Trials@uspto.gov
`571.272.7822
`
`
`
`
`
`
` Paper No. 34
`
` Entered: December 28, 2018
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`AUROBINDO PHARMA USA, INC.
`Petitioner,
`
`v.
`
`ANDRX CORPORATION,
`ANDRX LABORATORIES, INC.
`ANDRX LABORATORIES (NJ), INC.
`ANDRX EU LTD.
`ANDRX PHARMACEUTICALS, LLC,
`TEVA PHARMACEUTICAL INDUSTRIES LTD.
`Patent Owner(s)
`____________
`
`Case IPR2017-01648
`Patent 6,866,866 B1
`____________
`
`
`Before SUSAN L.C. MITCHELL, JO-ANNE M. KOKOSKI, and
`DEVON ZASTROW NEWMAN, Administrative Patent Judges.
`
`NEWMAN, Administrative Patent Judge.
`
`
`
`
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`
`
`
`
`

`

`IPR2017-01648
`Patent 6,866,866 B1
`
`
` INTRODUCTION
`This is a Final Written Decision in an inter partes review challenging
`the patentability of claims 1–25 of U.S. Patent No. 6,866,866 B1 (Ex. 1001,
`“the ’866 patent”). We have jurisdiction under 35 U.S.C. § 6. The
`evidentiary standard is a preponderance of the evidence. See 35 U.S.C.
`§ 316(e); 37 C.F.R. § 42.1(d). We issue this Final Written Decision
`pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
`Having reviewed the arguments of the parties and the supporting
`evidence, we determine that Petitioner has not demonstrated by a
`preponderance of the evidence that the challenged claims are unpatentable.
`
`A. Procedural History
`Aurobindo Pharma USA, Inc. (“Petitioner”) filed a Corrected Petition
`requesting an inter partes review of claims 1–25 of the ’866 patent. Paper 8
`(“Pet.”). The Petition relies upon the Declaration of Dr. Fatemeh Akhlaghi.
`Ex. 1019 (“Akhlaghi Decl.”).
` Andrx, LLC (“Patent Owner”) filed a Preliminary Response to the
`Petition.1 Paper 11 (“Prelim. Resp.”). We instituted an inter partes review
`of challenged claims 1–25 on one ground of unpatentability, pursuant to
`35 U.S.C. § 314. Paper 12 (“Inst. Dec.”), 21–22.
`After institution and before the due date for Patent Owner’s Response,
`however, the U.S. Supreme Court issued its decision in SAS Institute Inc. v.
`Iancu, 138 S. Ct. 1348 (2018). See Paper 20. Pursuant to SAS Institute, a
`decision to institute an inter partes review under 35 U.S.C. § 314 may not
`
`
`1 No other party named in the Petition entered an appearance on behalf of
`Patent Owner in this matter.
`
`2
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`IPR2017-01648
`Patent 6,866,866 B1
`institute trial on fewer than all claims challenged in the petition. SAS
`Institute, 138 S. Ct. at 1355–56, 1358. In this proceeding, we had instituted
`only on Petitioner’s ground based on § 103. See Inst. Dec. 22. Accordingly,
`we modified our Decision on Institution to include review of all challenged
`claims on all grounds presented in the Petition. Paper 20, 2–3. The parties
`subsequently submitted a Joint Motion to Limit the Petition, requesting that
`the Petition be limited to the ground based on § 103, for obviousness of
`claims 1–25 over Timmins2 and Cheng.3 Joint Motion 2. We granted the
`motion. Paper 23.
` Patent Owner filed a Response (Paper 25, “PO Resp.”), which relies
`upon the Declaration of Dr. Jennifer Dressman (“Dressman Decl.,”
`Ex. 2010). Petitioner filed a Reply (Paper 26, “Reply”).
`An oral hearing was held on September 24, 2018, and a transcript of
`the hearing is included in the record. Paper 33 (“Tr.”).
