Trials@uspto.gov
`571-272-7822
`
`
`
`
`
`
` Paper 60
` Entered: October 4, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CELLTRION, INC.,
`Petitioner,
`
`v.
`
`BIOGEN, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01095
`Patent 9,296,821 B2
`____________
`
`
`Before ERICA A. FRANKLIN, SHERIDAN K. SNEDDEN, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`571-272-7822
`
`
`
`
`
`
` Paper 60
` Entered: October 4, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CELLTRION, INC.,
`Petitioner,
`
`v.
`
`BIOGEN, INC.,
`Patent Owner.
`____________
`
`Case IPR2017-01095
`Patent 9,296,821 B2
`____________
`
`
`Before ERICA A. FRANKLIN, SHERIDAN K. SNEDDEN, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`
`IPR2017-01095
`Patent 9,296,821 B2
`
`
` INTRODUCTION
`
`Celltrion, Inc. (“Petitioner”) filed a Petition requesting an inter partes
`
`review of claims 1–6 of U.S. Patent No. 9,296,821 B2 (Ex. 1001, “the ’821
`
`patent”). Paper 2 (“Pet.”). Biogen, Inc. (“Patent Owner”) filed a Patent
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`Owner’s Preliminary Response to the Petition. Paper 10 (“Prelim. Resp.”).
`
`On October 6, 2017, we instituted an inter partes review of claims 1–
`
`3, 5, and 6. Paper 12 (“Dec. Inst.”).1 On February 7, 2018, Patent Owner
`
`filed a Patent Owner Response to the Petition. Paper 30 (“PO Resp.”).
`
`On April 30, 2018, in view of SAS Inst., Inc. v. Iancu, 138 S. Ct. 1348
`
`(2018), and Office Guidance on the Impact of SAS on AIA Trial
`
`Proceedings,2 we modified our institution decision to include claim 4 and all
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`grounds presented in the Petition. Paper 39. Upon doing so, we authorized
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`Patent Owner to file a Supplemental Patent Owner Response to address the
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`newly instituted claim and grounds, we authorized Petitioner to file a Reply
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`to address both the Patent Owner Response and the Supplemental Patent
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`Owner Response, and we modified the Scheduling Order accordingly.
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`Papers 40–42. On June 6, 2018, Patent Owner filed a Supplemental Patent
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`Owner Response. Paper 46 (“Supp. PO Resp.”). On July 5, 2018, Petitioner
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`filed a Reply to both Patent Owner Responses. Paper 47 (“Reply”).
`
`Thereafter, in response to Patent Owner’s request, we authorized
`
`Patent Owner to file a submission identifying specific arguments and
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`
`
` 1
`
` Petitioner filed a Request for Rehearing regarding the denial of inter partes
`review of claim 4. Paper 14. The request was denied. Paper 25.
`2 https://www.uspto.gov/patents-application-process/patent-trial-and-appeal-
`board/trials/guidance-impact-sas-aia-trial.
`
`2
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`IPR2017-01095
`Patent 9,296,821 B2
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`evidence in Petitioner’s Reply that Patent Owner asserts are beyond the
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`proper scope of the Reply, along with a short substantive response for each
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`identified matter. Ex. 3001 (Board e-mail authorizing supplemental filings).
`
`At the same time, we authorized Petitioner to respond to Patent Owner’s
`
`filing. Id. Patent Owner and Petitioner subsequently filed those authorized
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`submissions. Papers 52 and 54. The parties have not filed any motions to
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`exclude evidence. Patent Owner has not filed a motion to amend.
`
`On August 15, 2018, the parties presented arguments at an oral
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`hearing. The hearing transcript has been entered in the record. Paper 59
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`(“Tr.”).
`
`We issue this Final Written Decision pursuant to 35 U.S.C. § 318(a)
`
`and 37 C.F.R. § 42.73. Having considered the record before us, we
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`determine that Petitioner has shown by a preponderance of the evidence that
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`claims 1–6 of the ’821 patent are unpatentable. See 35 U.S.C. § 316(e).
`
`A.
`
`Related Proceedings
`
`Petitioner and Patent Owner explain that they are not aware of any
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`other pending proceedings involving the ’821 patent. Pet. 4; Paper 6, 2.
`
`Petitions for inter parties review of claims in related U.S. Patent Nos.
