IPR2016-01370
`U.S. Patent No. 8,664,231
`
`
`
`
`
`
`Attorney Docket No.
`110670-0009-651
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`___________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`___________________________________
`
`KOIOS PHARMACEUTICALS LLC
`Petitioner
`
`v.
`
`MEDAC GESELLSCHAFT FÜR KLINISCHE
`SPEZIALPRÄPARATE MBH
`Patent Owner
`
`___________________________________
`
`Case No. IPR2016-01370
`Patent Number 8,664,231
`
`
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`UNDER 37 C.F.R. § 42.107
`
`
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`

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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`TABLE OF CONTENTS
`
`Attorney Docket No.
`110670-0009-651
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`
`V.
`
`Introduction ...................................................................................................... 1
`I.
`‘231’s Claimed Method ................................................................................... 3
`II.
`III. MTX And The Treatment Of Inflammatory Autoimmune Diseases .............. 5
`IV. The Board Should Exercise Its Discretion And Not Institute Trial
`Under § 325(d) ................................................................................................. 8
`Petitioner’s Expert Declarations Should Be Given No Weight .................... 14
`A. Dr. Miller’s Opinions Should Be Given No Weight ........................... 14
`B. Dr. Schiff’s Opinions Should be Given No Weight ............................ 17
`VI. Claim Construction ........................................................................................ 20
`VII. Petitioner Has Not Established That Grint Anticipates Claims 1, 2, 4,
`5, 6, 11, 12, 13, 17, and 22 (Ground 1) ......................................................... 21
`VIII. Petitioner Has Not Established That Grint in View of Arthur, or
`Further in View of Moitra or Insulin Admin, Renders Obvious Claims
`7-10, 14-16, and 19-21 (Ground 2) ............................................................... 23
`IX. Petitioner Has Not Established That Wyeth or PDR for Wyeth
`Anticipates Claims 1-6, 11-13, 17-18 and 22 (Ground 4) ............................. 27
`Petitioner Has Not Established That Wyeth or PDR for Wyeth in
`View of Brooks and Arthur, Further in View of Moitra or Insulin
`Admin Renders Obvious Claims 1-22 (Ground 5) ........................................ 30
`XI. Petitioner Has Not Established That Hoekstra or Jørgensen in View of
`Arthur and/or Insulin Admin Renders Obvious Claims 1-22 (Ground 6)
` ....................................................................................................................... 32
`XII. Petitioner Fails to Fully Analyze Secondary Considerations ........................ 35
`XIII. Conclusion ..................................................................................................... 36
`
`X.
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
`110670-0009-651
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`TABLE OF AUTHORITIES
`
`
`CASES
`Apple Inc. v. Smartflash LLC,
`CBM2015-0015, Pap. 23 (PTAB Apr. 10, 2015) ......................................... 25, 31
`
`Page(s)
`
`Atofina v. Great Lakes Chemical Corp.,
`441 F. 3d 991 (Fed. Cir. 2006) ..................................................................... 21, 22
`
`Biomarin Pharm. Inc. v. Genzyme Therapeutics Prods. Ltd.,
`IPR2013-00537, Pap. 79 (PTAB Feb. 23, 2015) .................................................. 4
`
`Boston Scientific Neuromodulation Co. v. Nevro Corp.,
`IPR2015-01203, Pap. 10 (PTAB Nov. 30. 2015) ............................................... 25
`
`Butamax Advanced Biofuels LLC v. Gevo, Inc.,
`IPR2014-00581, Pap. 8 (PTAB Oct. 14, 2014) .................................................. 14
`
`Clearvalue, Inc. v. Pearl River Polymers, Inc.,
`668 F.3d 1340 (Fed. Cir. 2012) .................................................................... 21, 22
`
`Continental Automotive Systems, Inc. v. Wasica Finance GMBH & Bluearc
`Finance AG, IPR2014-01454, Pap. 14 (PTAB Feb. 13, 2015) .......................... 11
`
`CustomPlay,LLC v. ClearPlay, Inc.,
`IPR2014-00783, Pap. 9 (PTAB Nov. 7, 2014) ................................................... 14
`
`DirecTV, LLC v. Qurio Holdings, LLC,
`No. IPR2015-02007, Pap. 6 (PTAB Apr. 4, 2016) ....................................... 24, 31
`
`Fresenius USA, Inc. v. Baxter Int’l, Inc.,
`582 F.3d 1288 (Fed. Cir. 2009) .............................................................. 26, 32, 33
`
`Google Inc. v. ART+COM Innovationpool GmbH,
`IPR2015-00789, Pap. 8 (PTAB Sept. 2, 2015) ................................................... 24
