UNITED STATES PATENT AND TRADEMARK OFFICE
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`___________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
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`LUPIN LTD. and LUPIN PHARMACEUTICALS, INC.
`Petitioner,
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`v.
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`HORIZON THERAPEUTICS, LLC
`Patent Owner
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`
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`PETITIONERS’ MOTION TO EXCLUDE EVIDENCE
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`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`
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`LUPIN LTD. and LUPIN PHARMACEUTICALS, INC.
`Petitioner,
`
`v.
`
`HORIZON THERAPEUTICS, LLC
`Patent Owner
`
`
`
`Case IPR2016-00829
`Patent 9,095,559 B2
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`
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`PETITIONERS’ MOTION TO EXCLUDE EVIDENCE
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`I.
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`Statement of Precise Relief Requested
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`Pursuant to 37 C.F.R. § 42.64(c), the Board’s Scheduling Order (Paper 8),
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`and the Federal Rules of Evidence, Petitioners Lupin Ltd. and Lupin
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`Pharmaceuticals, Inc. (collectively, “Petitioners”) hereby move to exclude Patent
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`Owner’s Exhibits 2019 and 2041, and the portions of the Declaration of Dr. Enns
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`(Ex. 2006) that rely on Exhibit 2019.
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`II.
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`Identification of Original Objections
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`On February 17, 2017, Petitioners timely filed objections to Exhibits 2019
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`and 2041. Paper 28 at 6, 11. Petitioners asserted that Exhibits 2019 and 2041
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`were, inter alia, dated after September 30, 2011, and thus irrelevant and prejudicial
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`under Federal Rules of Evidence (“FRE”) 402 and 403, respectively, to the extent
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`they were relied upon for any teaching prior to September 30, 2011. Petitioners
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`also objected to the Declaration of Dr. Enns (Ex. 2006) to the extent it includes or
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`relies on such irrelevant information or information the probative value of which is
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`substantially outweighed by the danger of unfair prejudice, wasting time, or
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`needlessly presenting cumulative evidence.
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`Patent Owner did not respond, with supplemental evidence or otherwise, to
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`Petitioners’ objections to these exhibits.
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`III.
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`Identification of Where Patent Owner Relied Upon Evidence
`A.
`Exhibit 2019 is a purported copy of a 2012 article by Häberle et al., entitled
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` Exhibit 2019
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`Suggested Guidelines for the Diagnosis and Management of Urea Cycle Disorders,
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`published in ORPHANET JOURNAL OF RARE DISEASES.
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`In its Patent Owner’s Response (Paper 26), Patent Owner cited Exhibit 2019 in
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`support of the following assertions regarding the purported common practices of a
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`person of ordinary skill in the art at the time of the alleged invention:
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` “Clinicians only considered plasma ammonia levels well above the upper
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`limit of normal as cause to take further action.” (Paper 26 at 12.) Dr. Enns
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`made a similar assertion in Ex. 2006 at ¶ 43 (cited at Paper 26 at 12).
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` “[N]othing supports the assumption that a physician would have been
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`concerned or taken any action when a patient had a normal plasma ammonia
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`level, or that the action would have been to increase the dosage of nitrogen
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`scavenging medication as opposed to focusing on adjusting the patient’s
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`diet, health, or amino acid supplements. Dr. Vaux entirely omits any
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`discussion of the variable and multifaceted components of treating UCD
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`patients.” (Paper 26 at 34 (citations omitted).) For this proposition, Patent
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`Owner also cited Dr. Enns’s declaration, including ¶¶ 35-37, 41 and 87,
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`which in turn rely on Exhibit 2019.
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`Case IPR2016-00829
`Patent 9,095,559 B2
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` “[T]he prior art gave no indication regarding what should be adjusted or
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`changed in a patient with a normal plasma ammonia level. Dr. Enns further
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`explains that diet was the cornerstone of UCD treatment, especially because
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`diet was one of the reasons for plasma ammonia levels rising during the
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`day. . . . The prior art reflects Dr. Enns’s opinion and teaches stopping
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`protein intake when a patient’s plasma ammonia level goes above the upper
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`limit of normal; not increasing any medication dosage.” (Paper 26 at 35
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`(citations omitted).) For these propositions, Patent Owner also cited Dr.
