Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`REGENERON PHARMACEUTICALS, INC.,
`Petitioner
`
`v.
`
`NOVARTIS VACCINES AND DIAGNOSTICS, INC.,
`GRIFOLS WORLDWIDE OPERATIONS LIMITED
`Patent Owners
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`
`
`Patent No. 5,688,688
`Issued: November 18, 1997
`Filed: August 10, 1994
`
`Inter Partes Review No. IPR2019-01086
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`
`
`
`PETITION FOR INTER PARTES REVIEW
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`
`TABLE OF CONTENTS
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`
`
` Page
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`TABLE OF AUTHORITIES .................................................................................... iv
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II. MANDATORY NOTICES (37 C.F.R. §42.8) ................................................ 6
`
`A.
`
`Real Party-In-Interest ............................................................................ 6
`
`B.
`
`C.
`
`Related Matters ...................................................................................... 6
`
`Lead and Back-up Counsel ................................................................... 7
`
`D.
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`Service Information ............................................................................... 8
`
`III.
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`PAYMENT OF FEES ..................................................................................... 8
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`IV. GROUNDS FOR STANDING ........................................................................ 8
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`V.
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`STATEMENT OF PRECISE RELIEF REQUESTED ................................... 9
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`VI. THE CHALLENGED CLAIMS ..................................................................... 9
`
`VII. THE '688 PATENT ....................................................................................... 12
`
`A.
`
`Shared Specification of the '688 Patent and '894
`Application .......................................................................................... 14
`
`1.
`
`2.
`
`3.
`
`The specification focuses exclusively on HIV nucleotide
`sequences and polypeptides ...................................................... 14
`
`pCMV6a plasmid for expression of gp120 is the only
`example of an HCMV IE1 vector ............................................. 17
`
`No general teaching or genus of HCMV IE1 vectors, host
`cell expression systems with such vectors, or nucleic acid
`molecules .................................................................................. 17
`
`B.
`
`Prosecution History of the '688 Patent ................................................ 19
`
`
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`i
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`TABLE OF CONTENTS
`(continued)
`
` Page
`
`1.
`
`2.
`
`3.
`
`Patent Owner added claims directed to HCMV IE1
`sequences in 1995 ..................................................................... 19
`
`The PTO did not address the priority issue presented in
`this petition or apply Boshart 1985 to claim 17 during the
`original prosecution................................................................... 21
`
`The PTO did not address the priority issue presented in
`this petition or apply Boshart 1985 to claim 17 during
`reexamination ............................................................................ 22
`
`VIII. CLAIM CONSTRUCTION .......................................................................... 28
`
`A.
`
`The District Court Action .................................................................... 29
`
`B.
`
`"Mammalian Polypeptide" Has A Plain and Ordinary
`Meaning ............................................................................................... 31
`
`C.
`
`"Operably Linked" Has a Plain and Ordinary Meaning ..................... 34
`
`IX. PERSON OF ORDINARY SKILL IN THE ART ........................................ 37
`
`X. GROUND 1 OF UNPATENTABILITY ....................................................... 37
`
`A.
`
`B.
`
`The Effective Filing Date of the Challenged Claims Is No
`Earlier than August 10, 1994 ............................................................... 38
`
`The Challenged Claims Are Anticipated by the
`'949 Patent ........................................................................................... 51
`
`1.
`
`2.
`
`Overview of the '949 patent ...................................................... 53
`
`Claim-by-claim analysis ........................................................... 54
`
`XI. GROUND 2 OF UNPATENTABILITY ....................................................... 65
`
`A. Overview of Boshart 1985 .................................................................. 65
`
`B.
