Trials@uspto.gov
`571-272-7822
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` Paper No. 85
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` Entered: November 29, 2018
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CELLTRION, INC.,
`Petitioner,
`
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01374
`Patent 6,407,213 B1
`____________
`
`
`Before SHERIDAN K. SNEDDEN, ZHENYU YANG, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`
`
`FINAL WRITTEN DECISION
`Claims 1, 2, 4, 25, 29, 30, 31, 33, 62–64, 66, 67, 69, 72,
`78, 80, and 81 Shown to Be Unpatentable
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`
`
`
`
`
`
`
`571-272-7822
`
`
`
`
`
`
`
`
`
`
` Paper No. 85
`
` Entered: November 29, 2018
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CELLTRION, INC.,
`Petitioner,
`
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01374
`Patent 6,407,213 B1
`____________
`
`
`Before SHERIDAN K. SNEDDEN, ZHENYU YANG, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`
`
`FINAL WRITTEN DECISION
`Claims 1, 2, 4, 25, 29, 30, 31, 33, 62–64, 66, 67, 69, 72,
`78, 80, and 81 Shown to Be Unpatentable
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`
`
`
`
`
`
`
`
`IPR2017-01374
`Patent 6,407,213 B1
`
`
`ORDERS
`Denying Patent Owner’s Motion to Exclude (Paper 60)
`37 C.F.R. § 42.64(c)
`
`Denying Petitioner’s Motion to Exclude (Paper 62)
`37 C.F.R. § 42.64(c)
`
`Denying Patent Owner’s Motion to Strike (Paper 58)
`37 C.F.R. § 42.5
`
`Denying Patent Owner’s Motion to Seal (Paper 36) without Prejudice
`37 C.F.R. § 42.55
`
`Denying Petitioner’s Motions to Seal (Papers 51, 61, and 74)
`without Prejudice to Patent Owner
`37 C.F.R. § 42.55
`
`Modifying Previous Order Granting Patent Owner’s Motion to Seal
`37 C.F.R. § 42.55
`
`
`INTRODUCTION
`I.
`This is a Final Written Decision in an inter partes review challenging
`the patentability of claims 1, 2, 4, 12, 25, 29–31, 33, 42, 60, 62–67, 69, and
`71–81 of U.S. Patent No. 6,407,213 B1 (“the ’213 patent,” Ex. 1001). We
`have jurisdiction under 35 U.S.C. § 6.
`Having reviewed the arguments of the parties and the supporting
`evidence, we find that Petitioner has demonstrated by a preponderance of the
`evidence that claims 1, 2, 4, 25, 29, 30, 31, 33, 62–64, 66, 67, 69, 72, 78, 80,
`and 81 of the ’213 patent are unpatentable. Petitioner has not made that
`showing with respect to claims 12, 42, 60, 65, 71, 73–77, and 79.
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`
`Procedural History
`A.
`Petitioner, Celltrion, Inc., filed a Petition for an inter partes review of
`claims 1, 2, 4, 12, 25, 29–31, 33, 42, 60, 62–67, 69, and 71–81 the ’213
`patent.” Paper 2 (“Pet.”). Patent Owner, Genentech, Inc., timely filed a
`Preliminary Response. Paper 7 (“Prelim. Resp.”). Based on the record
`before us at the time, we instituted trial with respect to all challenged claims.
`Paper 15, 23–24 (“Dec.”).
`After institution of trial, Patent Owner filed its Patent Owner
`Response (Paper 37, “PO Resp.”) and Petitioner filed a Reply to the Patent
`Owner Response (Paper 52, “Pet. Reply”). Patent Owner filed a motion to
`strike evidence and argument presented in Petitioner’s Reply. Paper 58.
`Petitioner opposed. Paper 70.
`With respect to technical experts, Petitioner relies on the declarations
`of Lutz Riechmann, Ph.D. (Exs. 1003, 1143) and Robert Charles Frederick
`Leonard, Ph.D. (Ex. 1004); Patent Owner relies on the declarations of
`Drs. Leonard G. Presta (Ex. 2016), Paul J. Carter (Ex. 2017), and Ian A.