`
`B. Related Proceedings
`Petitioner identifies a currently pending district court action filed by
`Patent Owner against the Petitioner, asserting infringement of the ’866
`patent, Shionogi Inc. v. Aurobindo Pharma Ltd., Civ. Act. No. 1:17-cv-
`00072-UNA (D. Del. 1-25-17), and identifies multiple previous litigations in
`the District of Delaware, the Federal Circuit (Ex. 1006), and in the District
`of New Jersey. Pet. 7–8. Patent Owner identifies five prior individual or
`
`
`2 Timmins, Peter et al., WO 99/47128, published September 23, 1999
`(“Timmins” Ex. 1003).
`3 Cheng, Xiu, Xiu et al., WO 99/47125, published September 23, 1999
`(“Cheng” Ex. 1002).
`
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`IPR2017-01648
`Patent 6,866,866 B1
`consolidated actions that were filed and dismissed, including some by
`settlement. Paper 6, 3–4.
`
`C. The ’866 and Relevant Background
`The ’866 patent relates to “controlled release unit dose formulations
`containing an antihyperglycemic drug. . . . [specifically] an oral dosage form
`comprising a biguanide such as metformin.” Ex. 1001, 1:6–11. Metformin
`is used to manage non-insulin dependent diabetes mellitus (NIDDM). Id. at
`1:56–58.
`According to the Specification, various techniques have been used to
`provide controlled and extended-release pharmaceutical dosage forms that
`provide stable therapeutic serum levels of the drug, thereby minimizing the
`effect of missed doses. Id. at 1:14–18. Because metformin is a short-acting
`drug, it requires twice- or thrice-daily doses. Id. at 2:4–6. The ’866 patent
`states that, due to adverse events associated with use of metformin, reducing
`the dosage or using an extended-release form would provide a benefit, in
`addition to reducing the frequency of administration and improving the
`drug’s safety profile. Id. at 2:6–16.
`The ’866 patent discloses a controlled release dosage form of
`metformin that is suitable for once-a-day dosing in the “fed” state,
`preferably at dinner. Id. at 8:54–56. The ’866 patent states that, when
`administered in this manner, the bioavailability of the drug is improved
`relative to the fasted state, which is opposite of the commercially available
`form of metformin, GLUCOPHAGE®. Id. at 8:56–59. In addition, when
`dosed at dinnertime, the controlled release formulations provide a Tmax
`between 5.5 and 7.5 hours after oral administration (which is delayed
`relative to the Tmax provided by GLUCOPHAGE®), “such that the level of
`
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`IPR2017-01648
`Patent 6,866,866 B1
`the drug is greatest at the time when human patients are manufacturing
`glucose at highest levels.” Id. at 8:66–9:6.
`
`D. Challenged Claims and Reviewed Ground of Unpatentability
`As discussed above, the sole ground of review at issue is
`whether claims 1–25 are unpatentable under 35 U.S.C. § 103 based on
`the combination of Timmins and Cheng. See Inst. Dec. 22; Paper 23
`(granting Parties’ Joint Motion to Limit Petition).
`Claim 1 of the ’866 patent, the only independent claim, is
`representative and is reproduced below, with the limitation at issue
`italicized:
`1. A controlled release oral dosage form for the reduction of
`serum glucose levels in human patients with NIDDM, comprising
`an effective dose of metformin or a pharmaceutically acceptable
`salt thereof and a controlled-release carrier to control the release of
`said metformin or pharmaceutically acceptable salt thereof from
`said dosage form, said dosage form being suitable for providing
`once-a-day oral administration of the metformin or
`pharmaceutically acceptable salt thereof, wherein following oral
`administration of a single dose, the dosage form provides a mean
`time to maximum plasma concentration (Tmax) of the metformin
`from 5.5 to 7.5 hours after administration following dinner.
