`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`MYLAN PHARMACEUTICALS INC.,
`
`Petitioner
`
`v.
`
`BOEHRINGER INGELHEIM INTERNATIONAL GMBH,
`
`Patent Owner
`
`____________________________
`
`IPR2016-01563
`
`U.S. Patent No. 8,673,927
`
`____________________________
`
`
`
`PATENT OWNER'S PRELIMINARY RESPONSE UNDER 37 C.F.R. § 42.107
`
`
`
`
`
`
`
`IPR2016-01563
`U.S. Patent No. 8,673,927
`
`
`
`TABLE OF CONTENTS
`INTRODUCTION ....................................................................................... iv
`I.
`II. TECHNICAL OVERVIEW OF THE INVENTION ................................. 9
`III. MYLAN FALLS SHORT OF ESTABLISHING THAT CLAIMS
`18-24 OF THE ‘927 PATENT ARE ANTICIPATED .............................. 14
`IV. MYLAN FALLS FAR SHORT OF ESTABLISHING THAT THE
`GLUCOPHAGE LABEL IS A PRINTED PUBLICATION ................... 19
`A. A Reference Must Have Been “Publicly Accessible” To be A
`Printed Publication .............................................................................. 20
`
`B.
`
`The Glucophage Label (Exhibit 1004) Is Not A Section 102(b)
`Printed Publication Because There Is No Evidence That It Was
`Publicly Accessible ............................................................................. 21
`
`V. MYLAN FAILS TO ESTABLISH A REASON TO COMBINE
`THE TEACHING OF PRIOR ART REFERENCES OR
`REASONABLE EXPECTATION OF SUCCESS .................................... 24
`A. A Person of Skill in the Art Would Have Had No Reason To
`Select Linagliptin Of All Available DPP-IV Inhibitors ...................... 25
`
`B. A Person of Skill in the Art Would Have Had No Reason To
`Select Metformin as a Combination Partner for Linagliptin............... 28
`
`C. 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 ............................................................................. 34
`
`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 ............................................................................. 39
`
`VI. CONCLUSION ............................................................................................ 40
`
`
`i
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`IPR2016-01563
`U.S. Patent No. 8,673,927
`
`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) ................................ 24
`
`Atofina v. Great Lakes Chem. Corp.,
`441 F.3d 991 (Fed. Cir. 2006) ............................................................................ 17
`
`Coal. for Affordable Drugs IV LLC v. Pharmacyclics, Inc.,
`IPR2015-01076, 2015 WL 7303857 (P.T.A.B. Oct. 19, 2015) .......................... 23
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 24
`
`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc.,
`IPR2014-01162, 2015 WL 5578357 (P.T.A.B. Jan. 29, 2015) .......................... 18
`
`E Ink Corp. v. Research Frontiers Inc.,
`IPR2014-00422, 2014 WL 4078636 (P.T.A.B. Aug. 14, 2014) ......................... 19
`
`Frontier Therapeutics, LLC v. Medac Gesellschaft Fur Klinische
`Spezialpraparate MBH,
`Case IPR2016-00649, Paper 10 (P.T.A.B. September 1, 2016) ....... 21, 22, 23, 24
`
`Janssen Pharm., Inc. v. Watson Labs., Inc.,
`Case No. 08-5103, 2012 WL 3990221 (D.N.J. 2012) ........................................ 35
`
`Lindemann Maschinenfabrik GMBH v. Am. Hoist & Derrick Co.,
`730 F.2d 1452 (Fed. Cir. 1984) .......................................................................... 17
`
`Net MoneyIN, Inc. v. VeriSign, Inc.,
`545 F .3d 1359, 1371 (Fed. Cir. 2008) ............................................................... 16
`
`Northern Telecom, Inc. v. Datapoint Corp.,
`908 F.2d 931 (Fed. Cir. 1990) ............................................................................ 20
`
`OSRAM Sylvania, Inc. v. Am. Induction Techs., Inc.,
`701 F.3d 698 (Fed. Cir. 2012) ............................................................................ 17
`
`ii
`
`
`
`
`
`Sanofi–Synthelabo v. Apotex, Inc.,
`550 F.3d 1075 (Fed. Cir. 2008) .......................................................................... 17
`
`SRI Int’l, Inc. v. Internet Sec. Sys., Inc.,
`511 F.3d 1186 (Fed. Cir. 2008) .......................................................................... 20
`
`Therasense, Inc. v. Becton, Dickinson & Co.,
`593 F.3d 1325 (Fed. Cir. 2010) .......................................................................... 17
`
`Volkswagen Grp. of Am., Inc. v. Emerachem Holdings, LLC,
`IPR2014-01555, 2015 WL 1250947 (P.T.A.B. Mar. 16, 2015) ......................... 19
`
`Statutes
`35 U.S.C. § 102 .................................................................................................... 8, 24
`
`35 U.S.C. §102(b) ........................................................................................ 14, 20, 21
`
`35 U.S.C. §311(b) .............................................................................................. 20, 24
`
`Other Authorities
`MANUAL OF PATENT EXAMINING PROCEDURE § 2131.03 (2015) ............................ 18
`
`
`
`iii
`
`
`
`
`
`Exhibit
`No.