`Wilson (Ex. 2041). Patent Owner further relies on the testimony of research
`technician, Mr. John Ridgway Brady (Ex. 2018). With respect to records
`management and authentication, Petitioner relies on the testimony of
`Mathew Miner, Ph.D. (Ex. 1133); Patent Owner similarly relies on the
`testimony of Ms. Irene Loeffler (Ex. 2019).
`Patent Owner filed a motion for observations on the deposition of
`Dr. Riechmann (Paper 65), to which Petitioner responded (Paper 69).
`Patent Owner submitted one motion to exclude evidence. Paper 60.
`Petitioner opposed (Paper 67), and Patent Owner submitted a reply in
`support of its motion (Paper 71). Petitioner also submitted one motion to
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`exclude evidence. Paper 62. Patent Owner opposed (Paper 68), and
`Petitioner submitted a reply in support of its motion (Paper 81).
`Patent Owner submitted a first, unopposed motion to seal (Paper 8),
`which we granted (Paper 14) concurrent with entry of the Modified Default
`Standing Protective Order governing this case (Ex. 2030). The parties have
`since submitted additional, unopposed motions to seal. See Paper 36 (by
`Patent Owner); Papers 51, 61, and 74 (by Petitioner).
`We heard oral argument on July 16, 2018, in a joint proceeding
`involving this case and IPR2017-001373. A transcript of that proceeding is
`entered as Paper 82 (“Tr.”).
`
`B. Related Proceedings
`According to the parties, the ’213 patent is at issue in Amgen Inc. v.
`Genentech, Inc., No. 2-17-cv-07349 (C.D. Cal.) (dismissed); Genentech, Inc.
`v. Amgen Inc., No. 1-17-cv-01407 (D. Del.); Genentech, Inc. v. Amgen Inc.,
`No. 1-17-cv-01471 (D. Del.); and Genentech, Inc.. v. Pfizer, Inc. (D. Del.)
`1:17-cv-01672 (D. Del); Celltrion, Inc. v. Genentech, Inc., No. 3-18-cv-
`00274 (N.D. Cal.) (appeal docketed, No. 18-2160 (Fed. Cir. July 16, 2018);
`Genentech, Inc. v. Celltrion, Inc., No. 1-18-cv-00095 (D. Del.); Genentech,
`Inc. v. Amgen, Inc., No. 1-18-cv-00924 (D. Del.); and Genentech Inc. v.
`Celltrion, Inc., No. 1-18-cv-01025( D. Del.). See, e.g., Paper 83, 1–2; Paper
`84, 1–2.
`In addition to the present case, the ’213 patent is the subject of the
`following pending matters: IPR2017-01373 brought by Celltrion, Inc.;
`IPR2017-01488 and IPR2017-01489, brought by Pfizer, Inc.; and IPR2017-
`02139 and IPR2017-02140, brought by Samsung Bioepis Co., Ltd.
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`
`The ’213 patent was the subject of two earlier IPR proceedings filed
`by Mylan Pharmaceuticals Inc., IPR2016–01693 and IPR2016–01694,
`which we terminated on March 10, 2017, in response to the parties’ Joint
`Motion to Terminate. See IPR2016–01693, Paper 24; IPR2016–01694,
`Paper 23. The ’213 patent was also the subject of IPR2017-02031 and
`IPR2017-02032 brought by Boehringer Ingelheim Pharmaceuticals, Inc.,
`which we terminated in light of the Petitioner’s unopposed motions for
`adverse judgement. IPR2017-02031, Paper 32; IPR2017-02032, Paper 30.
`
`C.
`
`The ’213 Patent and Relevant Background
`The ’213 patent issued to Drs. Leonard G. Presta and Paul J. Carter on
`June 18, 2002, bearing the title “Method for Making Humanized
`Antibodies.” Ex. 1001, (45), (54), (75). According to the Specification, the
`patent relates to “methods for the preparation and use of variant antibodies
`and finds application particularly in the fields of immunology and cancer
`diagnosis and therapy.” Id. at 1:12–14.
