UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner
`
`v.
`
`BOEHRINGER INGELHEIM INTERNATIONAL GMBH,
`
`Patent Owner
`
`____________________________
`
`IPR2016-01566
`
`U.S. Patent No. 9,173,859
`
`____________________________
`
`
`
`PATENT OWNER'S PRELIMINARY RESPONSE UNDER 37 C.F.R. § 42.107
`
`
`
`
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner
`
`v.
`
`BOEHRINGER INGELHEIM INTERNATIONAL GMBH,
`
`Patent Owner
`
`____________________________
`
`IPR2016-01566
`
`U.S. Patent No. 9,173,859
`
`____________________________
`
`
`
`PATENT OWNER'S PRELIMINARY RESPONSE UNDER 37 C.F.R. § 42.107
`
`
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`INTRODUCTION ......................................................................................... 1
`
`TECHNICAL OVERVIEW OF THE INVENTION ................................. 3
`
`III. MYLAN FALLS SHORT OF ESTABLISHING THAT CLAIMS
`14 AND 20 OF THE ‘859 PATENT ARE ANTICIPATED ...................... 8
`
`IV. MYLAN FALLS FAR SHORT OF ESTABLISHING THAT THE
`GLUCOPHAGE LABEL IS A PRINTED PUBLICATION ................... 13
`A. A Reference Must Have Been “Publicly Accessible” To be A
`Printed Publication .............................................................................. 13
`
`B.
`
`The Glucophage Label (Exhibit 1004) Is Not A Section 102(b)
`Printed Publication Because There Is No Evidence That It Was
`Publicly Accessible ............................................................................. 14
`
`V. MYLAN FAILS TO ESTABLISH A REASON TO COMBINE
`THE TEACHING OF PRIOR ART REFERENCES OR
`REASONABLE EXPECTATION OF SUCCESS .................................... 17
`A. A Person of Skill in the Art Would Have Had No Reason To
`Select Linagliptin Of All Available DPP-IV Inhibitors ...................... 18
`
`B.
`
`C.
`
`A Person of Skill in the Art Would Have Had No Reason To
`Select Metformin as a Combination Partner for Linagliptin............... 21
`
`A Person of Skill In The Art Would Have Had No Reason To
`Modify the Teachings of the Cited Art to Arrive at the Claimed
`Linagliptin Dosages ............................................................................. 27
`
`D. A Person of Skill In The Art Would Have Had No Reason To
`Modify the Teachings of the Cited Art to Arrive at the Claimed
`Metformin Dosages ............................................................................. 32
`
`VI. CONCLUSION ............................................................................................ 33
`
`
`i
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Apple Inc. v. DSS Tech. Mgmt., Inc.,
`Case IPR2015-00369, Paper 14 (P.T.A.B. Aug. 12, 2015) ................................ 17
`
`Atofina v. Great Lakes Chem. Corp.,
`441 F.3d 991 (Fed. Cir. 2006) ............................................................................ 10
`
`Coal. for Affordable Drugs IV LLC v. Pharmacyclics, Inc.,
`IPR2015-01076, 2015 WL 7303857 (P.T.A.B. Oct. 19, 2015) .......................... 16
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 18
`
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`IPR2014-01162, 2015 WL 5578357 (P.T.A.B. Jan. 29, 2015) .................... 11, 12
`
`E Ink Corp. v. Research Frontiers Inc.,
`IPR2014-00422, 2014 WL 4078636 (P.T.A.B. Aug. 14, 2014) ......................... 12
`
`Frontier Therapeutics, LLC v. Medac Gesellschaft Fur Klinische
`Spezialpraparate MBH,
`Case IPR2016-00649, Paper 10 (P.T.A.B. September 1, 2016) ....... 14, 15, 16, 17
`
`Janssen Pharm., Inc. v. Watson Labs., Inc.,
`Case No. 08-5103, 2012 WL 3990221 (D.N.J. 2012) ........................................ 28
`
`Lindemann Maschinenfabrik GMBH v. Am. Hoist & Derrick Co.,
`730 F.2d 1452 (Fed. Cir. 1984) .......................................................................... 10
`
`Net MoneyIN, Inc. v. VeriSign, Inc.,
`545 F .3d 1359, 1371 (Fed. Cir. 2008) ............................................................... 10
`
`Northern Telecom, Inc. v. Datapoint Corp.,
`908 F.2d 931 (Fed. Cir. 1990) ............................................................................ 14
