Trials@uspto.gov
`Tel: 571-272-7822
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`
`UNITED STATES PATENT AND TRADEMARK OFFICE
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`
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`Paper: 10
`Date: February 6, 2020
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`LASSEN THERAPEUTICS 1, INC.,
`Petitioner,
`v.
`SINGAPORE HEALTH SERVICES PTE LTD., and NATIONAL
`UNIVERSITY OF SIGNAPORE
`Patent Owner.
`
`
`PGR2019-00053
`Patent 10,106,603 B2
`
`
`Before GEORGIANNA W. BRADEN, ROBERT A. POLLOCK, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`WISZ, Administrative Patent Judge.
`
`DECISION
`Denying Institution of Post-Grant Review
`35 U.S.C. § 324
`
`
`
`
`
`
`

`

`PGR2019-00053
`Patent 10,106,603 B2
`
`INTRODUCTION
`I.
`Lassen Therapeutics 1, Inc. (“Petitioner”) filed a Petition (Paper 1,
`“Pet.”) requesting a post-grant review of claims 1–10 of U.S. Patent
`No. 10,106,603 B2 (Ex. 1001, “the ’603 patent”). Singapore Health
`Services PTE LTD. and National University of Singapore (“Patent Owner”)
`filed a Preliminary Response (Paper 8, “Prelim. Resp.”).
`We have authority to determine whether to institute a post-grant
`review under 35 U.S.C. § 324 and 37 C.F.R. § 42.4(a). We may not institute
`a post-grant review unless “the information presented in the petition . . . , if
`such information is not rebutted, would demonstrate that it is more likely
`than not that at least 1 of the claims challenged in the petition is
`unpatentable.” 35 U.S.C. § 324(a).
`Applying that standard, and upon consideration of the information
`presented in the Petition and the Preliminary Response, we determine that
`the information presented fails to demonstrate it is more likely than not that
`at least 1 of the challenged claims of the ’603 patent is unpatentable.
`Accordingly, we deny institution of post-grant review of claims 1–10 of the
`’603 patent.
`
`A. Real Parties-in-Interest
`Petitioner identifies itself, “Lassen Therapeutics 1, Inc.,” as the sole
`real party-in-interest. Pet. 1. Patent Owner identifies Singapore Health
`Services PTE LTD., National University of Singapore, Enleofen Bio Pte
`Ltd., Boehringer Ingelheim International GmbH, Boehringer Ingelheim USA
`Corporation, and Boehringer Ingelheim Pharmaceuticals, Inc., as the real
`parties-in-interest. Paper 9, 1.
`
`2
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`PGR2019-00053
`Patent 10,106,603 B2
`B. Related Proceedings
`Patent Owner indicates that the application from which the ’603
`patent issued is a Division of U.S. Patent Application No. 15/381,622 (U.S.
`Patent No. 10,035,852). Paper 9, 1. Patent Owner further indicates that the
`’603 patent claims priority to United Kingdom Application No. 1522186.4,
`to which a number of non-U.S. patent matters claim priority, including
`European Patent 3298040 B1 (“EP ’040”). Id. at 2–3. Both parties indicate
`that an Opposition was filed against EP ’040. Pet. 2; Paper 9, 3. Patent
`Owner also indicates that the following pending applications claim the
`benefit of priority of the filing date of the ’603 patent: 16/055,245;
`16/055,251; 16/055,261; 16/055,270; 16/055,283; 16/055,295; 16/055,304;
`16/055,319; 16/106,041; 16/106,044; 16/106,047; and 16/106,050. Paper 9,
`1
`
`C. The ’603 Patent
`The ’603 patent is directed to methods of treating fibrosis, including
`in humans. Ex. 1001, code (57), 1:14–15, 35:45–50. According to the ’603
`patent, fibrosis is the formation of excess fibrous connective tissue in a
`tissue or organ. Id. at 33:25–44. Fibrosis can occur in many tissues of the
`body including the liver, lungs, kidney, heart, blood vessels, eye, skin,
`pancreas, intestine, brain, and bone marrow. Id. at 34:10–13.
