Trials@uspto.gov
`571-272-7822
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` Paper No. 15
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`Entered: February 3, 2017
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`BOEHRINGER INGELHEIM INTERNATIONAL GMBH,
`Patent Owner.
`____________
`
`Case IPR2016-01566
`Patent 9,173,859 B2
`____________
`
`
`Before TONI R. SCHEINER, BRIAN P.MURPHY, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
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`571-272-7822
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` Paper No. 15
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`Entered: February 3, 2017
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`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`BOEHRINGER INGELHEIM INTERNATIONAL GMBH,
`Patent Owner.
`____________
`
`Case IPR2016-01566
`Patent 9,173,859 B2
`____________
`
`
`Before TONI R. SCHEINER, BRIAN P.MURPHY, and
`ZHENYU YANG, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
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`
`
`
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`IPR2016-01566
`Patent 9,173,859 B2
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`
`INTRODUCTION
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`Mylan Pharmaceuticals Inc. (“Petitioner”) filed a Petition for an inter
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`partes review of claims 1–22 of U.S. Patent No. 9,173,859 B2 (“the ’859
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`patent,” Ex. 1001). Paper 2 (“Pet.”). Boehringer Ingelheim International
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`GmbH (“Patent Owner”) timely filed a Preliminary Response. Paper 9
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`(“Prelim. Resp.”). We review the Petition under 35 U.S.C. § 314.
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`Based on this record, we determine Petitioner has not established a
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`reasonable likelihood that it would prevail in showing the unpatentability of
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`at least one challenged claim. Therefore, we decline to institute an inter
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`partes review of claims 1–22 of the ’859 patent. See 35 U.S.C. § 314(a).
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`Related Proceedings
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`Patent Owner informs us that it has asserted the ’859 patent against
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`Petitioner in Boehringer Ingelheim Pharm. Inc. v. Mylan Pharm. Inc., Case
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`No. 1:15-cv-00145 (N.D.W.Va.), which is currently inactive. Paper 6, 3.
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`According to the parties, the ’859 patent is the subject of several other
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`cases in district courts, which have been consolidated into Boehringer
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`Ingelheim Pharm. Inc. v. HEC Pharm Group, Case No. 3:15-cv-05982
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`(D.N.J.). Pet. 5; Paper 6, 2. In that case, Patent Owner also asserted U.S.
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`Patent Nos. 8,673,927, 8,846,695, and 8,853,156. Pet. 5. Petitioner has
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`concurrently filed IPR2016-01563, IPR2016-01564, and IPR2016-01565,
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`challenging those patents respectively. Id.
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`The ’859 Patent
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`The ’859 patent describes selected DPP-4 inhibitors that are useful for
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`treating various diseases, including type 2 diabetes. Ex. 1001, 3:66–4:20,
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`16:45–17:2. Specifically, the ’859 patent identifies DPP-4 inhibitor 1-[(4-
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`2
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`IPR2016-01566
`Patent 9,173,859 B2
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`methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-
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`piperidin-1-yl)-xanthine, also known as BI 1356 or linagliptin, as
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`“particularly preferred.” Id. at 5:20–35.
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`DPP-4 inhibitors “influence the plasma level of bioactive peptides
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`including the peptide GLP-1 and are highly promising molecules for the
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`treatment of diabetes mellitus.” Id. at 1:21–23. The ’859 patent states that
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`the DPP-4 inhibitors disclosed therein may be used in conjunction with other
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`antidiabetic agents, such as metformin, “either in a free combination or in a
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`fixed combination in a tablet.” Id. at 8:60–9:11, 20:25–51. According to the
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`’859 patent:
`
`A particularly preferred example of an antidiabetic combination
`partner is metformin in doses of about 100 mg to 500 mg or 200
`mg to 850 mg (1-3 times a day), or about 300 mg to 1000 mg
`once or twice a day, or delayed-release metformin in doses of
`about 100 mg to 1000 mg or preferably 500 mg to 1000 mg once
`or twice a day or about 500 mg to 2000 mg once a day.
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`Id. at 14:6–12.
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`Illustrative Claims
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`Among the challenged claims, claims 1, 13, 14, and 16–18 are
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`independent. Claims 1 and 14 are representative and are reproduced below:
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`1.
