`571-272-7822
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` Paper 13
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` Entered: November 4, 2015
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`PAR PHARMACEUTICAL, INC.,
`Petitioner,
`
`v.
`
`HORIZON THERAPEUTICS, INC.,1
`Patent Owner.
`
`
`Case IPR2015-01117
`Patent 8,642,012 B2
`
`
`
`Before TONI R. SCHEINER, DEBORAH KATZ, and
`GRACE KARAFFA OBERMANN, Administrative Patent Judges.
`
`
`SCHEINER, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`1 “[E]ffective May 7, 2015, the name of Hyperion Therapeutics, Inc., was
`changed to Horizon Therapeutics, Inc. . . . Accordingly, Horizon
`Therapeutics, Inc. . . . is the Patent Owner of U.S. Patent No. 8,642,012.”
`Paper 5, 2.
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`
`
`IPR2015-01117
`Patent 8,642,012 B2
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`I. INTRODUCTION
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`Par Pharmaceutical, Inc. (“Petitioner”) filed a Petition (Paper 2,
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`“Pet.”) on April 29, 2015, requesting an inter partes review of claims 1–12
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`of U.S. Patent No. 8,642,012 B2 (Ex. 1001, “the ’012 patent”). Horizon
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`Therapeutics, Inc. (“Patent Owner”) filed a Preliminary Response (Paper 8,
`
`“Prelim. Resp.”) on August 5, 2015. We have jurisdiction under 35 U.S.C.
`
`§ 314, which provides that an inter partes review may not be instituted
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`“unless . . . there is a reasonable likelihood that the petitioner would prevail
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`with respect to at least 1 of the claims challenged in the petition.”
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`Upon consideration of the information presented in the Petition and
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`the Preliminary Response, we conclude that Petitioner has established a
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`reasonable likelihood that it would prevail in its challenges to claims 1–12 of
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`the ’012 patent. Accordingly, we institute an inter partes review.
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`A. Related Proceedings
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`Patent Owner filed suit against Petitioner, alleging infringement of the
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`’012 patent and U.S. Patent No. 8,404,215 B1 (“the ’215 patent) in Hyperion
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`Therapeutics, Inc. v. Par Pharmaceutical, Inc., Case No. 2:14-CV-384-JRG-
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`RSP (E.D. Tex.). Pet. 7; Paper 5, 3. In addition, concurrently with the
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`Petition under consideration here, Petitioner filed a petition challenging the
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`claims of the ’215 patent (IPR2015-01127), but represents that that patent is
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`not related to the ’012 patent. Pet. 7.
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`2
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`IPR2015-01117
`Patent 8,642,012 B2
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`B. The Asserted Grounds of Unpatentability
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`
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`Petitioner asserts the challenged claims are unpatentable on the
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`following grounds. Pet. 12–60:2
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`References
`
`Basis
`
`Claims Challenged
`
`Brusilow ’91,3 Sherwin,4
`Comte,5 and Shiple6
`
`§ 103
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`1, 3, 4, 7, 8, 10, 12
`
`
`2 Petitioner supports its challenge with a Declaration, executed April 29,
`2015, by Neal Sondheimer, M.D., Ph.D. (“Sondheimer Declaration”)
`(Ex. 1002).
`3 Saul W. Brusilow, Phenylacetylglutamine May Replace Urea as a Vehicle
`for Waste Nitrogen Excretion, 29 PEDIATRIC RESEARCH 147–150 (1991)
`(“Brusilow ’91”) (Ex. 1012).
`4 Carl P. Sherwin at al., The Maximum Production of Glutamine by the
`Human Body as Measured by the Output of Phenylacetylglutamine, 37 J.
`BIOL. CHEM. 113–119 (1919) (“Sherwin”) (Ex. 1016).
`5 Blandine Comte et al., Identification of phenylbutyrylglutamine, a new
`metabolite of phenylbutyrate metabolism in humans, 37 J. MASS SPECTROM.
`581–590 (2002) (“Comte”) (Ex. 1025).
`6 George J. Shiple & Carl P. Sherwin, Synthesis of Amino Acids in Animal
`Organisms. I. Synthesis of Glycocoll and Glutamine in the Human
`Organism, 44 J. AMER. CHEM. SOC. 618–624 (1922) (“Shiple”) (Ex. 1017).