`According to the ’603 patent, the role of the protein Interleukin 11
`(“IL-11”) in fibrosis was not clear from the published literature; however,
`the inventors identified IL-11 to have a pro-fibrotic action and the patent
`provides in vivo data demonstrating IL-11 to be pro-fibrotic in heart, kidney,
`lung, and liver tissue. Id. at 1:51–52, 2:34–35, 45:54–46:2; Figures 21B–
`21C.
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`PGR2019-00053
`Patent 10,106,603 B2
`
`The ’603 patent also describes methods of inhibiting or preventing the
`IL-11 mediated pro-fibrotic signal, e.g., as mediated by binding of IL-11 to
`an IL-11 receptor. Id. at 2:36–38. One disclosed method involves treating
`fibrosis by administering an Interleukin 11 receptor α (“IL-11Rα”) antibody
`capable of inhibiting signaling mediated by IL-11. Id. at 17:27–34. Such an
`antibody binds to the α component of a cell’s receptor for IL-11 and inhibits
`IL-11 from signaling via that receptor. Id. The ‘603 patent includes data
`showing that a neutralizing anti-IL-11Rα antibody had an antifibrotic effect.
`Id. at 46:51–67; Fig. 24.
`The ’603 patent lists examples of known anti-IL-11R antibodies
`including “monoclonal antibody clone 025 (Sino Biological), clone
`EPR5446 (Abcam), clone 473143 (R & D Systems), clones 8E2 and 8E4
`described in US 2014/0219919 A1 and the monoclonal antibodies described
`in Blanc et al (J. Immunol Methods. 2000 Jul. 31; 241(1–2); 43–59).” Id. at
`18:41–46. The ’603 patent teaches how to make new anti-IL-11Rα
`antibodies by conventional immunization techniques and also describes the
`use of phage display. Id. at 50:40–51:18; 54:55–57:46.
`
`D. Illustrative Claim
`Petitioner challenges claims 1–10 of the ’603 patent. Claim 1, which
`is the only independent claim of the ’603 patent, is illustrative of the
`challenged claims, and is reproduced below:
`
`1. A method of treating fibrosis in a human subject, the method
`comprising administering to the human subject in need of
`treatment a therapeutically effective amount of an Interleukin
`11 receptor α (IL-11Rα) antibody which is capable of inhibiting
`
`4
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`PGR2019-00053
`Patent 10,106,603 B2
`Interleukin 11 (IL-11) mediated signaling, wherein the fibrosis
`is fibrosis of the heart, liver, kidney or eye.
`Ex. 1001, 93:15–21.1 Challenged claims 2–10 depend directly from
`claim 1.
`
`E. The Asserted Grounds of Unpatentability
`Petitioner contends claims 1–10 of the ’603 patent are unpatentable in
`view of the following grounds. Pet. 3–4.
`Ground Claims Challenged
`35 U.S.C. § Reference(s)/Basis
`1
`1–10
`112(a)
`Written Description
`2
`1–10
`112(a)
`Enablement
`3
`1–4, 6, 8–10
`102
`Edwards2
`4
`1–10
`103
`Edwards
`5
`1–10
`103
`Edwards, Wynn3,
`Chegini4
`
`Petitioner submits the Declarations of Peter Bowers, Ph.D. (Ex. 1003)
`and Stephen Ledbetter, Ph.D. (Ex. 1004) in support of institution of post-
`grant review.
`
`
`1 The recited claim language incorporates the modifications from the
`Certificate of Correction issued on February 5, 2019. Ex. 1002, 1.
`2 Edwards et al., US 2014/0219919 A1, published Aug. 7, 2014 (Ex. 1008,
`“Edwards”).
`3 Thomas A. Wynn, Fibrotic Disease and the TH1/TH2 Paradigm, 4 Nat. Rev.
`Immunol., 583–594 (2004) (Ex. 1010, “Wynn”).
`4 Chegini et al., US 2008/0300147 A1, published Dec. 4, 2008 (Ex. 1065,
`“Chegini”).