`A naturally occurring antibody (immunoglobulin) comprises two
`heavy chains and two light chains. Id. at 1:18–20. Each heavy chain has a
`variable domain (VH) and a number of constant domains. Id. at 1:21–23.
`Each light chain has a variable domain (VL) and a constant domain. Id. at
`1:23–24.
`The variable domains (VH and VL) are involved directly in binding
`the antibody to the antigen. Id. at 1:36–38. Each variable domain
`“comprises four framework (FR) regions, whose sequences are somewhat
`conserved, connected by three hyper-variable or complementarity
`determining regions (CDRs).” Id. at 1:40–43. The constant domains are not
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`involved directly in binding the antibody to an antigen, but contribute to
`various effector functions. Id. at 1:33–34.
`Monoclonal antibodies are generally derived from animals, frequently
`mice, and target a specific antigen. See id. at 1:51–53. Prior to the filing of
`the ’213 patent, it was recognized that these antibodies were frequently
`antigenic in human clinical use, resulting in, for example, undesirable anti-
`globulin responses during therapy. Id. at 1:54–56. Researchers attempted to
`address this problem by constructing chimeric and humanized antibodies
`comprising mixtures of rodent and human sequences. In particular, the ’213
`patent defines chimeric antibodies as those “in which an animal antigen-
`binding variable domain is coupled to a human constant domain” (id. at
`1:60–63), whereas “humanized antibodies are typically human antibodies in
`which some CDR residues and possibly some FR residues are substituted by
`residues from analogous sites in rodent antibodies” (id. at 2:32–35).
`The ’213 patent also acknowledges the following as known in the
`prior art: The function of an antibody is dependent on its three-dimensional
`structure, and amino acid substitutions can change the three-dimensional
`structure of an antibody. Id. at 3:40–43. Although substituting the CDRs of
`a human antibody with CDRs from a rodent antibody may be sufficient to
`transfer high antigen binding affinity from the rodent antibody, it is
`sometimes necessary to further replace one or more of the human framework
`residues with a non-human residue. Id. at 2:53–61. Thus, “[f]or a given
`antibody[,] a small number of FR residues are anticipated to be important for
`antigen binding” because they either directly contact an antigen or “critically
`affect[] the conformation of particular CDRs and thus their contribution to
`antigen binding.” Id. at 2:62–3:8. In addition, an antibody variable domain
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`“may contain glycosylation sites, and that this glycosylation may improve or
`abolish antigen binding.” Id. at 3:9–12. Further, the antigen binding affinity
`of a humanized antibody can be increased by mutagenesis based upon
`molecular modelling. Id. at 3:44–46. 1
`Despite such knowledge in the field, according to the ’213 patent, at
`the time of its invention, humanizing an antibody with retention of high
`affinity for antigen and other desired biological activities was difficult to
`achieve using then-available procedures. Id. at 3:50–52. The ’213 patent
`purportedly provides methods for rationalizing the selection of sites for
`substitution in preparing humanized antibodies and thereby increasing the
`efficiency of antibody humanization. Id. at 3:53–55.
`
`
`1 Although undisputed that humanization tends to reduce immunogenicity as
`compared to the non-human parent antibody, Patent Owner points out that
`framework substitutions tend to “increase the potential for immunogenicity
`by introducing non-human residues into the humanized sequence,” and
`“[t]he purpose of framework substitutions is to improve binding affinity,
`which must be balanced against the increased risk of immunogenicity.” PO
`Resp. 60 n.12 (citing Ex. 2041 ¶¶ 83, 220).