`
`OSRAM Sylvania, Inc. v. Am. Induction Techs., Inc.,
`701 F.3d 698 (Fed. Cir. 2012) ............................................................................ 10
`
`ii
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`Sanofi–Synthelabo v. Apotex, Inc.,
`550 F.3d 1075 (Fed. Cir. 2008) .......................................................................... 10
`
`SRI Int’l, Inc. v. Internet Sec. Sys., Inc.,
`511 F.3d 1186 (Fed. Cir. 2008) .................................................................... 13, 14
`
`Therasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1325 (Fed. Cir. 2010) .......................................................................... 10
`
`Volkswagen Grp. of Am., Inc. v. Emerachem Holdings, LLC,
`IPR2014-01555, 2015 WL 1250947 (P.T.A.B. Mar. 16, 2015) ......................... 12
`
`Statutes
`35 U.S.C. § 102 .................................................................................................... 2, 17
`
`35 U.S.C. §102(b) .......................................................................................... 8, 13, 14
`
`35 U.S.C. §311(b) .............................................................................................. 13, 17
`
`Other Authorities
`MANUAL OF PATENT EXAMINING PROCEDURE § 2131.03 (2015) ............................ 11
`
`
`
`
`
`
`
`
`iii
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`
`INDEX OF EXHIBITS
`
`Description
`
`A Snapshot: Diabetes in the United States, Centers for Disease Control
`and Prevention (2014)
`
`Exhibit
`No.
`
`2001
`
`2002 Nathan, D.M., et al., Management of Hyperglycemia in Type 2 Diabetes:
`A Consensus Algorithm for the Initiation and Adjustment of Therapy, A
`Consensus Statement From the American Diabetes Association and the
`European Association for the Study of Diabetes, Diabetes Care, 29(8):
`1963-1972, (2006)
`
`2003
`
`2004
`
`Screening for Type 2 Diabetes – Report of a World Health Organization
`and International Diabetes Federation Meeting, World Health
`Organization, Geneva, Switzerland (2003)
`
`Szablewski, L., Glucose Homeostasis – Mechanism and Defects,
`Diabetes - Damages and Treatments, Prof. Everlon Rigobelo (Ed.),
`ISBN: 978-953-307-652-2, In Tech, 227-256 (2011). Available at:
`http://www.intechopen.com/books/diabetes-damages-and-
`treatments/glucose-homeostasis-mechanism-and-defects
`
`2005 Boron, W.E. and Boulpaep, E.L., Medical Physiology – A Cellular and
`Molecular Approach, Elsevier Science: Pennsylvania, 1066-1085 (2003)
`
`2006 Aronoff, S.L., et al., Glucose Metabolism and Regulation: Beyond
`Insulin and Glucagon, Diabetes Spectrum, 17(3):183-190 (2004)
`
`2007 Green, B.D., et al., Inhibition of Dipeptidyl Peptidase IV Activity as a
`Therapy of Type 2 Diabetes, Expert Opin. Emerging Drugs, 11(3):525-
`539 (2006)
`
`
`
`
`iv
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`Exhibit
`No.
`
`Description
`
`2008 Nathan, D.M., et al., Medical Management of Hyperglycemia in Type 2
`Diabetes: A Consensus Algorithm for the Initiation and Adjustment of
`Therapy, A Consensus Statement From the American Diabetes
`Association and the European Association for the Study of Diabetes,
`Diabetes Care, 32(1):193-203 (2009)
`
`2009 Kuhn, B., et al., Molecular Recognition of Ligands in Dipeptidyl
`Peptidase IV, Current Topics in Medicinal Chemistry, 7:609-619 (2007)
`
`2010
`
`2011
`
`Feng, J., et al., Discovery of Alogliptin: A Potent, Selective,
`Bioavailable, and Efficacious Inhibitor of Dipeptidyl Peptidase IV, J.
`Med. Chem., 50:2297-2300 (2007)
`
`Szczepankiewicz, B.G., and Kurukulasuriya, R., Aromatic Heterocycle-
`Based DPP-IV Inhibitors: Xanthines and Related Structural Types,
`Current Topics in Medicinal Chemistry, 7:569-578 (2007)
`
`2012 Weber, A.E., and Thornberry, N., Case History: Januvia™ (Sitagliptin),
`a Selective Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type
`2 Diabetes, Annual Reports in Medicinal Chemistry, 42:95-109 (2007)
`
`2013 U.S. Patent No. 7,317,109, Issued to Campbell et al.