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`8,329,172 B2 (IPR2017-01093) and 8,557,244 B1 (IPR2017-01094), filed
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`by Petitioner along with the Petition for this proceeding were denied.
`
`IPR2017-01093, Paper 12 (Denying Institution); IPR2017-01094, Paper 12
`
`(Denying Institution) and Paper 15 (Denying Rehearing Request).
`
`B.
`
`The ’821 Patent
`
`The ’821 patent relates to methods of treating B-cell lymphomas,
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`including low grade or follicular non-Hodgkin’s lymphoma (“NHL”), by
`
`administering chimeric anti-CD20 antibodies in combination with
`
`
`
`
`3
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`IPR2017-01095
`Patent 9,296,821 B2
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`chemotherapy, e.g., CVP (cyclophosphamide, vincristine, and prednisone)..
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`Ex. 1001, 2:21–31, 4:24–26, 23:60–67 (claim 1). A “preferred chimeric
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`[anti-CD20] antibody is C2B8 (IDEC Pharmaceuticals, Rituximab).” Id. at
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`3:3–5. According to the Specification, “it has been found that treatment
`
`with anti-CD20 antibody provides a beneficial synergistic effect when
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`administered in combination with cytokines, radiotherapy, myeloablative
`
`therapy, or chemotherapy.” Id. at 2:24–28.
`
`C.
`
`Illustrative Claims
`
`Each challenged claim is an independent claim. Claims 1 and 4 are
`
`reproduced below:
`
`1. A method for treating low grade or follicular non-
`Hodgkin’s lymphoma (NHL) comprising administering to a
`patient a therapeutically effective amount of rituximab during a
`chemotherapeutic regimen, wherein
`the chemotherapeutic
`regimen consists of cyclophosphamide, vincristine, and
`prednisone (CVP therapy), wherein the method comprises
`administering 375 mg/m2 of rituximab, and wherein the method
`provides a beneficial synergistic effect in the patient.
`
`4. A method for treating low grade or follicular non-
`Hodgkin’s lymphoma (NHL) comprising administering to a
`patient a therapeutically effective amount of rituximab during a
`chemotherapeutic regimen, wherein
`the chemotherapeutic
`regimen consists of cyclophosphamide, vincristine, and
`prednisone (CVP therapy), wherein the method comprises
`administering 375 mg/m2 of rituximab once every 3 weeks for 8
`doses, and wherein the method provides a beneficial synergistic
`effect in the patient.
`
`
`D.
`
`The Instituted Grounds of Unpatentability
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`Petitioner challenges the patentability of the claims as follows:
`
`
`
`
`4
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`IPR2017-01095
`Patent 9,296,821 B2
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`
`Claims Basis
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`References
`
`1–6
`
`Pre-AIA § 102 Marcus3
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`3 and 6 Pre-AIA § 103 Marcus and the ’137 Patent4
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`1–3
`
`Pre-AIA § 103 Czuczman,5 IDEC 10-K/A,6 Foon,7 and Dana8
`
`4–6
`
`Pre-AIA § 103 Czuczman, IDEC 10-K/A, Foon, Dana, Link,9
`and Piro10
`3 and 6 Pre-AIA § 103 Czuczman, IDEC 10-K/A, Foon, Dana, Link,
`Piro, and the ’137 Patent
`
`
`
` 3
`
` Marcus et al., CVP chemotherapy plus rituximab compare with CVP as
`first-line treatment for advanced follicular lymphoma, 105 BLOOD 1417–23
`(2005) (Ex. 1005).
`4 U.S. Patent 5,736,137 issued to Anderson et al. on Apr. 7, 1998. (Ex.
`1007).
`5 Czuczman et al., IDEC-C2B8 and CHOP Chemoimmunotherapy of Low-
`Grade Lymphoma, 86 BLOOD 10 Supp. 1:55a (Abstract 206) (1995) (Ex.
`1011).
`6 IDEC Pharmaceuticals Corp., Form 10-K/A Annual Report for the Fiscal
`Year Ended Dec. 31, 1997, filed with the U.S. Securities and Exchange
`Comm. (Ex. 1006).
`7 Foon et al., Chapter 111: Lymphomas, Williams Hematology, 5th Ed.
`1076–96 (1990) (Ex. 1008).