`
`5
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`PGR2019-00053
`Patent 10,106,603 B2
`II. ELIGIBILITY FOR POST-GRANT REVIEW
`The AIA’s post-grant review provisions apply to patents that
`“contain[] or contained at any time . . . a claim to a claimed invention that
`has an effective filing date . . . that is on or after [March 16, 2013].” Leahy-
`Smith America Invents Act (AIA) §§ 3(n)(1), 6(f)(2)(A) (2011). In addition,
`“[a] petition for a post-grant review may only be filed not later than the date
`that is 9 months after the date of the grant of the patent or of the issuance of
`a reissue patent (as the case may be).” 35 U.S.C. § 321(c) (2012); see 37
`C.F.R. § 42.202(a) (2019).
`Here, the ‘603 patent is eligible for post-grant review because the
`Petition was filed within nine months of the ’603 patent’s issue date and the
`earliest possible priority date of the ’603 patent is after March 16, 2013 (the
`effective date for the first inventor to file provisions of the Leahy-Smith
`America Invents Act). Ex. 1001, code (45) (showing an issue date of
`October 23, 2018); id. at 1:5–10 (claiming priority to a U.S. application and
`a United Kingdom application, the earliest of which was filed on
`December 16, 2015); id. at code (62), code (30); Paper 6 (according the
`Petition a filing date of July 23, 2019).
`
`III. ANALYSIS
`A. Person of Ordinary Skill in the Art
`In determining the level of skill in the art, we consider the type of
`problems encountered in the art, the prior art solutions to those problems, the
`rapidity with which innovations are made, the sophistication of the
`technology, and the educational level of active workers in the field. Custom
`Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962 (Fed. Cir.
`1986).
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`Patent 10,106,603 B2
`Petitioner, relying on testimony of Dr. Bowers (Ex. 1003) and Dr.
`Ledbetter (Ex. 1004), contends that a person of ordinary skill in the art as of
`the relevant date would have been a person with:
`a Ph.D. in immunology, molecular biology, cellular biology, or
`a similar field, or an M.D. with similar experience in one of the
`listed fields. [A person of ordinary skill in the art] would
`typically have had at least about five years of experience with
`antibodies and antibody engineering, or access to other
`individuals with that knowledge and experience. Likewise, a
`person of ordinary skill in the art would have had knowledge
`and experience in fibrosis, or access to a person with that
`knowledge and experience.
`Pet. 13 (citing Ex. 1003 ¶ 113; Ex. 1004 ¶ 53) (citations omitted).
`Patent Owner states that, for purposes of the preliminary response
`only, it does not challenge Petitioner’s definition of a person of ordinary
`skill in the art. Prelim. Resp. 19. Based on the current record and for the
`purposes of this Decision, we adopt Petitioner’s proposed description of the
`person of ordinary skill in the art. Furthermore, we find that the prior art of
`record reflects 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).
`
`B. Claim Construction
`Because this post-grant review is based on a petition filed after
`November 13, 2018,5 claim terms are construed using the same claim
`
`
`5 On October 11, 2018, the USPTO revised its rules to harmonize the
`Board’s claim construction standard with that used in civil actions under
`35 U.S.C. § 282(b) in federal district courts. Changes to the Claim
`Construction Standard for Interpreting Claims in Trial Proceedings Before
`the Patent Trial and Appeal Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018)
`(now codified at 37 C.F.R. pt. 42 (2019)). This rule change applies to
`petitions filed on or after November 13, 2018.
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`PGR2019-00053
`Patent 10,106,603 B2
`construction standard that would be used to construe the claim in a civil
`action under 35 U.S.C. § 282(b). 37 C.F.R. § 42.200(b) (2019). Under this
`claim construction standard, claim terms are given their ordinary and
`customary meaning as would have been understood by one of ordinary skill
`in the art at the time of the invention. See id.; Phillips v. AWH Corp.,
`415 F.3d 1303, 1313 (Fed. Cir. 2005) (en banc). A patentee may define a
`claim term in a manner that differs from its ordinary and customary
`meaning; however, any special definitions must be set forth in the
`specification with reasonable clarity, deliberateness, and precision. In re
`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`Petitioner provides proposed constructions for the terms “method of
`treating fibrosis,” “administering to the human subject in need of treatment a
`therapeutically effective amount,” “Interleukin 11 receptor α (IL-11Rα)
`antibody,” “capable of inhibiting Interleukin 11 (IL-11) mediated signaling,”
`and “wherein the fibrosis is fibrosis of the heart, liver, kidney, or eye.” Pet.
