Trials@uspto.gov
`571-272-7822
`
`
`
`
` Paper 10
`
` Date: September 1, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FRONTIER THERAPEUTICS, LLC,
`Petitioner,
`
`v.
`
`MEDAC GESELLSCHAFT FÜR KLINISCHE
`SPEZIALPRÄPARATE MBH,
`Patent Owner.
`____________
`
`Case IPR2016-00649
`Patent 8,664,231 B2
`____________
`
`Before TONI R. SCHEINER, ERICA A. FRANKLIN, and
`JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.
`
`BONILLA, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`571-272-7822
`
`
`
`
` Paper 10
`
` Date: September 1, 2016
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FRONTIER THERAPEUTICS, LLC,
`Petitioner,
`
`v.
`
`MEDAC GESELLSCHAFT FÜR KLINISCHE
`SPEZIALPRÄPARATE MBH,
`Patent Owner.
`____________
`
`Case IPR2016-00649
`Patent 8,664,231 B2
`____________
`
`Before TONI R. SCHEINER, ERICA A. FRANKLIN, and
`JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.
`
`BONILLA, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`IPR2016-00649
`Patent 8,664,231 B2
`
`I.
`
`INTRODUCTION
`Frontier Therapeutics, LLC (“Petitioner”) filed a Petition requesting
`an inter partes review of claims 1–22 of U.S. Patent No. 8,664,231 B2 (Ex.
`1001, “the ’231 patent”). Paper 1 (“Pet.”). medac Gesellschaft für klinische
`Spezialpräparate mbH (“Patent Owner”) filed a Preliminary Response to the
`Petition. Paper 9 (“Prelim. Resp.”).
`We have jurisdiction under 35 U.S.C. § 314, which provides that an
`inter partes review may not be instituted “unless . . . there is a reasonable
`likelihood that the petitioner would prevail with respect to at least 1 of the
`claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering
`the Petition and Preliminary Response, we determine that Petitioner has
`shown a reasonable likelihood that it would prevail in showing the
`unpatentability of claims 1–22. Accordingly, we institute an inter partes
`review of those claims.
`A. Related Proceedings
`Petitioner and Patent Owner identify a district court action involving
`the ’231 patent, titled medac Pharma, Inc. v. Antares Pharma, Inc., No.
`1:14-cv-01498-JBS-KMW (D.N.J.). Pet. 5; Paper 8, 2. The parties also
`identify a prior proceeding at the Board, IPR2014-01091, as well as a
`Decision on Institution in that case, addressing challenges of the same patent
`and claims at issue here. Pet. 5–6; Prelim. Resp. 2; Antares Pharma, Inc. v.
`medac Gesellschaft für klinische Spezialpräparate mbH, Case No. IPR2014-
`01091 (PTAB Jan. 6, 2015) (Paper 7) (“IPR2014-01091” or “prior IPR”).
`Both the district court litigation and the prior IPR settled in April 2015.
`Paper 8, 2.
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`Patent 8,664,231 B2
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`
`The parties also identify U.S. Patent Application 14/635,542, filed
`March 2, 2015, which is currently pending. Pet. 5–6, Paper 8, 2.
`B. The ’231 Patent (Ex. 1001)
`The ’231 patent relates to a method for treating inflammatory
`autoimmune diseases, such as rheumatoid arthritis, juvenile rheumatoid
`arthritis, or psoriasis, comprising administering subcutaneously a
`concentrated methotrexate solution comprising more than 30 mg/ml of
`methotrexate. Ex. 1001, Abstract. Methotrexate is a cytostatic agent that is
`well known for treating breast cancer, leukemia in children, and psoriasis.
`Id. at 1:24–30. “Over the years, methotrexate has become the gold standard
`in the treatment of rheumatoid arthritis.” Id. at 2:34–36. As a basic
`therapeutic for rheumatoid arthritis, methotrexate is administered once a
`week, orally or parenterally. Id. at 2:37–41.