`8 Dana et al., Long-Term Follow-Up of Patients with Low-Grade Malignant
`Lymphomas Treated with Doxorubicin-Based Chemotherapy or
`Chemoimmnotherapy, 11 J. CLIN. ONCOL. 644–51 (1993) (Ex. 1009).
`9 Link et al., Phase II Pilot Study of the Safety and Efficacy of Rituximab in
`Combination with CHOP Chemotherapy in Patients with Previously
`Untreated Intermediate- or High-Grade NHL, Program/Proceedings, 17
`AM. SOC. CLIN. ONCOL. 3a (Abstract 7) (1998) (Ex. 1010).
`10 Piro et al., RITUXANTM (rituximab, IDEC-C2B8): Interim analysis of a
`phase II study of once weekly times 8 dosing in patients with relapsed low-
`grade or follicular non-Hodgkin’s lymphoma, 90 BLOOD 10 Supp. 1:510a
`(Abstract 2272) (1997) (Ex. 1004).
`
`
`
`
`5
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`IPR2017-01095
`Patent 9,296,821 B2
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`
`Petitioner also relies upon the Declarations of Izidore Lossos, M.D.
`
`(Ex. 1002) and Walter Longo, M.D. (Ex. 1003). Patent Owner relies upon
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`the Declaration of Peter McLaughlin, M.D. (Ex. 2029).
`
` ANALYSIS
`
`A.
`
`Claim Construction
`
`In an inter partes review, the Board interprets claim terms in an
`
`unexpired patent according to the broadest reasonable construction in light
`
`of the specification of the patent in which they appear. 37 C.F.R.
`
`§ 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016)
`
`(affirming applicability of broadest reasonable construction standard to inter
`
`partes review proceedings). Under that standard, and absent any special
`
`definitions, we give claim terms their ordinary and customary meaning, as
`
`would be understood by one of ordinary skill in the art at the time of the
`
`invention. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
`
`2007). Any special definitions for claim terms must be set forth with
`
`reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d
`
`1475, 1480 (Fed. Cir. 1994).
`
`“beneficial synergistic effect”
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`Petitioner and Patent Owner propose constructions for the claim
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`phrase “beneficial synergistic effect,” recited by claims 1 and 4. Pet. 30–31;
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`PO Resp. 13–17. Petitioner asserts in the Petition that the broadest
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`reasonable construction of the claim phrase is “an improvement in clinical
`
`outcome.” Pet. 31. Petitioner supports that proposed construction by
`
`referring to (a) the Specification description that “it has been found that
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`treatment with anti-CD20 antibody provides a beneficial synergistic effect
`
`when administered in combination with cytokines, radiotherapy,
`
`
`
`
`6
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`IPR2017-01095
`Patent 9,296,821 B2
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`myeloablative therapy, or chemotherapy,” Ex. 1001, 2:24–28,11 and (b) a
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`description in Applicant’s Supplemental Information Disclosure Statement
`
`that “[p]atients treated with R-CVP experienced median progression free
`
`survival (PFS) of 2.4 years compared with 1.4 years in patients treated with
`
`CVP only, demonstrating a beneficial synergistic effect in the patient.” Ex.
`
`1069, 120.12
`
`Patent Owner asserts that Petitioner’s proposed construction reads
`
`“synergistic” out of the claim phrase. PO Resp. 14–16. Patent Owner
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`asserts that either the Board’s construction in the Institution Decision, i.e., “a
`
`clinical outcome resulting from combination therapy that reflects a greater
`
`beneficial effect than the additive effects of the uncombined therapies when
`
`administered alone,” Dec. Inst. 7, or Patent Owner’s initially proposed
`
`construction, i.e., “an effect better than the additive effects of rituximab and
`
`CVP administered alone” is proper, PO Resp. 13–14. Patent Owner
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`supports those constructions by referring to the Specification description of
`
`the term “synergistic” as meaning a therapeutic combination producing an
`
`effect “better than the additive effects of either therapy administered alone.”
`
`PO Resp. 14 (citing Ex. 1001, 3:44–47).
`
`Patent Owner also refers to Applicant’s discussion of the term
`
`“synergistic” during the prosecution of Application No. 11/840,956, the
`
`
`
`11 We join the parties in citing to the page numbering added to exhibits by
`the filing party, rather than the original page numbering therein, with an
`exception for the ’821 patent (Ex. 1001).
