Trials@uspto.gov
`571-272-7822
`
`
`
`
`
`
`
`
`
`
` Paper No. 87
`
`Entered: November 29, 2018
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PFIZER, INC. and
`SAMSUNG BIOEPIS CO., LTD.,
`Petitioners,
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01488
`Patent 6,407,213 B11
`____________
`
`
`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
`
`
`
`1 IPR2017-02139 has been joined to this case.
`
`
`
`
`
`571-272-7822
`
`
`
`
`
`
`
`
`
`
` Paper No. 87
`
`Entered: November 29, 2018
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PFIZER, INC. and
`SAMSUNG BIOEPIS CO., LTD.,
`Petitioners,
`v.
`
`GENENTECH, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01488
`Patent 6,407,213 B11
`____________
`
`
`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
`
`
`
`1 IPR2017-02139 has been joined to this case.
`
`
`
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`
`ORDERS
`Denying Patent Owner’s Motion to Exclude (Paper 63)
`37 C.F.R. § 42.64(c)
`Denying Petitioner’s Motion to Exclude (Paper 67)
`37 C.F.R. § 42.64(c)
`Denying Patent Owner’s Motion to Strike (Paper 61)
`37 C.F.R. § 42.5
`Denying Patent Owner’s Motion to Seal (Paper 43) without Prejudice
`37 C.F.R. § 42.55
`Denying Petitioner’s Motions to Seal (Papers 54 and 66)
`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 Petitioners have demonstrated by a preponderance of
`the evidence that claims 1, 2, 4, 25, 29, 30, 31, 33, 62–64, 66, 67, 69, 72, 76,
`78, 80, and 81 of the ’213 patent are unpatentable. Petitioners have not
`made that showing with respect to claims 12, 42, 60, 65, 71, 73–75, 77, and
`79.
`
`2
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`
`Procedural History
`A.
`Petitioner Pfizer, 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 1 (“Pet.”). Genentech, Inc. (“Patent Owner”) timely filed a
`Preliminary Response. Paper 6 (“Prelim. Resp.”). Based on the record
`before us at the time, we instituted trial with respect to all challenged claims.
`Paper 34, 34–35 (“Dec.”); Paper 35 (Erratum).
`Petitioner Samsung Bioepis Co., Ltd. (“Bioepis”) timely submitted a
`Petition presenting substantially the same challenges as set forth in Pfizer’s
`Petition along with a request for joinder to IPR2017-01488. IPR2017-
`02139. Paper 1. We granted Bioepis’s Petition and associated request for
`joinder to this case. IPR2017-02139, Paper 11, 6–7.
`After institution of trial and our grant of joinder, Patent Owner filed
`its Patent Owner Response (Paper 44, “PO Resp.”) and Petitioners filed a
`Reply to the Patent Owner Response (Paper 56, “Pet. Reply”). Patent
`Owner filed a motion to strike evidence and argument presented in
`Petitioners’ Reply. Paper 61. Petitioners opposed. Paper 73.
`With respect to technical experts, Petitioners rely on the declarations
`of Jefferson Foote, Ph.D. (Exs. 1003, 1202) and Timothy Buss (Ex. 1004);
`Patent Owner relies on the declarations of Dr. Leonard G. Presta (Ex. 2016),
`Dr. Paul J. Carter (Ex. 2017), and Dr. Ian A. Wilson (Ex. 2041). Patent
`Owner further relies on the testimony of research technician, Mr. John
`Ridgway Brady (Ex. 2018), as well as on the testimony of Dr. Edward Ball,
`M.D., from IPR2016-01694 (Ex. 2018). With respect to records
`management and authentication, Petitioners rely on the testimony of
`Mr. Benjamin Lasky (Ex. 1204) and Mr. Christopher Lowden (Ex. 1203);
`
`3
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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. Foote (Paper 64), to which Petitioners provide a response (Paper 71).
`Patent Owner submitted one motion to exclude evidence. Paper 63.