`
`3
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`IPR2015-01117
`Patent 8,642,012 B2
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`References
`
`Basis
`
`Claims Challenged
`
`Brusilow ’91 , Sherwin,
`Shiple, and Fernandes7
`Brusilow ’91, Sherwin,
`Shiple, and the ’647 patent8
`Brusilow ’91, Sherwin,
`Shiple, Kasumov,9 and the
`’979 patent10
`Brusilow ’91and Simell11
`
`§ 103
`
`5
`
`§ 103
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`2, 9
`
`§ 103
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`6, 11
`
`§ 103
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`1, 3, 4, 7, 8, 10, 12
`
`Brusilow ’91, Simell, and
`Fernandes
`Brusilow ’91, Simell, and the
`’647 patent
`Brusilow ’91, Simell, and
`Kasumov
`
`§ 103
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`5
`
`§ 103
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`2, 9
`
`§ 103
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`6, 11
`
`
`7 INBORN METABOLIC DISEASES: DIAGNOSIS AND TREATMENT 219–220
`(John Fernandes et al. eds., Springer Verlag 3d ed. 2000) (“Fernandes”)
`(Ex. 1011).
`8 U.S. Patent No. 4,284,647, issued August 18, 1981 to Brusilow et al. (“the
`’647 patent”) (Ex. 1018).
`9 Takhar Kasumov et al., New Secondary Metabolites of Phenylbutyrate in
`Humans and Rats, 32 DRUG METABOLISM AND DISPOSITION 10–19 (2004)
`(“Kasumov”) (Ex. 1015).
`10 U.S. Patent No. 5,968,979, issued October 19, 1999 to Brusilow (“the 979
`patent”) (Ex. 1026).
`11 Olly Simell et al., Waste Nitrogen Excretion Via Amino Acid Acylation:
`Benzoate and Phenylacetate in Lysinuric Protein Intolerance, 20 Pediatric
`Research 1117–1121 (1986) (“Simell”) (Ex. 1005).
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`4
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`Patent 8,642,012 B2
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`References
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`Basis
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`Claims Challenged
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`Brusilow ’91
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`§ 103
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`1–4, 7, 9, 10, 12
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`Brusilow ’91, Kasumov, and
`the ’979 patent
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`§ 103
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`6, 11
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`C. The ’012 Patent (Ex. 1001)
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`The ’012 patent, titled “Methods of Treatment Using Ammonia-
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`Scavenging Drugs,” is directed to “treatment of patients with nitrogen
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`retention states, in particular urea cycle disorders (UCDs) . . . [by]
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`administer[ing] compounds that assist in elimination of waste nitrogen from
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`the body.” Ex. 1001, 1:18–25. These compounds—or “nitrogen scavenging
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`drugs”12—include glyceryl tri-[4-phenylbutyrate] (HPN-100) and
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`phenylbutyric acid (PBA)—both of which are prodrugs that are converted in
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`vivo to phenylacetic acid (PAA). Id. at 3:61–66.
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`“For patients with nitrogen retention states such as UCD . . . the
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`body’s intrinsic capacity for waste nitrogen excretion is less than the body’s
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`waste nitrogen production based on a normal diet that contains significant
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`amounts of protein.” Id. at 2:22–25. “As a result, nitrogen builds up in the
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`body . . . and usually results in excess ammonia in the blood . . . [which] has
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`various toxic effects.” Id. at 2:25–28.
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`12 The terms “ammonia scavenger” and “nitrogen scavenger” are used
`interchangeably in the ’012 patent. Ex. 1001, 4:6–7.
`5
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`HPN-100 and PBA “reduce excess waste nitrogen and ammonia by
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`converting it to readily-excreted forms, such as phenylacetyl glutamine
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`(PAGN).” Id. at 2:45–47. “The capacity to eliminate excess ammonia in
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`treated patients can be considered the sum of the patient’s endogenous
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`capacity for nitrogen elimination (if any) plus the amount of additional
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`nitrogen-elimination capacity that is provided by a nitrogen scavenging
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`drug.” Id. at 2:39–44.