`12 File history of the ’821 patent (Application No. 13/524,896) (Ex. 1069).
`
`
`
`
`7
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`Patent 9,296,821 B2
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`parent application to the ’821 patent. Id. (citing Ex. 2006, 14–15).13
`
`According to Patent Owner, “applicant similarly equated more-than-additive
`
`results with ‘synergistic.’” Id. For example, Patent Owner refers to
`
`Applicant’s description of data from the study disclosed in Marcus as
`
`demonstrating that “[t]he complete responses (CRs) and extended median
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`TTP achieved with the presently claimed combination [R-CVP] were more
`
`than additive, i.e., they were synergistic results.” Id. at 14–15 (quoting Ex.
`
`2006, 14–15). Patent Owner notes that “Applicant cited to this same data
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`during the ’821’s prosecution” as evidence that the claimed methods provide
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`a beneficial synergistic effect. Id. (citing Ex. 1069, 121 and 137).
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`In the Reply, Petitioner asserts that requiring “beneficial synergistic
`
`effect” to involve a “greater beneficial effect than the additive effects of the
`
`uncombined therapies” is not the broadest reasonable interpretation of the
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`term as it, allegedly, “contradicts a POSA’s understanding of the term, as
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`PO’s expert testified.” Pet. Reply 6. According to Petitioner, Patent
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`Owner’s declarant, Dr. McLaughlin, “testified that a POSA would have
`
`found the Board’s construction too ‘stringent’” because the term “‘synergy’
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`in the field lacked ‘rigidity’ and often included ‘sensitization’ or
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`‘potentiation’ of the effects of one treatment by another – consistent with the
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`construction proposed by the Petitioner: ‘an improvement in clinical
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`outcome.’” Id. at 7 (quoting Ex. 2030, 49:22–50:8, 80:1–10). Petitioner
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`asserts that Dr. McLaughlin agreed that “sensitization means that you’re
`
`
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`13 Amendment and Reply under 35 C.F.R. § 1.111, filed Aug. 25, 2010, in
`Application No. 11/840,956 (Ex. 2006).
`
`
`
`
`8
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`Patent 9,296,821 B2
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`potentiating the activity of a compound that has an activity.” Id. (quoting
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`Ex. 2030, 81:14–19).
`
`Petitioner asserts that the description of “better than additive” effects
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`in the Specification and prosecution history “need not be limiting in light of
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`PO’s other uses of ‘synergy.’” Pet. Reply. 7. According to Petitioner, in the
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`prosecution history, Applicant did not rely only any “better-than-additive
`
`effect” when referring to an improvement in clinical outcome as meeting the
`
`definition of synergistic effect. Id. at 7–8. In particular, Petitioner refers to
`
`Applicant’s statement that “patients treated with R-CVP experienced median
`
`progression free survival (PFS) of 24 years compared with 1.4 years in
`
`patients treated with CVP only, demonstrating a beneficial synergistic effect
`
`in the patient.” Id. at 8 (quoting Ex. 1069, 120). As for the Specification,
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`Petitioner asserts that the disclosure includes a reference to “the results in
`
`Demidem 1997 (Ex. 1079), which describe rituximab-based sensitization of
`
`cells to chemotherapy, as an example of ‘synergy.’” Id. (citing Ex. 1001,
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`12:57–59). According to Petitioner, the broadest reasonable interpretation of
`
`“beneficial synergistic effect,” slightly altered from its initial proposed
`
`meaning of “an improvement in clinical outcome,” see Pet. 31, should be
`
`“an improvement in efficacy compared to one therapy alone,” Pet. Reply 8.
`
`The Specification summarizes the invention, in part, by stating, “[i]n
`
`particular, it has been found that treatment with anti-CD20 antibody
`
`provides a beneficial synergistic effect when administered in combination
`
`with cytokines, radiotherapy, myeloablative therapy, or chemotherapy.” Ex.
