UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`GENZYME CORPORATION,
`Petitioner
`
`V.
`
`GENENTECH, INC. AND CITY OF HOPE,
`Patent Owners
`
`
`

`
` 
`
`

`

 
`
`
`
`
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`U.S. Patent No. 6,331,415
`Appl. No. 07/205,419, filed June 10, 1988
`Issued: Dec. 18, 2001
`
`Title: Methods of Producing Immunoglobulins, Vectors
`and Transformed Host Cells for Use Therein
`
`IPR Trial No. IPR2016-00383
`
`PETITION FOR INTER PARTES REVIEW
`
`OF U.S. PATENT NO. 6,331,415
`
`  
`
`719038588
`
`

`

`TABLE OF CONTENTS
`
`BEE
`
`I.
`
`INTRODUCTION ........................................................................................ .. 1
`
`II.
`
`REQUIREMENTS FOR INTER PARTES REVIEW ................................. ..3
`
`A.
`
`B.
`
`Grounds for Standing ......................................................................... ..3
`
`Identification of Challenge ................................................................. ..3
`
`III. OVERVIEW OF THE '415 PATENT .......................................................... ..4
`
`A.
`
`B.
`
`Technology Background of the '415 Patent ....................................... ..5
`
`The Purported Invention of the '415 Patent and the Challenged
`Claims ................................................................................................. ..9
`
`IV.
`
`PERSON OF ORDINARY SKILL IN THE ART ..................................... .. 15
`
`V.
`
`CLAIM CONSTRUCTION ....................................................................... .. 16
`
`VI.
`
`THE STATE OF PRIOR ART rDNA ANTIBODY EXPRESSION IN
`
`APRIL 1983 AND OWNERS’ ARGUMENTS DURING REEXAM ....... .. 16
`
`A.
`
`Prior Art Platform Technologies for Expressing Foreign Genes
`in Mammalian Cells ......................................................................... .. 17
`
`1.
`
`2.
`
`The Axel Patent ...................................................................... .. 17
`
`The Southern Reference ......................................................... .. 19
`
`B.
`
`The Prior Art Taught Expression of Single Immunoglobulin
`Chains in Transformed Mammalian Host Cells ............................... ..21
`
`C.
`
`Owners’ Arguments During Reexamination Regarding Axel .......... ..22
`
`VII. STATEMENT OF GROUNDS FOR THE UNPATENTABILITY OF
`
`THE CHALLENGED CLAIMS ................................................................ ..26
`
`
`
`
`
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` . -',-)'3*=(C'62:4',"2('+(0)4B:*4@,'4..............................<7
`)
`
`Ground 1: The Salser Patent Anticipates Claims 1-4, 9, 11, 12,
`15-20 and 33 Under 35 U.S.C. § 102(e) .......................................... ..26
`
`A.
`
`  
`
`719038588
`
`1.
`
`Overview of the Salser Patent Disclosures ............................ ..26
`
`

`

`TABLE OF CONTENTS
`
`(continued)
`
`Page
`
`2.
`
`3.
`
`Applicable Law of Anticipation............................................. ..30
`
`The Salser Patent Anticipates Independent
`Claims 1, 15, 17, 18 and 33 ................................................... ..33
`
`a.
`
`Independent Process Claim 1 ...................................... ..33
`
`"A process for producing an
`immunoglobulin molecule or an
`immunologically functional
`immunoglobulin fragment comprising at
`least the variable domains of the
`
`immunoglobulin heavy and light chains, in a
`single host cell..." ............................................. ..33
`
`". . .comprising the steps of: (i) transforming
`said single host cell with a first DNA
`sequence encoding at least the variable
`domain of the immunoglobulin heavy chain
`and a second DNA sequence encoding at
`least the variable domain of the
`
`immunoglobulin light chain..." ......................... ..36
`
`i.
`
`ii.
`
`iii.
`
`
`
`
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`B'::.h.....................................................................8
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`))
`
`". .. and (ii) independently expressing said
`first DNA sequence and said second DNA
`sequence so that said immunoglobulin heavy
`and light chains are produced as separate
`molecules in said transformed single host
`cell." ................................................................... ..41
`
`b.
`
`Independent Process Claim 33 .................................... ..44
`
`c.
`
`d.
`
`Independent Composition Claims 15 and 17 .............. ..44
`
`Independent Composition Claim 18 ............................ ..45
`
`4.
`
`The Salser Patent Anticipates Dependent Claims 2, 3, 4,
`9,11,12,16,19 and 20 .......................................................... ..46
`
`  
`
`719038588
`
`