`The ’231 patent is directed to a ready-made syringe and carpule
`containing the methotrexate solution, as well as a pen-injector comprising
`the ready-made syringe and/or carpule. Id. at 1:10–13. Preparing
`methotrexate, including drawing it up in a syringe from a bottle, is subject to
`strict restrictions, such as requiring the preparation to occur within a suitable
`venting system. Id. at 2:7–17.
`Previously, ready-made syringes were developed to avoid the step of
`preparing a methotrexate solution for injection. Id. at 2:18–19. The ’231
`patent states, “[f]or the first time, the applicant in the present invention was
`able to have such ready-made syringes for subcutaneous application
`approved throughout Europe.” Id. at 2:19–22. Those ready-made syringes
`may be administered by the physician, medical staff, or by the patient as a
`
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`Patent 8,664,231 B2
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`self-application, without requiring any preparation of the injection. Id. at
`2:22–25.
`The ’231 patent discloses that “subcutaneous administration in
`particular has its difficulties . . . due to the problem of having to inject the
`required relatively large amount of active substance solution (e.g. up to 3 ml
`in the case of a certain dosage) under the skin every week.” Id. at 2:44–52.
`Thus, according to the ’231 patent, a need exists to provide a concentrated
`methotrexate solution for subcutaneous administration that allows a smaller
`volume of the solution to be injected. Id. at 2:53–60.
`The ’231 patent defines “inflammatory autoimmune disease” to
`encompass all inflammatory autoimmune diseases that can reasonably be
`treated with methotrexate, such as rheumatoid arthritis and psoriasis. Id. at
`3:57–67. It further states that “medicaments of the present invention are
`administered parenterally,” and in particular, “by intravenous, intramuscular
`or subcutaneous injection.” Id. at 4:4–6.
`C. Illustrative Claim
`Claim 1 of the ’231 patent, the only independent claim, is illustrative
`and is reproduced below:
`1. A method for the treatment of inflammatory autoimmune
`diseases in a patient in need thereof, comprising subcutaneously
`administering
`to said patient a medicament comprising
`methotrexate in a pharmaceutically acceptable solvent at a
`concentration of more than 30 mg/ml.
`Id. at 8:43–47. Dependent claims 2–22 recite additional limitations
`regarding methotrexate concentrations, solvent, inflammatory autoimmune
`diseases, and the medicament being contained in an injection device for a
`
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`Patent 8,664,231 B2
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`single application, such as a pen injector, or in a storage container, such as a
`carpule.
`D. Proposed Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1–22 of the ’231
`patent on the following grounds:
`
`Reference(s)
`
`Statutory
`Basis
`
`Claims Challenged
`
`Grint (Ex. 1003)1
`
`§ 102(b)
`
`1, 2, 4–6, 11–13, 17, and 22
`
`Grint and Insulin Admin.
`§ 103(a)
`(Ex. 1015)2
`
`7–10, 14–16, and 19–21
`
`Grint and Alsufyani (Ex. 1006)3 § 103(a)
`
`18
`
`
`
` 1
`
` Grint et al., U.S. Pat. No. 6,544,504 B1, issued Apr. 8, 2003 (“Grint”) (Ex.
`1003).
`2 American Diabetes Assn., Insulin Admin., 26 DIABETES CARE Supp. 1,
`S121–S124 (2003) (“Insulin Admin.”) (Ex. 1015).
`3 Alsufyani et al., The Role of Subcutaneous Adm. of Methotrexate in
`Children with Juvenile Idiopathic Arthritis Who Have Failed Oral
`Methotrexate, 31:1 J. RHEUMATOLOGY 179–82 (2004) (“Alsufyani”) (Ex.
`1006).
`
`
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`Reference(s)
`
`The PDR (Ex. 1007)4 or
`Hospira (Ex. 1009),5 and
`Brooks (Ex. 1008)6
`
`The PDR or Hospira, Brooks,
`and Insulin Admin.
`
`Statutory
`Basis
`
`Claims Challenged
`
`§ 103(a)
`
`1–5, 11–13, 17, and 22
`
`§ 103(a)
`
`7–10, 14–16, and 19–21
`
`Petitioner also relies upon the Declarations of M. Eric Gershwin, M.D.