`
`1001, 2:24–28 (emphasis added). Thereafter, when discussing the
`
`combination of anti-CD20 antibody (rituximab) and a cytokine, the
`
`Specification provides a description of such synergistic effect, as follows:
`
`
`
`
`9
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`IPR2017-01095
`Patent 9,296,821 B2
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`
` The combined therapies of the present invention include a
`method for treating B-cell lymphoma comprising administer-
`ing at least one chimeric anti-CD20 antibody and at least one
`cytokine. In particular, the invention includes a method for
`treating B-cell lymphoma comprising administering a syner-
`gistic therapeutic combination comprising at least one anti-
`CD20 antibody and at least one cytokine, wherein the thera-
`peutic effect is better than the additive effects of either
`therapy administered alone.
`
`
`Id. at 3:39–48 (emphasis added). According to the Specification the
`
`combination therapy is deemed synergistic when “the therapeutic effect is
`
`better than the additive effects of either therapy administered alone.” Id. at
`
`3:45–47. Based on the above disclosures, we find that the Specification sets
`
`forth with reasonable clarity and deliberateness the meaning of a
`
`“synergistic effect” in the context of administering rituximab in combination
`
`with another therapeutic compound of the invention, i.e., cytokines,
`
`radiotherapy, myeloablative therapy, or chemotherapy. Moreover, Patent
`
`Owner has shown persuasively that Applicant’s discussion during the
`
`prosecution of the ’821 Application explaining how the data disclosed in
`
`Marcus demonstrates a “beneficial synergistic effect” is consistent with the
`
`Specification description. Accordingly, based upon the Specification
`
`definition of the term “synergistic effect, we interpret the claim phrase
`
`“beneficial synergistic effect” as meaning “a therapeutic effect resulting
`
`from combination therapy that reflects a greater beneficial effect than the
`
`additive effects of either therapy when administered alone.”
`
`In the Reply, Petitioner acknowledges the Specification description of
`
`“synergistic effect” as requiring “better than the additive effects of either
`
`therapy administered alone,” but contends that other uses of “synergy” in the
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`
`
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`10
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`IPR2017-01095
`Patent 9,296,821 B2
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`Specification and prosecution history demonstrate the construction need not
`
`be so limiting. Pet. Reply 8. In support of that contention, Petitioner again
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`relies upon a reference in the Specification to Demidem 1997. Id.
`
`According to Petitioner, Demidem 1997 provides a broader description of
`
`“synergy” by referring to “rituximab-based sensitization of cells to
`
`chemotherapy, as an example of ‘synergy.’” Id. (citing Ex. 1001, 12:57–59,
`
`19:5–9; Ex. 1079).
`
`Demidem 1997 describes an “in vitro study examin[ing] the
`
`sensitizing effect of C2B8 antibody [rituximab] on the DHL-4B lymphoma
`
`line to various cytotoxic agents.” Ex. 1097, Abstract. Demidem 1997
`
`explains that the findings of the study “demonstrate that C2B8 antibody
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`potentiates the sensitivity of DHL-4 tumor cells to several cytotoxic agents.”
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`Id. The reference expressly refers to “synergy” when describing previous
`
`studies demonstrating “that combination treatments of cytokines/antibody
`
`and chemotherapeutic drugs result in potentiation of tumor cells sensitivity,
`
`reversal of drug resistance and synergy achieved with subtoxic
`
`concentration of cytotoxic agents.” Id. at 3 and 9 (emphasis added).
`
`The Specification refers to Demidem 1997 when describing a Phase II
`
`trial initiated to evaluate the combination of CHOP (cyclophosphamide,
`
`doxorubicin, vincristine, and prednisone) and Rituximab to treat low-grade
`
`or follicular NHL “because their mechanisms of action are not cross-
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`resistant, and Rituximab is synergistic with certain cytotoxic drugs,
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`including doxorubicin.” Ex. 1001, 12:53–58 (citing Ex. 1079).
`
`Dr. McLaughlin’s testimony, relied upon by Petitioner for this issue,
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`states that he has “use[d] the word ‘synergy’ with a looser definition than the
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`board’s” in one of his publications referring to Demidem 1997. Ex. 2030,
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`
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`11
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`79:12–80:10. Dr. McLaughlin explains that he used the term as meaning
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`“sensitization,” and further explained that his use of the term “synergy” may
`
`have been done so “ill-advisedly,” while noting that he thinks “there wasn’t
`
`rigidity about the use of that word,” and ultimately deciding “[s]ensitization
`
`would have been the better choice.” Id. at 80:24–81:5. Dr. McLaughlin
`
`agreed that “other people in the field used synergy when they meant
`
`sensitization,” and that “for better or worse, those words were used
`
`interchangeably.” Id. at 81:8–13.