`Petitioners opposed (Paper 70), and Patent Owner submitted a reply in
`support of its motion (Paper 74). Petitioners also submitted one motion to
`exclude evidence. Paper 67. Patent Owner opposed (Paper 72), and
`Petitioners submitted a reply in support of its motion (Paper 73).
`Patent Owner submitted a first, unopposed motion to seal (Paper 8),
`which we granted (Paper 25), 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 43 (by
`Patent Owner); Papers 54 and 66 (by Petitioners).
`We heard oral argument on July 16, 2018, in a joint proceeding
`involving this case and IPR2017-01489 (joined with IPR2017-01240). A
`transcript of that proceeding is entered as Paper 84 (“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.); Genentech, Inc. v. Amgen
`Inc., No. 1-17-cv-01407 (D. Del.); Genentech, Inc. v. Amgen Inc., No. 1-17-
`cv-01471 (D. Del.); 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.);
`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.
`
`4
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`Celltrion, Inc., No. 1-18-cv-01025 (D. Del.). Paper 16, 1; Paper 29, 1; Paper
`40, 1; Paper 41, 1; Paper 78, 1–2.
`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.
`In addition to the present case, the ’213 patent is the subject of the
`following pending matters: IPR2017-01489, brought by Pfizer, Inc.;
`IPR2017-01373 and IPR2017-01374, brought by Celltrion, Inc.; and
`IPR2017-02139 and IPR2017-02140, brought by Samsung Bioepis Co.,
`Ltd.
`
`The ’213 patent was also the subject of IPR2017-02031 and IPR2017-
`02032 brought by Boehringer Ingelheim Pharmaceuticals, Inc. but these
`cases have been terminated in light of the Petitioners’ unopposed motions
`for adverse judgement. IPR2017-02031, Paper 32; IPR2017-02032, Paper
`30.
`
`The ’213 Patent and Relevant Background
`C.
`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, (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
`
`5
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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 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 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 protein sequences. 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
`1:60–62), 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
`
`6
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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
`“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. 2
`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.
`
`
`2 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. 61 n.12 (citing Ex. 2041 ¶¶ 83, 223; Ex. 2039 55:5–9).
`7
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`9
`
`73 and 77
`
`74
`
`65 and 79
`
`30, 31, 33, and 42
`42
`
`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:
`Ground
`Claim(s)
`Basis
`1
`1, 2, 25, 29, 63, 66,
`§ 102 Kurrle3
`67, 71, 72, 75, 76, 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
`
`Reference(s)
`
`§ 102 Queen 19904
`
`§ 103 Kurrle and Queen 1990
`
`§ 103 Kurrle, Queen 1990, and
`Furey 5
`§ 103 Kurrle, Queen 1990, and
`Chothia & Lesk6
`§ 103 Kurrle, Queen 1990, and
`Chothia 19857
`§ 103 Kurrle, Queen 1990, Chothia
`& Lesk, and Chothia 1985
`§ 103 Queen 1990 and Hudziak8
`§ 103 Queen 1990, Hudziak and
`Furey
`
`
`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 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.
`8
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`
`Ground
`10
`
`60
`
`Claim(s)
`
`Reference(s)
`Basis
`§ 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]
`
`II. ANALYSIS
`
`Legal Standards
`A.
`To anticipate a claim under 35 U.S.C. § 102, “a single prior art
`reference must expressly or inherently disclose each claim limitation.”10
`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.
`
`
`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.
`
`9
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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
`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
`
`10
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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.
`
`Person of Ordinary Skill in the Art
`B.
`The parties propose similar definitions of a person of ordinary skill for
`the ’213 patent. See Pet. 15–16; Prelim. Resp. 18; PO Resp. 18. In our
`institution decision, we adopted Patent Owner’s proposal that “[a] person of
`ordinary skill for the ’213 patent would have had 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. 8. Petitioners do not contest
`
`11
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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
`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
`
`12
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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. 19.