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`A method of treating type 2 diabetes comprising
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`administering to a patient in need thereof (a) 1-[(4-methyl-
`quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a-
`mino-piperidin-1-yl)-xanthine, or a therapeutically active salt
`thereof, in an oral dosage of 2.5 mg or 5 mg, and (b) metformin
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`wherein the dose of metformin is 100 mg to 500 mg or 200 mg
`to 850 mg (1-3 times a day), or 300 mg to 1000 mg once or twice
`a day, or as delayed-release metformin in a dose of 500 mg to
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`3
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`IPR2016-01566
`Patent 9,173,859 B2
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`1000 mg once or twice a day, or 500 mg to 2000 mg once a day,
`or
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`wherein the dose of metformin is 500 mg, 850 mg or 1000 mg as
`a single dose with a total daily dose of metformin of 500-2850
`mg, or 500 mg, 1000 mg, 1500 mg or 2000 mg metformin in
`delayed release form, or
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`wherein the dose of metformin is 500 mg to 1000 mg.
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`14. An oral tablet formulation comprising 1-[(4-methyl-
`quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-a-
`mino-piperidin-1-yl)-xanthine in an amount of 2.5 mg or 5 mg
`optionally
`in
`combination with metformin,
`and
`a
`pharmaceutically acceptable carrier or diluent.
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`Asserted Grounds of Unpatentability
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`Petitioner asserts the following grounds of unpatentability:
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`Claims
`14–20
`1–22
`1–22
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`Basis
`§ 103
`§ 103
`§ 103
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`Reference(s)
`The ’510 publication1
`The ’510 publication and Glucophage® Label2
`The ’510 Publication and
`Ahrén,3 Hughes,4 and/or Brazg5
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`
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`1 Himmelsbach et al., U.S. Patent Publication No. 2004/0097510, published
`May 20, 2004 (Ex. 1003).
`2 Glucophage® and Glucophage® XR Label (Ex. 1004).
`3 Ahrén et al., Twelve and 52-Week Efficacy of the Dipeptidase IV Inhibitor
`LAF237 in Metformin-Treated Patients with Type 2 Diabetes, DIABETES
`CARE 27:2874–80 (2004) (Ex. 1005).
`4 Hughes, Int’l Pub. No. WO 2005/117861, published December 15, 2005
`(Ex. 1006).
`5 Brazg, et al., Effect of Adding MK-0431 to On-going Metformin Therapy in
`Type 2 Diabetic Patients Who Have Inadequate Glycemic Control on
`Metformin, DIABETES 54 (Suppl. 1):A3 (2005) (Ex. 1007).
`4
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`IPR2016-01566
`Patent 9,173,859 B2
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`In support of its patentability challenge, Petitioner relies on the
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`Declaration of Dr. Mayer B. Davidson. Ex. 1002.
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`ANALYSIS
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`Claim Construction
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`In an inter partes review, the Board interprets a claim term in an
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`unexpired patent according to its broadest reasonable construction in light of
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`the specification of the patent in which it appears. 37 C.F.R. § 42.100(b);
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`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016). Under
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`that standard, and absent any special definitions, we assign claim terms their
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`ordinary and customary meaning, as would be understood by one of ordinary
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`skill in the art at the time of the invention, in the context of the entire patent
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`disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
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`2007).
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`Claim terms need only be construed to the extent necessary to resolve
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`the controversy. Wellman, Inc. v. Eastman Chem. Co., 642 F.3d 1355, 1361
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`(Fed. Cir. 2011). On this record and for purposes of this Decision, we see no
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`need to construe any term expressly.
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`Anticipation by the ’510 Publication
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`Petitioner asserts that the ’510 publication anticipates claims 14 and
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`20. Pet. 30–31. Based on the current record, we determine Petitioner has
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`not established a reasonable likelihood that it would prevail in this assertion.