`
`Thus, according to Petitioner, Demidem 1997’s discussion of
`
`sensitization, potentiation, and synergy, along with Dr. McLaughlin’s
`
`recognition of his loose use of those terms, demonstrates that the
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`Specification description of “synergistic effect” as involving “greater than
`
`the additive effects of either therapy when administered alone” is non-
`
`limiting. We disagree. Rather, we view Petitioner’s evidence as
`
`demonstrating that those of skill in the art would have understood that
`
`potentiating tumor cells sensitivity to a compound may broadly, or loosely
`
`be considered synergy, in a general sense. However, with respect to the
`
`claimed invention, the Specification expressly sets forth specific
`
`requirements for demonstrating a beneficial synergistic effect in, as Dr.
`
`Laughlin describes, a more stringent manner.14 Even so, Demidem 1997
`
`
`
`14 We note that, contrary to Petitioner’s assertion, Dr. McLaughlin did not
`provide testimony that our initial interpretation of the claim phrase
`“beneficial synergistic effect” was “too stringent,” in view of the
`Specification description for that claim phrase. See, e.g., Ex. 2030, 49:22–
`50:8, 79:13–81:13. Rather, his testimony reveals that he views our
`interpretation to be more precise than his usage in other publications. See,
`e.g., id. at 80:24–81:13.
`
`
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`12
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`describes “potentiation of tumor cells sensitivity, reversal of drug resistance
`
`and synergy achieved” resulting from combination therapies. Ex. 1079, 3
`
`and 9. Whether or not potentiation and sensitization achieves a “synergistic
`
`effect” as defined by the Specification, i.e., “greater than the additive effects
`
`of either therapy when administered alone,” in every instance, we find that
`
`the Specification recognizes Demidem 1997’s report of “sensitiz[ing] the
`
`cells to the cytotoxic effect of various agents resulting in significant
`
`potentiation of tumor cell killing” as one such instance that meets the
`
`Specification description of synergistic effect. Ex. 1001, 12:56–58. As a
`
`result, we find that the use of the term “synergistic” in the Specification
`
`when referring to Demidem 1997 does not refer to a different or broader
`
`meaning for the claim phrase “beneficial synergistic effect” than what is set
`
`forth in the Specification description of “synergistic effect.” Rather, we
`
`view the reference to Demidem 1997 as a reference to a specific example of
`
`such synergistic effect, achieved via sensitization and potentiation of the
`
`studied cell line.
`
`Petitioner’s reference to Applicant’s use of the term “synergy” in the
`
`prosecution history does not persuade us to change our finding. Petitioner
`
`asserts that Applicant relies upon a broader interpretation of “beneficial
`
`synergistic effect by stating that “patients treated with R-CVP experienced
`
`median progression free survival (PFS) of 24 years compared with 1.4 years
`
`in patients treated with CVP only, demonstrating a beneficial synergistic
`
`effect in the patient.” Id. at 8 (quoting Ex. 1069, 120). Although the portion
`
`of Applicant’s Response to Office Action during the prosecution of the ’896
`
`application quoted by Petitioner does not include details regarding the effect
`
`of rituximab alone on PFS, the discussion that follows states that
`
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`13
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`“[a]dditional data obtained in accordance with the presently claimed
`
`invention is provided by Marcus,” along with a table summarizing “certain
`
`therapeutic results achieved with rituximab alone, CVP alone, or the
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`presently claimed combination,” i.e., R-CVP. Id. That comparative data
`
`reveals that the Median Time to Progression (“MTP”) and the percentage of
`
`patients achieving Complete Response (“CR”) with an R-CVP treatment
`
`regimen was better than the additive effects of treatment with rituximab
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`alone or CVP alone. Id. at 121. Thus, unlike with Applicant’s response
`
`regarding PFS, Applicant’s response regarding MTP and CR provide
`
`sufficient detail to demonstrate how the R-CVP combination achieves a
`
`beneficial synergistic effect in a manner prescribed by the Specification.