`
`Boshart 1985 Anticipates Claim 17 .................................................... 67
`
`
`
`
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`ii
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`TABLE OF CONTENTS
`(continued)
`
`XII. THE ARGUMENTS AND EVIDENCE SUBMITTED IN THIS
`PETITION WERE NOT PREVIOUSLY CONSIDERED BY THE
`PTO ................................................................................................................ 70
`
`XIII. CONCLUSION .............................................................................................. 72
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` Page
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`iii
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`TABLE OF AUTHORITIES
`
`
`
` Page(s)
`
`Cases
`
`Anascape, Ltd. v. Nintendo of Am., Inc.,
`601 F.3d 1333 (Fed. Cir. 2010) .............................................................. 46, 49, 50
`
`Ariad Pharms., Inc. v. Eli Lilly & Co.,
`598 F.3d 1336 (Fed. Cir. 2010) (en banc) ...................................................passim
`
`In re Baxter Travenol Labs,
`952 F.2d 388 (Fed. Cir. 1991) ...................................................................... 51, 68
`
`Brown v. 3M,
`265 F.3d 1349 (Fed. Cir. 2001) .......................................................................... 52
`
`Chiron Corp. v. Genentech, Inc.,
`363 F.3d 1247 (Fed. Cir. 2004) .......................................................................... 40
`
`Cont'l Can Co. v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) .......................................................................... 67
`
`CRFD Research, Inc. v. Matal,
`876 F.3d 1330 (Fed. Cir. 2017) .......................................................................... 51
`
`Donghee America, Inc. v. Plastic Omnium Advanced Innovation &
`Research, IPR2017-01654 (P.T.A.B.) ................................................................ 71
`
`D Three Enterprises, LLC v. SunModo Corp.,
`890 F.3d 1042 (Fed. Cir. 2018) .................................................................... 49, 50
`
`Dynamic Drinkware, LLC v. Nat'l Graphics, Inc.,
`800 F.3d 1375 (Fed. Cir. 2015) .......................................................................... 38
`
`Enzo Biochem, Inc. v. Gen-Probe, Inc.,
`323 F.3d 956 (Fed. Cir. 2002) ............................................................................ 48
`
`Genentech, Inc. v. Amgen Inc.,
`1999 U.S. Dist. LEXIS 24268 (N.D. Cal. May 14, 1999) .................................. 34
`
`
`
`
`
`iv
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`TABLE OF AUTHORITIES
`(continued)
`
` Page(s)
`
`ICU Med. Inc. v. Alaris Medical Sys. Inc.,
`558 F.3d 1368 (Fed. Cir. 2009) .......................................................................... 50
`
`L.A. Biomedical Research Inst. at Harbor-UCLA Med. Ctr. v. Eli Lilly
`& Co.,
`849 F.3d 1049 (Fed. Cir. 2017) .......................................................................... 38
`
`Lockwood v. Am. Airlines, Inc.,
`107 F.3d 1565 (Fed. Cir. 1997) .............................................................. 38, 39, 50
`
`In re Lukach,
`442 F.2d 967 (C.C.P.A. 1971) ............................................................................ 52
`
`Novartis Vaccines & Diagnostics, Inc. v. MedImmune LLC et al.,
`C.A. No. 11-cv-84-SLR-MPT (D. Del.) ......................................................... 7, 50
`
`Novartis Vaccines and Diagnostics, Inc. v. Regeneron
`Pharmaceuticals, Inc.,
`No. 18-cv-2434-DLC (S.D.N.Y.) ................................................................passim
`
`In re NTP, Inc.,
`654 F.3d 1268 (Fed. Cir. 2011) .......................................................................... 37
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) .......................................................... 36
`
`PowerOasis, Inc. v. T-Mobile USA, Inc.,
`522 F.3d 1299 (Fed. Cir. 2008) .............................................................. 39, 41, 50
`
`Purdue Pharma L.P. v. Faulding Inc.,
`230 F.3d 1320 (Fed. Cir. 2000) .......................................................................... 40
`
`Smith & Nephew, Inc. v. Arthrex, Inc.,
`IPR2017-00275 (P.T.A.B.) ..........................................................................passim
`
`In re Stautzenberger,
`454 F.2d 756 (C.C.P.A. 1972) ............................................................................ 40
`
`
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`v
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`TABLE OF AUTHORITIES
`(continued)
`
`Tronzo v. Biomet, Inc.,
`156 F.3d 1154 (Fed. Cir. 1998) .................................................................... 40, 49
`
`Vivid Techs., Inc. v. Am. Sci. & Eng'g, Inc.,
`200 F.3d 795 (Fed. Cir. 1999) ............................................................................ 30
`
` Page(s)
`
`Statutes
`
`35 U.S.C. §102 ..................................................................................................passim