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`The ’510 publication discloses a genus of substituted xanthine
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`compounds that act as DPP-IV inhibitors, particularly for the prevention and
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`treatment of type 2 diabetes. Ex. 1003, Abstract, ¶¶ 3, 4. It discloses
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`linagliptin as one in a series of 30 “[m]ost particularly preferred” substituted
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`5
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`IPR2016-01566
`Patent 9,173,859 B2
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`xanthine compounds. Id. ¶¶ 232, 245. It also lists the IC50 values of nearly
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`50 DPP-IV inhibitor compounds, including linagliptin.6 Id. ¶ 295.
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`Linagliptin is one of six compounds listed as having the highest potency in
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`the group, with the lowest IC50 value of 1 nM. Id.
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`According to the ’510 publication, the substituted xanthine
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`compounds disclosed therein, due to their “ability to inhibit DPP-IV
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`activity,” are expected to be suitable “for the prevention or treatment of
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`diseases or conditions such as type 1 and type 2 diabetes mellitus.” Id.
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`¶ 297. The ’510 publication discloses that “[t]he compounds according to
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`the invention may also be used in conjunction with other active substances,”
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`including antidiabetics, such as metformin. Id. ¶ 298.
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`Claim 14 of the ’859 patent recites “[a]n oral tablet formulation
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`comprising [linagliptin] in an amount of 2.5 mg or 5 mg optionally in
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`combination with metformin, and a pharmaceutically acceptable carrier or
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`diluent.” Claim 20 recites “[a] method of treating type 2 diabetes
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`comprising administering to a patient in need thereof the oral tablet of claim
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`14, wherein the daily oral amount of [linagliptin] administered to said
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`patient is 5 mg.”
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`Petitioner refers to the ’510 publication for disclosing that the
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`substituted xanthine compounds thereof may be orally administered in the
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`amount of “1 to 1000 mg, preferably 1 to 100 mg, in each case 1 to 4 times
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`therein a day,” to achieve a therapeutic effect. Pet. 22 (citing Ex. 1003
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`¶ 300). According to Petitioner, because the ’510 publication discloses “the
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`
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`6 Linagliptin is Example 2 (142)). Ex. 1003 ¶¶ 1933–1937, 2400.
`6
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`Patent 9,173,859 B2
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`most preferable oral dosage range for linagliptin” that encompasses the
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`doses recited in claims 14 and 20, it anticipates those claims. Id. at 22, 30.
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`We are not persuaded.
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`To anticipate a claim, a single prior art reference must disclose all
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`limitations “arranged as in the claim,” either expressly or inherently.
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`Connell v. Sears, Roebuck & Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983). To
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`be “arranged as in the claim,” the anticipatory reference must “show all of
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`the limitations of the claims arranged or combined in the same way as
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`recited in the claims, not merely in a particular order.” NetMoneyIn, Inc. v.
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`Verisign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008). Whether a generic
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`disclosure necessarily anticipates everything within the genus depends on
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`the factual aspects of the specific disclosure and the particular products at
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`issue. Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1083 (Fed. Cir.
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`2008).
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`The Federal Circuit’s opinion in OSRAM Sylvania, Inc. v. Am.
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`Induction Techs., Inc., 701 F.3d 698 (Fed. Cir. 2012) is instructive. In that
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`case, the dispute centered on whether the prior art disclosure of
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`“approximately 1 torr or less” anticipates the limitation “less than 0.5 torr”
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`in the challenged claim. Id. at 706. The Federal Circuit reversed the district
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`court’s granting of summary judgment of anticipation. Id. According to the
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`Federal Circuit, the patent challenger there relied on “the conclusory claim
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`that less than 0.5 torr necessarily falls within ‘approximately 1 torr or less’
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`as a matter of fact.” Id. The court explained:
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`While true, the inquiry does not end there. How one of ordinary
`skill in the art would understand the scope of the disclosure or,
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`stated differently, how one of ordinary skill in the art would
`understand the relative size of a genus or species in a particular
`technology is of critical importance.
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`Id.
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`The facts in this case are similar to those in OSRAM. Here, Petitioner
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`relies on a conclusory statement that “the most preferable oral dosage range
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`for linagliptin [disclosed in the ’510 publication] encompasses and thus
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`anticipates the claimed dose recited” in the challenged claims. Pet. 22, 30;
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`see also Ex. 1002 ¶ 51 (stating the same). But, Dr. Davidson does not
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`testify, and Petitioner does not argue, that an ordinary artisan would
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`understand any dosage within the preferred dose of 1 to 100 mg
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`administered “1 to 4 times a day” disclosed in the ’510 publication to be
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`efficacious.