`Dependent claims 2–25 recite additional or more restricted
`
`limitations with respect to those in claim 1, including narrower Tmax
`ranges (claims 2, 3, 23, and 24), specified dissolution profiles (claims
`4 and 5), specified heights of the mean plasma concentration/time
`curve at specific hours after dosing (claims 6 and 7), and specified
`Cmax, AUC0–24, AUC0–∞, and/or t1/2 values when certain dosing
`parameters are followed (claims 8–22). Claim 25 additionally recites
`
`5
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`IPR2017-01648
`Patent 6,866,866 B1
`that the dosage form contains a membrane with at least one
`passageway.
`
`II. ANALYSIS
`A. Principles of Law
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the subject matter sought to be patented and the prior art are such
`that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which that
`subject matter pertains.4 KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved based on underlying factual
`determinations including: (1) the scope and content of the prior art; (2) any
`differences between the claimed subject matter and the prior art; (3) the level
`of ordinary skill in the art; and (4) objective evidence of nonobviousness, if
`present. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`“[T]he [obviousness] analysis need not seek out precise teachings
`directed to the specific subject matter of the challenged claim, for a court
`can take account of the inferences and creative steps that a person of
`ordinary skill in the art would employ.” KSR, 550 U.S. at 418. Moreover,
`“any need or problem known in the field of endeavor at the time of invention
`and addressed by the patent can provide a reason for combining the elements
`in the manner claimed.” Id. at 420. Accordingly, a party that petitions the
`
`
`4 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”), amended 35 U.S.C. §§ 102 and 103. Because the
`challenged claims of the ’866 patent have an effective filing date before the
`effective date of the applicable AIA amendments, throughout this Final
`Written Decision we refer to the pre-AIA versions of 35 U.S.C. §§ 102 and
`103.
`
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`IPR2017-01648
`Patent 6,866,866 B1
`Board for a determination of unpatentability based on obviousness must
`show that “a skilled artisan would have been motivated to combine the
`teachings of the prior art references to achieve the claimed invention, and
`that the skilled artisan would have had a reasonable expectation of success in
`doing so.” In re Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381 (Fed.
`Cir. 2016) (citations omitted). This burden of persuasion never shifts to
`Patent Owner. See Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., 800
`F.3d 1375, 1378 (Fed. Cir. 2015) (discussing the burden of proof in inter
`partes review).
`We analyze the ground of unpatentability in accordance with these
`principles.
`
`B. Level of Ordinary Skill in the Art
`In determining the level of ordinary skill in the art, various factors
`may be considered, including the “type of problems encountered in the art;
`prior art solutions to those problems; rapidity with which innovations are
`made; sophistication of the technology; and educational level of active
`workers in the field.” In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995)
`(internal quotation and citation omitted).
`In our Institution Decision, we summarized the parties’ contentions,
`notably that Petitioner proposes that the person of ordinary skill would have
`had “a Pharm.D. and/or Ph.D. with experience in pharmaceutical sciences,
`dosage forms, clinical pharmacology or related fields, such as
`pharmacology,” and asserts that a person of ordinary skill in the art would
`have “experience in the research or development of pharmaceuticals and
`have the ability to gather and interpret pharmacokinetic data and the
`relationship between drug release from a dosage form and its effect on
`
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`IPR2017-01648
`Patent 6,866,866 B1
`pharmacokinetic parameters.” Inst. Dec. 5 (citing Ex. 1019 ¶¶ 91–96).
`Petitioner also contends that “pharmaceutical development is an inherently
`collaborative process,” and that the skilled artisan would have had “access
`to, or be part of a team including, other skilled individuals, such as an M.D.
`with experience in the field of diabetes treatment.” Id.
`We observed that Patent Owner proposes that a person of ordinary
`skill in the art at the time of the invention would have “held a degree in
`pharmacy, chemistry, chemical engineering, or a related field with at least
`three to five years of pharmacokinetics, biopharmaceutics, medicinal
`chemistry, pre-formulation, or formulation experience, research, or training
`[and would have been familiar] with the methods used in formulating oral
`dosage forms, modified release dosage forms, and osmotic delivery, and
`[understand] fundamental principles as to how osmotic dosage forms behave
`and function.” Id. at 6 (citing Prelim. Resp. 15–16).