`

`TABLE OF CONTENTS
`
`(continued)
`
`Page
`
`B.
`
`Ground 2: All of the Challenged Claims Are Obvious Over
`Salser in View of Ochi (I) ................................................................ ..47
`
`1.
`
`2.
`
`Claims 1-4, 9, 11, 12, 15-20 and 33 ....................................... ..47
`
`Claim 14 ................................................................................. ..50
`
`C.
`
`D.
`
`Explanation of Ground 3 for Unpatentability: Claims 2, 18 and
`20 Are Obvious Over Salser in View of Southern ........................... ..51
`
`The Immunoglobulin Co-Expression rDNA Work Reflected in
`the Boss Patent and Ochi (II) Supports a Finding of
`Obviousness ...................................................................................... ..54
`
`E.
`
`The Publicly Available Licensing Record of the '415 Patent
`Does Not Rescue the Challenged Claims from Obviousness .......... ..56
`
`VIII. MANDATORY NOTICES ........................................................................ ..5 8
`
`
`
`
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`
`A.
`
`B.
`
`Real Party-In-Interest ....................................................................... ..58
`
`Related Matters ................................................................................. ..58
`
`C.
`
`Lead and Back-up Counsel and Service Information ...................... ..59
`
`IX.
`
`CONCLUSION ........................................................................................... ..60
`
`  
`
`719038588
`
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`1012
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`National Library of Medicine, Medical
`Subject Headings Tree Structures, 1984
`(excerpts)
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`1013
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`Kuby, Immunology (2007) (excerpts)
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`Malcolm et al., Localization ofHuman
`Immunoglobulin IC Light Chain Variable
`Region Genes to the Short Arm of
`Chromosome 2 by in Situ Hybridization,
`Proceedings of the National Academy of
`Sciences USA, 79:4957-61 (1982)
`
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`Harris, Expression ofEukaryotic Genes
`in E. Coli, in Genetic Engineering 4,
`127-185 (1983)
`
`'415 patent reexamination, Declaration
`of Dr. Timothy John Roy Harris under
`37 C.F.R. § 1.132
`
`'415 patent reexamination, Office Action
`dated 2/16/07
`
`'415
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`U.S. Patent No. 4,399,216
`
`Colaianni and Cook-Deegan, Columbia
`University's Axel Patents: Technology
`Transfer and Implicationsfor the Bayh-
`Dole Act, The Milbank Quarterly,
`87:683-715 (2009)
`
`  
`
`719038588
`
`EXHIBIT LIST - 2
`
`Malcolm
`
`,
`
`Owners Resp. (11/25/05)
`
`,
`
`Owners Resp. (10/30/06)
`
`'6/
`
`a@F_
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`Harris
`
`Harris Decl.
`
`.
`Office Action (2/16/07)
`
`,
`
`Owners Resp. (5/21/07)
`
`Axel, or the Axel patent
`
`ColaiaI1ni
`
`