`
`2014 ClinicalTrials.gov Archive, NCT00103857: An Investigational Drug
`Study in Patients with Type 2 Diabetes Mellitus (2006). Available at:
`https://clinicaltrials.gov/archive/NCT00103857/2006_02_22
`
`2015 ClinicalTrials.gov Archive, NCT01196546: Efficacy and Safety of
`Combination Therapy of Vildagliptin/Metformin in Patients in Type 2
`Diabetes Mellitus (T2DM) (2010). Available at:
`https://clinicaltrials.gov/archive/NCT01196546/2010_09_07
`
`2016
`
`Lindsay, J.R., et al., Inhibition of Dipeptidyl Peptidase IV Activity by
`Oral Metformin in Type 2 Diabetes, Diabetic Medicine, 22:654-657
`(2004)
`
`
`
`
`v
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`Exhibit
`No.
`
`Description
`
`2017 Ortiz de Montellano, P., et al., Self-Catalyzed Inactivation of Hepatic
`Cytochrome P-450 by Ethynyl Substrates, The Journal of Biological
`Chemistry 255(12):5578–5585 (1980)
`
`2018 Kunze, K., et al., The Cytochrome P-450 Active Site, The Journal of
`Biological Chemistry 258(7):4202–4207 (1983)
`
`2019 Ortiz de Montellano, P., et al., Branchpoint for Heme Alkylation and
`Metabolite Formation in the Oxidation of Arylacetylenes by Cytochrome
`P-450, The Journal of Biological Chemistry 260(6):3330–3386 (1985)
`
`2020 Brunton, L.L., et al., Goodman & Gilman’s The Pharmacological Basis
`of Therapeutics, 12th Ed., 72-87 (2011)
`
`2021 U.S. Food and Drug Administration, FDA Drug Approval Process.
`Available at
`http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/UC
`M284393.pdf
`
`2022 Manzi, S., et al., Drug Interactions - A Review, Clinical Pediatric
`Emergency Medicine, 6:93-102 (2005)
`
`
`
`
`vi
`
`
`
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`I.
`
`INTRODUCTION
`Diabetes is a progressive metabolic disease affecting more than 29 million
`
`Americans. Additionally, another 86 million adults have pre-diabetes—a blood
`
`glucose level that is elevated above normal level but is not high enough to be
`
`classified as type 2 diabetes. About a third of the adults with pre-diabetes will
`
`develop type 2 diabetes in the next few years. (Ex. 2001, A Snapshot: Diabetes in
`
`the United States, Centers for Disease Control and Prevention (2014)).
`
`Diabetes can be managed through physical activity, diet, and appropriate use
`
`of oral medications to lower blood sugar levels. Ex. 2002, Nathan, D.M., et al.,
`
`Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the
`
`Initiation and Adjustment of Therapy, A Consensus Statement From the American
`
`Diabetes Association and the European Association for the Study of Diabetes,
`
`Diabetes Care, 29(8): 1963-1972, (2006) at 1964-65. There are numerous anti-
`
`diabetic agents that can be used in the treatment of type 2 diabetes. One example of
`
`a commonly used oral anti-diabetic agent is metformin. (Id.). When treatment with
`
`a single oral anti-diabetic agent becomes insufficient, other anti-diabetic agents are
`
`added to the treatment regimen. (Id.). The inventions of U.S. Patent No. 9,173,859
`
`concern tablet formulations of a novel DPP-IV inhibitor—linagliptin, as well as
`
`methods of using linagliptin in combination with metformin, where linagliptin is
`
`administered in a specific dose range.
`
`1
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`Mylan Pharmaceuticals Inc. (“Mylan”) requests inter partes review of all of
`
`the claims of the ‘859 patent. For the reasons set forth below, the Board should
`
`deny Mylan’s request.
