of Giuseppe Giaccone,
`
`M.D., Ph.D. (“Giaccone Decl.,” Ex. 1002).
`
`VI. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`A petition for Inter Partes Review must demonstrate “a reasonable
`
`likelihood that the petitioner would prevail with respect to at least one of the
`
`claims challenged in the petition.” 35 U.S.C. § 314(a). This Petition meets this
`
`threshold. Further, for each of the grounds of unpatentability proposed, there is a
`
`reasonable likelihood that Petitioners will prevail with respect to at least one of the
`
`challenged claims.
`
`VII. STATEMENT OF REASONS FOR THE RELIEF REQUESTED
`As set forth in detail below, claims 44-47 and 53 of the ’221 patent are
`
`unpatentable based on the following grounds:
`
`Ground I: Claims 44-46 and 53 are Unpatentable Under 35 U.S.C.
`
`§ 103(a) (pre-AIA) as Obvious Over Schnur In View of OSI’s
`
`10-K or Gibbs.
`
`Ground II: Claim 47 is Unpatentable under 35 U.S.C. § 103(a) (pre-AIA)
`
`as Obvious Over Schnur and Gibbs or Wakeling, in view of
`
`Moscatello.
`
`4
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`Ground III: In the Alternative, Claims 44-47 and 53 are Unpatentable
`
`Under 35 U.S.C. § 102(b) (pre-AIA) as Anticipated by
`
`Schnur.
`
`A. Overview of the ’221 Patent
`The ’221 patent is titled “Stable Polymorph on N-(3-Ethynylphenyl)-6, 7-
`
`Bis (2-Methoxyethoxy)-4-Quinazolinamine Hydrochloride, Methods of
`
`Production, and Pharmaceutical Uses Thereof.” The compound “N-(3-
`
`Ethynylphenyl)-6, 7-Bis (2-Methoxyethoxy)-4-Quinazolinamine” is commonly
`
`known as erlotinib. (See Ex. 1002 at ¶¶ 28 and 31.) Further, the Abstract of the
`
`’221 patent discloses that:
`
`The present invention relates to a stable crystalline form
`of N-(3-ethynylphenyl)-6, 7-bis(2-methoxyethoxy)-4-
`quinazolinamine [i.e., erlotinib] hydrochloride designated
`the B polymorph, its production in essentially pure form,
`and
`its use.
` The
`invention also relates
`to
`the
`pharmaceutical compositions containing
`the stable
`polymorph B form of N-(3-ethynylphenyl)-6, 7-bis(2-
`methoxyethoxy)-4-quinazolinamine as hydrochloride, as
`well other forms of the compound, and to methods of
`treating hyperproliferative disorders, such as cancer, by
`administering the compound.
`
`(Ex. 1001 at 1, Abstract.)
`
`5
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`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`Thus, both the Title and Abstract of the ’221 patent indicate that the claimed
`
`invention is directed to a new, stable crystalline form of erlotinib, and methods of
`
`using the same to treat hyperproliferative disorders. (Ex. 1001 at Abstract; col. 7,
`
`l. 64–col. 11, l. 33.) Indeed, the vast majority of the claims of the ’221 patent refer
`
`to compositions and methods of treatment that require polymorph B of erlotinib.
`
`However, claims 44-47 and 53 of the ’221 patent include no limitation on
`
`the crystalline form of erlotinib used to practice the claimed methods. Instead,
`
`claims 44-47 and 53 broadly claim the use of erlotinib to treat a variety of
`
`hyperproliferative disorders without any limitation regarding the crystalline form
`
`of the active ingredient. (See Ex. 1001 at col. 35, l. 26–col. 36, l. 19; Ex. 1002 at
`
`¶ 32.) Specifically, independent claim 44 of the ’221 patent requires:
`
`44. A method for the treatment of NSCLC (non-small
`cell lung cancer) . . . comprising administering to said
`mammal a
`therapeutically effective amount of a
`pharmaceutical composition comprised of at least one of
`N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-
`quinazolinamine, or pharmaceutically acceptable salts
`thereof in anhydrous or hydrate forms and a carrier.
`
`(Ex. 1001, col. 35, ll. 26-36; col. 35, l. 66–col. 36, l. 19.) Claims 45-47 and 53
`
`depend directly from claim 44, and likewise do not include any limitations that
`
`further require a specific crystalline form of erlotinib. (See Ex. 1001, col. 35, ll.
`
`37-65.) Thus, unlike the vast majority of other claims in the ’221 patent, claims
`
`6
`
`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`44-47 and 53 include no limitation as to the crystalline form of erlotinib that is
`
`administered to practice the claimed methods of treatment.