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`Enns’s declaration, including ¶¶ 37 and 87, which in turn rely on Exhibit
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`2019.
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` “Persons skilled in the art viewed a normal plasma ammonia level as
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`acceptable because treating a UCD patient involved a difficult balance
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`between diet, amino acid supplements, nitrogen scavenging drugs, and the
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`patients’ health. The skilled artisan treating a patient with a urea cycle
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`disorder was constantly concerned about maintaining normal growth and
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`avoiding hyperammonemic episodes.” (Paper 26 at 40 (citations omitted).)
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`For these propositions, Patent Owner also cited Dr. Enns’s declaration,
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`including ¶¶ 34, 35 and 113, which in turn rely on Exhibit 2019.
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` “In another example, Haberle includes a table of the suggested actions to
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`take in symptomatic patients based on their ammonia level. The Table does
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`not list any action to take when a patient is within a normal range of plasma
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`ammonia. When the ammonia level is ‘above upper limit of normal,’
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`Haberle recommends stopping protein intake, IV glucose, and continued
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`monitoring of plasma ammonia. Only at the next level, when ammonia
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`level is even higher than the upper limit of normal, does the table
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`recommend increasing the dosage of nitrogen scavenging drugs.” (Paper 26
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`at 42-43 (citations omitted).) For these propositions, Patent Owner also
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`cited Dr. Enns’s declaration, ¶ 118, which in turn relies on Exhibit 2019.
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` “For this reason, clinicians looked at the total picture of a UCD patient
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`when considering treatment including diet, health, and supplements, and did
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`not unnecessarily increase a patient’s dosage.” (Paper 26 at 45.) For this
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`proposition, Patent Owner also cited Dr. Enns’s declaration, ¶ 87, which in
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`turn relies on Exhibit 2019.
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`Patent Owner and Dr. Enns also cited Exhibit 2019 for the following general
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`propositions regarding urea cycle disorders:
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` “It is estimated that one out of only 35,000 live births have this disorder,
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`resulting in only 113 new patients in the U.S. per year.” (Paper 26 at 8;
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`Enns Declaration (Ex. 2006) at ¶ 33.)
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` “Because of the rarity of this disorder [UCDs] (only approximately 113 new
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`patients per year) and high mortality rate, a general pediatrician would not
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`Patent 9,095,559 B2
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`have extensive exposure to these types of patients.” (Enns Declaration (Ex.
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`2006) at ¶ 28.)
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` “Symptoms of this disorder often appear within 24 to 48 hours after a
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`normal birth when a newborn begins to exhibit progressive lethargy,
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`hypothermia, and apnea. Onset of symptoms, however, can appear at any
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`age.” (citations omitted.) (Paper 26 at 8; Enns Declaration (Ex. 2006) at ¶
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`34.)
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` “But even when plasma ammonia levels are brought back down to normal,
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`the prior periods of high ammonia levels often cause irreversible damage to
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`the central nervous system, leaving patients with severe neurological and
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`developmental disabilities.” (Paper 26 at 9.)
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` “A UCD diagnosis therefore presents a patient and one’s family with a
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`lifetime of coordinating with a complex therapeutic regimen that involves
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`promoting a child’s growth/development while concurrently trying to avoid
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`the potentially devastating consequences of a hyperammonemic crises.”
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`(Paper 26 at 9.)
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` “The main goal of treatment is therefore a balance between correcting the
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`biochemical issue, preventing the development of hyperammonemia, and
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`ensuring that the patient’s nutritional needs for growth and development are
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`met.” (Enns Declaration (Ex. 2006) at ¶ 35, cited at Paper 26 at 9.)