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ............................................................................................ 2, 35
`
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
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`
`In re Suitco Surface, Inc.,
`603 F.3d 1255 (Fed. Cir. 2010) .......................................................................... 20
`
`In re Urbanski,
`809 F.3d 1237 (Fed. Cir. 2016) .......................................................... 2, 26, 32, 33
`
`Ineos USA LLC v. Berry Plastics Corp,
`783 F.3d 865 (Fed. Cir. 2015) ............................................................................ 22
`
`Innogenetics, N.V. v. Abbott Labs.,
`512 F.3d 1363 (Fed. Cir. 2008) .......................................................... 2, 26, 32, 34
`
`Intelligent Bio-Systems, Inc. v. Illumina Cambridge Limited,
`IPR2013-00324, Pap. 19 (PTAB Nov. 21, 2013) ............................................... 12
`
`Kinetic Techs., Inc. v. Skyworks Solutions, Inc.,
`IPR2014-00529, Pap. 8 (PTAB Sept. 23, 2014) ............................... 27, 31, 32, 34
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .....................................................................................passim
`
`Leo Pharm. Prods., Ltd. v. Rea,
`726 F.3d 1346 (Fed. Cir. 2013) .......................................................................... 35
`
`Lupin Ltd. v. Vertex Pharmaceuticals Inc.,
`IPR2015-00405, Pap. 13 (Jul. 9, 2015) .............................................................. 35
`
`MaxLinear, Inc. v Cresta Technology Corporation,
`IPR2015-00593, Pap. 9 (Aug. 14, 2015) ............................................................ 13
`
`Medtronic, Inc. v. Mark A. Barry,
`IPR2015-00782, Pap. 6 (PTAB Sept. 9, 2015) ............................................. 18, 19
`
`Medtronic, Inc. v. Robert Bosch Healthcare Systems, Inc.,
`IPR2014-00436, Pap. 17 (PTAB June 19, 2014) ............................................... 12
`
`Merial Ltd. v. Virbac,
`IPR2014-01279, Pap. 13 (P.T.A.B. Jan. 22, 2015) ............................................ 35
`
`NetApp Inc. v. Crossroads Sys., Inc.,
`IPR2015-00772, Pap. 12 (PTAB Sept. 3, 2015) ................................................. 13
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
`110670-0009-651
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`
`Nike, Inc. v. Adidas AG,
`812 F.3d 1326 (Fed. Cir. 2016) .............................................................. 26, 32, 33
`
`OSRAM Sylvania, Inc. v. Am. Induction Techs., Inc.,
`701 F.3d 698 (Fed. Cir. 2012) ............................................................................ 23
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................................... 20
`
`Symantec Corp. v. The Tr. of Columbia Univ. in the City of New York,
`IPR2015-00370, Pap. 13 (PTAB June 17, 2015) ............................................... 24
`
`Transocean Offshore Deepwater Drilling, Inc. v. Maersk Drilling USA, Inc.,
`699 F.3d 1340 (Fed. Cir. 2012) .......................................................................... 35
`
`TRW Automotive US, LLC v. Magna Elecs. Inc.,
`IPR2014-01347, Paper 25 (PTAB Jan. 6, 2016) ................................................ 24
`
`W.L. Gore & Assoc., Inc. v. Garlock, Inc.,
`721 F.2d 1540 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984) ................... 29
`
`Wowza Media Sys., LLC v. Adobe Sys. Inc.,
`IPR2013-00054, Pap. 12 (PTAB Apr. 8 2013) ............................................. 25, 31
`
`STATUTES
`
`35 U.S.C. § 312(a) ..................................................................................................... 2
`
`35 U.S.C. § 315(c) ................................................................................................... 13
`
`35 U.S.C. § 325(d) ............................................................................................passim
`
`OTHER AUTHORITIES
`
`37 C.F.R. § 42.24 ....................................................................................................... 1
`
`37 C.F.R. § 42.100(b) .............................................................................................. 20
`
`37 C.F.R. § 42.107 ..................................................................................................... 1
`
`37 C.F.R. § 42.107 ..................................................................................................... 2
`
`
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
`110670-0009-651
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`EXHIBITS
`
`Kurnick D. et al., “Bioavailability of oral vs. subcutaneous low-dose
`methotrexate in patients with Crohn’s disease,” Aliment. Pharmacol.