`
`As an initial matter, Mylan has failed to present any evidence that some of
`
`the publications on which it relies are prior art “printed publications” as required
`
`by 35 U.S.C. § 102. Moreover, Mylan neglects that the references it cites, even if
`
`assumed to be prior art printed publications, when considered individually or in
`
`combination fail to disclose the specific dosage of linagliptin claimed by the ‘859
`
`patent. Further, all of Mylan’s patentability challenges rely on U.S. Patent
`
`Publication No. 2004/0097510 A1 (“the ‘510 Publication, Ex. 1003), which
`
`discloses several hundred DPP-IV inhibitors, including, linagliptin, as well as
`
`references that discuss other DPP-IV inhibitors. However, Mylan and its expert,
`
`Dr. Davidson, have failed to point to any reason that a skilled artisan (1) would
`
`have been motivated to select linagliptin from the numerous DPP-IV inhibitors
`
`available in the art generally and the hundreds disclosed by the ‘510 Publication
`
`specifically; (2) would have combined the teachings of the ‘510 Publication with
`
`the other cited references addressing unrelated and structurally distinct DPP-IV
`
`inhibitors; and (3) would have modified those combinations of teachings to arrive
`
`at the claimed invention. Finally, Mylan and its expert have failed to show that a
`
`
`
`
`2
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`person of skill in the art would have had a reasonable expectation of success in
`
`modifying the teachings of the prior art to arrive at the claimed invention.
`
`Mylan’s Petition does not establish a reasonable likelihood of success and
`
`should be denied.
`
`II. TECHNICAL OVERVIEW OF THE INVENTION
`Diabetes mellitus is a metabolic disorder characterized by elevated blood
`
`glucose levels resulting from defects in insulin secretion, insulin resistance, or
`
`both. See Ex. 2003, Screening for Type 2 Diabetes – Report of a World Health
`
`Organization and International Diabetes Federation Meeting, World Health
`
`Organization, Geneva, Switzerland (2003) at 1. Glucose is the primary source of
`
`energy for the cells and must be readily available for cells to function normally.
`
`Therefore, the body tightly regulates blood glucose levels to ensure that the level
`
`of glucose in the blood is high enough for energy production, but is not so high as
`
`to reach a toxic level. This regulatory process is known as glucose homeostasis.
`
`(Ex. 2004, Szablewski, L., Glucose Homeostasis – Mechanism and Defects,
`
`Diabetes - Damages and Treatments, Prof. Everlon Rigobelo (Ed.), ISBN: 978-
`
`953-307-652-2, In Tech, 227-256 (2011) at 227).
`
`When the blood glucose level decreases below a certain threshold—during
`
`physical activity, for example—a process known as glycogenolysis occurs. In
`
`response to the lowered blood glucose level, the pancreas releases glucagon.
`
`
`
`
`3
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`Glucagon is a peptide hormone that raises the concentration of glucose in the
`
`bloodstream, and hence, its effect is opposite to that of insulin, which lowers the
`
`glucose concentration. As a result, when glycogenolysis occurs, blood glucose
`
`levels increase. (Ex. 2005, Boron, W.E. and Boulpaep, E.L., Medical Physiology –
`
`A Cellular and Molecular Approach, Elsevier Science: Pennsylvania, 1066-1085
`
`(2003) at 1067-68, 1076).
`
`On the other hand, when the blood glucose level is high—after a meal, for
`
`instance—the pancreas releases insulin, promoting the creation and storage of
`
`glycogen polysaccharides in the muscles and liver. (Id. at 1076-77) This process is
`
`known as glycogenesis. Glycogenesis usually begins when the blood glucose level
`
`reaches an upper threshold in the gastrointestinal tract. (Id.). High concentration of
`
`glucose causes nearby cells to secrete incretin hormones, such as glucagon-like
`
`peptide (GLP-1) and the glucose-dependent insulotropic polypeptide (GIP). (Id. at
`
`1073). Once in circulation, GLP-1 and GIP cause the pancreas to increase insulin
`
`secretion and decrease glucagon secretion, leading to a decreased level of glucose
`
`in circulation. (Id.)
`
`Glucose regulation is a complex process involving a delicate balance
`
`between the function of many organs and hormones. A simplified schematic
`
`representation is presented below:
`
`
`
`
`4
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`
`(Ex. 2006, Aronoff, S.L., et al., Glucose Metabolism and Regulation: Beyond
`
`Insulin and Glucagon, Diabetes Spectrum, 17(3):183-190 (2004) at 186).