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`Case IPR2016-00829
`Patent 9,095,559 B2
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` “Chronic UCD treatment also requires a balanced therapeutic regimen
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`involving low-protein diets, amino acid supplementation, and alternative
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`pathway therapy with nitrogen scavenging drugs.” (Paper 26 at 9-10.) Dr.
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`Enns made a similar assertion in Ex. 2006 at ¶ 36 (cited at Paper 26 at 10).
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` “Dietary treatment is the ‘cornerstone of therapy’ for UCD patients because
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`minimizing protein intake will decrease the nitrogen load on the urea cycle.
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`But protein restriction decreases the nutrients needed for growth and normal
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`development that are essential for a growing child. Therefore
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`supplementation with essential amino acid mixtures or the use of nitrogen
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`scavenging drugs is often necessary to achieve good metabolic control.”
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`(Paper 26 at 10-11 (citations omitted).) Dr. Enns made a similar assertion
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`in Ex. 2006 at ¶ 37 (cited at Paper 26 at 10-11).
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` “In addition to a therapeutic regimen for controlling plasma ammonia
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`levels, a UCD patient also must endure the lifelong monitoring of the
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`patient’s growth and development, use of dietary assessments, and
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`laboratory testing of plasma glutamine levels, plasma ammonia levels, and
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`amino acid profiles.” (Paper 26 at 11.) Dr. Enns made a similar assertion in
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`Ex. 2006 at ¶ 41 (cited at Paper 26 at 11).
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`With respect to these propositions, Patent Owner’s citation of Exhibit 2019
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`is merely cumulative of other cited exhibits and Dr. Enns’s testimony.
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`B.
`Exhibit 2041
`Exhibit 2041 is a purported copy of the Prescribing Information for Ravicti®.
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`Patent Owner cites Exhibit 2041 on page 26 of Patent Owner’s Response (Paper
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`26) in support the following assertion:
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` “Glyceryl tri-[4-phenylbutyrate] is an oral medication, not an intravenous
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`medication, and it is approved for the long-term management of plasma
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`ammonia levels in UCD patients. It is not indicated for the treatment of
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`acute hyperammonemia.”
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`Dr. Enns did not cite Ex. 2041.
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`IV. Objections and Explanations Thereof
`Exhibits 2019 and 2041 should be excluded for at least the following
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`reasons.
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`A. Exhibit 2019 Should Be Excluded Under FRE 402/403
`Patent Owner attempts to use Exhibit 2019 to prove the state of the art prior
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`to September 30, 2011 (the relevant priority date in this proceeding), specifically to
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`demonstrate that a person of ordinary skill in the art purportedly would not take
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`any treatment action in a UCD patient who has a normal plasma ammonia value.
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`See supra Section III(A). Exhibit 2019 states on its face that it was published on
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`May 29, 2012 (Ex. 2019 at 24), which is several months after the September 30,
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`2011 priority date of U.S. Patent No. 9,095,559. Accordingly, Exhibit 2019 is not
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`prior art, and is thus irrelevant for purposes of establishing the purported prior art
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`practices of persons of ordinary skill in the art. To the extent Patent Owner relies
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`on Exhibit 2019 for any other purposes, that reliance is merely cumulative of other
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`evidence on which Patent Owner relies. Having this irrelevant document in the
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`record is prejudicial, as Patent Owner is relying on it for improper purposes.
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`The probative value of Exhibit 2019 is substantially outweighed by the
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`undue prejudice stemming from Patent Owner’s improper reliance on this non-
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`prior art document to show purported prior art practices, and by its cumulative
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`nature. Exhibit 2019 should therefore be excluded under FRE 402 and 403.
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`Exhibit 2041 Should Be Excluded Under FRE 402/403
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`B.