`Ther., 2003, vol. 18:57-63
`Breslin, et al., “Improving Tolerance and Bioavailability of
`Methotrexate by Switching from Oral to Subcutaneous Route of
`Administration,” Rheumatology 388 (2005)
`Balis, et al., “Pharmacokinetics of Subcutaneous Methotrexate,” Journal
`of Clinical Oncology 6(12):1882-1886 (1988)
`Chapter 16: Human: Veterinary Technology Cross Over, Long Acting
`Animal Health Drug Products: Fundamentals and Applications, Baird et
`al., Springer (2013)
`Chapter 3: Drug Administration, Drug Therapy In Nursing, 3rd Ed.,
`Aschenbrenner DS and Venable SJ, Wolters Kluwer Health (2009)
`Antares Pharma Press Release, “Antares Pharma Announces the
`Publication of a Head-to-Head, Randomized, Crossover Study of Oral
`versus Subcutaneous Methotrexate in Patients with Rheumatoid
`Arthritis,” Business Wire (Apr. 17, 2014)
`Consulting Agreement between Medac Pharma, Inc. and Dr. Michael
`Schiff, M.D., executed September 7, 2012
`RA Advisory Council: Overview & Meeting Objectives, October 5,
`2012
`Koios Pharmaceuticals LLC Press Release, “Koios Pharmaceuticals
`Files Challenge to High-Cost Drug’s Patent,” Business Wire (July 20,
`2016)
`Declaration of Brian Gummow in Support Of Patent Owner’s
`Preliminary Response
`Declaration of Terri Shoemaker in Support Of Patent Owner’s
`Preliminary Response
`U.S. Patent 8,480,631
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`2001
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`2002
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`2003
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`2004
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`2005
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`2006
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`2007
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`2008
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`2009
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`2010
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`2011 
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`2012
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`

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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
`110670-0009-651
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`Pursuant to 37 C.F.R. § 42.107, Patent Owner medac Gesellschaft für
`
`
`
`
`Klinische Spezialpräparate mbH (hereinafter “Medac” or “PO”) submits this
`
`Preliminary Response to the above-captioned Petition for Inter Partes Review
`
`(“IPR”) of U.S. Patent 8,664,231 (“the ‘231 patent”) (“Pet.,” Pap. 1).
`
`I.
`
`Introduction
`
`IPR2016-01370 is the third IPR filed on the ’231 patent. For that reason
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`alone, the Board should exercise its discretion and not institute trial under §325(d).
`
`Further, the Petition fails to provide the basic evidence required for institution.