`(Ex. 1012) and David C. Gammon, B.S.Ph. (Ex. 1013).
`II. ANALYSIS
`A. 35 U.S.C. § 325(d)
`In the prior IPR involving a different Petitioner, IPR2014-01091, we
`instituted an inter partes review based on the same grounds of
`unpatentability, regarding the same patent and claims, raised by Petitioner in
`this case. IPR2014-01091, slip op. 24 (PTAB Jan. 6, 2015), (Paper 7); Pet.
`16–17. Several months later, in April 2015, the parties in the prior IPR
`settled the case, as well as a related district court litigation involving the
`other Petitioner as a defendant. Paper 8, 2. Because of the settlement and
`
`
`
` 4
`
` Edward R. Barnhart, Physicians’ Desk Reference (39th ed. 1985) (“The
`PDR”) (Ex. 1007).
`5 Hospira UK Ltd, Product Summary for Methotrexate 100mg/ml Injection
`(Rev. 2005) (“Hospira”) (Ex. 1009).
`6 Brooks et al., Pharmacokinetics of Methotrexate Adm. by Intramuscular
`and Subcutaneous Injections in Patients with Rheumatoid Arthritis, 33(1)
`ARTHRITIS AND RHEUMATOLOGY 91–94 (1990) (“Brooks”) (Ex. 1008).
`
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`subsequent termination of the prior IPR, we did not address the patentability
`of challenged claims in a final written decision.
`Patent Owner contends that the “Board should not countenance this
`behavior by a reverse patent troll [i.e., Petitioner here], who is looking for no
`more than a quick payoff” in the form of a settlement. Prelim. Resp. 3–4.
`Patent Owner contends that going forward with a trial in this case is “neither
`fair nor just” and would “not foster the purpose of IPRs.” Id. at 4.
`On the record here and under the circumstances before us, we decline
`to exercise our discretion under 35 U.S.C. § 325(d) as a basis to deny
`institution of a trial here. As noted above, in the prior IPR involving an
`entirely different Petitioner, we instituted trial on the same grounds at issue
`here, but terminated the proceeding before issuing a final written decision.
`In addition, by statute, the Leahy-Smith America Invents Act provides that
`“a person who is not the owner of a patent may file with the Office a petition
`to institute an inter partes review of the patent.” 35 U.S.C. § 311. In any
`case, even if we were to take into account Patent Owner’s “reverse patent
`troll” contention, evidence of record indicates that Petitioner has stated to
`Patent Owner that Petitioner is “focused on commercializing” drug products
`and “intends to approach its development partners to prepared and file an
`ANDA for Rasuvo®.” Ex. 2001, 1.
`B. Real Parties-In-Interest
`Patent Owner contends that Petitioner fails to identify all real parties-
`in-interest (“RPI”) in its Petition, as required under 35 U.S.C. § 312(a)(2).
`Prelim. Resp. 11–14. Patent Owner contends that, in addition to Frontier
`Therapeutics, LLC, Petitioner also should have identified Jason Paul Group
`LLC and Jason Paul Greer Enterprises Limited Liability Company, as all
`
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`three entities are “alter egos” of Mr. Jason Greer and share his personal
`address. Id. at 12–13. Citing documents filed with the State of Washington
`and “Whois Data for Frontiertherapeuticsnw.com” (“Whois Data”),
`Petitioner asserts that Mr. Greer “on his own or acting through his corporate
`alter ego Jason Paul Greer Enterprises Limited Liability Company, doing
`business as Jason Paul Group LLC, exercised or could have exercised
`control over Frontier’s participation in this IPR.” Id. at 13–14 (citing Exs.
`2002–2005).
`A patent owner challenging a petitioner’s RPI disclosure must provide
`sufficient evidence to show the disclosure is inadequate. Intellectual
`Ventures Mgmt., LLC v. Xilinx, Inc., Case IPR2012-00018, slip op. at 3–4
`(PTAB Jan. 24, 2013) (Paper 12). When a patent owner provides sufficient
`evidence prior to institution that reasonably brings into question the
`accuracy of a petitioner’s identification of real parties-in-interest, the overall
`burden remains with the petitioner to establish that it has complied with the
`statutory requirement to identify all real parties-in-interest. Zerto, Inc. v.