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`We emphasize that in an inter parte review, Petitioner has the ultimate
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`burden of persuasion to prove unpatentability by a preponderance of the
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`evidence. 35 U.S.C. § 316(e); Dynamic Drinkware, LLC v. Nat’l Graphics,
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`Inc., 800 F.3d 1375, 1378–79 (Fed. Cir. 2015). Here, the only evidence
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`Petitioner relies on is a broad range of potential linagliptin dosages. That
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`does not amount to a preponderance of the evidence.
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`Petitioner cites Perricone v. Medicis Pharma. Corp., 432 F.3d 1368
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`(Fed. Cir. 2005). Pet. 22, 25. The facts in this case are distinguishable from
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`those in Perricone. There, the prior art discloses a composition having an
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`active ingredient in a concentration range that not only encompasses, but
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`also “does not significantly deviate from,” the claimed ranges. Perricone,
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`432 F.3d at 1377. In contrast, in the present case, the dosage range disclosed
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`8
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`Patent 9,173,859 B2
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`in the prior art is from 20% to 160 times the claimed dosages (i.e., 1 mg in
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`the ’510 publication versus 5 mg claimed (20%), and 400 mg in the ’510
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`publication versus 2.5 mg claimed (160 times)). Petitioner does not explain
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`why, based on the disclosure of a genus of dosage ranges for DPP-4
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`inhibitors, a person of skill in the art would immediately envisage
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`administering linagliptin in the dosage amounts recited in the challenged
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`claims 14 and 20. See OSRAM, 701 F.3d at 706 (explaining that “prior art’s
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`teaching of a broad genus does not necessarily disclose every species within
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`that genus”).
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`As a result, we determine Petitioner has not shown a reasonable
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`likelihood of prevailing in its assertion that the ’510 publication anticipates
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`claims 14 and 20 of the ’859 patent.
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`Obviousness over the ’510 Publication and Glucophage® Label
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`Petitioner asserts that claims 1–22 would have been obvious over the
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`combination of the ’510 publication and Glucophage® Label. Pet. 18–30.
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`Based on the current record, we determine Petitioner has not established a
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`reasonable likelihood that it would prevail in this assertion.
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`Claims 1–13, 15–19, 21, and 22
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`The Glucophage® Label provided by Petitioner as Exhibit 1004
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`includes a cover page stating it is the “FINAL PRINTED LABELING” for
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`application number 20-357/S019 at the Food and Drug Administration
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`(“FDA”) Center for Drug Evaluation and Research. Ex. 1004, 1.
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`Glucophage® is described in the document as metformin hydrochloride
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`tablets and Glucophage® XR is described as metformin hydrochloride
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`extended release tablets, both indicated for the treatment of type 2 diabetes.
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`9
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`Id. at 2. The Glucophage® Label contains a date “Revised January 2001.”
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`Id. at 7.
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`Relying on the Davidson Declaration, Petitioner contends that the
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`Glucophage® Label qualifies as prior art under 35 U.S.C. §102(b) because it
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`was approved and published by the FDA for treating type 2 diabetes in
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`February 2001. Pet. 19 (citing Ex. 1002 ¶ 48). Patent Owner counters
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`Mylan has not met its burden to show that Exhibit 1004, “purporting to be
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`the Glucophage label as-approved, is, in fact, a printed package insert, much
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`less one that was publically available prior to” the priority date of the ’510
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`patent. Prelim. Resp. 14–17. We agree with Patent Owner.
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`Under 35 U.S.C. § 311(b), a petitioner in an inter partes review may
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`only challenge the claims of a patent based on “prior art consisting of patents
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`or printed publications.” 35 U.S.C. § 311(b). Petitioner has the ultimate
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`burden of persuasion to prove unpatentability by a preponderance of the
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`evidence. Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., 800 F.3d 1375,
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`1378–79 (Fed. Cir. 2015). Petitioner also bears the initial burden of
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`production to establish the existence of prior art that renders the claims
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`unpatentable. Id. To satisfy the initial burden of production, we have often
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`required a petitioner to make a threshold showing that the reference relied
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`upon was publicly accessible as a printed publication prior to the effective
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`filing date of a challenged patent. See, e.g., Frontier Therapeutics, LLC v.