`
`B. Relevant Prosecution History of the ’221 Patent and Reasons for
`Allowance of the Challenged Claims
`The prosecution history of the ’221 patent shows that claims 44-47 and 53
`
`were allowed to issue on the basis that the use of erlotinib to treat the disorders
`
`recited in claim 44 was not known in the prior art. Claims 44-47 and 53 of the
`
`’221 patent correspond to independent claim 64 and dependent claims 65-67, and
`
`88 that were pending during prosecution. Pending claims 64-67 were entered by
`
`way of an amendment dated June 28, 2002, and pending claim 88 was entered by
`
`way of an amendment dated March 6, 2003. (See Ex. 1003 (Amendment dated
`
`June 19, 2002) at 28-29; Ex. 1006 (Amendment dated February 28, 2003) at 37.)
`
`Pending claims 64-67 were rejected under 35 U.S.C. § 102(e) (pre-AIA) as
`
`anticipated by U.S. Patent No. 5,747,498 (“Schnur”, Ex. 1010). (See Ex. 1004 at
`
`10-11 (citing Ex. 1010 at col. 14, ll. 6-16, 28; col. 16, ll. 46-51; claims 28 and 29).)
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`The PTO found that each and every limitation in claims 64-67 were disclosed by
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`Schnur and communicated to OSI that “[c]laims 62-68 are rejected under 35
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`U.S.C. 102(e) as being anticipated by Schnur (‘498). Applicant (OSI
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`Pharmaceuticals Inc. or “OSI”) admit that the prior art material [Schnur] and the
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`composition made from it contain polymorph B [of N-(3-ethynylphenyl)-6,7-bis(2-
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`methoxyethoxy)-4-quinazolinamine hydrochloride].” (Ex. 1004 at 10, ¶ 15.)
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`7
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`OSI argued that, whereas Schnur discloses the use of erlotinib to treat lung
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`cancer, the use of erlotinib to treat non-small cell lung cancer (NSCLC) is not
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`mentioned or disclosed. (See Ex. 1005 at 23; Ex. 1002 at ¶ 34.) OSI further added
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`claim 88 which depended on claim 64 and narrowed the treatment to NSCLC.
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`The PTO subsequently allowed pending claims 64-67 and 88 to issue as
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`claims 44-47 and 53 of the ’221 patent based on a finding that the claims were
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`“drawn to treatment of specific cancers by any polymorph of the claimed
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`compounds. These specific cancers are not found in Schnur (’498).” (See
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`Ex. 1006 (Notice of Allowance dated June 18, 2003) at 6; Ex. 1002 at ¶ 35.)
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`Thus, the PTO found that each and every limitation of claims 44-47 and 53
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`were disclosed in Schnur except for the treatment of NSCLC as specified in OSI’s
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`February 28, 2003 Office Action Response. (Ex. 1005 at 23; Ex. 1006 at 2; Ex.
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`1002 at ¶ 36.) OSI did not respond to the PTO’s Reasons for Allowance, and
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`therefore is presumed to have acquiesced to the PTO’s factual findings.1
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`1 37 CFR § 1.104(e); see 65 Fed. Reg. 54633 (Sept. 8, 2000) (“The deletion of this
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`statement from the rule should require applicant to set forth his or her position in
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`the file if he or she disagrees with the examiner’s reasons for allowance, or be
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`subject to inferences or presumptions to be determined on a case-by-case basis by a
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`court reviewing the patent, the Office examining the patent in a reissue or
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`reexamination proceeding . . . .”).
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`8
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`As discussed below, facts not available to the PTO during prosecution of the
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`’221 patent conclusively show that a person of ordinary skill in the art would have
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`reasonably expected erlotinib to be effective in treating at least NSCLC in view of
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`the prior art. Thus, the knowledge of a person of ordinary skill in the art in view of
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`the prior art discloses, teaches, or suggests every limitation of the challenged
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`claims, including the subject matter the Office found missing from the prior art in
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`the undisputed reason for allowance.
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`C.
`Priority Date of the Challenged Claims
`The earliest priority date to which claims 44-47 and 53 should be accorded
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`under 35 U.S.C. § 119(e) is March 30, 2000. The ’221 patent was filed on
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`November 9, 2000, and issued on May 31, 2005. The ’221 patent claims priority
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`to the following Provisional Applications:
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`Appl. No.