`EMC Corp., Case IPR2014-01254, slip op. at 6–7 (PTAB Feb 12, 2015)
`(Paper 32) (“Zerto”).
`As stated in our Trial Practice Guide, whether a party who is not a
`named participant in a given proceeding is a “real party-in-interest” to that
`proceeding “is a highly fact-dependent question.” Office Patent Trial
`Practice Guide, 77 Fed. Reg. 48,756, 48,759 (Aug. 14, 2012) (“Trial Practice
`Guide”). There is no “bright line test.” Id. Considerations may include
`whether a non-party “funds and directs and controls” an IPR petition or
`proceeding; the non-party’s relationship with the petitioner; the non-party’s
`relationship to the petition itself, including the nature and/or degree of
`
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`IPR2016-00649
`Patent 8,664,231 B2
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`involvement in the filing; and the nature of the entity filing the petition. Id.
`at 48,760. A party does not become a RPI merely through association with
`another party in an endeavor unrelated to the AIA7 proceeding. Id.
`The RPI requirement exists to ensure that a non-party is not “litigating
`through a proxy.” Aruze Gaming Macau, Ltd. v. MGT Gaming, Inc., Case
`IPR2014-01288, slip op. at 12 (PTAB Feb. 20, 2015) (Paper 13). The RPI
`analysis, moreover, is an inquiry into the “relationship between a party and a
`proceeding;” not “the relationship between parties.” Id. at 11. Thus, we
`consider “the degree of control the nonparty could exert over the inter partes
`review, not the petitioner.” Id.
`The record before us presents insufficient evidence as to whether any
`unnamed entity had the ability itself (e.g., via its own legal counsel, for
`example) to exert control over the IPR. Similarly, insufficient evidence
`exists as to whether any unnamed entity funded or otherwise paid for
`expenses associated with the Petition, or whether any unnamed entity itself
`generates any revenue on its own (outside of revenue generated by Frontier
`Therapeutics, LLC, for example). The record presents little to no
`information as to how any unnamed entity relates to, or could have
`participated in, this proceeding in particular. Patent Owner’s evidence in the
`form of printed copies of purported electronic search results from the “WA
`Secretary of State,” “Search Business Licenses,” and “Whois Data” is
`insufficient to address the considerations at hand. Prelim. Resp. 12–14
`(citing Exs. 2002–2005).
`
`
`
` 7
`
` The Leahy-Smith America Invents Act, Pub. L. No. 112−29, 125 Stat. 284
`(2011) (“AIA”).
`
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`
`Based on the particular facts of this case, in view of the evidence
`before us on the present record, we are not persuaded that Patent Owner has
`provided sufficient evidence to show that Petitioner’s disclosure of real
`parties-in-interest is inadequate in relation to other unnamed entities.
`C. Declarations by Petitioner’s Witness
`Patent Owner asserts that Declarations from Petitioner’s witnesses Dr.
`Gershwin (Ex.1012) and Mr. Gammon (Ex.1013) lack credibility and
`foundation, and that we should accord them no weight. Prelim. Resp. 14–
`19. For example, Patent Owner contends that “Dr. Gershwin’s ‘opinions’
`are plagiarized” from a Declaration of another witness in the prior IPR2014-
`01091. Patent Owner also asserts that both Dr. Gershwin and Mr. Gammon
`fail to exhibit sufficient expertise needed to support their statements and fail
`to address certain points raised by Patent Owner. Prelim. Resp. 15–19.