`
`35 U.S.C. §112 ............................................................................................. 22, 38, 50
`
`35 U.S.C. §120 ..................................................................................................... 3, 37
`
`35 U.S.C. §325(d) .................................................................................................... 70
`
`Other Authorities
`
`37 C.F.R. § 42.6 ......................................................................................................... 2
`
`37 C.F.R. §42.8 ...................................................................................................... 6, 1
`
`37 C.F.R. §42.15 ........................................................................................................ 8
`
`37 C.F.R. §42.24 ........................................................................................................ 1
`
`37 C.F.R. §42.100 .............................................................................................. 28, 32
`
`MPEP § 2131.01.II (Ninth Edition, Rev. 08.2017, last revised January
`2018) ............................................................................................................. 51, 68
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`
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`vi
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`EXHIBIT LIST
`
`Exhibit Citation
`
`U.S. Patent No. 5,688,688
`
`U.S. Application No. 07/138,894
`
`Declaration of Michael Green, M.D., Ph.D.
`
`U.S. Patent No. 5,156,949
`
`U.S. Application No. 08/288,336
`
`Lodish et al., Molecular Cell Biology (3d ed. 1995)
`
`'688 File History - Petition for Correction of Inventorship
`
`'688 File History - 3/27/95 Preliminary Amendment
`
`'688 File History - 6/15/95 Non-Final Rejection
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`'688 File History - 10/25/95 Amendment and Response
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`'688 File History - 4/24/96 Rejection
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`'688 File History - 10/24/96 Amendment and Response
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`'688 File History - Notice of Allowance
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`'688 Reexamination - Third Party Request
`
`'688 Reexamination – Grant of Request
`
`'688 Reexamination - 11/21/06 Rejection
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`'688 Reexamination - 1/22/07 Response
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`'688 Reexamination – Declaration of Dr. Truett
`
`'688 Reexamination - 11/2/07 Appeal Brief
`
`'688 Reexamination – 3/07/08 Reply Brief
`
`'688 Reexamination - Notice of Intent to Issue
`
`U.S. Application No. 08/107,377
`
`U.S. Application No. 08/083,391
`
`U.S. Application No. 07/931,191
`
`vii
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`1001
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`1002
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`1003
`
`1004
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`1005
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`1006
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`1007
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`1008
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`1009
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`1010
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`1011
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`1012
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`1013
`
`1014
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`1015
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`1016
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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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`1022
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`1023
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`1024
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`Exhibit Citation
`
`Boshart et al., "A Very Strong Enhancer Is Located Upstream of an
`Immediate Early Gene of Human Cytomegalovirus," Cell 41: 521-530
`(1985)
`
`Murakami et al., "Species-Specific in vitro synthesis of DNA
`containing the polyoma virus origin of replication," PNAS 83:
`6347-6351 (1986)
`
`Munholland et al., "Cell specificity of transcription regulation by
`papovavirus T antigens and DNA replication," EMBO J. 11(1):
`177-184 (1992)
`
`Spaete & Mocarski et al., "Regulation of Cytomegalovirus Gene
`Expression: α and β Promoters Are trans Activated by Viral Functions
`in Permissive Human Fibroblasts," J. Virol. 56(1): 135-143 (1985)
`
`U.S. Patent No. 5,024,939
`
`Chapman et al., "Effect of intron A from human cytomegalovirus
`(Towne) immediate-early gene on heterologous expression in
`mammalian cells," Nucleic Acids Research 19(14):3979-3986 (1991)
`
`Deposition Transcript of Dr. Truett, Novartis Vaccines and
`Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc., No.