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`Medac Gesellschaft Fur Klinische Spezialpraparate MBH, Case IPR2016-
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`00649, slip op. at 22 (PTAB September 1, 2016) (Paper 10) (finding that an
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`alleged “printed package insert” was not a printed publication); Symantec
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`Corp. v. Trs. of Columbia Univ., Case IPR2015-00371, slip op. at 5–9
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`(PTAB June 17, 2015) (Paper 13); Temporal Power, Ltd. v. Beacon Power,
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`LLC, Case IPR2015-00146, slip op. at 8–11 (PTAB Apr. 27, 2015) (Paper
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`10); Dell, Inc. v. Selene Comm’n Techs., LLC, Case IPR2014-01411, slip op.
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`at 21–22 (PTAB Feb. 26, 2015) (Paper 23).
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`“A given reference is “publicly accessible” upon a satisfactory
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`showing that such document has been disseminated or otherwise made
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`available to the extent that persons interested and ordinarily skilled in the
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`subject matter or art exercising reasonable diligence, can locate it.”
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`Bruckelmyer v. Ground Heaters, Inc., 445 F.3d 1374, 1378 (Fed. Cir. 2006).
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`Here, the Glucophage® Label does not contain any source identifying
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`information, e.g. as an FDA-approved label, or other indicia of when the
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`document became publicly available. See Prelim. Resp. 15. For example,
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`the Glucophage® Label submitted by Petitioner contains no indicia that it
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`(1) is a certified copy of a public record, (2) is copied from an official 2001
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`publication such as the United States Pharmacopoeia–National Formulary,
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`(3) is copied from a recognized periodical published in 2001 such as the
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`Physicians’ Desk Reference, or (4) otherwise bears the hallmarks of a self-
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`authenticating document published in 2001. See Fed. R. Evid. 902 (4)–(7),
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`(11). Exhibit 1004 indicates the label was revised in January 2001, but it
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`bears no source identifying information from the FDA, a copyright date, or
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`any other indicia of a publication date.
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`Dr. Davidson states that Glucophage® IR, a metformin hydrochloride
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`immediate release tablet, has been available since 1994, and Glucophage®
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`XR, a long-acting extended-release form of metformin, has been available
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`since 2000. Ex. 1002 ¶¶ 29, 49. He, however, cites the January 2001
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`11
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`revision of the Glucophage® Label in support. Id. ¶ 29. With regard to the
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`Glucophage® Label, Dr. Davidson merely parrots the same statement in the
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`Petition, that is, the label was approved and published by the FDA for
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`treating type 2 diabetes in February 2001. Id. ¶ 48.
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`Dr. Davidson does not provide a sufficient explanation or foundation
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`to establish his personal knowledge of the Glucophage® Label’s alleged
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`publication in February 2001. The statements that Glucophage® was
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`approved by the FDA in 1994 and Glucophage® XR in 2000, by
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`themselves, are insufficient as a threshold showing that the Glucophage®
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`Label was a publicly available printed publication as of February 2001.
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`Earlier FDA approval of the Glucophage® drug products is not co-extensive
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`with a February 2001 publication date of the revised Glucophage® Label, on
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`which Petitioner relies for proof of the specific metformin doses recited in
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`claims 1–13, 15–19, 21, and 22. See Pet. 21–29.
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`In sum, Petitioner has not satisfied its burden to show that the
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`Glucophage® Label was available as a prior art printed publication.
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`Therefore, we determine Petitioner has not shown a reasonable likelihood of
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`prevailing on its assertion that claims 1–13, 15–19, 21, and 22 of the ’859
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`patent would have been obvious over the ’510 publication and the
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`Glucophage® Label.
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`Claims 14 and 20
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`Neither claim 14 nor claim 20 recites a specific metformin dose.
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`Nevertheless, we find Petitioner has not shown a reasonable likelihood of
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`prevailing on its assertion that claims 14 and 20 of the ’859 patent would
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`have been obvious over the ’510 publication and the Glucophage® Label.