`5–13. Patent Owner disputes Petitioner’s construction of “Interleukin 11
`receptor α (IL-11Rα) antibody.” Prelim. Resp. 17–19. We discuss this term
`below.
`
`1. “Interleukin 11 receptor α (IL-11Rα) antibody”
`Petitioner asserts that the term “Interleukin 11 receptor α (IL-11Rα)
`antibody” should be construed as “any natural or synthetic, monoclonal or
`polyclonal antibody made using any animal system including phage, or
`fragment or derivative thereof that binds to IL-11Rα of any species.” Pet. 10
`(citing Ex. 1003 ¶ 108; Ex. 1004 ¶ 46). Petitioner asserts that nothing in the
`’603 patent or its prosecution history limits the antibodies to human
`antibodies and, in fact, indicates that non-human antibodies are included by
`
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`Patent 10,106,603 B2
`explicitly mentioning that human antibodies are preferable. Id. (citing Ex.
`1001, 18:14–15; Ex. 1003 ¶ 105). Petitioner concludes that “other animal
`anti-IL-11Rα antibodies fall within the full scope of an ‘IL-11Rα antibody’,
`including antibodies directed against other animal IL-11R and IL-11Rα
`antigens.” Id. (citing Ex. 1003 ¶ 105).
`Patent Owner does not propose a specific construction for the term
`“Interleukin 11 receptor α (IL-11Rα) antibody” but disagrees with
`Petitioner’s construction to the extent it includes antibodies that bind to any
`species. Prelim. Resp. 17–19. According to Patent Owner, the “plain
`language of claim 1 requires administering the antibody ‘to [a] human
`subject in need of treatment’ in ‘a therapeutically effective amount’ for
`‘treating fibrosis in [the] human subject.’” Id. at 18. Therefore, Patent
`Owner contends that Petitioner’s construction improperly fails to “giv[e]
`effect to all terms in the claim.” Id. at 17 (citing Bicon v. Straumann, 441
`F.3d 945, 950 (Fed. Cir. 2006)).
`We agree with Patent Owner that “Interleukin 11 receptor α (IL-
`11Rα) antibody” should not be construed to include antibodies that bind to
`IL-11Rα of non-human species but not to the human version of this protein
`because such a construction does not comport with the language of claim 1,
`which is clearly directed to treating a human subject. See Pause Tech. v.
`TiVo, 419 F.3d 1326, 1331 (Fed. Cir. 2005) (rejecting interpretation of claim
`element that ignored “other language appearing later in the claim” in stating
`that ‘“[p]roper claim construction . . . demands interpretation of the entire
`claim in context, not a single element in isolation.’”) (citing Hockerson–
`Halberstadt, Inc. v. Converse Inc., 183 F.3d 1369, 1374 (Fed.Cir.1999)).
`Construing this term to include antibodies that bind solely to non-human IL-
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`PGR2019-00053
`Patent 10,106,603 B2
`11Rα would be inconsistent with a claim directed to treatment of a human.
`Accordingly, for purposes of this decision, we construe “Interleukin 11
`receptor α (IL-11Rα) antibody” to mean “any natural or synthetic,
`monoclonal or polyclonal antibody made using any animal system including
`phage, or fragment or derivative thereof, that binds to human IL-11Rα.”
`Upon review of the parties’ arguments and the evidence of record, we
`determine that no other terms of the ’603 patent require express construction
`for purposes of this Decision. See Nidec Motor Corp. v. Zhongshan Broad
`Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs.,
`Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly
`those terms need be construed that are in controversy, and only to the extent
`necessary to resolve the controversy.”)).
`
`C. Asserted Lack of Written Description of Claims 1–10
`Petitioner contends that claims 1–10 of the ’603 patent lack written
`description support. Pet. 22–27. Patent Owner disputes Petitioner’s
`contentions. Prelim. Resp. 20–44.
`
`1. Principles of Law
`To satisfy the written description requirement under 35 U.S.C.
`§ 112(a), the specification must “reasonably convey[] to those skilled in the
`art that the inventor had possession” of the claimed invention as of the filing
`date. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir.
`2010) (en banc). An adequate description does not require any particular
`form of disclosure or that the specification recite the claimed invention in
`haec verba, but must do more than render the claimed invention obvious.