`18-cv-2434-DLC (S.D.N.Y.)
`
`Opinion and Order on Claim Construction, Novartis Vaccines and
`Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc., No.
`18-cv-2434-DLC (S.D.N.Y.)
`
`Novartis's Opening Brief on Claim Construction, Novartis Vaccines
`and Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc., No.
`18-cv-2434-DLC (S.D.N.Y.)
`
`Regeneron's Responsive Brief on Claim Construction, Novartis
`Vaccines and Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc.,
`No. 18-cv-2434-DLC (S.D.N.Y.)
`
`Novartis's Reply Brief on Claim Construction, Novartis Vaccines and
`Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc., No.
`18-cv-2434-DLC (S.D.N.Y.)
`
`Excerpts of Deposition Transcript of Dr. Calame (Claim
`Construction), Novartis Vaccines and Diagnostics, Inc. v. Regeneron
`
`viii
`
`1025
`
`1026
`
`1027
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`1028
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`1029
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`1030
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`1031
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`1032
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`1033
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`1034
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`1035
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`1036
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`Exhibit Citation
`
`Pharmaceuticals, Inc., No. 18-cv-2434-DLC (S.D.N.Y.)
`
`Webster's Third New International Dictionary (1993)
`
`Oxford English Dictionary (Second Edition 1989)
`
`Webster's II New College Dictionary (1995)
`
`Akrigg et al., "The structure of the major immediate early gene of
`human cytomegalovirus strain AD169," Virus Res. 2:107-121 (1985)
`
`Stenberg et al., "Structural Analysis of the Major Immediate Early
`Gene of Human Cytomegalovirus," J. Virol. 49:190-199 (1984)
`
`Thomsen et al., "Promoter-regulatory region of the major immediate
`early gene of human cytomegalovirus," PNAS 81:659-663 (1984)
`
`Excerpts of Deposition Transcription Dr. Sodroski, Novartis Vaccines
`& Diagnostics, Inc. v. Biogen Idec, Inc. and Alexion Pharmaceuticals,
`Inc., C.A. No. 11-cv-84-SLR-MPT (D. Del.).
`
`U.S. Patent No. 6,096,505
`
`Affidavit of Service, Novartis Vaccines and Diagnostics, Inc. v.
`Regeneron Pharmaceuticals, Inc., No. 18-cv-2434-DLC (S.D.N.Y.)
`
`Stipulation and Partial Judgment of Noninfringement, Novartis
`Vaccines and Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc.,
`No. 18-cv-2434-DLC (S.D.N.Y.)
`
`Second Amended Answer and Counterclaims, Novartis Vaccines and
`Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc., No.
`18-cv-2434-DLC (S.D.N.Y.)
`
`ix
`
`1037
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`1038
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`1039
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`1040
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`1041
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`1042
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`1043
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`1044
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`1045
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`1046
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`1047
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`
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`Petitioner Regeneron Pharmaceuticals, Inc. ("Regeneron") respectfully
`
`requests inter partes review ("IPR") under 35 U.S.C. §§311-319 and 37 C.F.R., Part
`
`42 of claims 1-2, 4-6, 8-9, 13-14 and 17 of U.S. Patent No. 5,688,688 ("the '688
`
`patent") (Ex.1001), which issued on November 18, 1997 and expired on November
`
`18, 2014. There is a reasonable likelihood that Petitioner will prevail in establishing
`
`that at least one challenged claim is unpatentable.
`
`I.