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`According to the ’012 patent, “[i]t has generally been assumed . . .
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`that a prodrug would be converted with 100% efficiency into PAGN for
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`elimination” (id. at 9:21–23), but “[i]t has now been found that HPN-100
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`and phenylbutyrate are both converted into urinary PAGN at an overall
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`efficiency of about 60% to about 75% on average (about 60% conversion
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`efficiency was seen in UCD patients and about 75% conversion was seen in
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`cirrhotic patients, for example)” (id. at 9:27–32). “[C]onsequently, this
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`efficiency factor can be used to more accurately calculate or determine
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`initial dosing levels for these drugs, or dietary protein levels acceptable for
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`patients who use these drugs.” Id. at 9:32–35. Moreover, “urinary PAGN
`
`provides a convenient method for monitoring ammonia elimination induced
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`by the administered drug, which does not require drawing blood and directly
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`relates to the actual nitrogen elimination provided by the . . . drug without
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`being influenced by the many other factors that can affect plasma ammonia
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`levels.” Id. at 7:24–30.
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`One embodiment of the invention is a method for determining
`and/or adjusting the dose of ammonia scavenging drugs in
`patients with UCDs, whereby the dose would be based on the
`amount of dietary protein the patient is consuming, the
`anticipated conversion of the drug to PAGN, and the patient’s
`residual urea synthetic capacity, if any. Dose adjustments, if
`necessary, would be based on the observed urinary excretion of
`PAGN and/or total urinary nitrogen (TUN), the difference
`between the two reflecting the patient’s endogenous capacity
`for waste nitrogen excretion . . . referred to sometimes as their
`residual urea synthesis capacity.
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`Id. at 8:16–30.
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`D. Illustrative Claims
`
`Petitioner challenges claims 1–12 of the ’012 patent. Claims 1 and 8
`
`are independent claims. Claims 1 and 8, reproduced below (with indenting
`
`added), are illustrative.
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`1. A method of treating a patient having a urea cycle
`disorder comprising
`(a) determining a target urinary phenylacetyl glutamine
`(PAGN) output
`(b) calculating an effective initial dosage of phenylacetic
`acid (PAA) prodrug selected from glyceryl tri-[4-
`phenylbutyrate] (HPN-100) and phenylbutyric acid (PBA) or a
`pharmaceutically acceptable salt of PBA, wherein the effective
`dosage of PAA prodrug is calculated based on a mean
`conversion of PAA prodrug to urinary PAGN of about 60%;
`and
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`(c) administering the effective initial dosage of PAA
`prodrug to the patient.
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`
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`7
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`A method of administering a phenylacetic acid (PAA)
`8.
`prodrug selected from glyceryl tri-[4-phenylbutyrate] (HPN-
`100) and phenylbutyric acid (PBA) or a pharmaceutically
`acceptable salt of PBA to a patient having a urea cycle disorder
`comprising
`(a) administering a first dosage of the PAA prodrug;
`(b) determining urinary phenylacetyl glutamine (PAGN)
`excretion following administration of the first dosage of the
`PAA prodrug;
`(c) determining an effective dosage of the PAA prodrug
`based on the urinary PAGN excretion, wherein the effective
`dosage is based on a mean conversion of PAA prodrug to
`urinary PAGN of about 60%; and
`(d) administering the effective dosage to the patient.
`
`Id. at 42:16–15, 41–52.
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`II. ANALYSIS
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`A. Real Party-In-Interest
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`Petitioner identifies Par Pharmaceutical, Inc. (“Par Inc.”) as the real
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`party-in-interest. Pet. 7. We note that Petitioner represents that Par Inc. is a
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`wholly owned subsidiary of Par Pharmaceutical Companies, Inc., but does
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`not identify Par Pharmaceutical Companies, Inc. as a real party-in-interest.
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`Pet. 7 n.4.
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`Patent Owner argues that Par Pharmaceutical Companies, Inc. (“Par
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`Co.”) was not properly identified as a real party-in-interest. Prelim. Resp. 5.