`

`Rigby and Shenk, Paul Berg, on His
`65th Birthday, Nucleic Acids Research,
`19:7041 (1991)
`
`Oi et al., Immunoglobulin Gene
`Expression in Transformed Lymphoid
`Cells, Proceedings of the National
`Academy of Sciences USA, 80:825-829
`(1983)
`
`Kabat et al., Sequences of Proteins of
`Immunological Ir1terest (1983) (excerpt)
`
`'415 patent reexamination, Final Office
`Action dated 2/25/08
`
`'415
`
`t
`
`t
`
`ReSpI?::[:drg7:/Egglna Ion wners
`
`1026
`
`1027
`
`1028
`
`Rice and Baltimore, Regulated
`Expression of an Immunoglobulin K
`Gene Introduced into a Mouse Lymphoid
`Cell Line, Proceedings of the National
`Academy of Sciences USA, 79:7862-65
`(1982)
`
`X®¯W !)DF_2+>6C'+`&˜|€‹q}pŠvru~y
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`c/%]%$b%6$H
`
`'
`
`t’
`
`, 0
`
`'
`
`1029
`
`U.S. Patent No. 4,237,224
`
`1030
`
`Cline, Research on Gene Therapy, in
`Basic Biology of New Developments in
`Biotechnology, 77-92 (1983)
`
`1031
`
`Alberts et al., Molecular Biology of the
`Cell (2002) (excerpts)
`
`Efstratiadis et al., The Structure and
`Evolution of the Human fl-Globin Gene
`Family, Cell, 21:653-68 (1980)
`
`Rogers et al., Sequence Analysis of
`Cloned cDNA Encoding Part ofan
`Chain, Nucleic
`
`EXHIBIT LIST - 3
`
`  
`
`719038588
`
`!)DF_
`!)B'
` )
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`1)+2: ==)B'#B()*+
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`
`:)+'
`#:F',(4f< <g
`=4(,2()2>)4
`!*D',4
`
`Kabat
`
`Final Office Action
`(2/25/08)
`
`,
`
`Owners Resp. (6/6/08)
`
`Cohen & Boyer patent
`
`Cline
`
`Alberts (2002)
`
`Efstratiadis
`
`

`

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`

`

`Antigen, Journal of Immunology,
`141:4053-60 (1988)
`
`Sahagan et al., A Genetically Engineered
`MurineflIuman Chimeric Antibody
`Retains Specificity for Human Tumor-
`Associated Antigen, Journal of
`Immunology, 137: 1066-74 (1986)
`
`Nishimura et al., Recombinant Human-
`Mouse Chimeric Monoclonal Antibody
`Specificfor Common Acute Lymphocytic
`Leukemia Antigen, Cancer Research,
`47:999-1005 (1987)
`
`Final Decision, Patent Interference
`
`102,572, Paper No. 57 (Jul. 6, 1998)
`
`Medlmmune, Inc. v. Genentech, Inc., No.
`
`03-02567 (C.D. Cal. Aug. 17, 2007),
`Expert Report of E. Fintan Walton
`
`1046
`
`Complaint in Medlmmune v. Genentech,
`No. 03-02567 (C.D. Cal.)
`
`Stipulation and order of dismissal in
`Medlmmune v. Genentech, No. 03-02567
`
`(C.D. Cal.)
`
`Komori et al., Production ofHeavy-
`Chain Class-Switch Variants ofHuman
`Monoclonal Antibody by Recombinant
`DNA Technology, Clinical &
`Experimental Immunology, 71 :5 08-16
`(1988)
`
`nrz~pqr&?*@,+2:*=%EE@+*:*D_&
` 8 A8 H7 f g
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`c/%]%$b%6$H
`  
`
`1048
`
`1049
`
`Complaint in Centocor v. Genentech,
`No. 08-CV-3573 (C.D. Cal.)
`
`Order of dismissal in Centocor v.
`Genentech, No. 08-CV-3573 (C.D. Cal.)
`
`719038588
`
`EXHIBIT LIST - 5
`
`Sahagan
`
`Nishimura
`
`62C2D2+
`)4C)E@,2
`a*E*,)
`%+(',=','+B'1)+2:
`0'B)4)*+
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`H
`H
`H
`H
`
`Interference Final
`
`Decision
`
`Walton Expert Rep.
`
`