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`
`D. Challenged Claims and Reviewed Ground of Unpatentability
`We instituted trial on claims 1, 2, 4, 12, 25, 29–31, 33, 42, 60, 62–67,
`69, and 71–81 under the following Grounds:2
`
`Claim(s)
`1, 2, 25, 29, 63, 65,
`66, 71, 75, 76, 78, 80,
`and 81
`1, 2, 4, 29, 62–64, 80,
`and 81
`1, 2, 4, 25, 29, 62–64,
`66, 67, 69, 71, 72, 75,
`76, 78, 80, and 81
`12
`
`Ground
`1
`
`2
`
`3
`
`4
`
`5
`
`Basis
`§ 102 Kurrle3
`
`Reference(s)
`
`§ 102 Queen 19904
`
`§ 103 Kurrle and Queen 1990
`
`§ 103 Kurrle, Queen 1990, and
`Furey 5
`65, 73, 74, 77, and 79 § 103 Kurrle, Queen 1990, and
`Chothia & Lesk6, and Chothia
`19857
`
`
`2 Petitioner did not expressly recite claim 65 in its statement of grounds in
`the Petition, nor did we initially institute on this claim in our Decision. Both
`parties, however, present arguments and evidence presuming the inclusion of
`claim 65 in this proceeding, and Patent Owner has not objected to our order
`at oral hearing including claim 65 in Ground 1. See Tr. 5:10–7:6.
`3 Kurrle, et al., European Patent Application Publication No. 0403156 A1,
`published December 19, 1990. Ex. 1071.
`4 Queen, et al., International Publication No. WO 1990/07861, published
`July 26, 1990. Ex. 1050.
`5 Furey et al., Structure of a Novel Bence-Jones Protein (Rhe) Fragment at
`1.6 Å Resolution, 167 J. MOL. BIOL. 661–92 (1983). Ex. 1125.
`6 Chothia and Lesk, Canonical Structures for the Hypervariable Regions of
`Immunoglobulins, 196 J. MOL. BIOL. 901–17 (1987). Ex. 1062.
`7 Chothia et al., Domain Association in Immunoglobulin Molecules: The
`Packing of Variable Domains, 186 J. MOL. BIOL. 651–63 (1985). Ex. 1063.
`8
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`
`Ground
`6
`7
`
`Claim(s)
`30, 31, and 33
`42
`
`Reference(s)
`Basis
`§ 103 Queen 1990 and Hudziak8
`§ 103 Queen 1990, Kurrle, Hudziak,
`and Furey
`§ 103 Queen 1990, Hudziak, and
`Chothia & Lesk
`Claims 1, 30, 62–64, 66, 79, and 80 are independent. Claim 1 is
`illustrative:
`1. A humanized antibody variable domain comprising non-
`human Complementarity Determining Region (CDR) amino acid
`residues which bind an antigen incorporated into a human
`antibody variable domain, and further comprising a Framework
`Region (FR) amino acid substitution at a site selected from the
`group consisting of: 4L, 38L, 43L, 44L, 58L, 62L, 65L, 66L,
`67L, 68L, 69L, 73L, 85L, 98L, 2H, 4H, 36H, 39H, 43H, 45H,
`69H, 70H, 74H, and 92H, utilizing the numbering system set
`forth in Kabat.[9]
`
`8
`
`60
`
`II. ANALYSIS
`
`A.
`
`Legal Standards
`To anticipate a claim under 35 U.S.C. § 102, “a single prior art
`reference must expressly or inherently disclose each claim limitation.”10
`
`8 Hudziak et al., p185HER2 Monoclonal Antibody Has Antiproliferative
`Effects In Vitro and Sensitizes Human Breast Tumor Cells to Tumor
`Necrosis Factor, 9 MOL. CELL BIOL. 1165–72 (1989). Ex. 1021.
`9 See Ex. 1001, 10:45–56 (indicating that the Kabat numbering scheme for
`antibodies “assign[s] a residue number to each amino acid in a listed
`sequence”).
`10 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”), amended 35 U.S.C. §§ 102 and 103. Because the
`challenged claims of the ’213 patent have an effective filing date before the
`effective date of the applicable AIA amendments, throughout this Final
`Written Decision we refer to the pre-AIA versions of 35 U.S.C. §§ 102 and
`103.
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`Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1334 (Fed. Cir. 2008).
`That “single reference must describe the claimed invention with sufficient
`precision and detail to establish that the subject matter existed in the prior
`art.” Verve, LLC v. Crane Cams, Inc., 311 F.3d 1116, 1120 (Fed. Cir.