`
`Dipeptidyl peptidase IV (DPP-IV) enzymes are key players in the
`
`glycogenesis process through their interaction with GLP-1 and GIP. As discussed,
`
`GLP-1 and GIP, which increase insulin secretion and decrease glucagon secretion,
`
`are secreted during glycogenesis leading to decreased levels of glucose in
`
`circulation. DPP-IV enzymes, however, rapidly inactivate GLP-1 and GIP
`
`hormones. In essence, DPP-IV enzymes degrade the hormones responsible for the
`
`release of insulin, thereby depressing the level of insulin in the body. Because
`
`
`
`
`5
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`DPP-IV enzymes are expressed in many tissues and are also abundantly present in
`
`plasma, under natural conditions, GLP-1 and GIP are quickly deactivated, with
`
`half-lives on the order of minutes. (Ex. 2007, Green, B.D., et al., Inhibition of
`
`Dipeptidyl Peptidase IV Activity as a Therapy of Type 2 Diabetes, Expert Opin.
`
`Emerging Drugs, 11(3):525-539 (2006) at 525-26).
`
`The formulations and methods described in the ‘859 patent alter the above-
`
`described natural process through introducing a foreign compound to the body.
`
`DPP-IV inhibitors are synthetic compounds that bind to DPP-IV enzymes, thereby
`
`inactivating them. The inhibition of DPP-IV enzymes through introducing DPP-IV
`
`inhibitors artificially lengthen the half-lives of GLP-1 and GIP hormones. (Ex.
`
`2008, Nathan, D.M., et al., Medical Management of Hyperglycemia in Type 2
`
`Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy, A
`
`Consensus Statement From the American Diabetes Association and the European
`
`Association for the Study of Diabetes, Diabetes Care, 32(1):193-203, at 199). The
`
`resulting increased levels of GLP-1 and GIP hormones causes the pancreas to
`
`increase insulin secretion and decrease glucagon secretion, in turn leading to a
`
`decreased level of glucose in circulation. (Id.) The end result of this series of
`
`reactions is that the body has a lower blood glucose level. (Id.)
`
`Around the priority date of the ‘859 patent, May 4, 2006, American Diabetes
`
`Association (“ADA”) and the European Association for the Study of Diabetes
`
`
`
`
`6
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`(“EASD”) published a consensus algorithm outlining the treatment plan of type 2
`
`diabetes accepted in the field at the time. (Ex. 2002, at 1964-65). According to this
`
`ADA algorithm, type 2 diabetes was initially treated with lifestyle interventions
`
`(diet and exercise), followed by the addition of antidiabetic agents such as, among
`
`others, metformin, insulin, sulfonylureas, and thiazolidinediones (TZDs). Notably,
`
`although some DPP-IV inhibitors were known at the time, they were not
`
`commonly accepted for the treatment of diabetes and were not a part of the ADA
`
`Consensus Algorithm. In point of fact, DPP-IV inhibitors were not added to the
`
`algorithm until December 2008, with only one DPP-IV inhibitor, sitagliptin,
`
`having been approved in the US and two, sitagliptin and vildagliptin, having been
`
`approved in Europe at that time. (Ex. 2008, at 199). Importantly, the DPP-IV
`
`inhibitors available at the time were unrelated and structurally distinct:
`
`
` Boehringer discovered and developed linagliptin—a novel, structurally
`
`distinct DPP-IV inhibitor, which offered various advantages over pre-existing
`
`DPP-IV inhibitors:
`
`
`
`
`7
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`
`
`The inventions of the ‘859 patent relate to linagliptin formulations and
`
`methods of treating type II diabetes by administering metformin in combination
`
`with linagliptin in a specific therapeutic dose.
`
`III. GROUND 2: MYLAN FALLS SHORT OF ESTABLISHING THAT
`CLAIMS 14 AND 20 OF THE ‘859 PATENT ARE ANTICIPATED
`Mylan argues in Ground 2 that claims 14 and 20 of the ‘859 patent are
`
`anticipated under 35 U.S.C. §102(b) by the ‘510 Publication. But Mylan has failed
`
`to show that every element of the challenged claims is taught by the ‘510
`
`Publication. Mylan’s challenge must therefore fail.