`

`H
`H
`H
`H
`H
`H
`H
`H
`]2,*+0'B:.
`
`Baron D601’
`
`1050
`
`1051
`
`1052
`
`Complaint in Glaxo Group Ltd. v.
`Genentech, No. 10-02764 (C.D. Cal.)
`
`Order of dismissal in Glaxo Group Ltd.
`v. Genentech, No. 10-02764 (C.D. Cal.)
`
`Complaint in Human Genome Sciences
`v. Genentech, No. 11-CV-6519 (C.D.
`Cal.)
`
`Order of dismissal in Human Genome
`
`1053
`
`Sciences v. Genentech, No. 11-CV-6519
`(C.D. Cal.)
`
`1054
`
`1055
`
`1056
`
`1057
`
`Complaint in Eli Lilly and ImClone
`Systems LLC v. Genentech, No. 13-CV-
`7248 (C.D. Cal.)
`
`Stipulation of dismissal in Eli Lilly and
`ImClone Systems LLC v. Genentech, No.
`13-CV-7248 (C.D. Cal.)
`
`Complaint in Bristol-Myers Squibb v.
`Genentech, No. 13-CV-5400 (C.D. Cal.)
`
`Stipulation of dismissal in Bristol-Myers
`Squibb v. Genentech, No. 13-CV-5400
`(C.D. Cal.)
`
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`
`Declaration of Margaret H. Baron, M.D.,
`Ph.D., in Support of Genzyme's Petition
`for Inter Partes Review of U.S. Patent
`
`1058
`
`No. 6,331,415
`
`  
`
`719038588
`
`c/%]%$b%6$H7
`
`EXHIBIT LIST - 6
`
`

`

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`


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`
`
`  
`
`

`

`the Salser patent (Ex. 1002). For this reason, the present Petition is not simply the
`
`'415 patent reexamination redux.
`
`According to Owners, Axel failed to disclose multiple (two or more)
`
`different genes of interest in a single genetically engineered host cell. (Axel
`
`disclosed only multiple copies of the same gene.) Such a disclosure would be
`
`necessary to support the Office's assertions that the Axel process
`
`specifically teaches production of intact antibodies, because only that
`
`interpretation leads to the possibilig; that two different polypeptides §i.e.,
`
`the heafl and light chains of the immunoglobulin) would be produced by
`
`the Axel process.
`
`Ex. 1016, Owners’ Resp. (10/30/06), at 44, n. 26 (emphasis added).
`
`The Salser patent does not suffer from the infirmities of Axel. Salser
`
`expressly discloses the introduction of "two or more" genes into a single
`
`genetically engineered mammalian cell; and it makes it clear (including by way of
`
`example) that these can be multiple different genes of interest—e.g., a "plurality of
`
`unrelated genes." Salser also teaches that immunoglobulins are among the wide
`
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`  
`
`Variety of proteins that can be produced by the inventors’ disclosed methods. Taken
`
`together, those teachings would have been understood by a person of ordinary skill
`
`in the art (POSITA) as an unambiguous instruction to introduce into a single
`
`mammalian cell the two DNA sequences needed to make an immunoglobulin. The
`
`Salser patent therefore anticipates the challenged claims or makes them obvious in
`
`719038588
`
`

`

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`There is no redundancy between any of the grounds of the Petition. Ground 2 with
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`respect to claims 1-4, 9, 11, 12, 15-20 (i.e., all of the challenged claims except
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`claim 14) is argued in the alternative to Ground 1 should the Board find that the
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`Salser patent's disclosure of the small genus of "globulins" would not permit a
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`POSITA to at once envisage the species of "immunoglobulins" that is the subject
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`of the '415 patent claims. Likewise, Ground 3 is presented as an alternative to
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`Ground 1 should the Board find that the Salser patent