`As we noted in the Institution Decision, we do not “discern an
`appreciable difference in the parties’ respective definitions of the level of
`ordinary skill in the art.” Id. Because the parties agreed “that a person of
`ordinary skill in the art would have had experience with and knowledge of
`the development of pharmaceuticals and the ability to analyze
`pharmacokinetic data including the relationship between oral dosage forms
`and osmotic delivery,” and we found “that the prior art itself demonstrates
`the level of skill in the art at the time of the invention,” we determined it was
`unnecessary to resolve any perceived differences in the parties’ definitions
`of the level of ordinary skill in the art for purposes of the Institution
`Decision. Id. (citing Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir.
`2001)).
`
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`Patent 6,866,866 B1
`In the Patent Owner Response, Patent Owner acknowledged the
`Board’s characterization of the knowledge of an ordinarily skilled artisan as
`consistent with the proposals of both parties (PO Resp. 12–13), and neither
`party further addressed the proper level of ordinary skill in the art or
`disagreed with our characterization from the Institution Decision. See PO
`Resp., Reply. Our determination regarding the patentability of the
`challenged claims does not turn on the differences between the parties’
`definitions. We adopt Petitioner’s assessment, but note that our conclusions
`would be the same under Patent Owner’s assessment.
`C. Testimony of Dr. Akhlaghi
`Patent Owner argues that Dr. Akhlaghi’s testimony “should be given
`minimal [or no] weight” because the opinions vary, are inconsistent, and
`reveal a lack of understanding of the subject matter of the claims of the ’866
`patent. PO Resp. 13–17. Patent Owner further argues that Dr. Akhlaghi is
`not an expert in formulation development, including formulations of the
`types relevant to this proceeding. Id. at 14.
`Petitioner responds that Patent Owner’s selective quotations
`mischaracterize Dr. Akhlaghi’s deposition testimony and are responsive to
`deposition questions asked in a confusing manner. Pet. Reply 1–4.
`Petitioner reiterates Dr. Akhlaghi’s substantial expertise and experience with
`pharmaceutical formulations. Id. at 1–2.
`We agree with Petitioner that Dr. Akhlaghi’s qualifications and
`deposition testimony, when read in context, indicate that Dr. Akhlaghi is
`sufficiently experienced to opine on the knowledge of one of skill in the art
`at the time of the ’866 patent. As noted in the August 13, 2018 update to our
`Trial Practice Guide:
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`An expert witness must be qualified as an expert by
`knowledge, skill, experience, training, or education to testify in
`the form of an opinion. Fed. R. Evid. 702. There is, however,
`no requirement of a perfect match between the expert’s
`experience and the relevant field. SEB S.A. v. Montgomery Ward
`& Co., 594 F.3d 1360, 1373 (Fed. Cir. 2010). A person may not
`need to be a person of ordinary skill in the art in order to testify
`as an expert under Rule 702, but rather must be “qualified in the
`pertinent art.” Sundance, Inc. v. DeMonte Fabricating Ltd., 550
`F.3d 1356, 1363–64 (Fed. Cir. 2008).
`See Notice of Update to Office Patent Trial Practice Guide, 83 Fed. Reg.
`156, (Aug. 13, 2018) (text of update available at
`https://www.uspto.gov/sites/default/files/documents/2018_Revised_Trial_Pr
`actice_Guide.pdf). In addition, we are well able to consider the value of an
`expert opinion and afford it appropriate weight. Perreira v. Secretary of the
`Dept. of HHS, 33 F.3d 1375, 1377 n.6 (Fed. Cir. 1994) (“An expert opinion
`is no better than the soundness of the reasons supporting it.”)