`Dr. Gershwin’s Declaration indicates that he is a Professor of
`Medicine and the Chief of Rheumatology, Allergy, and Clinical
`Immunology in the School of Medicine at the University of California,
`Davis, among other credentials. Ex. 1012 ¶¶ 5–20. He also indicates that he
`has “published on the use of MTX [methotrexate] to treat autoimmune
`diseases such as rheumatoid arthritis,” a point that Patent Owner disputes
`based its own search of publications authored by “Gershwin.” Id. ¶ 19;
`Prelim. Resp. 15–16. Mr. Gammon indicates that, among other credentials,
`he has practiced as a Clinical Pharmacy Specialist, where he has prepared
`chemotherapy and cytotoxic drugs for the treatment of patients and
`“compounded these drugs for injection, which would include formulating
`varying concentrations of these active ingredients for injection.” Ex. 1013
`¶¶ 4–8.
`
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`IPR2016-00649
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`
`For the purpose of institution, based on the record before us, we are
`not persuaded that either witness lacks credibility or the Declarations lack
`foundation to the extent that we should accord those Declarations no weight
`whatsoever. Absent more information in the record, the credentials of both
`witnesses provide sufficient reason to consider the Declarations in our
`deliberations.
`We acknowledge Patent Owner’s points that Dr. Gershwin’s
`Declaration is “virtually identical” to a Declaration by a different witness in
`IPR2014-01091, and that Dr. Gershwin’s Declaration does not list that prior
`Declaration expressly in his paragraph entitled “Materials Reviewed.”
`Prelim. Resp. 15 (citing Ex. 2006; Ex. 2007; Ex. 1012 ¶ 23). Nonetheless,
`without more in the record, Patent Owner’s contentions in this regard do not
`persuade us that Dr. Gershwin’s Declaration lacks all credibility or
`foundation. For example, Dr. Gershwin’s overall credentials appear to be
`relevant and appropriate, and he declares that all of his statements are “made
`herein of my own knowledge” and “that all statements made on information
`and belief are believed to be true,” with the understanding that willful false
`statements “are punishable by fine or imprisonment.” Ex. 1012 ¶ 104. We
`will take into account, however, Patent Owner’s above-mentioned points
`when determining the weight to give Dr. Gershwin’s testimony.
`D. 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, 2144–46
`(2016). Under that standard, and absent any special definitions, we give
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`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).
`Petitioner discusses the meaning of five claim terms, explaining that
`those terms are “presumed to take on their ordinary and customary meaning
`that they would have to one of ordinary skill in the art.” Pet. 14–16. For
`example, Petitioner asserts that “subcutaneously” means “under the skin.”
`Id. at 15. Patent Owner does not propose different constructions for the
`claims terms, but clarifies that “subcutaneously” is distinct from, and does
`not include, “intramuscular” or “intravenous,” despite the fact that all three
`involve administration “literally” under the skin. Prelim. Resp. 26–27.
`We agree with Patent Owner that subcutaneously is a route of
`administration that is distinct from intramuscular (in a muscle) or
`intravenous (in a vein), even if all three involve to administration under the
`skin. The specification of the ’231 patent expressly uses those three terms
`separately, indicating that they have different meanings. Ex. 1001, 4:4–6
`(“The medicaments of the present invention are administered parenterally.
`In particular, the medicaments are administered by intravenous,
`intramuscular or subcutaneous injection.”); id. at 5:32–35.
`In view of our analysis, we determine that construction of the
`remaining claim terms is not necessary for purposes of this Decision.
`A. Anticipation by Grint (Ex. 1003)
`Petitioner asserts that Grint anticipates claims 1, 2, 4–6, 11–13, 17,
`
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`and 22 of the ’231 patent. Pet. 19–28. Patent Owner opposes Petitioner’s
`assertion. Prelim. Resp. 27–35.
`1. Grint
`Grint discloses a method for controlling autoimmune diseases,
`including rheumatoid arthritis and psoriasis, by administering a combination
`of methotrexate and interleukin 10. Ex. 1003, 1:13–18. This combination
`therapy causes a synergistic suppression of T cell proliferation, such that
`methotrexate can be used in lower amounts, “thereby avoiding or reducing
`the serious side effects normally associated with the use of this drug.” Id. at
`2:44–65. According to Grint, methotrexate and interleukin 10 may be
`administered either at the same time, or at different times during the course
`of a common treatment schedule. Id. at 3:12–26. Methotrexate may be
`administered orally, intraperitoneally, or parenterally, e.g. subcutaneously or
`intramuscularly. Id. at 3:25–26, 5:64–65, 7:54–59. Grint teaches that it is
`especially advantageous to formulate parenteral compositions in dosage unit
`form, i.e., physically discrete units suited as unitary dosages. Id. at 6:52–56.