`
`INTRODUCTION
`
`The '688 patent belongs to a family of patents directed to the human
`
`immunodeficiency virus ("HIV"). The '688 patent focuses exclusively on certain
`
`HIV polypeptides from a particular HIV strain, and their use for diagnostic
`
`purposes. The '688 patent claims priority from U.S. Application No. 07/138,894
`
`("the '894 application"), which shares the same specification. Of the patent
`
`specification, only two paragraphs in 75 columns of text concern the claims of the
`
`'688 patent. Those two paragraphs discuss an effort to improve expression of a
`
`particular HIV polypeptide (called "gp120") using a particular vector that has a
`
`transcription regulatory region from the human cytomegalovirus (called "HCMV
`
`IE1").1 Such vectors had already been used in the art by scientists to express
`
`1 The abbreviations "HCMV IE1," "HCMV IE-1," "HCMV," "hCMV," and "CMV"
`
`in cited documents and in this Petition all refer to human cytomegalovirus.
`
`1
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
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`polypeptides of interest. While the specification places no significance on that one
`
`vector or any of its regulatory components, the claims of the '688 patent are drawn
`
`broadly to vectors containing HCMV IE1 sequences to express nearly any
`
`polypeptide (human or viral) in a mammalian or non-human mammalian cell.
`
`None of the '688 patent's genus claims are patentable. They are not entitled to
`
`priority from the '894 application (or any of the intervening applications to which
`
`they also claim priority) because the inventors never disclosed the later-claimed
`
`generic subject matter in those applications. And, as detailed below, without the
`
`benefit of priority to the '894 application, the '688 patent claims are anticipated by a
`
`patent with the exact same specification as the '688 patent: U.S. Patent No.
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`5,156,949 ("the '949 patent").
`
`The history of this patent family demonstrates that the '688 patent claims were
`
`an afterthought, divorced from the actual disclosure. For years, Patent Owner2
`
`sought claims concerning HIV and HIV diagnostic tools—the subject of the
`
`
`2 The '688 patent was prosecuted by and assigned to Chiron Corporation. In 2005,
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`Novartis Vaccines and Diagnostics, Inc. acquired the patent. As of 2014, Grifols
`
`Worldwide Operations Limited also allegedly has an ownership interest in the
`
`patent. Patent Owner is used throughout to refer to these entities.
`
`2
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
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`specification—across the '688 patent family of applications, including the
`
`application that resulted in the '688 patent, U.S. Application No. 08/288,336 ("the
`
`'336 application"). It was not until 1995 (nearly eight years after the specification
`
`was first submitted), during prosecution of the '336 application, that Patent Owner
`
`changed course and submitted claims that did not require the presence of sequences
`
`encoding an HIV polypeptide. The new claims were broadly directed to a genus of
`
`vectors comprising "a transcription regulatory region" from HCMV IE1 or methods
`
`of making such vectors or isolated nucleic acids with HCMV IE1 sequences. At that
`
`time, Patent Owner represented to the Patent and Trademark Office that "the
`
`significance" of the plasmids had previously been "overlooked," and that a patent
`
`attorney had for the first time "discovered the unclaimed plasmids"3 in 1994. For the
`
`new claims covering this previously "overlooked" subject matter, Patent Owner
`
`claimed priority back to the '894 application, which was filed on December 24,
`
`1987.
`
`But Patent Owner cannot claim the benefit of an earlier filing date under 35
`
`U.S.C. §120 because the '894 application (and the three intervening applications to
`
`
`3 The terms "vector" and "plasmid" are used interchangeably throughout the '688
`
`patent, prosecution history, and this Petition.
`
`3
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`
`
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`which the '688 patent also claims priority) does not disclose the claimed generic
`
`vectors, host cell expression systems with such vectors, methods, or isolated nucleic
`
`acid molecules. Those applications cannot reasonably be read to disclose the broad
`
`subject matter that Patent Owner claimed nearly eight years after filing its '894
`
`application on December 24, 1987. The '894 application discloses only a single
`
`HCMV-based vector (the pCMV6a vector) with a specific arrangement of
`
`components, used in only one instance to transiently express one HIV (viral)
`
`polypeptide, gp120, in one non-human mammalian cell type, COS monkey cells.