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`Each of claims 14 and 20 recites a specific linagliptin dosage. Claim
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`14 requires an oral tablet formulation of linagliptin in an amount of 2.5 mg
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`or 5 mg, and claim 20 requires administering linagliptin in a daily amount of
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`5 mg. In its obviousness challenge, Petitioner relies on the same conclusory
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`statement of linagliptin dosage as in its anticipation argument, that is, the
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`’510 publication discloses “the most preferable oral dosage range for
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`linagliptin encompasses and thus anticipates the claimed dose recited” in the
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`challenged claims. Pet. 22, 30. Again, such a single sentence, devoid of any
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`further analysis, does not satisfy Petitioner’s burden to prove unpatentability
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`by a preponderance of the evidence. See 35 U.S.C. § 316(e).
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`For example, Petitioner does not explain why an ordinary artisan
`
`would have had a reason to modify the teachings of the ’510 publication to
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`arrive at the claimed linagliptin dosage of 2.5 mg or 5 mg. Indeed, the ’510
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`publication teaches drug formulation for oral administration with 75 mg to
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`150 mg DPP-4 inhibitor. Ex. 1003 ¶¶ 2898–911. While this does not, as
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`Patent Owner asserts, amounts to teaching away from the claimed linagliptin
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`dosage (see Prelim. Resp. 29), Petitioner presents no credible evidence or
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`otherwise explains why one of ordinary skill in the art, in view of such a
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`teaching, would have had a reason to pursue a dosage more than 10-fold
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`lower than suggested in the ’510 publication.
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`As a result, we determine Petitioner has not shown a reasonable
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`likelihood of prevailing on its assertion that claims 14 and 20 of the ’859
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`patent would have been obvious over the ’510 publication and the
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`Glucophage® Label.
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`Obviousness over the ’510 Publication and Ahrén, Hughes, and/or Brazg
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`Petitioner asserts that claims 1–22 would have been obvious over the
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`combination of the ’510 publication and Ahrén, Hughes, and/or Brazg. Pet.
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`31–43. Based on the current record, we determine Petitioner has not
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`established a reasonable likelihood that it would prevail in this assertion.
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`Ahrén describes the clinical effect of DPP-4 inhibitor LAF237
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`(vildagliptin) when combined with metformin to treat patients with type 2
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`diabetes. Ex. 1005, 2874–75. Ahrén compares two groups of type 2
`
`diabetes patients treated with either metformin monotherapy (1500 to 3000
`
`mg per day), or metformin (1,500 to 3,000 mg per day) and vildagliptin (50
`
`mg once per day) combination therapy. Id. at 2874. Ahrén shows that
`
`“when added to metformin treatment, LAF237 was effective at improving
`
`glycemic control for at least 1 year in patients with type 2 diabetes and
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`appeared to be well tolerated.” Id. at 2878.
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`Like Ahrén, Hughes teaches a method of treating patients with type 2
`
`diabetes using a combination of LAF237 (vildagliptin) and metformin over
`
`an extended period of time. Ex. 1006, Abstract, 3–4, 137. It teaches that
`
`vildagliptin may be administered in an oral daily dosage “between 1 and 100
`
`mg; preferably between 10 and 100 mg e.g. 10 mg; most preferably between
`
`25 and 100 mg e.g. 25 mg or 30 or 40 or 50, 61, 70, 90, 100 mg.” Id. at 23.
`
`Metformin is administered at a daily dosage in the range of about 50 mg to
`
`about 3000 mg, preferably from about 500 mg to about 2000 mg, using
`
`commercially available 500 mg tablets. Id. Hughes describes a clinical
`
`
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`7 Page references are to the exhibit pages, not the internal document pages.
`14
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`IPR2016-01566
`Patent 9,173,859 B2
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`study treating patients with type 2 diabetes who were already receiving
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`metformin. Id. at 25. In the Hughes study, patients were treated with
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`vildagliptin (50 mg once daily) in addition to metformin (1500–3000 mg
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`daily). Id. Hughes reports that the combination therapy achieved better
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`clinical results when compared to metformin plus placebo treatment. Id. at
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`26–33.