`For example, a unit dosage form generally contains methotrexate from 0.1 to
`about 40 mg/ml of carrier. Id. at 6:60–7:1.
`2. Analysis
`Independent claim 1 recites “subcutaneously administering . . . a
`medicament comprising methotrexate . . . at a concentration of more than 30
`mg/ml.” In its arguments and claim charts, Petitioner points to where Grint
`discloses every limitation of claim 1, as well as limitations of other
`challenged claims, such as claim 2 (reciting that the methotrexate
`concentration is “more than 30 mg/ml to 100 mg/ml”) and claim 22 (reciting
`that the methotrexate concentration is “from 40 mg/ml to 80 mg/ml”). Pet.
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`19–28. As noted by Petitioner, “more than 30 mg/ml” and “from 40 mg/ml”
`fall within the range of methotrexate concentration (“about 0.1 to about 40
`mg/ ml”) expressly disclosed in Grint in relation to any “unit dosage form.”
`Patent Owner asserts that Petitioner provides no evidence that “any
`person ever administered MTX subcutaneously at a concentration greater
`than 30mg/ml to treat any disease.” Prelim. Resp. 27, 33–34. According to
`Patent Owner, Petitioner “arbitrarily pick[s] and choose[s] among disparate
`parts in Grint” in its anticipation challenge. Id. at 28. Patent Owner points
`to where Grint states that “MTX may be administered in a manner as is
`conventionally practiced,” and argues that Petitioner has not shown it was
`“conventional practice” to subcutaneously administer methotrexate at the
`recited concentration of more than 30mg/ml. Id. at 28, 30–35 (citing Ex.
`1003, 5:22–23). Patent Owner discusses Example 1 in Grint (Ex. 1003,
`7:40–8:58), which discloses a safety and tolerance study involving
`subcutaneous administration of methotrexate at a dose of 12.5–25 mg/week,
`noting that it does not disclose the methotrexate concentration (mg/ml) used
`in the study. Prelim. Resp. 29–30.
`Patent Owner further argues that Grint’s general discussion of
`methotrexate concentrations of 0.1–40 mg/ml (Ex. 1003, 6:66–7:1) in
`relation to parenteral administration is insufficient to meet the recited
`concentration because a “skilled artisan would also recognize that
`concentrations at the lower end of Grint’s range (0.1mg/ml) would require
`too large a drug volume (10ml) for subcutaneous administration for a 1mg
`dose,” and “concentrations at the higher end of Grint’s range (40mg/ml)
`would generate a volume of 0.025ml for a 1mg dose,” which would be too
`small to accurately draw up an accurate volume and dose. Id. at 31–32, 35.
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`Patent Owner argues that Petitioner “has ignored the significant differences
`in the claimed range (above 30mg/ml) and the Grint concentration range
`(0.1–40mg/ml).” Id. at 35.
`Based on the record before us, Petitioner reasonably contends that
`evidence, such as Grint itself, fails to indicate sufficiently a “criticality of the
`overlapping range (30–40 mg/ml)” or demonstrate a meaningful difference
`between the claimed range (such as more than 30 mg/ml) and the range in
`the prior art (0.1–40 mg/ml). Pet. 23; ClearValue, Inc. v. Pearl River
`Polymers, Inc., 668 F.3d 1340, 1345 (Fed. Cir. 2012); Atofina v. Great
`Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir. 2006); Prelim. Resp. 34–
`35. For example, Grint does not indicate that different concentrations within
`its disclosed range of 0.1–40 mg/ml would have functioned differently in a
`method for treating an autoimmune disease by subcutaneous administration
`of methotrexate, such as presented in Example 1 in Grint. OSRAM Sylvania,
`Inc. v. Am. Induction Techs., Inc., 701 F.3d 698, 705–06 (Fed. Cir. 2012).