`D. Claim Interpretation
`In an inter partes review, the Board currently interprets claim terms in
`an unexpired patent according to the broadest reasonable construction in
`light of the specification of the patent in which they appear.5 37 C.F.R.
`§ 42.100(b); Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2142 (2016)
`(affirming applicability of broadest reasonable construction standard to inter
`
`
`5 The Office recently changed the claim construction standard applicable to
`an inter partes review. See Changes to the Claim Construction Standard for
`Interpreting Claims in Trial Proceedings Before the Patent Trial and Appeal
`Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018). The rule changing the claim
`construction standard, however, does not apply to this proceeding because
`Petitioner filed its Petition before the effective date of the final rule, i.e.,
`November 13, 2018. Id. at 51,340 (rule effective date and applicability
`date), 51,344 (explaining how the Office will implement the rule).
`10
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`partes review proceedings). Under that standard, and absent any special
`definitions, we give claim terms their ordinary and customary meaning, as
`would be understood by one of ordinary skill in the art at the time of the
`invention. See In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
`2007). Any special definitions for claim terms must be set forth with
`reasonable clarity, deliberateness, and precision. See In re Paulsen, 30 F.3d
`1475, 1480 (Fed. Cir. 1994).
`We address the construction of only certain claim terms raised by the
`parties, and we do so only to the extent necessary to determine whether
`Petitioner has demonstrated unpatentability by a preponderance of the
`evidence. See 35 U.S.C. § 316(e); Nidec Motor Corp. v. Zhongshan Borad
`Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (“[W]e need only
`construe terms ‘that are in controversy, and only to the extent necessary to
`resolve the controversy.’”) (quoting Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999)).
`“Tmax”
`In our Institution Decision, we noted that the term “Tmax” appears in
`each of the challenged claims, and that both parties agreed that Tmax should
`be construed as stated in the Specification: “the time period which elapses
`after administration of the dosage form at which the plasma concentration of
`the drug attains the highest plasma concentration of drug attained within the
`dosing interval (i.e., about 24 hours).” Inst. Dec. 7 (citing Pet. 24; Prelim
`Resp. 18; Ex. 1001, col. 7, ll. 49–53). We concluded that the proposed
`definition was consistent with the Specification and defined the claim term
`with reasonable clarity, deliberateness, and precision, and we adopted the
`parties’ construction.
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`Neither party addressed the issue of construction of Tmax in further
`briefing, but the parties disagree about how Dr. Akhlaghi applied the
`definition in her testimony. See, eg., Pet. Reply 9–10. For purposes of
`analyzing the patentability of the challenged claims, we continue to interpret
`the term as “the time period which elapses after administration of the dosage
`form at which the plasma concentration of the drug attains the highest
`plasma concentration of drug attained within the dosing interval (i.e., about
`24 hours),” because that definition is consistent with the Specification, and
`because the parties themselves agreed to the definition of Tmax. Inst. Dec. 7.
`
`E. Overview of the Prior Art
`1.
`Timmins (Ex. 1003)
`Timmins relates to a “biphasic controlled release delivery system for
`pharmaceuticals . . . such as the antidiabetic metformin HCl salt.” Ex. 1003,
`Abstract. Timmins discloses “a new dosage form for medicaments [such as]
`metformin, which provides for extended release of the drug and also for
`prolonged gastric residence which enables efficient delivery of drugs
`normally absorbed in the gastrointestinal tract,” and methods of preparing
`the dosage form. Id. at 1:5–11.
`Petitioner alleges “Timmins[’] disclosure covers Bristol-Myers
`Squibb’s product, GLUCOPHAGE XR®, which was approved for
`marketing (October 13, 2000) before the priority date of the ’866 patent.”
`Pet. 18.
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`Example 3 of Timmins discloses a 0.5 mg metformin hydrocholoride
`tablet that revealed the following profile of in vitro release of metformin:
`
`
`
`The Table above shows the in vitro release profile of metformin by hour
`intervals. Ex. 1003, 32:20–33:9.