`
`Beyond this narrow disclosure of a single entity (pCMV6a expressing gp120), the
`
`'894 application does not describe—or even contemplate—any host cell expression
`
`system, vector or isolated nucleic acid molecule with HCMV IE1 sequences; any
`
`other arrangement for a vector or nucleic acid molecule containing such sequences;
`
`or using the pCMV6a vector to express any other polypeptide, much less a
`
`mammalian polypeptide. Indeed, the specification contains no broadening language
`
`or suggestion of the later-claimed generic HCMV IE1-based vector, host cell
`
`expression systems with vectors, methods, or isolated nucleic acid molecules
`
`whatsoever.
`
`Nor can the inventors claim that their single gp120-expressing pCMV6a
`
`vector is a preferred embodiment of a broader generic invention, because the
`
`4
`
`
`
`
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
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`specification describes nothing broader in the first place. Where the specification
`
`describes a particular composition or method but "contains no broadening language
`
`of any kind," later-claimed generic subject matter "has not been described." Ariad
`
`Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010) (en banc).
`
`Given the lack of written description support in the '894 application,
`
`intervening applications, and original claims, the earliest effective filing date of the
`
`'688 patent claims is August 10, 1994, the actual filing date of the '336 application.
`
`Based on this date, Patent Owner's own intervening prior art anticipates the
`
`challenged claims. Specifically, the '949 patent—which issued on October 20, 1992
`
`from the '894 application—is §102(b) prior art. The '949 patent discloses the
`
`identical single (anticipating) species as the '688 patent: pCMV6a plasmid
`
`(expressing gp120 in COS monkey cells). As detailed below, the '949 patent
`
`discloses each and every element of the '688 patent claims, rendering them
`
`unpatentable.
`
`Further, unlike the '688 patent, the prior art disclosed using HCMV IE1-based
`
`vectors and isolated nucleic acid molecules with nucleic acid sequences encoding
`
`mammalian proteins. Claim 17, the only claim at issue in this Petition that is also
`
`being asserted against Regeneron in related district court proceedings, is anticipated
`
`by Boshart et al., A Very Strong Enhancer Is Located Upstream of an Immediate
`
`5
`
`
`
`
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`

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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
`
`
`Early Gene of Human Cytomegalovirus, Cell 41:521-530 (1985) ("Boshart 1985").
`
`Boshart 1985 constructed a plasmid that included an HCMV IE1 transcription
`
`regulatory region (comprising a promoter, enhancer, and first intron) and showed
`
`that it resulted in transcription of a gene encoding a mammalian polypeptide. Claim
`
`17 is unpatentable for this further reason.
`
`II. MANDATORY NOTICES (37 C.F.R. §42.8)
`
`A. Real Party-In-Interest
`
`Petitioner, Regeneron, is the real party-in-interest for this Petition. No other
`
`party is a real party-in-interest or a privy of Regeneron for this Petition.
`
`B. Related Matters
`
`Novartis Vaccines and Diagnostics, Inc. v. Regeneron Pharmaceuticals, Inc.,
`
`No. 18-cv-2434-DLC (S.D.N.Y.) ("the District Court Action") is an ongoing district
`
`court proceeding in which Novartis Vaccines and Diagnostics, Inc. ("Novartis"),
`
`Novartis Pharma AG ("NP"), and Grifols Worldwide Operations Limited assert that
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`Regeneron's cell line for producing the EYLEA® and ZALTRAP® products
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`infringes the '688 patent. Patent Owner first served the complaint on May 24, 2018.
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`Ex.1045, 1.
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`The district court issued a decision on claim construction on March 20, 2019.
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`Ex.1032. Following the decision, on April 1, 2019 the district court entered
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`judgment of noninfringement in Regeneron's favor on claims 1-2, 4-6, 8-9, and
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`13-14 of the '688 patent ("the vector claims") subject to appeal. Regeneron's
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`invalidity counterclaims as to those claims were dismissed without prejudice.