`
`Petitioner’s obviousness arguments fail to make clear what disclosures are missing
`
`from the primary references, and which secondary references it proposes
`
`combining for what limitations. Petitioner’s obviousness arguments also fail to
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`clearly lay out its proposed combination(s) or provide any analysis of the
`
`combinations on an element by element basis. In cobbling together numerous
`
`obviousness combinations (frequently hidden in “or further in view of” and
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`“and/or” framing of Grounds 2 and 6, for instance), Petitioner never articulates the
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`specific combinations, or what is being supplied by a given secondary reference
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`that is otherwise missing from the primary reference’s disclosures. Petitioner
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`apparently expects Medac and the Board to guess and piece together what
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`Petitioner might have intended from among the multiple proposed grounds. Further,
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`for many of the apparent combinations, Petitioner fails to offer any argument
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
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`regarding motivation to combine. For the other combinations, Petitioner’s
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`
`
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`arguments are, at best, entirely conclusory. Such conclusory statements fall far
`
`short of the necessary “articulated reasoning with some rational underpinning to
`
`support the legal conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc., 550
`
`U.S. 398, 418 (2007) (quotations omitted); see also § 312(a)(3); In re Urbanski,
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`809 F.3d 1237, 1241 (Fed. Cir. 2016) (“Obviousness is a question of law based on
`
`underlying factual findings, including . . . the existence of a reason to combine
`
`references”) (citations omitted); Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363,
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`1374 (Fed. Cir. 2008) (“[S]ome kind of motivation must be shown from some
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`source, so that the jury can understand why a person of ordinary skill would have
`
`thought of either combining two or more references or modifying one to achieve
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`the patented method”) (quotations omitted). Further, Petitioner’s expert’s
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`assertions are conclusory and internally inconsistent. Finally, Petitioner fails to
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`provide an analysis of secondary indicia of which it is certainly aware, rendering
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`its obviousness arguments fatally incomplete under the mandatory Graham
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`analysis. Graham v. John Deere Co. of Kansas City, 383 U.S. 1 (1966).
`
`If the Board nonetheless institutes trial, PO will address in detail in its
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`§42.120 Response the numerous substantive errors and shortcomings that underlie
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`each of Petitioner’s arguments and the purported evidence on which it relies.
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`II.
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`‘231’s Claimed Method
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`Attorney Docket No.
`110670-0009-651
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`The ‘231 is entitled “Concentrated Methotrexate Solutions.” It explicitly
`
`states the need that Medac’s inventor was attempting to satisfy:
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`There is [] a need for pharmaceutical formulations of
`methotrexate which can be administered to the patient,
`including children, as easily and pain-free as possible,
`while providing good bioavailability, over a long period
`of time at regular intervals, in particular weekly, which
`therefore leads to a high degree of patient compliance.
`As an added advantage, the patient should be able to self-
`administer the pharmaceutical formulation.
`
`Ex.1001 2:53-60. The ‘231 also explained that prior art subcutaneous injections of
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`higher doses of MTX had the disadvantage that “relatively large amounts of liquid
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`have to be injected under the patient’s skin” due to the low MTX concentrations
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`that were used in standard clinical practice. Id. 4:65-5:5. It also notes that this has
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`a negative impact on patient compliance. Id. 5:11-13.
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`The ‘231 method achieves its objective and solves the problems of the prior
`
`art
`
`through
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`the subcutaneous administration of MTX solutions having
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`concentrations above 30mg/ml. Id. 8:43-47. This allows lower volumes for a
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`given dose, avoiding both discomfort and multiple injections, while at the same
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`time retaining the bioavailability advantages of injectable MTX. The result of
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
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`PO’s method is a dosage form of MTX which exhibits good biological availability
`
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`
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`and can be administered in a single injection over prolonged periods, largely free
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`of pain and discomfort, thereby resulting in high patient compliance. Id. 5:22-23.
`
`The ‘231 claims numerous embodiments, all relating to the use of MTX for
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`subcutaneous administration at a concentration above 30mg/ml in the treatment of
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`inflammatory autoimmune diseases. Id. 3:1-15. Certain of the claimed
`
`embodiments relate to ready-made syringes. Id. 9:4-5. Others relate to carpules to
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`be used in conjunction with injection devices, including pens. Id. 9:15-18,
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`10:12-13.
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`The ‘231 also claims numerous MTX concentration ranges: “more than
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`30mg/ml to 150mg/ml;” and “about 50mg/ml;” Id. 8:43-52. Finally, ‘231 claims
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`various MTX dosages: 5-40 mg, adjustable in 2.5 mg intervals. Id. 10:1-3; 8-11.