`2002). While the elements must be arranged in the same way as is recited in
`the claim, “the reference need not satisfy an ipsissimis verbis test.” In re
`Gleave, 560 F.3d 1331, 1334 (Fed. Cir. 2009). Moreover, “it is proper to
`take into account not only specific teachings of the reference but also the
`inferences which one skilled in the art would reasonably be expected to draw
`therefrom.” In re Preda, 401 F.2d 825, 826 (CCPA 1968).
`In order to support an anticipation rejection, a prior art “reference
`must clearly and unequivocally disclose the claimed [invention] or direct
`those skilled in the art to the [invention] without any need for picking,
`choosing, and combining various disclosures not directly related to each
`other by the teachings of the cited reference.” In re Arkley, 455 F.2d 586,
`587 (CCPA 1972)(emphasis omitted). Moreover, when a
`prior art reference merely discloses a genus and the claim at
`issue recites a species of that genus . . . the issue of anticipation
`turns on whether the genus was of such a defined and limited
`class that one of ordinary skill in the art could “at once
`envisage” each member of the genus.
`Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1361
`(Fed. Cir. 2012) (citing Eli Lilly & Co. v. Zenith Goldline Pharm., Inc., 471
`F.3d 1369, 1376 (Fed. Cir. 2006)).
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the subject matter sought to be patented and the prior art are such
`that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which that
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`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved based on underlying factual
`determinations including (1) the scope and content of the prior art; (2) any
`differences between the claimed subject matter and the prior art; (3) the level
`of ordinary skill in the art; and (4) objective evidence of nonobviousness, if
`present. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`“[T]he [obviousness] analysis need not seek out precise teachings
`directed to the specific subject matter of the challenged claim, for a court
`can take account of the inferences and creative steps that a person of
`ordinary skill in the art would employ.” KSR, 550 U.S. at 418. Moreover,
`“any need or problem known in the field of endeavor at the time of invention
`and addressed by the patent can provide a reason for combining the elements
`in the manner claimed.” Id. at 420. Accordingly, a party that petitions the
`Board for a determination of unpatentability based on obviousness must
`show that “a skilled artisan would have been motivated to combine the
`teachings of the prior art references to achieve the claimed invention, and
`that the skilled artisan would have had a reasonable expectation of success in
`doing so.” In re Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381 (Fed.
`Cir. 2016) (citations omitted).
`We analyze the instituted grounds of unpatentability in accordance
`with these principles.
`
`B.
`
`Person of Ordinary Skill in the Art
`The parties propose similar definitions of a person of ordinary skill
`with respect to the ’213 patent. See Pet. 12–13; Prelim. Resp. 17–18; PO
`Resp. 17–18. In our institution decision, we adopted Patent Owner’s
`proposal that “[a] person of ordinary skill for the ’213 patent would have had
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`a Ph.D. or equivalent in chemistry, biochemistry, structural biology, or a
`closely related field, and experience with antibody structural
`characterization, engineering, and/or biological testing, or an M.D. with
`practical academic or industrial experience in antibody development.” Dec.
`10–11. Petitioner does not contest this definition in its Reply and we find no
`reason to revise our earlier determination.
`We further note that the prior art itself demonstrates this level of skill
`in the art at the time of the invention. See Okajima v. Bourdeau, 261 F.3d
`1350, 1355 (Fed. Cir. 2001) (explaining that specific findings on ordinary
`skill level are not required “where the prior art itself reflects an appropriate
`level and a need for testimony is not shown” (quoting Litton Indus. Prods.,
`Inc. v. Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir. 1985)).
`
`C. Claim Construction
`In an inter partes review, claim terms in an unexpired patent are
`interpreted according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b)
`(2018); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016)
`(upholding the use of the broadest reasonable interpretation standard).
`Under that standard, we presume that a claim term carries its “ordinary and
`customary meaning,” which “is the meaning that the term would have to a
`person of ordinary skill in the art in question” at the time of the invention.
`In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007); see also
`Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed. Cir. 2016) (“Under
`a broadest reasonable interpretation, words of the claim must be given their
`plain meaning, unless such meaning is inconsistent with the specification
`and prosecution history.”). Any special definition for a claim term must be
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`set forth in the specification with reasonable clarity, deliberateness, and
`precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Limitations,
`however, may not be read from the specification into the claims (In re Van
`Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993)), nor may the Board “construe
`claims during [an inter partes review] so broadly that its constructions are
`unreasonable under general claim construction principles” (Microsoft Corp.