`Id. at 1352. The written description requirement for a claimed genus
`requires the disclosure of “either a representative number of species falling
`
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`PGR2019-00053
`Patent 10,106,603 B2
`within the scope of the genus or structural features common to the members
`of the genus so that one of skill in the art can ‘visualize or recognize’ the
`members of the genus.” Id. at 1350.
`In evaluating the adequacy of the disclosure, a court may consider
`“the existing knowledge in the particular field, the extent and content of the
`prior art, the maturity of the science or technology, [and] the predictability
`of the aspect at issue.” Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir.
`2005) (cited with approval in Ariad, 598 F.3d at 1352); see also Boston Sci.
`Corp. v. Johnson & Johnson, 647 F.3d 1353, 1366 (Fed. Cir. 2011) (holding
`that because the assessment for written description is made from the
`perspective of a person of ordinary skill in the art, in some instances, a
`patentee can rely on information that is “well-known in the art” to satisfy
`written description).
`
`2. Petitioner’s Position
`Petitioner asserts that claims 1–10 of the ’603 patent lack written
`description support because “[n]o structural identification is provided for
`any species falling within the vast claimed genus of anti-IL-11Rα
`antibodies.” Pet. 22 (citing Ex. 1003 ¶ 93). Petitioner argues that “there is
`no evidence within the ’603 patent ‘the ordinarily skilled artisan would be
`able to identify any compound based on its vague functional description’ . . .
`of binding to IL-11Rα and inhibiting IL-11 mediated signaling by the anti-
`IL-11Rα antibody.” Id. at 22–23 (quoting Univ. of Rochester v. G.D. Searle
`Co., 358 F.3d. 916, 928 (Fed. Cir. 2004)).
`According to Petitioner, “[t]here is no guidance in the ’603 patent
`regarding the sequence/structural properties of the anti-IL-11Rα antibodies
`that provide therapeutic benefit, their specificity, their binding affinity, or
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`Patent 10,106,603 B2
`binding epitope.” Id. at 24 (citing Ex. 1003 ¶ 116). Petitioner further asserts
`that “the ’603 patent provides no information that would allow [a person of
`ordinary skill in the art] to determine what antibody sequences would bind to
`an IL-11Rα and be capable of inhibiting IL-11 mediated signaling in a
`human subject (i.e., blocking the binding of IL-11 to an IL-11R or
`preventing signal transduction via the gp130 co-receptors).” Id. at 24–25
`(citing Ex. 1003 ¶ 119). Petitioner also contends that the ’603 patent does
`not include any working examples of treating fibrosis with an IL-11Rα
`antibody or of IL-11Rα antibodies inhibiting IL-11 mediated signaling, and
`does not identify a structure/function correlation. Id. at 25–27 (citing
`Ex. 1003 ¶¶ 120–127, 130–135).
`
`3. Patent Owner’s Position
`Patent Owner argues that Petitioner’s written description arguments
`fail because, inter alia, they ignore the ’603 patent Specification’s disclosure
`of known antibodies suitable for use in the claimed method and ignore
`evidence establishing that a person of ordinary skill in the art was aware of
`numerous antibody species known to have the capabilities suitable for use in
`the claimed method of treatment. Prelim. Resp. 20–44.
`
`4. Analysis
`We agree with Patent Owner that Petitioner appears to have
`overlooked the ’603 patent Specification’s disclosure of anti-IL-11Rα
`antibodies. Specifically, the ’603 patent lists “monoclonal antibody clone
`025 (Sino Biological), clone EPR5446 (Abcam), clone 473143 (R & D
`Systems), clones 8E2 and 8E4 described in US 2014/0219919 A1 [Edwards]
`and the monoclonal antibodies described in Blanc et al (J. Immunol
`Methods. 2000 Jul. 31; 241(1–2); 43–59).” Ex. 1001, 18:41–46; Ex. 1003
`
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`Patent 10,106,603 B2
`¶ 176.6 Edwards, which Petitioner relies on for its obviousness and
`anticipation grounds, is directed to antibodies “that bind to IL-11Rα and
`neutralize IL-11 signaling.” Ex. 1008 ¶ 13. Table 1 of Edwards lists clones
`8E2 and 8E4 and sixty-three other antibodies (including variants of 8E2) as
`“exemplary IL-11Rα-binding proteins.” Id. ¶ 362. Table 1 of Edwards also
`includes the sequence ID numbers for the heavy and light chains of the
`variable regions of each of these sixty-five clones and the amino acid
`sequences for each are disclosed in the sequence listing. Id. ¶ 362, p. 46–
`104.7
`Furthermore, Table 3 of Edwards provides data regarding binding
`affinity (“KD”) and potency (“as determined in BaF Human IL-11R cell
`proliferation assay”) for sixty-two variants of 8E2 identified in Table 1. Id.