`We are persuaded to go forward with a trial on the ground that Grint
`anticipates claims 1, 2, 4–6, 11–13, 17, and 22 of the ’231 patent. Patent
`Owner does not persuade us otherwise based on its contention that no
`witness has stated that they “had actually subcutaneously administered MTX
`[], or prepared an MTX solution for subcutaneous administration[], at a
`concentration above 30mg/ml.” Prelim. Resp. 33 (emphasis added). An
`anticipation analysis addresses whether a prior art reference discloses each
`and every limitation of a challenged claim and enables one of skill in the art
`to practice an embodiment of the claimed invention without undue
`experimentation. ClearValue, 668 F.3d 1340, 1344 (citing Am. Calcar, Inc.
`v. Am. Honda Motor Co., 651 F.3d 1318, 1341 (Fed. Cir. 2011)). A finding
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`of anticipation does not require that anyone actually perform the recited
`method before the relevant date.
`Nor are we persuaded by the fact that Grint states that “MTX may be
`administered in a manner as is conventionally practiced.” Ex. 1003, 5:22–23
`(emphasis added); Prelim. Resp. 28, 30–35. In the same paragraph, Grint
`discloses, “[f]or example,” that methotrexate may be administered orally.
`Ex. 1003, 5:25–29. Later on, however, Grint expressly states that
`methotrexate may be administered parenterally (including subcutaneously,
`as disclosed in Example 1), and also states that a unit dose form “is generally
`present in from about 0.1 to about 40 mg/ml of carrier.” Grint’s generic
`statement that methotrexate may be administered “as is conventionally
`practiced” does not persuade us that Grint limited its disclosed methods to
`administrating lower concentrations of methotrexate when administering the
`drug subcutaneously. Id. at 5:22–23.
`Regarding Patent Owner’s picking and choosing argument, we are
`sufficiently persuaded, based on the record before us, that relevant
`disclosures in Grint are related directly to each other based on teachings in
`the reference itself. Prelim. Resp. 28 (citing In re Arkley, 455 F.2d 586, 587
`(CCPA 1972)). For example, as discussed above, Grint refers generally to
`oral and parenteral administration, such as subcutaneous or intramuscular,
`using a relevant range of methotrexate concentration, in a method to treat
`autoimmune diseases, such as rheumatoid arthritis. Ex. 1003, 2:22–30;
`3:20–22; 5:25, 64–65; 6:60–7:1, 40–59; Pet. 20–21, 23–25. For the same
`reasons, Patent Owner does not persuade us with its contention that Grint
`“never correlates any MTX concentration with any mode of administration.”
`Prelim. Resp. 30–32. On this record, we have insufficient reason to doubt
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`that the methods, dosing, and drug concentrations disclosed in Grint would
`have failed to work, i.e., lacked enablement, for example.
`Based on the information presented at this stage of the proceeding, we
`are persuaded that Petitioner has shown a reasonable likelihood of
`establishing sufficiently that each limitation of claims 1, 2, 4–6, 11–13, 17,
`and 22 is disclosed by Grint. Pet. 19–28.
`B. Obviousness over Grint (Ex. 1003) and Insulin Admin. (Ex. 1015)
`Petitioner asserts that dependent claims 7–10, 14–16, and 19–21 are
`obvious over Grint in view of Insulin Admin. Pet. 28–32. Patent Owner
`opposes Petitioner’s assertion. Prelim. Resp. 36–40.
`1. Insulin Admin.
`Insulin Admin. addresses issues regarding the use of conventional
`insulin administration in the self-care of an individual with diabetes. Ex.
`1015, S121. The article explains that several pen-like devices and insulin-
`containing cartridges are available that deliver insulin subcutaneously
`through a needle. Id. at S123. These devices have been shown to improve
`accuracy of insulin administration and/or adherence. Id. The article also
`explains that certain individuals, such as those dependent on others for
`drawing their insulin, may benefit from using prefilled syringes. Id.