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`Ex.1046, 3. Therefore, the invalidity of the vector claims is not before the court.
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`The District Court Action is only proceeding as to claim 17 and is in early expert
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`discovery. In April 2019, Regeneron filed its second amended counterclaims of
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`noninfringement, invalidity, and unenforceability. Ex.1047. No trial date has been
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`set in the District Court Action.
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`The '688 patent was also the subject of a district court proceeding brought by
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`Novartis and NP for alleged infringement by MedImmune LLC, Biogen Idec, Inc.,
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`and Alexion Pharmaceuticals, Inc. in the District of Delaware in 2011 ("the
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`Delaware Action"). Novartis Vaccines & Diagnostics, Inc. v. MedImmune LLC et
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`al., C.A. No. 11-cv-84-SLR-MPT (D. Del.). The Delaware Action concluded in
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`2014 without a claim construction or dispositive decision.
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`C. Lead and Back-up Counsel
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`Lead Counsel
`Irena Royzman
`Reg. No. 73,354
`iroyzman@pbwt.com
`(212) 336-2081
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`Back-up Counsel
`Andrew D. Cohen
`Reg. No. 61,508
`acohen@pbwt.com
`(212) 336-2605
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`D.
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`Service Information
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`Service on Petitioner may be made by mail or hand delivery to: Patterson
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`Belknap Webb & Tyler LLP, 1133 Avenue of the Americas, New York, NY 10036.
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`A telephone number for counsel is (212) 336-2000. A fax number for counsel is
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`(212) 336-7936.
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`Petitioner consents to electronic service by email at:
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`ChironIPR@pbwt.com.
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`III. PAYMENT OF FEES
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`The Director is authorized to charge the fee specified by 37 C.F.R. §42.15(a)
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`to Deposit Account No. 50-6642.
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`IV. GROUNDS FOR STANDING
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`Petitioner certifies that the '688 patent is available for IPR and that Petitioner
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`is not barred or estopped from requesting IPR of the '688 patent. This Petition is
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`being filed less than one year after the date on which Petitioner was served with a
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`complaint alleging infringement of the '688 patent. Ex.1045, 1. The challenged
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`claims have not been the subject of any prior petitions by the Petitioner.
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`V.
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`STATEMENT OF PRECISE RELIEF REQUESTED
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`Petitioner respectfully requests claims 1-2, 4-6, 8-9, 13-14, and 17 of the '688
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`patent be held unpatentable on the grounds set forth below, and therefore cancelled.
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`Petitioner presents the following two grounds for trial:
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`Ground 1: Claims 1-2, 4-6, 8-9, 13-14, and 17 are anticipated under 35
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`U.S.C. §102(b) by the '949 patent (Ex.1004) based on an effective filing date of no
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`earlier than August 10, 1994.
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`Ground 2: Claim 17 is anticipated by Boshart 1985 (Ex.1025) under 35
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`U.S.C. §102(b).
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`VI. THE CHALLENGED CLAIMS
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`Petitioner challenges claims 1-2, 4-6, 8-9, 13-14, and 17 as unpatentable.
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`Claim 1 of the '688 patent recites:
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`A non-human mammalian host cell expression system for
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`improved
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`expression
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`comprising
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`a
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`non-human
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`mammalian host cell with a vector for expression of a
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`polypeptide in a mammalian cell comprising a first
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`polynucleotide sequence that comprises:
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`a) an upstream SV40 origin of replication;
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`b) a downstream SV40 polyadenylation region;
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`c) a
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`transcription
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`regulatory
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`region
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`from human
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`cytomegalovirus immediate early region HCMV IE1,
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`wherein the transcription regulatory region includes the
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`first HCMV IE1 intron proximal to the 3' end of the
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`HCMV IE1 promoter, is interposed between the SV40
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`origin of replication and the SV40 polyadenylation region,
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`and is capable of directing the transcription of a
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`polypeptide coding sequence operably linked downstream
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`from the transcription regulatory region, and
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`d)
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`the polypeptide coding sequence encoding a
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`heterologous polypeptide operably linked downstream of
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`the transcription regulatory region.