`¶ 492. The ’603 patent discloses that such “Ba/F3 cell proliferation assays”
`are suitable to assess whether an antibody can “[i]nhibit IL-11 mediated
`signaling.” Ex. 1001, 15:21–25, 17:41–44. The results in Table 3 of
`Edwards show that all but one or two8 of the sixty-two variants bind to IL-11
`
`
`6 We note that Petitioner’s declarant, Dr. Bowers, references these examples
`of anti-IL-11Rα antibodies provided in the ’603 patent Specification in
`stating that “[n]one of these clones claims to be functional, and therefore
`does not describe or bound a therapeutically active genus of antibodies.”
`Ex. 1003 ¶ 176. However, Petitioner fails to discuss this disclosure in the
`Petition other than broadly stating, in its enablement ground that, “[w]hile
`commercial antibodies are mentioned in the ’603 patent, their suitability is
`not suggested with regard to the putative anti-IL-11Rα antibodies that
`allegedly have IL-11 binding activity.” Pet. 33.
`7 The cited page numbers in Ex. 1001 refer to the page numbers in the
`original document at the top of the page.
`8 No potency was shown for hu8E2-TS-13 and “an accurate KD was difficult
`to determine” for hu8E2-TS-213. Ex. 1008 ¶ 492.
`
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`Patent 10,106,603 B2
`receptors “with a KD of 1 µM or less” (i.e., 1 x 10-6), consistent with the ’603
`patent’s description of binding affinity for antibodies that can be used in the
`claimed method. Ex. 1001, 17:38–40; Ex. 1008 ¶ 492. Furthermore, sixty-
`one variants of 8E2 inhibited IL-11 mediated signaling, as demonstrated by
`“an IC50 of 10 µg/ml or less,” also consistent with the ’603 patent’s
`description of inhibition for antibodies that can be used in the claimed
`method. Ex. 1001, 17:51–52; Ex. 1008 ¶ 492.
`Petitioner’s failure to address the ’603 patent’s disclosure of known
`anti-IL-11Rα antibodies results in their failure to consider “the specification
`as a whole” and the existing knowledge in the field, which renders their
`written description argument unpersuasive. In re Wright, 866 F.2d 422, 425
`(Fed. Cir. 1989). We, therefore, determine that Petitioner has not presented
`sufficient persuasive evidence that the ’603 patent Specification fails to
`provide either a representative number of species or sufficient structural
`features to convey to a person of ordinary skill in the art that Patent Owner
`was in possession of the claimed invention. Accordingly, on this record,
`Petitioner has not established that it is more likely than not that the ‘603
`patent Specification lacks written description support for the claims.
`
`D. Asserted Lack of Enablement of Claims 1–10
`Petitioner contends that claims 1–10 of the ’603 patent are not
`enabled. Pet. 27–37. Patent Owner disputes Petitioner’s contentions.
`Prelim. Resp. 44–55.
`
`1. Principles of Law
`Under 35 U.S.C. § 112(a), enablement is separate and distinct from
`the written description requirement. Ariad, 598 F.3d at 1344. “The test of
`enablement is whether one reasonably skilled in the art could make or use
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`the invention from the disclosures in the patent coupled with information
`known in the art without undue experimentation.” U.S. v. Telectronics, Inc.,
`857 F.2d 778, 785 (Fed. Cir. 1988). “[A] patent specification complies with
`the statute even if a ‘reasonable’ amount of routine experimentation is
`required in order to practice a claimed invention.” Enzo Biochem, Inc. v.