`
`We determine that construction of additional claim terms is not
`
`necessary for purpose of this Decision. See Vivid Techs., Inc. v. Am. Sci. &
`
`Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (only terms that are in
`
`controversy need to be construed, and only to the extent necessary to resolve
`
`the controversy).
`
`B.
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`Level of Ordinary Skill in the Art
`
`The level of skill in the art is a factual determination that provides a
`
`primary guarantee of objectivity in an obviousness analysis. Al-Site Corp. v.
`
`VSI Int’l Inc., 174 F.3d 1308, 1324 (Fed. Cir. 1999) (citing Graham v. John
`
`Deere Co., 383 U.S. 1, 17–18 (1966); Ryko Mfg. Co. v. Nu-Star, Inc., 950
`
`F.2d 714, 718 (Fed. Cir. 1991)).
`
`According to Petitioner, a person of ordinary skill in the art at the time
`
`of the invention would have been “a practicing physician specializing in
`
`hematology or oncology, with at least three years of experience in treating
`
`patients with NHL.” Pet. 31–32 (citing Ex. 1002 ¶ 24). Patent Owner does
`
`
`
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`14
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`IPR2017-01095
`Patent 9,296,821 B2
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`not address Petitioner’s position on this matter and does not propose its own
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`description for a person of ordinary skill in the art at the time of the
`
`invention.
`
`Based on the record as a whole, we determine that Petitioner’s
`
`description sufficiently characterizes the level of ordinary skill in the art
`
`relevant to the claimed invention. Moreover, after reviewing the credentials
`
`of Drs. Lossos and McLaughlin, we consider each of them to be qualified to
`
`provide an opinion on the knowledge of a person of ordinary skill in the art
`
`at the time of the invention.15 We also note that the applied prior art reflects
`
`the appropriate level of skill at the time of the claimed invention. See
`
`Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001). The relative
`
`weight that we assign such testimony, however, is subject to additional
`
`factors. See, e.g., Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756,
`
`48,763 (Aug. 14, 2012) (“Opinions expressed without disclosing the
`
`underlying facts or data may be given little or no weight.”).
`
`C.
`
`The ‘821 Patent Priority Date
`
`The ’821 patent issued from U.S. Application No. 13/524,896 (“the
`
`’896 application”) filed on June 15, 2012. Exs. 1001 and 1069. The ’896
`
`application is a divisional of U.S. Application No. 11/840,956, which is a
`
`continuation of U.S. Application No. 10/196,732, which is in turn a
`
`continuation of U.S. Application No. 09/372,202 (“the ’202 application”)
`
`filed on August 11, 1999. Exs. 1001 and 1034, 1 (the ’202 application file
`
`
`
`15 Petitioner does not rely on Dr. Longo’s testimony (Ex. 1003) to support its
`unpatentability contentions. See, e.g., Pet. 17 (referring to Ex. 1003 as
`support for the public availability of the E1496 Protocol and Consent Form-
`a reference not included in any unpatentability ground).
`
`
`
`
`15
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`
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`IPR2017-01095
`Patent 9,296,821 B2
`
`history indicating a corrected filing date of August 11, 1999, for the ’202
`
`application).
`
`Petitioner asserts that none of the claims of the ’821 patent are entitled
`
`to a priority date earlier than June 15, 2012, because each of those claims
`
`lacks written description support in the specification of the ’202 application.
`
`Pet. 18–30. Patent Owner disagrees, asserting that the disclosures of the
`
`’202 application demonstrate that the inventor had possession of the
`
`inventions set forth in the claims of the ’821 patent. See PO Resp. 56–64.16
`
`For the reasons that follow, based on the record as a whole, we determine
`
`that Petitioner has shown persuasively that claims 4–6 are not supported by
`
`the disclosures of the ’202 application. As for claims 1–3, we agree with
`
`Patent Owner that the evidence of record demonstrates that the ’202
`
`application provides written description support for those claims.
`
`“Patent claims are awarded priority on a claim-by-claim basis based
`
`on the disclosure in the priority applications.” Lucent Technologies, Inc. v.