`
`Claim 14 of the ‘859 patent recites:
`
`14. An oral tablet formulation comprising 1-[(4-methyl-
`quinazolin-2-yl)-methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-
`®-amino-peperidin-1-yl)-xanthine
`[linagliptin]
`in an
`amount of 2.5 mg or 5 mg optionally in combination with
`metformin, and a pharmaceutically acceptable carrier or
`diluent.
`
`Claim 20 recites:
`
`20. A method of treating type 2 diabetes comprising
`administering to a patient in need thereof the oral table to
`f claim 14, wherein the daily oral amount of 1-[(4-
`methyl-quinazolin-2-yl)-methyl]-3-methyl-7-(2-butyn-1-
`
`
`
`
`8
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`yl)-8-(3-®-amino-peperidin-1-yl)-xanthine administered
`to said patient is 5 mg.
`
`Mylan argues that the ‘510 Publication discloses linagliptin in an amount of
`
`2.5 mg or 5 mg optionally in combination with metformin. orally administering a
`
`combination of metformin (Paper 2, at 30). Mylan is wrong.
`
`Mylan points to paragraph [0300] of the ‘510 Publication as disclosing the
`
`claimed dosages of linagliptin. Paragraph [0300], however, far from disclosing
`
`linagliptin in an amount of 2.5 mg or 5 mg, only notes that “[t]he dosage required
`
`to achieve such an effect is expediently, by intravenous route, 1 to 100 mg,
`
`preferably 1 to 30 mg, and by oral route 1 to 1000 mg, preferably 1 to 100 mg, in
`
`each case 1 to 4 times a day.” The disclosure of Paragraph [0300] furthermore,
`
`pertains to “the compounds of formula 1—some several hundred compounds—and
`
`says nothing about linagliptin specifically. In essence, Mylan argues that the
`
`disclosure of the genus of 1 to 4000 mg per day of any of the hundreds of active
`
`agents disclosed, with a preferred range of 1 to 400 mg per day anticipates the
`
`species of narrow linagliptin dosages to which claims 14 and 20 of the ‘859 patent
`
`are directed. But Mylan has failed to make a prima facie showing of anticipation
`
`and therefore Ground 2 must fail.
`
`To show anticipation, Mylan must show that the prior art discloses every
`
`element of the claims. “[I]t is not enough that the prior art reference discloses part
`
`of the claimed invention, which an ordinary artisan might supplement to make the
`
`
`
`
`9
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`whole, or that it includes multiple, distinct teachings that the artisan might
`
`somehow combine to achieve the claimed invention.” Net MoneyIN, Inc. v.
`
`VeriSign, Inc., 545 F .3d 1359, 1371 (Fed. Cir. 2008). “The requirement that the
`
`prior art elements themselves be ‘arranged as in the claim’ means that claims
`
`cannot be ‘treated . . . as mere catalogs of separate parts, in disregard of the part-to-
`
`part relationships set forth in the claims and that give the claims their meaning.’”
`
`Therasense, Inc. v. Becton, Dickinson & Co., 593 F.3d 1325, 1332 (Fed. Cir. 2010)
`
`(quoting Lindemann Maschinenfabrik GMBH v. Am. Hoist & Derrick Co., 730
`
`F.2d 1452, 1459 (Fed. Cir. 1984)).
`
`Furthermore, “[i]t is well established that the disclosure of a genus in the
`
`prior art is not necessarily a disclosure of every species that is a member of that
`
`genus.” Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir. 2006).
`
`Rather, “whether a generic disclosure necessarily anticipates everything within the
`
`genus . . . depends on the factual aspects of the specific disclosure and the
`
`particular products at issue.” Sanofi–Synthelabo v. Apotex, Inc., 550 F.3d 1075,
`
`1083 (Fed. Cir. 2008). Of “critical importance” in conducting this analysis is “how
`
`one of ordinary skill in the art would understand the relative size of a genus or
`
`species in a particular technology.” OSRAM Sylvania, Inc. v. Am. Induction Techs.,
`
`Inc., 701 F.3d 698, 706 (Fed. Cir. 2012).
`
`
`
`
`10
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`With respect to claims directed to numerical ranges, “[w]hen the prior art
`
`discloses a range which touches or overlaps the claimed range, but no specific
`
`examples falling within the claimed range are disclosed, a case by case
`
`determination must be made as to anticipation. In order to anticipate the claims, the
`
`claimed subject matter must be disclosed in the reference with ‘sufficient
`
`specificity to constitute an anticipation under the statute.’” MANUAL OF PATENT
`
`EXAMINING PROCEDURE § 2131.03 (2015). “[I]t is the Petitioner's burden to
`
`demonstrate that the claimed subject matter was disclosed in the prior art with
`
`sufficient specificity to constitute an anticipation of the challenged claims.”