`
`In describing the subcutaneous administration of the above 30mg/ml MTX
`
`concentrations for the treatment of inflammatory autoimmune diseases, the ‘231
`
`makes clear that its methods encompasses all inflammatory autoimmune diseases
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`which can reasonably be treated with methotrexate. Id. 3:57-59. The ‘231 then
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`claims treatment of some of these diseases, including rheumatoid arthritis and
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`psoriasis, stating that “[t]he medicaments of the present invention are especially
`
`preferred for the treatment of rheumatoid arthritis, including juvenile arthritis . . . .”
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`Id. 3:59-4:3; 8:57-64.
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`IPR2016-01370
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`Finally, the ‘231 claims MTX in a form “suitable for patient self-
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`administration.” Id. 8:65-67. Self-application has the advantage that frequent
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`doctor visits are not necessary. Id. 4:16-18.
`
`III. MTX And The Treatment Of Inflammatory Autoimmune Diseases
`MTX was discovered in the early 1950s. Ex.1001 1:14-17. It was initially
`
`used as a cancer treatment, primarily to treat breast cancer and childhood leukemia.
`
`Id. 1:24-27. When used in the treatment of cancer, MTX is administered at very
`
`high doses. Id. 1:56-60. Soon after the discovery of MTX, it was also found
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`effective for treating psoriasis, an inflammatory autoimmune disease. Id. 1:28-30.
`
`MTX was later also used to treat rheumatoid arthritis (“RA”), another
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`inflammatory autoimmune disease. Id. 1:30-32.
`
`RA is a chronic disease. Thus, treatment with MTX (and other basic
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`therapeutics) is generally long-term, and often continues throughout the patient’s
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`lifetime. Id. 1:42-55. Treatment of inflammatory autoimmune diseases (such as
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`RA) with MTX has typically involved significantly lower doses (sometimes up to
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`1,000 times lower) than treatments of cancer with MTX. Id. 1:56-60. The use of
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`MTX in those inflammatory autoimmune diseases is therefore referred to as “low-
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`dosage [MTX] therapy.” Id. 1:59-60. For example, a common dosage of MTX for
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`RA ranges from 5mg to 30 or 40 mg (more typically 25mg) per week. Id. 1:60-65.
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`Initially, MTX was administered orally for the treatment of inflammatory
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`IPR2016-01370
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`autoimmune diseases, particularly RA, using tablets. Id. 1:67-68. Generally, each
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`
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`tablet contained 2.5 mg of MTX. See, e.g., Ex.2001 at 2. Thus, a 25mg/week dose
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`would require ten (2.5mg) tablets. Injectable forms of MTX later became available,
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`initially administered using manual syringes. Ex.1001 2:4-36. In January 2013
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`with the European launch of its METOJECT®, PO became the first to offer a
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`subcutaneous injectable MTX using an autoinjector. Nonetheless, historically, oral
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`MTX administration was preferred due to its ease of use. Id. 1:29-31.
`
`Orally administered MTX, however, was sometimes associated with
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`gastrointestinal side effects. See, e.g., Ex.2002 at 6. Furthermore, variable and
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`reduced bioavailability was observed at higher oral doses (e.g., above 15-20mg).
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`Ex.2012 1:32-34; see also Ex.2015 at 4-5. In other words, the plasma
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`concentration following administration of oral MTX was found to plateau, above
`
`which there was no increase despite administration of higher doses. Id. at 4-5.
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`Parenteral MTX, on the other hand, is resorbed more reliably than tablets
`
`and without a dose plateau. Ex.1001 2:1-3. In fact, following parenteral
`
`administration, MTX is rapidly and nearly completely absorbed into the
`
`bloodstream. Ex.2012 19:37-40; see also Ex.2003 at 1; Ex.1019 at 3.