`v. Proxyconn, Inc., 789 F.3d 1292, 1298 (Fed. Cir. 2015) (overruled on other
`grounds by Aqua Products, Inc. v. Matal, 872 F.3d 1290 (Fed. Cir. 2017)).
`
`1. “Consensus human variable domain”
`Patent Owner proposes that we construe the term “consensus human
`variable domain,” which appears in claims 4, 33, 62, and 69, to mean “a
`human variable domain which comprises the most frequently occurring
`amino acid residues at each location in all human immunoglobulins of any
`particular subclass or subunit structure.” Prelim. Resp. 18–19; PO Resp. 18.
`Petitioner does not contest this definition in their Reply.
`Patent Owner’s proposed construction derives from the ’213 patent’s
`definition of consensus sequence as “refer[ing] to an amino acid sequence
`which comprises the most frequently occurring amino acid residues at each
`location in all human immunoglobulins of any particular subclass or subunit
`structure.” Ex. 1001, 11:32–38. In the context of the patent as a whole,
`however, we do not understand the term to require a consensus of “all”
`human immunoglobulins in the literal sense because the embodiments in the
`patent were generated using the most common residue at each position
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`identified in Kabat 1987. 11 See id. at 10:34–63, 11:55–60; Ex. 2016 ¶¶ 25–
`26. And though Patent Owner attempts to distinguish Queen 1990 as
`describing “a consensus framework from many human antibodies,’ not all as
`in the ’213 patent,’” it presents no argument as to why we should interpret
`the claim in this manner. See PO Resp. 47. Moreover, at oral argument,
`Patent Owner did not contest Petitioner’s assertion that the reference to “all
`sequences” in the patent, “refer[s] to all known sequences and there’s no
`dispute . . . that was really synonymous with Kabat 1987.” Tr. 15:4–16:4.12
`Accordingly, we adopt the parties proposed construction, with a
`clarifying modification, specifically, “a human variable domain which
`comprises the most frequently occurring amino acid residues at each
`location in all human immunoglobulins of any particular subclass or subunit
`structure, as set forth in Kabat 1987.”
`
`2. “lacks immunogenicity compared to a non-human parent
`antibody”
`Independent claim 63 is directed to “[a] humanized antibody which
`lacks immunogenicity compared to a non-human parent antibody upon
`repeated administration to a human patient.” Consistent with claim 63’s
`
`
`11 Kabat et al., Sequences of Proteins of Immunological Interest: Tabulation
`and Analysis of Amino Acid and Nucleic Acid Sequences of Precursors, V-
`Regions, C-Regions, J-Chain, T-Cell Receptor for Antigen, T-Cell Surface
`Antigens β2-Microglobulin, Major Histocompatibility Antigens, Thy-1
`Complement, C-Reactive Protein, Thymopoietin, Post-Gamma Globulin, and
`α2-Macroblobulin, 41–175 (4th Ed. 1987). Ex. 1052.
`12 In a parallel proceeding involving the same patent, counsel for Patent
`Owner acknowledged that the term “all human immunoglobulins” refers to
`“all reasonably available[,] all known at the time of the invention.”
`IPR2017-01373, Paper 83, 47:21–48:5.
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`express comparison between the immunogenicity of the claimed humanized
`antibody and that of its non-human parent, the Specification states that one
`object of the invention is to “to provide methods for the preparation of
`antibodies which are less antigenic in humans than non-human antibodies
`but have desired antigen binding and other characteristics and activities.”
`Ex. 1001, 4:24–28. The Specification similarly states that embodiments
`within the scope of the claims have “low immunogenicity,” or are designed
`to “minimize the potential immunogenicity of the resulting humanized
`antibody in the clinic.” Id. at 52:54–58, 61:57–61. Moreover, with
`reference to claim 63 in particular, Patent Owner points to the ’272
`application as “explain[ing] that the purpose of humanizing antibodies using
`its consensus sequence approach is to reduce immunogenicity versus the
`non-human parent antibody. (Id., 6:24–30, 84:24–30.).” Prelim. Resp. 43
`(citing Ex. 1094 (File History for U.S. Patent Application No. 07/715,272
`(“the ’272 application”)); see also id. at 38 (indicating that the limitation is
`satisfied where “[o]nly 1 out of 885 patients experienced an immunogenic
`response . . . which was a substantial improvement over the murine 4D5
`antibody”).