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`Filing Date
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`60/164,907
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`November 11, 1999
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`60/193,191
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`March 30, 2000
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`60/206,420
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`May 23, 2000
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`
`(See Ex. 1001 at col. 1, ll. 8-13.) However, methods of using erlotinib to treat the
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`hyperproliferative disorders recited in claims 44-47 and 53, and specifically
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`NSCLC, were not recited in Provisional Appl. No. 60/164,907 (“the ’907
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`application”). (See Ex. 1007; Ex. 1002 at ¶ 38.) Instead, the ’907 application
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`9
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`merely discloses the use of erlotinib hydrochloride (i.e., the hydrochloride salt of
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`N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine) to treat lung
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`cancer in the same manner as described in Schnur. (See Ex. 1002 at ¶ 38,
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`discussing Ex. 1007 at 6, l. 8 to 8, l. 8; and 10, l. 3 to 11, l. 24; compare Ex. 1009
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`at col. 14, ll. 1-30.) Therefore, under 35 U.S.C. § 119(e) claims 44-47 and 53
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`should not be accorded a priority date of November 11, 1999, due to a failure by
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`the ’907 application to satisfy the requirements under 35 U.S.C. § 112, first
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`paragraph. Namely, the use of erlotinib to treat NSCLC is not mentioned or
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`disclosed in the ’907 application.
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`The first written disclosure concerning the use of N-(3-ethynylphenyl)-6,7-
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`bis(2-methoxyethoxy)-4-quinazolinamine (i.e., erlotinib) to treat NSCLC as recited
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`in claims 44-47 and 53 is found in Provisional Appl. No. 60/193,191 (“the ’191
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`application”), filed March 30, 2000. (See Ex. 1008 (Provisional Appl. No.
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`60/193,191) at 1, ll. 20-26; 2, l. 21–3, l. 30; 4, ll. 10-13; and 7, claims 1-10; Ex.
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`1002 at ¶ 37.) Accordingly, pursuant to 35 U.S.C. § 119(e), the earliest priority
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`date to which claims 44-47 and 53 can claim benefit is March 30, 2000.
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`D.
`Prior Litigation Involving the ’221 Patent
`The ’221 patent was previously asserted by the Patent Owner in a district
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`court litigation (OSI Pharmaceuticals, Inc., Pfizer, Inc., and Genentech Inc. v.
`
`10
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`Mylan Pharmaceuticals Inc., Civil Action No. 09-cv-185-SLR (D. Del.)).2 There,
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`claim 53 of the ’221 patent was found not anticipated by the prior art—namely,
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`Schnur and an abstract entitled “Development of a Potent, Specific Inhibitor of
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`Epidermal Growth Factor Receptor Tyrosine Kinase (CP-358,774) as an Anti-
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`Cancer Therapeutic Agent” by Kenneth K. Iwata et al.
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`The district court found that claim 53 of the ’221 patent was not anticipated
`
`by Schnur on the basis that an oncologist would not read Schnur to teach that every
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`compound disclosed therein (including erlotinib) was actually effective for the
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`treatments that are disclosed. (See Ex. 1028 (District Court Opinion) at 36-37.)
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`However, absent evidence to the contrary, “proof of efficacy is not required for a
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`prior art reference to be enabling for purposes of anticipation.” See Impax Labs.,
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`Inc. v. Aventis Pharma Inc., 468 F.3d 1366, 1383 (Fed. Cir. 2006); Rasmusson v.
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`SmithKline Beecham Corp., 413 F.3d 1318, 1325-26 (Fed. Cir. 2005).
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`Relevant to the Grounds set forth herein, the district court also found that
`
`claim 53 was not obvious in view of the prior art because “a person of ordinary
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`skill in the art would not have had a reasonable expectation that inhibiting EGFR
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`would result in the treatment of NSCLC.” (See Ex. 1028 at 44.) While not
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`binding on these proceedings, this finding is also legally irrelevant because the
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`2 Also involved in this prior litigation were U.S. Reissue Patent No. RE41,065 (a
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`reissue of Schnur), and U.S. Patent No. 7,087,613.
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`11
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`

`

`U.S. Patent No. 6,900,221–Petition for Inter Partes Review
`
`question is not whether a disclosure of EGFR inhibition would lead to a reasonable
`
`expectation of success, but instead whether Schnur’s disclosure of erlotinib’s use
`
`for treating lung cancer would lead a person of ordinary skill in the art to
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`reasonably expect efficacy in treating NSCLC.
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`The district court also found that the Patent Owner set forth evidence to
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`show that others had tried, and failed to obtain FDA-approval for drugs to treat
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`NSCLC. (See Ex. 1028 at 44.) To the extent that the Patent Owner attempts to
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`introduce such evidence of the failure by others here, Petitioners respectfully
`
`submit that such evidence is legally irrelevant. First, there is no requirement in the
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`plain language of claims 44 or 53 that the claimed method of treating NSCLC be
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`FDA-approved. Second, to the extent that there was skepticism as to whether
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`erlotinib would be useful to treat NSCLC, the prior art disclosures of erlotinib’s
`
`use to treat lung cancer (Schnur), and in particular to treat NSCLC (OSI’s 10-K and
`
`Gibbs) would have given more than a reasonable expectation of success. As
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`discussed at length in Dr. Giaccone’s Declaration (Ex. 1002 at ¶¶ 1