`
`There are at least eighteen forms of parenteral administration, including
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`intravenous, intra-arterial, intraosseous, intramuscular, intradermal, subcutaneous,
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`intracardiac, intrathecal, intraperitoneal, intravesical, intravitreal, intracavernous,
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`epidural, intracerebral, intracerebroventricular, intrapleural, inhalational, and
`
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`
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`transdermal. Ex.2004 at 19; Ex.2005 at 13, 16-21. When MTX is administered
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`intravenously, bioavailability is close to 100% because the MTX “does not get
`
`destroyed in the gastrointestinal tract and cleared from the subject’s body” and
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`“does not have any tissue architecture or constituents to traverse prior to being
`
`systematically available.” Ex.2012 17:56-62. In 2014, Dr. Schiff, one of
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`Petitioner’s experts, published a study (Ex.1019) and told the world in an
`
`accompanying April 17, 2014 Press Release (Ex.2006) that subcutaneous
`
`administration of MTX was surprisingly advantageous over oral administration:
`
`The study results show for the first time that plasma levels of
`oral dosed MTX are no greater for 20 mg or 25 mg doses than
`for 15 mg doses . . . . If a patient fails to respond to 15 mg of
`MTX orally, it may be more effective to switch to a
`subcutaneous regimen rather than continue to raise the oral dose.
`
`Ex.2006, 1 (emphasis added). The priority date of ‘231 was eight years earlier.
`
`Subcutaneous injection, however, presents certain difficulties. Ex.1001
`
`2:44-45. This is especially true for patients who require higher doses.
`
`Traditionally, the maximum concentration of injectable MTX for the treatment of
`
`rheumatoid arthritis was 25mg/ml. Id. 2:26-30; Ex.1034¶123. Prior to PO’s
`
`invention, when an MTX dose above 25mg was required, the approach was either:
`
`(a) to increase the injection volume to more than 1ml (2:44-52); or (b) to
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
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`administer multiple injections. Ex.1034¶123; Ex.1010. Either of these options
`
`
`
`
`allows the concentration of subcutaneously injected MTX to remain at the
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`conventional 25mg/ml, while still providing an increase in the absolute weekly
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`dose. Id. Yet, both approaches have clinical disadvantages. Large volumes of
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`liquid administered under the skin can be painful, and patients generally disfavor
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`multiple injections. Ex.1001 2:47-52; Ex.1033¶71.
`
`IV. The Board Should Exercise Its Discretion And Not Institute Trial Under
`§ 325(d)
`
`Under the facts of this IPR, the Board should exercise its discretion and not
`
`institute trial because “the same or substantially the same prior art or arguments
`
`previously were presented to the Office”—not once, but twice. 35 U.S.C. § 325(d).
`
`Indeed, this is the third IPR on the same claims of the ‘231 patent, and in filing
`
`when it did, Petitioner had the advantage of an institution decision and two
`
`preliminary responses by PO on the very claims challenged here, providing a
`
`roadmap to a third bite at the apple.
`
`Antares filed a petition (IPR2014-01091, “Antares IPR”) on the ’231 on July
`
`1, 2014. That case ultimately settled (Antares IPR, Pap. 21 (PTAB April 30,
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`2015)). Frontier Therapeutics LLC subsequently filed an IPR (IPR2016-00649,
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`“Frontier IPR”) on a subset of grounds asserted in the Antares IPR (copied
`
`verbatim). Frontier Therapeutics, LLC v Medac Gesellschaft für Klinische
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`IPR2016-01370
`U.S. Patent No. 8,664,231
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`Attorney Docket No.
`110670-0009-651
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`Spezialpräparate mbH, IPR2016-00649 (“Frontier IPR”). And now, Koios has
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`
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`filed a similar petition, which repeats and rehashes arguments and/or art made in
`
`the previous IPRs.
`
`With respect to Petitioner’s Grounds 1-3, 5 and 6, the same or very similar
`
`grounds were previously asserted in the first two IPRs on the ‘231 patent. Indeed
`
`Grounds 1 and 3 are exactly the same, and 2, 5 and 6 are the same with the
`
`exception of the addition of two secondary references. These secondary references,
`
`Arthur and Moitra, are merely cumulative of the art in the Antares and Frontier
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`IPRs—Petitioner has provided no argument to the contrary. For example,
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`Petitioner relies on Arthur for teaching self-administration; pre-filled syringes; an
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`injection device for a single application; and a pen injector. Pet. 23-25 and 38-44.