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`Brazg reports the efficacy of combining the DPP-4 inhibitor MK-0431
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`(sitagliptin) with ongoing metformin therapy in type 2 diabetes patients. Ex.
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`1007, 2. Brazg notes that “[m]etformin is a commonly used first-line
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`antihyperglycemic agent.” Id. Brazg states that “[c]ombination treatment
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`with MK-0431 [sitagliptin] and metformin may be useful since these agents
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`target different pathophysiologic process leading to hyperglycemia in [type
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`II diabetes].” Id. In the Brazg study, “the combination of MK-0431
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`[sitagliptin] and metformin was efficacious and generally well-tolerated as a
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`treatment regimen” for patients with type 2 diabetes. Id.
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`Petitioner argues that the combination of the asserted prior art teaches
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`each limitation in the challenged claims. Pet. 36–37, 40–43. Petitioner also
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`contends that an ordinary artisan would have had a reason to combine the
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`prior-art teachings and would have had a reasonable expectation of success
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`in doing so. Id. at 38–39. Patent Owner challenges each assertion by
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`Petitioner. See Prelim. Resp. 17–33.
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`For purposes of this Decision, we assume, without deciding, that one
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`of ordinary skill in the art would have combined the teachings of the prior
`
`art. Petitioner, however, has not presented credible evidence or otherwise
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`15
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`IPR2016-01566
`Patent 9,173,859 B2
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`persuasively argued that such an artisan would have arrived at the linagliptin
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`dosages recited in the challenged claims.
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`Petitioner, again, in a conclusory fashion, argues that the ’510
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`publication teaches the claimed linagliptin dosages. See Pet. 36 (“The ’510
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`Publication discloses the combination of metformin and the recited oral
`
`doses of a DPP-IV Inhibitor (linagliptin).”); id. at 41 (“As described in Table
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`1 above in Ground 1, the ’510 Publication discloses linagliptin dosages of
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`2.5mg and 5mg.”) (citing Ex. 1003 ¶ 300). As explained above, based on
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`the current record, we are not persuaded that an ordinary artisan would have
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`had a reason to modify the teachings of the ’510 publication—a preferred
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`dose of 1 to 100 mg administered “1 to 4 times a day”—to arrive at the
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`claimed linagliptin dosage of 2.5 mg or 5 mg.
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`We note Petitioner’s assertion “the ’510 Publication reports that
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`linagliptin [is] more potent than vildagliptin or sitagliptin.” Pet. 38 (citing
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`Ex. 1002 ¶ 85; Ex. 1003, ¶ 295; Ex. 1011, 158). Dr. Davidson, however,
`
`testifies that “[l]inagliptin’s purported higher potency would have
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`potentially allowed for smaller doses of DPP-IV inhibitor to be administered
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`to the patient.” Ex. 1002 ¶ 85. Such testimony is speculative and again,
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`does not amount to a preponderance of the evidence. As a result, we
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`determine Petitioner has not established a reasonable likelihood that it would
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`prevail in showing claims 1–22 obvious over the combination of the ’510
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`publication and Ahrén, Hughes, and/or Brazg.
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`16
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`IPR2016-01566
`Patent 9,173,859 B2
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`CONCLUSION
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`For the foregoing reasons, we determine that Petitioner has not shown
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`there is a reasonable likelihood that it would prevail in proving the
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`unpatentability of claims 1–22 of the ’859 patent.
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`In consideration of the foregoing, it is hereby:
`
`ORDER
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`ORDERED that pursuant to 35 U.S.C. § 314(a), the Petition for inter
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`partes review of the ’859 patent is denied and no trial is instituted.
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`PETITIONER:
`
`Thomas Parker
`thomas.parker@alston.com
`
`Chris McArdle
`chris.mcardle@alston.com
`
`Ellen Cheong
`ellen.cheong@alston.com
`
`Charles Naggar
`charles.naggar@alston.com
`
`
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`17
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`IPR2016-01566
`Patent 9,173,859 B2
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`PATENT OWNER:
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`Leora Ben-Ami
`leora.benami@kirkland.com
`
`Eugene Goryunov
`egoryunov@kirkland.com
`
`Mira Mulvaney
`mira.mulvaney@kirkland.com
`
`
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`18
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