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`Patent Owner argues that because of this deficiency, the Petition violates the
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`statutory and regulatory requirements for receiving a filing date, citing 35
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`U.S.C. § 312(a) and 37 C.F.R. § 42.8(b)(1). Patent Owner argues further
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`that because the Petition was filed exactly one year after Par Inc. was served
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`with the complaint in litigation in the Eastern District of Texas, Petitioner
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`cannot correct the failure to name all the real parties-in-interest by filing a
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`new petition. Prelim. Resp. 5.
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`According to Patent Owner, Par Co. is a real party-in-interest to the
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`proceeding because it is involved in developing, manufacturing, and
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`distributing generic pharmaceutical products. Prelim. Resp. 8 (citing Ex.
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`2003 ¶ 4; Ex. 2004, 42; Ex. 2005). Patent Owner also provides evidence
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`that Par Co., in a different proceeding, pleaded guilty pursuant to an
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`agreement with the United States Attorney for the District of New Jersey,
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`and agreed to perform certain actions on behalf of Petitioner. Prelim. Resp.
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`10 (citing Ex. 2007, 1).
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`In addition, Patent Owner cites to a Securities and Exchange
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`Commission (SEC) filing that defines the term “we” as including Petitioner
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`and Par Co. Prelim. Resp. 11–13 (citing Ex. 2004, 8). Patent Owner also
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`cites to the statement in the SEC filing that “[o]n April 29, 2015, we filed
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`Inter Partes Review petitions seeking institution of a trial on invalidity at the
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`U.S. Patent and Trademark Office for both of the patents asserted in the
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`Texas litigation [the ’012 patent and the ’215 patent].” Id. at 11 (citing Ex.
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`2004, 36). Patent Owner argues that the use of “we” in this statement was a
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`deliberate indication that the current Petition was filed at the behest of Par
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`Co. Prelim. Resp. 12.
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`Finally, Patent Owner asserts that Thomas J. Haughey is the General
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`Counsel and CAO of both Par Co. and Par Inc. and is also the President of
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`Par Inc., indicating the unified nature of the relationship between Par Co.
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`and the Petitioner. Prelim. Resp. 15 (citing Ex. 2008, 70; Ex. 2009).
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`Nevertheless, on this record, we are not persuaded that the Petition
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`failed to name all real parties-in-interest. Specifically, the use of the term
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`“we” in an SEC filing, even if used deliberately when referring to what
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`could be the current Petition, does not establish adequately that Par Co. has
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`control over this proceeding. Nor does the evidence show that Par Co.
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`exerts control over this proceeding merely because Par Co. and Petitioner
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`are in a similar business and the same person has roles in both Par Co. and
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`Par Inc. Similarly, evidence of control in a different, unrelated litigation is
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`not evidence of Par Co.’s role in this proceeding. Patent Owner has failed to
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`provide us with evidence of actual control by an unnamed entity sufficient to
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`indicate that Petitioner failed to name all real parties-in-interest. See Taylor
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`v. Sturgell, 553 U.S. 880, 893–95 (2008).
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`B. Claim Construction
`
`In an inter partes review, claim terms in an unexpired patent are
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`interpreted according to their broadest reasonable construction in light of the
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`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
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`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,
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`2012); In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275–79 (Fed. Cir.
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`2015). Under that standard, claim terms are given their ordinary and
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`10
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`customary meaning, as would be understood by one of ordinary skill in the
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`art in the context of the entire disclosure. In re Translogic Tech., Inc., 504
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`F.3d 1249, 1257 (Fed. Cir. 2007).
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`1. “mean conversion . . . of about 60%”
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`
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`Petitioner argues that the term “mean conversion of PAA prodrug to
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`urinary PAGN of about 60%” should be construed “as encompassing a range
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`of mean conversion between 53–67%.” Pet. 10–12.
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`However, we determine it is not necessary to construe the term for
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`purposes of this decision, and will interpret the term, should it become
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`necessary, based on the full record developed at trial.
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`C. Claims 1, 3, 4, 7, 8, 10, 12—Asserted Obviousness over
`Brusilow ’91, Sherwin, Comte, and Shiple
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`1. Brusilow ’91 (Ex. 1012)
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`Brusilow ’91 reports the results of an evaluation of PAG nitrogen
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`(PAGN) as an alternate vehicle for waste nitrogen excretion in patients with
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`inborn errors of urea synthesis (i.e., urea cycle disorders, or UCDs).