`Calgene, Inc., 188 F.3d 1362, 1371 (Fed. Cir. 1999). Whether undue
`experimentation is needed is not a single, simple factual determination, but
`rather is a conclusion reached by weighing many factual considerations. In
`re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). These factors, referred to as
`the Wands factors, include:
`(1) the quantity of experimentation necessary, (2) the amount of
`direction or guidance presented, (3) the presence or absence of
`working examples, (4) the nature of the invention, (5) the state
`of the prior art, (6) the relative skill of those in the art, (7) the
`predictability or unpredictability of the art, and (8) the breadth
`of the claims.
`
`Id.
`
`2. Petitioner’s Position
`Petitioner asserts that “[t]he ’603 patent specification simply does not
`teach one of ordinary skilled [sic] in the art how to make and use the full
`scope of antibodies that inhibit IL-11 mediated signaling and treat fibrosis of
`the heart, liver, kidney, or eye as required by claims 1-10.” Pet. 28 (citing
`Ex. 1003 ¶ 28). Petitioner provides an analysis of the Wands factors
`(Pet. 28–37) and, similar to the written description arguments, asserts that
`“the sequences within the scope of the claims encompass a vast set of
`diverse antibodies” and “[t]here is no guidance in the ’603 patent regarding
`the sequence/structural properties of the claimed anti-IL-11Rα antibodies.”
`Pet. 29 (citing Ex. 1003 ¶ 140, 141). Similarly, Petitioner argues:
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`neither the claims nor the ’603 patent provides any guidance
`beyond the claimed functions for which antibody structures
`inhibit IL-11 mediated signaling and also treat fibrosis of the
`heart, liver, kidney, or eye if given in a therapeutically effective
`amount. [Ex. 1003 ¶ 144]. This requires one of ordinary skill
`in the art to design and screen an enormous number of
`antibodies to determine which bind to IL-11Rα, and inhibit IL-
`11 mediated signaling, and treat fibrosis in at least one of the
`claimed organs, if administered to a human subject in a
`therapeutically effective amount. Id. As discussed above, the
`’603 patent fails to provide antibody structures or even epitope
`or information to identify or compare new antibodies with what
`is putatively disclosed in the patent.
`Pet. 31.
`3. Patent Owner’s Position
`Patent Owner contends that Petitioner’s enablement argument fails for
`many of the same reasons as the written description ground including, inter
`alia, it is based on an improper claim construction, it “ignores the
`specification’s disclosure of known antibodies suitable for use in the
`claimed method,” and it “ignores the evidence establishing that a [person of
`ordinary skill in the art] was aware of numerous antibody species known to
`have capabilities suitable for use in the claimed method and could easily
`make more.” Prelim. Resp. 44. With regard to claim construction, Patent
`Owner argues that Petitioner misstates the breadth of the claims (Wands
`Factor 8) because the Petition “depends on the extraordinary assertion that
`the specification fails to enable the claimed method of treating fibrosis in
`humans because it fails to enable the ‘full scope of antibodies that inhibit IL-
`11 mediated signaling’ for ‘any species,’ including antibodies that do not
`bind to human IL-11Rα, and therefore could not be used to practice the
`claimed invention.” Id. at 45–46 (citing Pet. 28).
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`Patent 10,106,603 B2
`Furthermore, as with the written description ground, Patent Owner
`points out that Petitioner’s enablement arguments ignore the ’603 patent’s
`disclosure of two antibody clones from Edwards and also ignores Edwards’
`teaching of sixty-two other anti-IL-11Rα antibodies that are capable of
`binding to IL-11Rα and neutralizing IL-11 signaling. Prelim. Resp. 47.
`(citing Ex. 1004 ¶ 78; Pet. 39). Patent Owner contends that a person of
`ordinary skill in the art would not have needed to design or screen a single
`antibody to practice claim 1, but could have used any of the numerous
`examples of anti-IL-11Rα antibodies taught by Edwards. Id.