`
`2001
`
`IPR2016-01563
`U.S. Patent No. 8,673,927
`
`INDEX OF EXHIBITS
`
`Description
`
`A Snapshot: Diabetes in the United States, Centers for Disease Control
`and Prevention (2014)
`
`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)
`
`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)
`
`iv
`
`
`
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`Exhibit
`No.
`
`Description
`
`IPR2016-01563
`U.S. Patent No. 8,673,927
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`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)
`
`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)
`
`v
`
`
`
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`Exhibit
`No.
`
`Description
`
`IPR2016-01563
`U.S. Patent No. 8,673,927
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`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
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`I.
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`IPR2016-01563
`U.S. Patent No. 8,673,927
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`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.). DPP-IV inhibitors are one class of anti-
`
`diabetic agents used in the treatment of type 2 diabetes. The inventions of U.S.
`
`Patent No. 8,673,927 concern methods of using a novel DPP-IV inhibitor—
`
`7
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`
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`linagliptin—in combination with metformin, where linagliptin and metformin are
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`U.S. Patent No. 8,673,927
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`administered in a specific dose range.
`
`Mylan Pharmaceuticals Inc. (“Mylan”) requests inter partes review of all of
`
`the claims of the ‘927 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 ‘927
`
`patent. Further, all of Mylan’s patentability challenges rely on U.S. Patent
`
`Publication No. 2004/0097510 A1 (“the ‘510 Publication,” Exhibit 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
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`8
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`
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`at the claimed invention. Finally, Mylan and its expert have failed to show that a
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`U.S. Patent No. 8,673,927
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`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
`
`9
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`
`
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`response to the lowered blood glucose level, the pancreas releases glucagon.
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`IPR2016-01563
`U.S. Patent No. 8,673,927
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`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:
`
`10
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`
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`(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
`
`11
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`
`
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`release of insulin, thereby depressing the level of insulin in the body. Because
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`IPR2016-01563
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`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 methods described in the ‘927 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.)
`
`12
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`
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`Around the priority date of the ‘927 patent, May 4, 2006, American Diabetes
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`Association (“ADA”) and the European Association for the Study of Diabetes
`
`(“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:
`
`
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`13
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`
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` Boehringer discovered and developed linagliptin—a novel, structurally
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`IPR2016-01563
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`
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`distinct DPP-IV inhibitor, which offered various advantages over pre-existing
`
`DPP-IV inhibitors:
`
`
`
`The inventions of the ‘927 patent relate to methods of treating type II
`
`diabetes by administering metformin in combination with linagliptin in a specific
`
`therapeutic dose.
`
`III. GROUND 1: MYLAN FALLS SHORT OF ESTABLISHING THAT
`CLAIMS 18-24 OF THE ‘927 PATENT ARE ANTICIPATED
`Mylan argues in Ground 1 that claims 18-26 of the ‘927 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.
`
`Independent claim 18 of the ‘927 patent recites:
`
`18. A method of treating type II diabetes mellitus
`comprising administering to a patient in need thereof a
`pharmaceutically effective oral amount of 1-[(4-methyl-
`quinazolin-2-yl)-methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-
`(R)-amino-peperidin-1-yl)-xanthine [linagliptin] which is
`
`14
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`IPR2016-01563
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`an oral daily dose of from 2.5 to 10 mg, and a
`pharmaceutically effective amount of metformin.
`
`Claim 19 mirrors claim 18, but is directed to a combination of 5 mg of
`
`linagliptin and a pharmaceutically effective amount of metformin.