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`Briefly, the daily protein intake of a 7½-year-old boy with a UCD was
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`used to calculate his required waste nitrogen excretion, and the required
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`nitrogen excretion was used to calculate a target amount of urinary PAGN to
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`be excreted. The target amount of PAGN to be excreted was used, in turn,
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`to calculate initial doses of PAA and PBA, based on complete (i.e., 100%)
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`conversion of the drugs to PAGN. Urinary excretion of PAGN was
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`measured over three, three-day periods in which the patient was treated once
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`with sodium phenylacetate (NaPAA) and twice with sodium phenylbutyrate
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`(NaPBA). Ex. 1012, 147.
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`The resultant measurements showed that the conversion of NaPBA
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`was not complete—rather, “90% of the predicted amount of PAG[N]
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`synthesized [was] excreted” following the first dose of NaPBA. Id. at 148.
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`The second dose of NaPBA was increased to account for the lower than
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`expected conversion of NaPBA to PAGN, and only 80% of the predicted
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`amount of PAGN was excreted. Id., Table 1.
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`2. Sherwin (Ex. 1016)
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`
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`Sherwin discusses the results of a study of the conversion of PAA into
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`urinary PAGN in humans. Varying doses of PAA were administered to a
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`normal man (i.e., a healthy subject). Ex. 1016, 114. The subject ingested
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`doses of PAA ranging from 2.5–15.0 grams, and each dose was taken all at
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`once over three to five minutes. Id. The subject’s urine was collected
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`during twenty-four hour periods beginning at the time of ingestion of the
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`dose. Id. Urinary PAGN was measured and a percent conversion from PAA
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`to PAGN was calculated. Id. at 114, 116 , Table I. The conversion rate
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`ranged from about 50–67% for all doses, and from about 51–52% for doses
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`of 10 grams or more. Id. Moreover, Sherwin suggests that “[t]t is probable
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`that more of the [PAGN] would have appeared in the urine after each dose
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`of the acid, had the acid been ingested at regular intervals covering a period
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`of 10 or 12 hours.” Id. at 118.
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`12
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`3. Comte (Ex. 1025)
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`Comte discloses that metabolism of PBA in humans produces PAGN,
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`as well as another metabolite, phenylbutyrlglutamine. Ex. 1025, 581.
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`Comte observed about 54% conversion of PBA to urinary PAGN in seven
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`normal subjects. Id. at 585–586.
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`4. Shiple (Ex. 1017)
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`
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`Shiple discloses that PAA suppresses urea production in normal
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`subjects, and glutamine is synthesized at the expense of urea nitrogen in the
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`presence of PAA. Ex. 1025, 619, 623.
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`Claim 1
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`5. Analysis
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`Petitioner contends that Brusilow ’91 discloses all the steps of the
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`claimed method of treating a patient suffering from a UCD by administering
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`a PAA prodrug, except that Brusilow ’91’s effective dose of the PAA
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`prodrug was calculated based on a mean conversion of PAA prodrug to
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`urinary PAGN of about 90%, rather than about 60%, as recited in claim 1.
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`Pet. 20.
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`Nevertheless, Petitioner, supported by the testimony of its witness,
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`Dr. Sondheimer, contends that a person of ordinary skill in the art,
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`recognizing that “Brusilow ’91 involved only a single subject and observed a
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`range of conversion rates (80–90%)” in that single subject, would have
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`looked to other references, such as Sherwin and Shiple, to find more
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`information on conversion rates, “because each discusses the conversion of
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`PAA to PAGN” (Pet. 17 (citing Ex. 1002 ¶¶ 42–45)). Petitioner contends
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`that these additional references, in turn, would have led one of ordinary skill
`
`in the art to expect a lower conversion rate of PAA prodrugs to urinary
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`PAGN—i.e., about 60%. Id. at 19.