`
`Example 5 of Timmins discloses a Tmax range of 4–8 hours, with a
`median (not mean) Tmax of 5 hours for a single dose after dinner
`administration:
`
`
`
`The Table above shows the “interpatient variability in pharmacokinetic
`parameters” as illustrated by the provided parameters. Id. at 34:11–30.
`Timmins does not report a mean Tmax for its disclosed formulation, the tablet
`of Example 3.
`
`Cheng (Ex. 1004)
`2.
`Cheng relates to “an oral dosage form comprising a biguanide such as
`metformin . . . or a pharmaceutically acceptable salt thereof.” Ex. 1004,
`1:7–9. Cheng has the same inventive entity as the ’866 patent. Id. at [75].
`
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`Cheng discloses a controlled release pharmaceutical tablet comprising 1) a
`core, including an antihyperglycemic drug, a binding agent, and an
`absorption enhancer; 2) a semipermeable membrane coating that is
`permeable to water and biological fluids but impermeable to the
`antihyperglycemic drug that covers the core; and 3) at least one passageway
`in the membrane for the release of the antihyperglycemic drug. Id. at 9:61–
`10:6. Cheng discloses that “the term passageway includes an aperture,
`orifice, bore, hole, weaken[ed] area or an erodible element such as a gelatin
`plug that erodes to form an osmotic passageway for the release of the
`antihyperglycemic drug from the dosage form.” Id. at 5:8–11.
`Example 2 of Cheng is reproduced below:
`
`
`Example 2 discloses the formula of “a controlled release tablet containing
`850 mg of metformin HCl.” Id. at 7:35–44. Cheng discloses that “an
`additional hole was drilled on the plain side of the coated tablet.” Id. at 9:1–
`2. A depiction of the “in vivo plasma profile” of the product is shown below
`in Figure 8:
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`
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`
`
`
` Figure 8 depicts the in vivo plasma profiles of the sustained release
`metformin product and the GLUCOPHAGE® product when administered
`“shortly after dinner.” Id. at 9:28–32.
`F. Obviousness over Timmins and Cheng
`
`Petitioner challenges claims 1–25 as unpatentable under
`35 U.S.C. § 103 based on the combination of Timmins and Cheng. Pet. 20–
`23, 40–53. Pet. Reply. 2–24. Petitioner relies on the Akhlaghi Declaration
`in support of its contentions. Id. Patent Owner disagrees with Petitioner’s
`assertions, and relies on the Dressman Declaration. Prelim. Resp. 26–30;
`PO Resp. 1–55.
`
`Claim 1
`1.
`Petitioner argues that Cheng discloses a dosage form of metformin
`hydrochloride that “is essentially identical to that described in the ’866
`patent in terms of the types and amounts of excipient components, and [that]
`releases metformin approximately the same as the tablets disclosed in the
`’866 patent.” Pet. 20. Petitioner acknowledges two differences between the
`Cheng formulation and the claimed invention: 1) Example 2 of the ’866
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`patent shows two laser drilled holes in the dosage form rather than the single
`hole disclosed in Cheng; and 2) claim 1 of the ’866 patent specifies a Tmax
`range of 5.5 to 7.5 hours, while Cheng discloses a Tmax of 8–12 hours. Id. at
`20–22 (citing Ex. 1019 (Akhlaghi Decl.) ¶¶ 148, 155).
`Petitioner argues that drilling a second hole in the dosage form to
`match the invention of the ’866 patent is “trivial” and is an “option plainly
`suggested by the language of [Cheng].” Id. at 22 (citing Ex. 1019 ¶ 148).
`Petitioner argues that upon making this change, the skilled artisan “would
`expect the Tmax of the altered product to be concisely within the Tmax range
`recited in claim 1, and to match the other pharmacokinetic parameters
`recited in the claims dependent on claim 1 of the ’866 patent (i.e., claim[s]
`2–25).” Id.