`
`Claim 20 recites:
`
`20. A method of treating type 2 diabetes or pre-diabetes
`comprising administering to a patient in need thereof a
`therapeutically effective oral dose of 1-[(4-methyl-
`quinazolin-2-yl)-methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-
`(R)-amino-peperidin-1-yl)-xanthine in combination with
`a therapeutically effective dose of metformin, wherein
`the 1-[(4-methyl-quinazolin-2-yl)-methyl]-3-methyl-7-(2-
`butyn-1-yl)-8-(3-(R)-amino-peperidin-1-yl)-xanthine
`is
`administered in an oral dose of from 0.5 mg to 50 mg.
`
`Claims 21 through 26 depend from claim 20, and are directed to
`
`administering linagliptin in the following dosages:
`
`Claim
`21
`22
`23
`34
`25
`26
`
`Claimed Dosage of Linagliptin
`2.5 mg - 50 mg
`2.5 mg - 10 mg
`0.5 mg, 1 mg, 2.5 mg, or 10 mg
`1 mg, 2.5 mg, or 5 mg.
`2.5 mg or 5 mg;
`5 mg
`
`
`
`Mylan argues that the ‘510 Publication discloses orally administering a
`
`combination of metformin and the DPP-IV inhibitor linagliptin as an effective
`
`combination therapy for treating type II diabetes, and further discloses “each oral
`
`15
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`
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`dose of linagliptin recited,” and therefore anticipates the challenged claims. (Paper
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`IPR2016-01563
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`2, at 16-21). 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
`
`“each oral dose of linagliptin recited,” 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 of any of the hundreds of active agents disclosed, with a
`
`preferred range of 1-400 mg, anticipates the species of narrow linagliptin dosages
`
`to which claims 18-26 of the ‘927 patent are directed. But Mylan has failed to
`
`make a prima facie showing of anticipation and therefore Ground 1 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
`
`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
`
`16
`
`
`
`
`prior art elements themselves be ‘arranged as in the claim’ means that claims
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`IPR2016-01563
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`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
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`genus.” Atofina v. Great Lakes Chem. Corp., 441 F.3d 991, 999 (Fed. Cir. 2006).
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`Rather, “whether a generic disclosure necessarily anticipates everything within the
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`genus . . . depends on the factual aspects of the specific disclosure and the
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`particular products at issue.” Sanofi–Synthelabo v. Apotex, Inc., 550 F.3d 1075,
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`1083 (Fed. Cir. 2008). Of “critical importance” in conducting this analysis is “how
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`one of ordinary skill in the art would understand the relative size of a genus or
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`species in a particular technology.” OSRAM Sylvania, Inc. v. Am. Induction Techs.,
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`Inc., 701 F.3d 698, 706 (Fed. Cir. 2012).
`
`With respect to claims directed to numerical ranges, “[w]hen the prior art
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`discloses a range which touches or overlaps the claimed range, but no specific
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`examples falling within the claimed range are disclosed, a case by case
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`determination must be made as to anticipation. In order to anticipate the claims, the
`
`17
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`
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`claimed subject matter must be disclosed in the reference with ‘sufficient
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`IPR2016-01563
`U.S. Patent No. 8,673,927
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`specificity to constitute an anticipation under the statute.’” MANUAL OF PATENT
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`EXAMINING PROCEDURE § 2131.03 (2015). “[I]t is the Petitioner's burden to
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`demonstrate that the claimed subject matter was disclosed in the prior art with
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`sufficient specificity to constitute an anticipation of the challenged claims.”
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`Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., IPR2014-01162, 2015 WL
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`5578357, at *7 (P.T.A.B. Jan. 29, 2015). Mylan has failed to meet this burden here.
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`Specifically, Mylan only points to the very broad disclosure of Paragraph
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`[0300] of the ‘510 Publication as “disclos[ing] each oral dose of linagliptin recited
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`[in claims 18-26].” (Paper 2, at 21). But the narrowest disclosure of Paragraph
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`[0300] of a preferred dosage range of active substance between 1 and 400 mg is
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`eight times broader than the broadest claimed dosage range of 0.5 mg to 50 mg.