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`In this regard, Dr. Sondheimer testifies, “[a]s seen in Table I of
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`Sherwin, the conversion of PAA into normal PAGN in normal subjects
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`ranged from about 50–67 for all doses” and “at clinically relevant doses (10
`
`grams or higher), Sherwin teaches a 51–52% conversion of PAA into urinary
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`PAGN in normal subjects.” Ex. 1002 ¶ 52 (citing Ex. 1016, 114, 116,
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`Table I). According to Dr. Sondheimer, “[a] person of ordinary skill
`
`reviewing Sherwin would understand that the 51–52% figures are low”
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`because “Sherwin further states that ‘[i]t is probable that more of the
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`[PAGN] would have appeared in the urine after each dose of the acid, had
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`the acid been ingested at regular intervals covering a period of 10 or 12
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`hours.’” Id. (citing Ex. 1016, 118).
`
`Dr. Sondheimer further testifies that one of ordinary skill in the art
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`would also understand that “Sherwin’s figures are lower than one would
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`expect to see in a UCD patient” because “UCD patients are not dosed with a
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`single large dose . . . and by dosing smaller doses over the course of a day,
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`the percent conversion of PAA to PAGN would be higher.” Ex. 1002 ¶ 53.
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`In addition, Dr. Sondheimer testifies that Shiple “demonstrates that urea
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`synthesis in normal people is suppressed when treated with PAA” (id. ¶ 54
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`(citing Ex. 1017, 620, Table II, 623)), and “a person of ordinary skill in the
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`14
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`art would have understood from reading Shiple and Brusilow ’91 that a
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`normal subject treated with PAA excretes urea at about the same rate as a
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`UCD patient” (id. ¶ 55). According to Dr. Sondheimer,
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`A person of ordinary skill in the art would have understood that
`the conversion rates observed in Sherwin for the normal subject
`would also be applicable to the UCD patient. Therefore, a
`person of ordinary skill in the art reading Sherwin in view of
`Shiple would have understood that the percentage conversion of
`administered PAA to PAGN observed in the healthy volunteer
`of Sherwin would also have been observed in a UCD patient.
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`Ex. 1002 ¶ 55.
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` Consequently, Petitioner, supported by the testimony of
`
`Dr. Sondheimer, contends that one of ordinary skill in the art “would have
`
`used Sherwin’s conversion rate to obtain the effective dosage of NaPBA to
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`be administered [to a UCD patient] according to the method described in
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`Brusilow ’91.” Pet. 22–23 (citing Ex. 1002 ¶ 56).
`
`Claim 8
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`With respect to independent claim 8, Petitioner’s contentions and
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`cited evidence, discussed on pages 23 through 27 of the Petition, are
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`essentially the same as for claim 1.
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`Dependent Claims 3, 4, 7, 10, and 12
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`Claims 3 and 12 depend from claims 1 and 12, respectively, and
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`require that administration of the effective initial dosage of PAA prodrug
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`produces a normal plasma ammonia level in the patient. Petitioner cites
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`Brusilow ’91’s teaching that treatment with NaPBA produces a mean plasma
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`ammonium level within the normal range as meeting this limitation (Pet. 27
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`(citing Ex. 1012, 148–149)).
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`Claim 4 depends from claim 1 and recites that calculation of the target
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`PAGN output takes into account the patient’s dietary protein intake.
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`Petitioner asserts that Brusilow ’91 takes dietary protein intake into account
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`in calculating the dosage for the PAA prodrug (Pet. 28 (citing Ex. 1012,
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`147)).
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`Claims 7 and 10 depend from claims 1 and 8, respectively, and require
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`that the pharmaceutically acceptable salt of PBA is sodium PBA. Petitioner
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`cites Brusilow ’91’s disclosure of treating the patient with NaPBA as
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`meeting this limitation (Pet. 28 (citing Ex. 1012, 147–148, Table 1)).
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`6. Conclusion
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`Patent Owner has not addressed Petitioner’s contentions, and is under
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`no obligation to do so. In the absence of any countervailing argument,
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`however, at this stage of the proceedings, Petitioner’s contentions appear to
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`be supported adequately, and we are persuaded that, on this record,
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`Petitioner has demonstrated a reasonable likelihood of showing that claims
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`1, 3, 4, 7, 8, 10, and 12 would have been obvious over Brusilow ’91,
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`Sherwin, Comte, and Shiple.