`Patent Owner correctly points out that this “construction comes directly
`from the definition provided in the ’213 patent.” Prelim. Resp. 19 (citing
`Ex. 1001, 11:32–38). Petitioners expressly adopt this construction in their
`Reply. Pet. Reply 5–6. We do not agree, however, that the claims demand a
`consensus of “all” human immunoglobulins in the literal sense. Indeed,
`Petitioners point out that “the ‘consensus’ sequence used for the patent
`variants was generated using the most common residue at each position
`identified in [Kabat 198711].” Pet. Reply 15 (citations omitted). 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.
`
`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.
`13
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`See PO Resp. 47. Moreover, in a parallel proceeding involving the same
`patent, Patent Owner did not dispute 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.” See IPR2017-01374 Paper 82,
`Tr. 15:4–16:4; see Ex. 1202 ¶ 157; Ex. 2105 ¶¶ 24–25; Ex. 2107 ¶¶ 18–19;
`Ex. 1198, 56:20–61:24; Ex. 1199, 27:14–28:13, 29:25–36:2, 57:1–58:6,
`115:7–17, 165:17–169:9. Indeed, in a similar parallel proceeding, 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. 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.” In our institution decision, we
`determined that this claim language “refer[s] to a humanized antibody
`having reduced immunogenicity in a human patient as compared to its non-
`humanized parent antibody.” Dec. 10–12. Neither party disputes this
`interpretation. See PO Resp. 19; Pet. Reply 5–6.
`Consistent with claim 63’s 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
`
`14
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`“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, 61:56–61. 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. 42 (citing Ex. 2032 (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”).
`In light of the above, we do not 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.
`
`3. Other Limitations
`On pages 16–18 of its Petition, Petitioners propose constructions for
`“humanized” (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); and “up to
`
`15
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`3-fold more” (claim 65). Patent Owner does not dispute Petitioners’
`proposed constructions, but asserts that “[n]o construction of those terms is
`necessary.” Prelim. Resp. 19; PO Resp. 19. On the present record, we agree
`with Patent Owner that the terms identified by Petitioners 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).
`
`Prior-Art Status of Kurrle and Queen 1990
`D.
`Petitioners assert that Kurrle and Queen 1990 are prior art for all
`challenged claims. Pet. 1–2 & n.3, 13, 19–23, 27. Patent Owner disagrees,
`at least with respect to claims 12, 42, 60, 65, 71, 73–74, and 79. 12 PO Resp.
`23–44. 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
`
`12 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. 24).
`
`
`16
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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
`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 Petitioners 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, Petitioners have satisfied their initial burden of
`
`17
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`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.
`
`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.
`As noted by Petitioners, “the ’272 application identifies . . . eight
`humanized antibody variants made by the inventors—huMAb4D5-1 through
`8.” Pet. Reply 7 (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. 42–44. 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, Petitioners broadly contend that
`the ’272 application fails to support the full scope of the claims because
`“[e]ven if one or more variants was within the claims, the claims also
`encompass countless other variants with any combination of recited
`
`18
`
`
`
`IPR2017-01488
`Patent 6,407,213 B1
`
`substitutions, most being unrepresented in any ’272 embodiment.” Pet.
`Reply 8. We do not find Petitioners’ argument persuasive in light of Patent
`Owner’s evidence showing that the ’272 application discloses, inter alia,
`each of the framework substitutions recited in claims 12, 42, 60, 65, 71, 73–
`74, and 79 (collectively, 66L, 71H, 73H, 78H, 93H), along with “a
`generalized scheme for humanizing any non-human antibody.” See PO
`Resp. 43–44 (citing Ex. 2032, 87–90, 93; Ex. 2041 ¶¶ 91–95).
`Petitioners further reference the language of claims 1 and 30 (from
`which claims 12, 42, 60, 65, 71, and 73–74 depend), requiring a “non-human
`Complementarity Determining Region (CDR),” and corresponding language
`in claim 79 (“Complementarity Determining Region (CDR) amino acid
`residues of the non-human p
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