`With regard to the motivation of the skilled artisan, Petitioner relies
`on the Federal Circuit’s finding in Sciele Pharma, Inc.6 v. Lupin Ltd., 684
`F.3d 1253, 1261 (Fed. Cir. 2012) (Ex. 1006). In Sciele, the court reviewed
`the district court’s grant of a preliminary injunction precluding Lupin from
`selling its generic version of a pharmaceutical, Fortamet, which Sciele
`claimed was covered by the ’866 patent. Id. at 5. Lupin denied
`infringement on the basis that the “’866 patent was invalid, unenforceable,
`and/or would not be infringed” by Lupin’s products because the combination
`of Cheng and Timmins rendered the claims obvious. Id.
`On review, the Court vacated the preliminary injunction and
`remanded to the district court, finding that Cheng in view of Timmins raised
`a substantial question of invalidity for obviousness. Id. at 13. The Court
`
`
`6 Sciele Pharma Inc. is a predecessor of Patent Owner Shionogi Pharma Inc.
`Ex. 1006, 2.
`
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`also found that the skilled artisan would have been motivated to combine
`Cheng and Timmins “to better match the Tmax profile of Glucophage while
`providing the convenience of an extended release” and that the data provided
`in Timmins, while not in the form of a mean Tmax as claimed, is “raw data
`from which one skilled in the art could compute the range of possible Tmax
`values.” Id. at 14–15.
`In reliance on these findings, which are reviewed and endorsed by Dr.
`Akhlaghi, Petitioner argues that the skilled artisan “would have used the
`teaching of Timmins . . . to lower the Tmax value taught by Cheng . . . to
`reach a mean range of about 4.67–6.33 hours, well within the range claimed
`by [claim 1 of] the ’866 patent.” Pet. 22–23; Ex. 1019 ¶¶ 162–165.
`Petitioner further argues that, following modification of the Tmax to
`within the range of claim 1, the skilled artisan would expect that the altered
`tablet would exhibit the same pharmacokinetic parameters as those recited in
`the dependent claims, making those claims obvious as well. Pet. 22 (citing
`Ex. 1019 ¶ 177).
`Patent Owner disputes these contentions and asserts that the skilled
`artisan would not have been motivated to combine the teachings of Cheng
`and Timmins, and that the combination of Cheng and Timmins fails to teach
`or suggest key limitations (e.g., a mean Tmax of 5.5 hours to 7.5 hours)
`recited in the claims of the ’866 patent. See generally PO Resp. Patent
`Owner argues that a skilled artisan would not have been motivated to derive
`a mean Tmax from the data disclosed in Timmins (PO Resp. 17–19; 27–34),
`and that to the extent any mean Tmax values were derived from the data of
`Timmins, the value would have been lower than the mean Tmax range of
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`claim 1. See e.g., Id. at 35–37. Patent Owner additionally provides evidence
`of objective indicia of nonobviousness. Id. at 50–54.
`Petitioner’s arguments with respect to the sole disputed limitation of
`claim 1 – the mean Tmax range of 5.5 to 7.5 – including Dr. Akhlaghi’s
`relevant declaration statements, are premised entirely on the findings of the
`Federal Circuit in Sciele. The Petition and evidence of record provide no
`independent factual basis for the argument that the combination of Timmins
`and Cheng renders this limitation obvious. Rather, the Petition relies on Dr.