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`D. Claim 5—Asserted Obviousness over Brusilow ’91, Sherwin,
`Shiple, and Fernandes
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`Claim 5 depends from claim 1 and requires that the target PAGN
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`output take into account the patient’s dietary protein intake.
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`Fernandes discusses diagnosis and treatment of inborn metabolic
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`diseases, including UCDs. Ex. 1011, 219–20. Fernandes discloses a
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`guideline for the management of patients with UCDs, which includes the
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`administration of nitrogen scavenging drugs such as phenylbutyrate.
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`Id. at 219, Fig. 17.2. Fernandes teaches that nitrogen scavenging drugs
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`reduce the load on the urea cycle in patients with UCDs. Id. at 219.
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`Fernandes further discusses general aspects of therapy and, specifically, that
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`the balance of diet and medicine is important (id. at 219), and that protein
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`intake of patients varies considerably and that residual enzyme activity of
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`the UCD patient must be taken into account during treatment (id. at 219–20).
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`Petitioner contends that the subject matter of claim 5 would have been
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`obvious because a person of ordinary skill in the art “reading Brusilow ’91
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`and Fernandes would have considered the residual enzyme activity of the
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`patient, and therefore his or her residual urea synthesis capacity.” Pet. 30
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`(citing Ex. 1002 ¶ 76).
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`Petitioner’s contentions appear to be supported adequately on this
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`record, and we are persuaded that Petitioner has demonstrated a reasonable
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`likelihood of showing that claim 5 would have been obvious over
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`Brusilow ’91, Sherwin, Shiple, and Fernandes.
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`E. Claims 2 and 9—Asserted Obviousness over Brusilow ’91,
`Sherwin, Shiple, and the ’647 Patent
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`Claims 2 and 9 depend from claims 1 and 8, respectively, and recite
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`that target urinary PAGN output is determined as a ratio of the concentration
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`of urinary PAGN to urinary creatinine.
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`Petitioner notes that “Brusilow ’91 teaches measuring creatinine levels
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`in the UCD patients treated with phenylacetate or NaPBA (Ex. 1012 at 148)
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`but does not expressly mention determining target urinary PAGN output as a
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`ratio of urinary PAGN to urinary creatinine.” Pet. 33.
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`However, Petitioner cites the ’647 patent as disclosing measuring
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`urinary creatinine, urinary PAGN, and total urinary nitrogen in a UCD
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`patient after PAA administration, and as disclosing using the ratio of urinary
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`PAGN to creatinine as a convenient measure for an increase in urinary
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`excretion of nitrogen that does not require collection of total daily urine.
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`Pet. 33 (citing Ex. 1018, 3:53–4.6, 4:35–50).
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`Petitioner contends that one of ordinary skill in the art would have
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`recognized that target urinary PAGN could conveniently be determined as a
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`ratio of urinary PAGN to urinary creatinine. Pet. 33.
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`Petitioner’s contentions appear to be supported adequately on this
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`record, and we are persuaded that Petitioner has demonstrated a reasonable
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`likelihood of showing that claims 2 and 9 would have been obvious over
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`Brusilow ’91, Sherwin, Shiple, and the ’647 patent.
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`IPR2015-01117
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`F. Claims 6 and 11—Asserted Obviousness over Brusilow ’91,
`Sherwin, Shiple, and Kasumov
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`Claims 6 and 11 depend from claims 1 and 8, respectively, and recite
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`that the PAA prodrug is HPN-100.
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`Petitioner acknowledges that none of Brusilow ’91, Sherwin, or
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`Shiple discloses HPN-100 as the nitrogen scavenging drug.
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`However, Petitioner argues that it would have been obvious to
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`substitute HPN-100 for NaPBA in Brusilow ’91’s method because Kasumov
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`discloses that NaPBA may be toxic at high doses (Pet. 34 (citing Ex. 1015,
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`10, 13)), and because the ’979 patent also discloses HPN-100, and teaches
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`that such drugs are useful to treat patients with diseases of nitrogen
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`accumulation.
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`Petitioner’s contentions appear to be supported adequately on this
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`record, and we are persuaded that Petitioner has demonstrated a reasonable
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`likelihood of showing that claims 6 and 11 would have been obvious over
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`Brusilow ’91, Sherwin, Shiple, Kasumov, and the ’979 patent.