`We previously stated that the language of claim 63, “refer[s] to a
`humanized antibody having reduced immunogenicity in a human patient as
`compared to its non-humanized parent antibody.” IPR2017-01488, Paper 27
`at 10–12. Patent Owner does not dispute this interpretation. See PO Resp.
`19. Petitioner argues that the recited reduction in immunogenicity is both an
`inherent aspect of the claimed humanized antibodies, and “the stated goal of
`all humanization projects, including that of Queen 1990 and Kurrle.” Pet.
`Reply, 28, 43. Petitioner also contends that the term is not a claim limitation
`
`15
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`and “simply a statement of the intended result of the claimed compositions,”
`but, nevertheless, states: “For the purpose of the present petition only,
`Petitioner will assume that the preambles are limiting.” Pet. 13 n.3.
`On balance, we see no need to alter our prior determination that “[a]
`humanized antibody which lacks immunogenicity compared to a non-human
`parent antibody upon repeated administration to a human patient,” refers to a
`humanized antibody having reduced immunogenicity in a human patient as
`compared to its non-humanized parent antibody. Nevertheless, to the extent
`Petitioner is correct that the preambles should be accorded no weight, such a
`determination would not alter the outcome of this proceeding.
`
`3. Other Limitations
`On pages 13–15 of its Petition, Petitioner proposes constructions for
`“humanized” antibodies (claims 1, 30, 62–64, 66, 79, 80); “and further
`comprising a Framework Region (FR) amino acid substitution at a site
`selected from the group consisting of” (claims 1, 30, 62, 63, 66, 79, and 80);
`“numbering system set forth in Kabat” (claims 1, 30, 62, 63, 66, 79, and 80)
`13; and “up to 3-fold more” (claim 65). Patent Owner does not dispute
`Petitioner’s proposed constructions, but asserts that “[n]o construction of
`those terms is necessary.” Prelim. Resp. 19; PO Resp. 18. On the present
`
`13 Petitioner states that the ’213 Patent “ties its numbering system to” both
`Kabat 1987 and Kabat 1991 (Kabat, et al. Sequences of Proteins of
`Immunological Interest 5th Ed., Tabulation and Analysis of Amino Acid and
`Nucleic Acid Sequences of Precursors, V-Regions, C-Regions, J-Chain, T-
`Cell Receptor for Antigen, T-Cell Surface Antigens, (National Institutes of
`Health, Bethesda, Md.) (1991) (Ex. 1055)), but concedes that the priority
`application relies only on Kabat 1987 and that there are no significant
`differences between the two numbering systems. Pet. 14–15 & n.4; Ex.
`1003 ¶ 167 n.5.
`
`16
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`IPR2017-01374
`Patent 6,407,213 B1
`
`record, we agree with Patent Owner that the terms identified by Petitioner
`need not be construed to resolve the issues presently before us. See
`Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011)
`(instructing that claim terms need only be construed to the extent necessary
`to resolve the controversy).
`
`D.
`
`Prior-Art Status of Kurrle and Queen 1990
`Petitioner asserts that Kurrle and Queen 1990 are prior art for all
`challenged claims. See e.g., Pet. 1, 4. Patent Owner disagrees, at least with
`respect to claims 12, 42, 60, 65, 71, 73–74, and 79. 14 PO Resp. 22–44. In
`particular, Patent Owner contends that each element of those claims was
`reduced to practice prior to the publication of Kurrle and Queen 1990, i.e.,
`before July 26, 1990. Id.