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`In brief, claim 1 is directed to a genus of host cell expression systems with vectors
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`having the following components for expression of any heterologous polypeptide: 1)
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`an upstream SV40 origin of replication; 2) a downstream SV40 polyadenylation
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`region; and 3) a transcription regulatory region from HCMV IE1, including the
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`promoter and first intron. Ex.1003, ¶¶30-31, 37-46, 49.
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`Claims 2, 6, and 8 depend from claim 1. Claim 2 further requires a restriction
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`site for insertion of the coding region of the polypeptide. Claim 6 requires "a
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`selectable marker." Claim 8 requires "a bacterial origin of replication." Ex.1003,
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`¶¶32-33, 47-48.
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`Independent claims 4, 5, and 9 are each directed to "[a] vector for expression
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`of a polypeptide in a mammalian cell." The vector requirements are similar to those
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`of claim 1, but additionally require sequences from particular plasmids. Claim 4
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`requires the SV40 polyadenylation region from "plasmid pSV7d." Claim 5 requires
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`the SV40 origin of replication from "plasmid pSVT2." Claim 9 requires the vector
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`to comprise "HCMV sequences present in plasmid pCMV6ARV120tpa, ATCC
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`Accession No. 68249." Ex.1003, ¶34.
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`Independent claim 13 recites a "vector produced by the process comprising
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`linking together in an operative manner" vector components of: 1) an SV40 origin of
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`replication, 2) an SV40 polyadenylation region, 3) a transcription regulatory region
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`from HCMV IE1, and 4) a polypeptide coding sequence encoding "a mammalian
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`polypeptide or a heterologous mammalian virus polypeptide." Claim 14 depends
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`from claim 13 and specifies that the "vector is arranged in the same manner as
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`plasmid pCMV6a." Ex.1003, ¶¶35, 37-46, 49.
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`Independent claim 17 is directed to any "isolated nucleic acid molecule
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`comprising an enhanced promoter" from HCMV IE1 (comprising the promoter,
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`enhancer, and first intron), wherein the promoter is "operably linked to a nucleic
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`acid sequence encoding a mammalian polypeptide or a heterologous mammalian
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`virus polypeptide." Ex.1003, ¶¶36, 49.
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`VII. THE '688 PATENT
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`The '688 patent is entitled "Vector for Expression of a Polypeptide in a
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`Mammalian Cell." Ex.1001. It issued on November 18, 1997 from the August 10,
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`1994 '336 application (Ex.1005), and expired on November 18, 2014.
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`The '688 patent claims priority, through three intervening applications, to the
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`'894 application (Ex.1002), which was filed on December 24, 1987 and issued as the
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`'949 patent (titled "Immunoassays For Antibody To Human Immunodeficiency
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`Virus Using Recombinant Antigens" on October 20, 1992). As illustrated below,
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`the '336 application is a divisional of U.S. Application No. 08/107,377 (Ex.1022)
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`(abandoned), which is a divisional of U.S. Application No. 08/083,391 (Ex.1023)
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`(issued as U.S. Patent No. 6,458,527, titled "HIV Immunoassays Using Gag
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`Polypeptides"), which is a continuation of U.S. Application No. 07/931,191
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`(Ex.1024) (abandoned), which is a divisional of the '894 application. Ex.1003, ¶28.
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`Petition for Inter Partes Review of U.S. Patent No. 5,688,688
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`A.
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`Shared Specification of the '688 Patent and '894 Application
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`The shared specification of the '688 patent and '894 application concerns
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`polynucleotide sequences from a particular HIV strain, and expressing HIV
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`polypeptides encoded by those polynucleotide sequences for diagnostic purposes.
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`Ex.1003, ¶¶50-56. The specification references various vectors for expressing HIV
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`po