`According to Patent Owner, the ’603 patent “explains clearly that
`‘[i]nhibition of IL-11 with a neutralizing antibody prevents TGFβ1-induced
`fibrosis.’” Id. at 48 (citing Ex. 1001, 7:48–49). Patent Owner also cites to
`Petitioner’s declarant, Dr. Ledbetter who states that, “‘Edwards teaches anti-
`IL-11Rα antibodies capable of binding to IL-11Rα and neutralizing IL-11
`signaling’” and that such antibodies “‘can be successfully used to treat any
`condition that is caused by, or exacerbated by, IL-11 in a human subject.’”
`Id. at 48 (citing Ex. 1004 ¶ 78, ¶ 87 (alleging that inhibiting IL-11 signaling
`treats fibrosis)).
`
`4. Analysis
`We agree with Patent Owner that Petitioner misstates the breadth of
`the claims because they rely on an overly broad construction of the term
`“Interleukin 11 receptor α (IL-11Rα) antibody” by including antibodies that
`bind only to non-human IL-11Rα. As explained above, we construe this
`term to require binding to human IL-11Rα.
`We also agree with Patent Owner that Petitioner has again overlooked
`the ’603 patent’s disclosure of clones 8E2 and 8E4 from Edwards, which,
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`Patent 10,106,603 B2
`according to Petitioner’s own declarant, are capable of being used in the
`claimed invention. See Ex. 1001, 18:41–46; Ex. 1004 ¶¶ 70, 72, 78, 87. As
`discussed above, Edwards provides the amino acid sequences for the heavy
`and light chain regions for sixty-five anti-IL-11Rα antibodies, and discusses
`how to make these clones and obtain antibodies from phagemid libraries.
`Ex. 1008 ¶¶ 362, 482, 483, 489, 492, Table 1.
`Petitioner’s failure to adequately address the disclosure of these
`antibodies from Edwards pervades their analysis of the Wands factors and
`results in a failure to sufficiently establish that the claims of the ’603 patent
`lack enablement. In view of the ’603 patent’s disclosure of anti-IL-11Rα
`antibodies and Edwards’ disclosure of how to obtain anti-IL-11Rα
`antibodies, Petitioner has not established that undue experimentation would
`have been required to practice the claimed invention. Accordingly, on this
`record, Petitioner has not established that it is more likely than not that the
`claims of the ‘603 patent lack enablement.
`
`E. Asserted Anticipation of Claims 1–4, 6, and 8–10 over Edwards (Ex.
`1008)
`Petitioner contends that the subject matter of claims 1–4, 6, and 8–10
`of the ’603 patent are inherently anticipated by the disclosure of Edwards
`as evidenced by Wynn or Chegini. Pet. 37–48. Patent Owner disputes
`Petitioner’s contentions. Prelim. Resp. 60–83.
`
`1. Principles of Law
`To establish anticipation under 35 U.S.C. § 102, each and every
`element in a claim, arranged as recited in the claim, must be found in a
`single prior art reference. Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d
`1359, 1369 (Fed. Cir. 2008); Karsten Mfg. Corp. v. Cleveland Golf Co.,
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`Patent 10,106,603 B2
`242 F.3d 1376, 1383 (Fed. Cir. 2001). Each element of the challenged
`claim must be found, either expressly or inherently, in the single prior art
`reference. Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d 628,
`631 (Fed. Cir. 1987). While the elements must be arranged or combined in
`the same way as in the claim, “the reference need not satisfy an ipsissimis
`verbis test,” i.e., identity of terminology is not required. In re Gleave, 560
`F.3d 1331, 1334 (Fed. Cir. 2009); In re Bond, 910 F.2d 831, 832 (Fed. Cir.
`1990). Thus, the dispositive question is whether one skilled in the art
`would have reasonably understood or inferred from a prior art reference
`that every claim element is disclosed in that reference. Eli Lilly v. Los
`Angeles Biomedical Research Inst. at Harbor–UCLA Med. Ctr., 849 F.3d
`1073, 1074–75 (Fed. Cir. 2017).
`
`2. Edwards (Ex. 1008)
`As discussed supra, Edwards is directed to “proteins comprising
`antigen binding sites of antibodies that bind to interleukin-11 (IL-11)
`receptor alpha (IL-11Rα) and uses thereof, e.g. in therapy.” Ex. 1008, code
`(57). Edwards teaches that IL-11 and/or IL-11Rα is overexpressed in liver
`cancer, pancreatic cancer, gastric cancer, osteosarcoma, en