`
`Gateway, Inc., 543 F.3d 710, 718 (Fed. Cir. 2008). To receive the benefit of
`
`a previous application, every feature recited in a particular claim at issue
`
`must be described in the prior application. See In re Van Langenhoven, 458
`
`F.2d 132, 137 (CCPA 1972) (“The fact that some of the elements of the
`
`breech claims have the support of the parent and foreign applications does
`
`not change the result. As to given claimed subject matter, only one effective
`
`
`
`16 Patent Owner does not assert priority based upon the filing date of the
`provisional or intervening applications. See PO Resp. 56–64. Thus, we
`consider the issue of priority with respect to the ’202 application only.
`
`
`
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`16
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`IPR2017-01095
`Patent 9,296,821 B2
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`date is applicable.” (emphases added)); accord In re Chu, 66 F.3d 292, 297
`
`(Fed. Cir. 1995).
`
`As the Federal Circuit has noted, however, “[i]n order to satisfy the
`
`written description requirement, the disclosure as originally filed does not
`
`have to provide in haec verba support for the claimed subject matter at
`
`issue.” Purdue Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1323 (Fed.
`
`Cir. 2000). Rather, “the test for sufficiency is whether the disclosure of the
`
`application relied upon reasonably conveys to those skilled in the art that the
`
`inventor had possession of the claimed subject matter as of the filing date.”
`
`Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010).
`
`Regarding claims 1–3, Petitioner asserts that “[t]he ’202 application
`
`does not describe the combination of administering rituximab during CVP
`
`chemotherapy to treat low-grade or follicular lymphoma, where the method
`
`provides a beneficial synergistic effect.” Pet. 20–21. Petitioner recognizes
`
`the ’202 application “mention[s] the words in the recited elements,”
`
`however, Petitioner contends that the disclosures “do[] not describe
`
`combining these elements to achieve the claims methods of treatment.” Id.
`
`at 21–22, 26–27. According to Petitioner, “the cited elements are dispersed
`
`throughout the specification” without conveying that Applicant had
`
`“possession of the combination of (1) a method of treating low grade NHL;
`
`(2) comprising administering anti-CD20 antibody during CVP
`
`chemotherapy; (3) to achieve a beneficial synergistic effect.” Id. at 22 (citing
`
`Ex. 1002 ¶ 80.), see also PO Reply 4–5. We note that third element is
`
`required by claim 1, but not claims 2 and 3. See Ex. 1001, 23:60–24:67.
`
`We view Petitioner’s argument as requiring the ’202 application to
`
`provide in haec verba support for the claimed subject matter. Such argument
`
`
`
`
`17
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`IPR2017-01095
`Patent 9,296,821 B2
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`is not well taken. See Purdue Pharma, 230 F.3d at 1323; see also Ariad, 598
`
`F.3d at 1352 (written description need not be in any particular form or an in
`
`haec verba recitation of the claimed invention). When considered under the
`
`proper written description standard, we determine that the undisputed
`
`disclosures in the ’202 application would have reasonably conveyed to those
`
`skilled in the art that the inventor had possession of the claimed subject
`
`matter as of the filing date.
`
`In particular, Petitioner acknowledges the following disclosures in the
`
`’202 application: (a) original claim 17 recites “[a] method for treating B-cell
`
`lymphoma comprising administering to a patient a therapeutically effective
`
`amount of anti-CD20 antibody before, during or subsequent to a
`
`chemotherapeutic regimen,” Pet. 22 (quoting Ex. 1034, 58); (b) original
`
`claim 29 depends from claim 17 and describes “low grade/follicular” NHL
`
`as a subtype of B-cell lymphoma that can be treated with the method of
`
`claim 17, id. at 23 (citing Ex. 1034, 61); (c) CVP is disclosed as a
`
`chemotherapeutic regimen administered prior to rituximab maintenance
`
`therapy (“375 mg/m2 weekly times 4 every 6 months”) to treat low-grade
`
`NHL, id. at 25–26 (citing Ex. 1034, 32), and (d) that “treatment with anti-
`
`CD20 antibody provides a beneficial synergistic effect when administered in
`
`combination with . . . chemotherapy,” id. at 26 (quoting Ex. 1034, 6).
`
`Based upon our review, a person of ordinary skill in the art would
`
`have considered those disclosures together and not as separate, unrelated
`
`descriptions. Disclosures (b) and (c) provide exemplary descriptions for
`
`certain method elements recited in disclosure (a), i.e., the B-cell lymphoma
`
`can be low grade NHL, the chemotherapeutic regimen can be CVP t
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