`Akhlaghi’s review of the relevant findings in the Sciele decision and her
`statements that generally she agrees with the findings. See Pet. 19–23; 40–
`53; Ex. 1019 ¶¶ 72–75, 162–165, 182–184, 191, 192, 194, 196. The sole
`information in the record regarding Dr. Akhlaghi’s own efforts to calculate
`the mean Tmax using the information provided in Example 5 of Timmins is
`from her deposition testimony, in which she concludes that her calculation
`was “around 5.75, or something like that . . . [depending on] . . . how you set
`your confidence values.” Ex. 2011, 70:8–72:12. Dr. Akhlaghi testifies that
`her calculations are “very close” to the numbers reported in the Sciele
`decision. Id. at 72:13–20. However, neither the calculations that resulted in
`the Court’s opinion in Sciele that “Timmins discloses a range of possible
`mean Tmax between 4.67 and 6.33 hours” (Ex. 1006, 14), nor those
`performed by Dr. Akhlaghi, are of record in this proceeding.7 Dr. Akhlaghi
`
`
`7 Although the parties at oral argument addressed a purported agreement to
`file Dr. Akhlaghi’s calculations in the record, because neither party
`ultimately did so, we rely only upon Dr. Akhlaghi’s deposition testimony
`describing that she used an “equal distribution between 4, 5, 6, 7, and 8” to
`reach “5.75, or around that number” as her calculation of the mean Tmax
`disclosed by Timmins. See e.g., Tr. 42:6–16; 43:9–20; 47:17–2; Ex. 2011
`70:8–72:12; 73:7–13.
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`admitted at her deposition that her Declaration, filed in support of the
`Petition, did not address her calculation of a mean Tmax of 5.75:
` Q: Okay. Now, there’s no place in your declaration
`where you report the calculation of the 5.75 hours. Right?
`A: No, I haven’t. I just, like, went through what the
`Federal Circuit said.
`Ex. 2011, 75:2–6. Dr. Akhlaghi also testified she understood that the
`Federal Circuit had not calculated a particular mean Tmax, but rather the
`possible range for the mean Tmax as between 4.67–6.33 hours, and that her
`knowledge of those calculations was limited to the Sciele decision, which
`does not state any of the assumptions made regarding the data that formed
`the basis for the calculated range. Id. at 75:7–78:22.
`Based on our review of the record, we determine that Petitioner has
`not shown sufficiently that combining the teachings of Timmins and Cheng
`as Petitioner contends would have resulted in a dosage form that provides a
`mean Tmax of metformin from 5.5 to 7.5 hours after administration.
`As an initial matter, we are not bound by the Sciele court’s factual
`findings, as the issue heard was a matter of injunctive relief. See Univ. of
`Tex. v. Camenisch, 451 US 390, 395 (1981) (“[T]he findings of fact and
`conclusions of law made by a court granting a preliminary injunction are not
`binding at trial on the merits.”); Abbott Labs v. Andrx Pharm., 473 F.3d
`1196, 1206–1207 (Fed. Cir. 2007) (no collateral estoppel where the district
`court’s preliminary injunction proceeding addressed only whether the party
`challenging the patent demonstrated a likelihood of success in proving
`invalidity, and did not make conclusive findings); Momenta Pharm. v. Teva
`Pharm., 809 F.3d 610 (Fed. Cir. 2015). Patent Owner, therefore, is entitled
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`to a full trial on the merits on the issue of invalidity, given our decision to
`institute.
` Nevertheless, we need not disagree with the Court’s holding to find
`that Petitioner has not carried its burden. The Court’s finding that “Timmins
`discloses a range of possible mean Tmax between 4.67 and 6.33 hours” does
`not mean that the Timmins mean Tmax would be within the range of 5.5–7.5
`hours as recited in claim 1. Ex. 1006, 14. As Patent Owner’s expert Dr.
`Dressman explains, although the possible Tmax values from the data of
`Example 5 of Timmins fall between 4.67–6.33, “[t]his does not suggest that
`Timmins discloses an actual mean Tmax of either 4.67 hours or 6.33 hours, or
`any other single mean Tmax value. . . . Instead, a POSA could only determine
`that, statistically, the mean Tmax of Timmins falls somewhere between these
`two values, but neither Dr. Akhlaghi nor the Federal Circuit offered any
`information on where in the range that would occur.” Ex. 2010 ¶ 73. Fully
`half of the potential range, 4.67–5.49, does not fall within the range of 5.5–
`7.5 hours recited in claim 1. Moreover, Dr. Ahklaghi stated that if additional
`patients were “basical