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`Moreover, the disclosure of Paragraph [0300] of the ‘510 Publication pertains to
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`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
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`broad disclosure, a person of skill in the art would immediately envisage
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`administering the compound linagliptin in the dosage amounts claimed by claims
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`18-26 of the ‘927 patent. See Dynamic Drinkware, 2015 WL 5578357, at *7
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`(finding that Petitioner has failed to demonstrate a reasonable likelihood that it
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`would prevail in demonstrating anticipation where, despite overlap between
`
`18
`
`
`
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`dimension ranges disclosed by the prior art and those claimed, “the Petition and
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`IPR2016-01563
`U.S. Patent No. 8,673,927
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`testimony of Mr. Raymond do not provide a sufficient and credible explanation as
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`to why one skilled in the art would immediately envisage forming a lenticular lens
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`having the dimensions that fall within the claim.”); Volkswagen Grp. of Am., Inc. v.
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`Emerachem Holdings, LLC, IPR2014-01555, 2015 WL 1250947, at *17 (P.T.A.B.
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`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
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`Corp. v. Research Frontiers Inc., IPR2014-00422, 2014 WL 4078636, at *9
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`(P.T.A.B. Aug. 14, 2014) (finding that Petitioner has not demonstrated a
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`reasonable likelihood of prevailing on anticipation and noting that “given the
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`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
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`here, Mylan has pointed to no disclosure of the specific dosages of claims 18-26 of
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`the ‘927 patent, and to no disclosure discussing the pertinent dosages of linagliptin
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`specifically as opposed to any other DPP-IV inhibitor. Accordingly, Mylan has
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`failed to meet its burden of showing that the disclosure of the ‘510 Publication is
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`sufficiently specific to be anticipatory.
`
`IV. GROUND 2: MYLAN FALLS FAR SHORT OF ESTABLISHING
`THAT THE GLUCOPHAGE LABEL IS A PRINTED PUBLICATION
`
`19
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`IPR2016-01563
`U.S. Patent No. 8,673,927
`A patent claim can be challenged in inter partes review “only on the basis of
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`
`
`prior art consisting of patents or printed publications.” 35 U.S.C. §311(b). Mylan’s
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`petition relies on the Glucophage Label—Exhibit 1004—but Mylan has not shown
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`that this document was publically accessible before the priority date of the ‘927
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`patent. Thus, Mylan has not shown that the Glucophage Label is a “printed
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`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
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`such document has been disseminated or otherwise made available to the extent
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`that persons interested and ordinarily skilled in the subject matter or art[,]
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`exercising reasonable diligence, can locate it.” Id. Thus, in order to show that a
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`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
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`person of skill would have had access to the reference. See id. at 1196 (“The record
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`. . . 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
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`directory structure to find the Live Traffic paper.”); Northern Telecom, Inc. v.
`
`20
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`IPR2016-01563
`U.S. Patent No. 8,673,927
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`Datapoint Corp., 908 F.2d 931, 936-37 (Fed. Cir. 1990) (disclosure within a
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`limited group of persons and organizations does not make a document “generally
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`available”). Measured under these standards, Ex. 1004 is not a printed publication.
`
`B.
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`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
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`available. This ground must fail. See, e.g., Frontier Therapeutics, LLC v. Medac
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`Gesellschaft Fur Klinische Spezialpraparate MBH, Case IPR2016-00649, Paper 10
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`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®
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`(‘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
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`21-22). However, simply stating that Glucophage was approved in February 2001
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`does not satisfy Mylan’s burden of showing that the document attached at Ex.
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`1004, purporting to be the Glucophage label as-approved, is, in fact, a printed
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`package insert, much less one that was publically available prior to May 4, 2006.
`
`21
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`
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`IPR2016-01563
`U.S. Patent No. 8,673,927
`In Frontier Therapeutics, LLC, the Petitioner attempted to introduce an
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`
`
`alleged “printed package insert . . . which is dated November 22, 2005” as a
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`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
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`and that “[t]he first page of Hospira . . . is insufficient in this regard.” (Id.). This
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`was so, despite the fact that the first page of the document was entitled “Product
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`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
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`the document was publically available even though the last page provided the
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`“Date of First Authorisation/Renewal of Authorisation” and “Date of Revision of
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`the Text.” (IPR2016-00649, Paper 10 at 22; IPR2016-00649, Ex. 1009 at 14). The
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`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.” (IPR2016-00649, Paper 10 at 22).
`
`Likewise here, the docum