`2. Analysis
`Claim 7 requires the medicament comprising methotrexate of
`independent claim 1 to be “present in a form suitable for patient self-
`administration.” Claims 8 and 9 specifically require the medicament to be
`contained in an injection device for a single application, while claim 10
`further requires the injection device to be a ready-made syringe, and claim
`20 requires the injection device to be a pen injector. Claims 14–16, 19, and
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`21 recite additional limitations relating to the medication storage, the
`injection device and the dosages per application administered by the device.
`Petitioner asserts that Grint discloses methods for treating
`inflammatory autoimmune diseases by administering subcutaneous
`injections of concentrated methotrexate, as discussed above with respect to
`the anticipation ground. Pet. 28. Petitioner acknowledges, however, that
`Grint does not disclose expressly that its methotrexate is packaged in a form
`suitable for self-administration, such as an injection device. Id. According
`to Petitioner, packaging medications in forms suitable for self-
`administration, such as being contained in an injection device for a single
`application, or prepared as a ready-made syringe, were known in the art
`prior to the claimed invention. Id. In support of this assertion, Petitioner
`relies on Insulin Admin. as disclosing the use of a “pen-like device,” i.e., an
`injection device or a pen injector, and the use of a “prefilled syringe,” i.e., a
`“ready-made syringe” for self-administration of insulin. Id. at 28–32; Ex.
`1015, S121, S123.
`Petitioner further relies on the Declarations of Dr. Gershwin and Mr.
`Gammon as providing evidence of a reason to prepare an injectable
`medication in a form suitable for patient self-administration, i.e., for
`convenience, compliance, and cost-savings. Pet. 28–29; Ex. 1012 ¶ 33; Ex.
`1013 ¶¶ 50, 51. Petitioner asserts also that the ’231 patent itself recognizes
`that it was routine in the art at the time of the invention to formulate
`injectable drugs into ready-made syringes and injection devices to allow for
`self-administration, and to increase patient compliance and comfort. Pet. 29;
`Ex. 1001, 2:26–36, 6:54–61. According to Petitioner, based on the teachings
`of the prior art and the knowledge of those skilled in the art at the time of the
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`invention, providing Grint’s concentrated methotrexate solution in a form
`suitable for patient self-administration, such as contained in an injection
`device, ready-made syringe, or pen injector, would have required no more
`than routine effort by an ordinary artisan. Pet. 29.
`Patent Owner responds that Insulin Admin. does not remedy the
`alleged deficiencies of Grint with respect to independent claim 1. Prelim.
`Resp. 39–40. Petitioner, however, does not rely on Insulin Admin. to
`address the limitations of claim 1. Nor has Patent Owner established, on this
`record, that a deficiency exists regarding the limitations of the independent
`claim with respect to Grint’s disclosure.
`Petitioner reasonably contends that Insulin Admin. indicates that the
`specific injection devices recited by the challenged claims were known at the
`time of the invention. Pet. 28–29. As Petitioner also notes, the ’231 patent
`acknowledges that ready-made syringes containing methotrexate were also
`known in the prior art. Id. at 30; Ex. 1001, 2:26–31. Indeed, the ‘231 patent
`explains that this dosage form was provided prior to the invention to
`eliminate the step of drawing up a methotrexate formulation in a syringe and
`to avoid the strict restrictions applicable to such a step. Id. at 2:7–19.
`Thus, based on the information presented at this stage of the
`proceeding, Petitioner has shown sufficiently that there is a reasonable
`likelihood that Petitioner would prevail in showing that claims 7–10, 14–16,
`and 19–21 are unpatentable over Grint and Insulin Admin.
`C. Obviousness over Grint (Ex. 1003) and Alsufyani (Ex. 1006)
`Petitioner asserts that dependent claim 18 is obvious over Grint in
`view of Alsufyani. Pet. 33–34. Patent Owner opposes Petitioner’s assertion.
`Prelim. Resp. 40–41.
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