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`G. Remaining Challenges
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`Petitioner also challenges claims 1–12 as obvious over Brusilow ’91
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`alone, or in combination with one or more of Simell, Fernandes, the ’647
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`patent, and Kasumov. Pet. 36–60. In light of our determination, discussed
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`above, that there is a reasonable likelihood that Petitioner would prevail in
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`showing that claims 1–12 are unpatentable as obvious over Brusilow ’91,
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`Sherwin, Comte, and Shiple, together with Fernandes, the ’647 patent, or
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`IPR2015-01117
`Patent 8,642,012 B2
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`Kasumov, we exercise our discretion under 37 C.F.R. § 42.108(a) and
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`decline to institute trial as to claims 1–12 based on the remaining asserted
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`grounds. Specifically, in that regard, Petitioner does not direct us to
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`information sufficient to persuade us that going forward to trial on multiple
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`grounds, directed to the same patent claims, is an efficient allocation of
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`Board or party resources. See 35 U.S.C. § 316(b) (regulations for AIA post-
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`grant proceedings take into account “the efficient administration of the
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`Office” and “the ability of the Office to timely complete [instituted]
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`proceedings”); 37 C.F.R. § 42.1(b) (patent rules promulgated for AIA post-
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`grant proceedings, including those pertaining to institution, are “construed to
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`secure the just, speedy, and inexpensive resolution of every proceeding”); 37
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`C.F.R. § 42.108 (a) (the Board has discretion to authorize an inter partes
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`review “on all or some” grounds stated in Petition) (emphasis added)).
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`III. CONCLUSION
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`Having considered the information presented in the Petition and the
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`Preliminary Response, we institute an inter partes review, as we determine
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`that Petitioner has established a reasonable likelihood that it would prevail in
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`its challenges to claims 1–12 of the ’012 patent.
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`At this stage in the proceeding, the Board has not made a final
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`determination as to the construction of any claim term or the patentability of
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`any challenged claim. Our final determination will be based on the record as
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`fully developed at trial.
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`IPR2015-01117
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`It is
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`IV. ORDER
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`ORDERED that pursuant to 35 U.S.C. § 314(a), an inter partes
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`review is instituted as to claims 1–12 of U.S. Patent No. 8,642,012 B2 on the
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`following grounds of unpatentability:
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`Claims 1, 3, 4, 7, 8, 10, and 12 under 35 U.S.C. § 103 as unpatentable
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`over Brusilow ’91, Sherwin, Comte, and Shiple;
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`claim 5 under 35 U.S.C. § 103 as unpatentable over Brusilow ’91,
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`Sherwin, Shiple, and Fernandes;
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`claims 2 and 9 under 35 U.S.C. § 103 as unpatentable over Brusilow
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`’91, Sherwin, Shiple, and the ’647 patent; and
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`claims 6 and 11 under 35 U.S.C. § 103 as unpatentable over Brusilow
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`’91, Sherwin, Shiple, and Kasumov.
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`It is
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`FURTHER ORDERED that pursuant to 35 U.S.C. § 314(c) and 37
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`C.F.R. § 42.4, notice is hereby given of the institution of a trial commencing
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`on the entry date of this decision; and
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`FURTHER ORDERED that no other grounds of unpatentability are
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`authorized for this inter partes review other than those identified above.
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`IPR2015-01117
`Patent 8,642,012 B2
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`For PETITIONER:
`
`Michael J. Freno: michael.freno@klgates.com
`David H. Silverstein: david.silverstein@parpharm.com
`Sanjay K. Murthy: sanjay.murthy@klgates.com
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`
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`For PATENT OWNER:
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`Lauren Stevens
`Dennis Bennett
`GLOBAL PATENT GROUP, LLC
`lstevens@globalpatentgroup.com
`dennisbennett@globalpatentgroup.com
`
`Matthew Phillips (Reg. No. 43,403)
`RENAISSANCE IP LAW GROUP LLP
`9600 S.W. Oak Street, Suite 560
`Portland, Oregon 97223
`matthew.phillips@renaissanceiplaw.com
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