`
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., IPR2014-01162, 2015 WL
`
`5578357, at *7 (P.T.A.B. Jan. 29, 2015). Mylan has failed to meet this burden here.
`
`Specifically, Mylan only points to the very broad disclosure of Paragraph
`
`[0300] of the ‘510 Publication as disclosing 2.5 mg and 5 mg doses of linagliptin.
`
`But the narrowest disclosure of the Paragraph [0300] of a preferred dosage range
`
`of active substance between 1 and 400 mg is eighty times broader than the highest
`
`claimed dosage level of 5 mg. Moreover, the disclosure of Paragraph [0300] of the
`
`‘510 Publication pertains to the hundreds of DPP-IV inhibitors disclosed in the
`
`publication and says nothing about linagliptin. Mylan has not provided any
`
`explanation as to why, based on this broad disclosure, a person of skill in the art
`
`would immediately envisage administering the compound linagliptin in the dosage
`
`
`
`
`11
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`amounts claimed by claims 14 and 20 of the ‘859 patent. See Dynamic Drinkware,
`
`2015 WL 5578357, at *7 (finding that Petitioner has failed to demonstrate a
`
`reasonable likelihood that it would prevail in demonstrating anticipation where,
`
`despite overlap between dimension ranges disclosed by the prior art and those
`
`claimed, “the Petition and testimony of Mr. Raymond do not provide a sufficient
`
`and credible explanation as to why one skilled in the art would immediately
`
`envisage forming a lenticular lens having the dimensions that fall within the
`
`claim.”); Volkswagen Grp. of Am., Inc. v. Emerachem Holdings, LLC, IPR2014-
`
`01555, 2015 WL 1250947, at *17 (P.T.A.B. Mar. 16, 2015) (finding that prior art
`
`range of 25-700 m2/g is not an anticipatory description of the claimed ranges of 50-
`
`350, 100-325, and 200-300 m2/g); E Ink Corp. v. Research Frontiers Inc.,
`
`IPR2014-00422, 2014 WL 4078636, at *9 (P.T.A.B. Aug. 14, 2014) (finding that
`
`Petitioner has not demonstrated a reasonable likelihood of prevailing on
`
`anticipation and noting that “given the difference between the claimed range and
`
`the range in the Saxe (which is larger and has no lower limit), we conclude that
`
`Saxe does not describe the claimed range with sufficient specificity to anticipate
`
`this limitation of the claim.”). Likewise here, Mylan has pointed to no disclosure of
`
`the specific dosages claimed by claims 14 and 20 of the ‘859 patent, and to no
`
`disclosure discussing the pertinent dosages of linagliptin specifically, as opposed to
`
`any other DPP-IV inhibitor. Accordingly, Mylan has failed to meet its burden of
`
`
`
`
`12
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`showing that the prior art disclosure of the ‘510 Publication is sufficiently specific
`
`to be anticipatory.
`
`IV. GROUND 1: MYLAN FALLS FAR SHORT OF ESTABLISHING
`THAT THE GLUCOPHAGE LABEL IS A PRINTED PUBLICATION
`A patent claim can be challenged in inter partes review “only on the basis of
`
`prior art consisting of patents or printed publications.” 35 U.S.C. §311(b). Mylan’s
`
`petition relies on the Glucophage Label—Exhibit 1004—but Mylan has not shown
`
`that this document was publically accessible before the priority date of the ‘859
`
`patent. Thus, Mylan has not shown that the Glucophage Label is a “printed
`
`publication.” The Board should not institute trial on this reference
`
`A. A Reference Must Have Been “Publicly Accessible” To be A
`Printed Publication
`“‘[P]ublic accessibility’ has been called the touchstone in determining
`
`whether a reference constitutes a ‘printed publication’ bar under 35 U.S.C.
`
`§ 102(b).” SRI Int’l, Inc. v. Internet Sec. Sys., Inc., 511 F.3d 1186, 1194 (Fed. Cir.