`Patent Owner uses Exhibit 2041 to argue that a person of ordinary skill in
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`the art would not have been motivated to combine Simell (Ex. 1005) with the ’859
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`Publication (Ex. 1007). Patent Owner’s reasoning is that the nitrogen scavenging
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`drugs in Simell, benzoate and phenylacetate, are approved for different indications
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`than one of the nitrogen scavenging drugs discussed in the ’859 Publication,
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`glyceryl tri-[4-phenylbutyrate], and that these drugs have different routes of
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`administration. (Paper 26 at 26.) In support of this argument, Patent Owner relies
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`in part on Exhibit 2041. But Exhibit 2041 states on its face that it was revised in
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`September 2016 (Ex. 2041 at 1), and fails to indicate its actual publication date,
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`which in any event must be several years after the September 30, 2011 priority
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`date of U.S. Patent No. 9,095,559. Accordingly, because Patent Owner has
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`improperly used Exhibit 2041—which is dated after the September 30, 2011
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`priority date of U.S. Patent No. 9,095,559 and is thus not prior art—for the
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`exclusive purpose of establishing purported facts available to persons of ordinary
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`skill in the art as of the priority date, Exhibit 2041 should be excluded as irrelevant
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`and prejudicial under FRE 402 and 403.
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`Portions of Exhibit 2006 Should Be Excluded Under FRE 402/403
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`C.
`Horizon’s Gregory M. Enns, MD (Exhibit 2006) relies in part on Exhibit
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`2019. See Section III(A). As stated above, Exhibit 2019 should be excluded under
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`FRE 402/403 as its probative value is substantially outweighed by the undue
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`prejudice stemming from Patent Owner’s improper reliance on this non-prior art
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`document to show purported prior art practices, and by its cumulative nature.
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`Therefore, to the extent Dr. Enns relies in his declaration on Ex. 2019 (e.g. in Ex.
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`2006 ¶¶ 28, 33-37, 41, 43, 87, 113 and 118), that reliance should similarly be
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`excluded under FRE 402/403.
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`V. Conclusion
`For at least the foregoing reasons, Petitioners respectfully request that this
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`motion be granted and that Patent Owner’s Exhibits 2019 and 2041 be excluded,
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`and that portions of Ex. 2006 be excluded to the extent they rely on Ex. 2019.
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`Dated: June 12, 2017
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`Respectfully submitted,
`/Cynthia Lambert Hardman/
`Elizabeth J. Holland (Reg. No. 47,657)
`Cynthia Lambert Hardman (Reg. No.
`53,179)
`Robert V. Cerwinski (pro hac vice)
`GOODWIN PROCTER LLP
`The New York Times Building
`620 Eighth Avenue
`New York, NY 10018
`(212) 813-8800 (telephone)
`(212) 355-3333 (facsimile)
`
`Counsel for Petitioners
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`CERTIFICATE OF SERVICE
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`Case IPR2016-00829
`Patent 9,095,559 B2
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`The undersigned hereby certifies that PETITIONERS’ MOTION TO EXCLUDE
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`EVIDENCE was served electronically via email on June 12, 2017 on the
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`following:
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`James B. Monroe (lead counsel, Reg. No. 33,971)
`Maureen D. Queler (backup counsel, Reg. No. 61,879)
`FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, LLP
`James.monroe@finnegan.com
`Maureen.queler@finnegan.com
`
`
`
`Matthew Phillips (backup counsel, Reg. No. 43,403)
`LAURENCE & PHILLIPS IP LAW LLP
`mphillips@lpiplaw.com
`
`
`
`Robert Green (Reg. No. 27,555)
`Emer Simic (Reg. No. 61,235)
`Jessica Tyrus (Reg. No. 64,742)
`GREEN, GRIFFITH & BORG-BREEN, LLP
`rgreen@greengriffith.com
`esimic@greengriffith.com
`jtyrus@greengriffith.com
`
`
`
`Dennis Bennett (Reg. No. 34,457)
`GLOBAL PATENT GROUP LLC
`dennisbennett@globalpatentgroup.com
`
`Dated: June 12, 2017
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`
`
`
`
`/Cynthia Lambert Hardman/
`Cynthia Lambert Hardman
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