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`In the Antares and Frontier IPRs, those claim elements were allegedly satisfied by
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`Insulin Admin. and alleged admissions in the ‘231 patent, upon which Petitioner
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`also relies here.1 Pet 23-25 and 38-44; see also Antares IPR, Pap. 1 at 24-26 and
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`Frontier IPR, Pap. 1 at 30-32. Similarly, Moitra is relied upon for self-
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`administration, subcutaneous administration, and treatment of rheumatic disease.
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`1 Other than to attempt avoidance of § 325(d) by substituting similar references to
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`make the same arguments, it is unclear why PO relies on these additional
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`references.
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`Pet. 23, 40, 41. As noted above, that claim element in the Antares and Frontier
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`IPRs was allegedly satisfied with Insulin Admin. and Brooks, upon which
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`Petitioner also relies. Pet 23-25, 38-41; see also Antares IPR, Pap. 1 at 24-26 and
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`39-41 and Frontier IPR, Pap. 1 at 30-32 and 42-48. Accordingly, Petitioner’s
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`reliance on Arthur and Moitra accomplishes no more than its reliance on Brooks
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`and Insulin Admin., which both Antares and Frontier relied on in the previous IPRs.
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`And, Petitioner relies on Insulin Admin for, e.g., Claims 14 and 15 using the same
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`disclosures as in the previous IPRs. (Pet. 24, 28, 43, 48, 51, 54).
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`The only ground in which Petitioner asserts entirely new art is Ground 4
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`(Wyeth and PDR for Wyeth). The arguments, however, are nevertheless
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`substantially the same. In particular, the disclosure of Wyeth and PDR for Wyeth
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`are virtually identical to PDR for Mexate (Ex.1007 from the Antares and Frontier
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`IPRs) and Hospira (Ex.1009 from the Antares and Frontier IPRs). Indeed, in
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`Ground 5, Petitioner seemingly relies on Wyeth and PDR for Wyeth for precisely
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`the same assertions that PDR for Mexate and Hospira were relied on in the Antares
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`and Frontier IPRs, e.g., MTX to treat inflammatory autoimmune disease, MTX in
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`pharmaceutically acceptable solvents, MTX at a concentration of 50mg/ml, MTX
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`to treat psoriasis, MTX in a storage container, MTX in a vial, and an isotonic
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`sodium chloride solution. Pet. 38-44. The main difference between (1) Wyeth and
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`PDR for Wyeth and (2) PDR for Mexate and Hospira is that Wyeth and PDR for
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`Wyeth contains an esoteric statement about the absorption and side effects of MTX
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`
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`following intramuscular or subcutaneous administration “despite too few published
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`data.” Ex.1021 at 23, 78; Ex.1022 at 7. Neither Wyeth nor PDR for Wyeth,
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`however, instructs the skilled artisan to use their products for subcutaneous
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`administration. Ex.1021 at 4, 58; Ex.1022 at 3. In Ground 5, however, Petitioner
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`relies on Brooks, Moitra, and Arthur, not Wyeth or PDR for Wyeth, to establish
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`subcutaneous administration. Pet. 39-40. And, while Petitioner asserts that its
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`grounds rely on different art, it provides no explanation as to why these grounds
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`are not redundant and cumulative.
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`As noted in PO’s Preliminary Responses in both the Antares IPR (Antares
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`IPR, Pap. 6 at 3) and the Frontier IPR (Frontier IPR, Pap. 9 at 6), it was known in
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`the art that MTX solutions having a concentration of more than 30mg/ml existed
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`and that MTX was used to treat inflammatory autoimmune disease. Petitioner
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`simply points to Wyeth and PDR for Wyeth to provide these exact some points.
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`Petitioner does not explain how or why the new art is not redundant and
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`cumulative to the art used in the Antares and Frontier IPRs to establish these exact
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`same points. Accordingly, the Board should exercise its § 325(d) discretion to
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`deny institution of this petition because, at least, Petitioner’s allegedly “new” art is
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`relied upon to satisfy the same claim elements as the art in the Antares and Frontier
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`IPRs, upon which art Petitioner also relies. See Cont’l Auto. Sys., Inc. v. Wasica
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`Fin. GmbH & Bluearc Fin. AG, IPR2014-01454, Pap. 14 at 5 (PTAB Feb. 13,
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`
`
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`2015) (denying institution when “Petitioner's asserted art and arguments are
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`substantially similar to the art and arguments asserted in [the previous IPR],”
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`which was filed by a different petitioner); see also Intelligent Bio-Sys., Inc. v.