`“In an [inter partes review], the petitioner has the burden from the
`onset to show with particularity why the patent it challenges is
`unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
`Cir. 2016) (citing 35 U.S.C. § 312(a)(3) (requiring inter partes review
`petitions to identify “with particularity . . . the evidence that supports the
`grounds for the challenge to each claim”)). This burden of persuasion never
`shifts to Patent Owner. See Dynamic Drinkware, LLC v. Nat’l Graphics,
`Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015). The petitioner also has the
`initial burden of production to show that an asserted reference qualifies as
`
`14 Patent Owner initially attempted to disqualify Kurrle and Queen 1990 as
`prior art with respect to all challenged claims, arguing that each claim was
`actually reduced to practice before either Kurrle or Queen 1990 was
`published (Prelim. Resp. 20–43), but now limits it antedation contentions to
`claims 12, 42, 60, 65, 71, 73–74, and 79 (see PO Resp. 22–23).
`
`
`17
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`prior art under 35 U.S.C. § 102. Id. at 1379; Mahurkar v. C.R. Bard, Inc., 79
`F.3d 1572, 1576 (Fed. Cir. 1996) (holding that the challenger “bore the
`burden of persuasion . . . on all issues relating to the status of [the asserted
`reference] as prior art”). Should Petitioner meet that initial burden, the
`burden of production shifts to the patent owner to argue or produce evidence
`that either the asserted reference does not render the challenged claims
`unpatentable, or the reference is not prior art. Dynamic Drinkware, 800 F.3d
`at 1378 (citing Tech. Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1327
`(Fed. Cir. 2008)). Patent Owner may, therefore, antedate Kurrle and Queen
`1990 by establishing reduction to practice prior to the earliest priority date of
`the ’213 patent. See Purdue Pharma L.P. v. Boehringer Ingelheim GMBH,
`237 F.3d 1359, 1365 (Fed. Cir. 2001) (“To antedate . . . an invention, a party
`must show either an earlier reduction to practice, or an earlier conception
`followed by a diligent reduction to practice.”) (citation omitted).
`The ’213 patent issued from application number 08/146,206 (“the
`’206 application”), which is an application that entered the national stage on
`November 17, 1993, from a PCT application filed on June 15, 1992.
`Ex. 1001, (21), (22), (86). The ’206 application is also a continuation-in-
`part of the ’272 application, filed on June 14, 1991. Id. at (63). Kurrle was
`published on December 19, 1990 (Ex. 1071, (43)), and Queen 1990 was
`published on July 26, 1990 (Ex. 1050, (43)), both of which predate the
`earliest possible priority date, June 14, 1991, shown on the face of the ’213
`patent. Accordingly, Petitioner has satisfied its initial burden of showing
`that Kurrle and Queen 1990, on their face, qualify as prior art to the
`challenged claims. We next consider whether Patent Owner has antedated
`these references.
`
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`
`1. Whether Kurrle and Queen 1990 are prior art under
`§ 102(b)
`As a preliminary matter, antedating a reference is unavailable if the
`reference qualifies as prior art under 35 U.S.C. § 102(b). See 37 C.F.R.
`§ 1.131(a)(2). Accordingly, we need not address Patent Owner’s antedation
`evidence unless the challenged claims are entitled to benefit of priority no
`more than one year from the publication date of Kurrle and Queen 1990.
`See id. To make that assessment we first consider the priority date
`entitlement of claims 12, 42, 60, 65, 71, 73–74, and 79.
`Petitioner notes “[t]he only examples in the ’272 application are the
`eight variants of the humanized 4D5 antibody,” designated huMAb4D5-1
`through huMAb4D5-8. See Pet. Reply 6 (citing Ex. 2032, 93). Relying on
`the characterization of those variants in the ’272 application, and the detailed
`testimony of Dr. Wilson (Ex. 2041 ¶¶ 88–95), Patent Owner argues that
`claims 12, 42, 60, 65, 71, 73–74, and 79 are entitled to a priority date of June
`14, 1991, because each element of those claims finds written description and
`enablement support in the ’272 application. PO Resp. 41–44. Accordingly,
`Patent Owner argues, Kurrle and Queen 1990 do not qualify as prior art
`under § 102(b) because they were published within one year of the critical
`date (December 19, 1990 and July 26, 1990, respectively). Id.
`In opposing Patent Owner’s position, Petitione
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