`
`2008). “A given reference is ‘publicly accessible’ upon a satisfactory showing that
`
`such document has been disseminated or otherwise made available to the extent
`
`that persons interested and ordinarily skilled in the subject matter or art[,]
`
`exercising reasonable diligence, can locate it.” Id. Thus, in order to show that a
`
`reference qualifies as a printed publication, a Petitioner must show that (1) person
`
`of skill could have located the reference; and (2) once the reference was located, a
`
`
`
`
`13
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`person of skill would have had access to the reference. See id. at 1196 (“The record
`
`. . . does not show that an anonymous user skilled in the art in 1997 would have
`
`gained access to the FTP server and would have freely navigated through the
`
`directory structure to find the Live Traffic paper.”); Northern Telecom, Inc. v.
`
`Datapoint Corp., 908 F.2d 931, 936-37 (Fed. Cir. 1990) (disclosure within a
`
`limited group of persons and organizations does not make a document “generally
`
`available”). Measured under these standards, Ex. 1004 is not a printed publication.
`
`B.
`
`The Glucophage Label (Exhibit 1004) Is Not A Section 102(b)
`Printed Publication Because There Is No Evidence That It Was
`Publicly Accessible
`Mylan provides no evidence that the Glucophage Label (Ex. 1004), on
`
`which it relies in Ground 2, is a prior art, printed publication. Specifically, Mylan
`
`offers no evidence when (or even if) the document was published and publicly
`
`available. This ground must fail. See, e.g., Frontier Therapeutics, LLC v. Medac
`
`Gesellschaft Fur Klinische Spezialpraparate MBH, Case IPR2016-00649, Paper 10
`
`at 22 (P.T.A.B. September 1, 2016) (finding that an alleged “printed package
`
`insert” is not a printed publication).
`
`Mylan simply states that “[t]he Final Printed Label for Glucophage®
`
`(‘Glucophage Labe’) was approved and published by the U.S. Food and Drug
`
`Administration (FDA”) for treating type II diabetes in February 2001.” (Paper 2 at
`
`21-22). However, simply stating that Glucophage was approved in February 2001
`
`
`
`
`14
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`does not satisfy Mylan’s burden of showing that the document attached at Ex.
`
`1004, purporting to be the Glucophage label as-approved, is, in fact, a printed
`
`package insert, much less one that was publically available prior to May 4, 2006.
`
`In Frontier Therapeutics, LLC, the Petitioner attempted to introduce an
`
`alleged “printed package insert . . . which is dated November 22, 2005” as a
`
`printed publication invalidating the challenged claims. (IPR2016-00649, Paper 10
`
`at 22). The Board, however, found that the Petitioner had not presented sufficient
`
`evidence indicating that the exhibit presented was, in fact, a printed package label
`
`and that “[t]he first page of Hospira . . . is insufficient in this regard.” (Id.). This
`
`was so, despite the fact that the first page of the document was entitled “Product
`
`Summary.” (IPR2016-00649, Ex. 1009 at 1). Similarly, the Board noted that “dates
`
`presented on the last page of that document . . . are inadequate” to establish when
`
`the document was publically available even though the last page provided the
`
`“Date of First Authorisation/Renewal of Authorisation” and “Date of Revision of
`
`the Text.” (Id. Paper 10 at 22; id. Ex. 1009 at 14). The Board further rejected
`
`Petitioner’s expert declaration asserting that the reference in question was prior art,
`
`noting that it presented “conclusory assertions without citing sufficient evidence in
`
`support.” (Id. Paper 10 at 22).
`
`Likewise here, the document contains no source identifying information nor
`
`does it contain any information identifying when it became publically available.
`
`
`
`
`15
`
`
`
`IPR2016-01566
`U.S. Patent No. 9,173,859
`Even assuming that the document is the label that the FDA approved, Mylan has
`
`provided no evidence that it became publically available at the same time as
`
`approval. The only date on the document appears on the final page, noting that the
`
`document was “revised date of January 2001.” But as the Board recognized in
`
`Frontier Therapeutics, a revision date is not synonymous with a publication date.
`
`(IPR2016-00649, Paper 10 at 22). By its plain terms, that date only indicates when
`
`the document was revised, and has no bearing on whether and when it became
`
`publically available.
`
`Mylan’s expert declaration likewise only provides conclusory allegations
`
`that the Glucophage Label is prior art,
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