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`Illumina Cambridge Limited, IPR2013-00324, Pap. 19 at 5-7 (PTAB Nov. 21,
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`2013) (denying institution when the teachings in the new art are “substantially the
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`same” as those found in the art relied upon in an earlier petition) and Medtronic,
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`Inc. v. Robert Bosch Healthcare Systems, Inc., IPR2014-00436, Pap. 17 at 12
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`(PTAB June 19, 2014) (denying institution when petition “involve[s] the same, or
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`substantially the same, prior art [] and the same, or substantially the same,
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`arguments previously presented”).
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`Petitioner argues that the Board should not exercise its §325(d) discretion
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`because the Antares IPR was terminated via a private settlement and the Board had
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`not yet decided whether to institute the Frontier IPR when Petitioner filed its IPR.
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`But this is mere gamesmanship attempting to distort the optics here: Petitioner
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`filed its IPR a scant few weeks before it knew the Board would make its Institution
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`Decision in the Frontier IPR. It was plainly trying to take advantage of PO’s
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`detailed preliminary responses in the Antares and Frontier IPRs, the Board’s
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`institution decision in the Antares IPR, while relying on what it knew to be the
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`Board’s schedule so that it could argue as it has (for § 325(d) purposes) that it did
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`not have the advantage of the Frontier institution decision, while at the same time
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`
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`repeating substantially the same prior art and arguments for a third time. Indeed,
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`the Board subsequently instituted the Frontier IPR. The Board has noted that
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`instituting multiple IPRs “would risk encouraging parties to engage in a pattern of
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`duplicative filings that harass patent owners.” MaxLinear, Inc. v Cresta
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`Technology Corporation, IPR2015-00593, Pap. 9 at 5 (PTAB Aug. 14, 2015). To
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`minimize this risk, the Board notes that a more appropriate mechanism is a request
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`for joinder under 35 U.S.C. § 315(c). Id.; see also Cont’ Auto, IPR2014-01454,
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`Pap. 14 at 7 (“Petitioner's concern that [a previous IPR] can settle at any time is
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`unpersuasive. Petitioner had the opportunity, but did not choose to file for joinder
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`in [the previous IPR].”) (internal citation omitted). Much like it did in MaxLinear
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`and Cont’l Auto, the Board should exercise its § 325(d) discretion to deny
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`institution to avoid serial Petitions against PO.
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`Petitioner has relied on the roadmap provided by PO’s preliminary responses
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`in the Antares and Frontier IPRs and the Board’s Institution Decision in the
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`Antares IPR to provide itself an unfair advantage in drafting its IPR Petition. Pet.
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`iv, 17, 18, 38, 57, and 61. The Board has regularly declined to institute a second
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`IPR (and here a third) where, as here, the Petitioner exploits the Board’s decision
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`in a first proceeding as an advisory opinion for a second Petition. See, e.g., NetApp
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`Inc. v. Crossroads Sys., Inc., IPR2015-00772, Pap. 12 at 7 (PTAB Sept. 3, 2015)
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`(“Petitioner’s use of the guidance in the [previous] Institution Decision to improve
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`
`
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`the present Petition weighs in favor of exercising our discretion to deny the
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`Petition.”); CustomPlay,LLC v. ClearPlay, Inc., IPR2014-00783, Pap. 9 at 9
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`(PTAB Nov. 7, 2014) (denial of institution because a previous decision “should not
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`act as a how-to guide” for a subsequent petition); Butamax Adv. Biofuels LLC v.
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`Gevo, Inc., IPR2014-00581, Pap. 8 at 12–13 (PTAB Oct. 14, 2014) (rejecting a
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`petition that used “our prior decision as a roadmap to remedy [the petitioner’s]