`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`___________________
`
`
`NOVEN PHARMACEUTICALS, INC.
`AND MYLAN PHARMACEUTICALS INC.,
`Petitioners
`
`v.
`
`NOVARTIS AG AND LTS LOHMANN THERAPIE-SYSTEME AG,
`Patent Owners
`
`___________________
`
`
`Inter Partes Review IPR2014-005501
`
`U.S. Patent No. 6,335,031
`
`
`PETITIONERS’ RESPONSE TO PATENT OWNERS’ MOTION FOR
`OBSERVATIONS ON CROSS-EXAMINATION OF DR. SCHÖNEICH
`
`
`
`1 Case IPR2015-00268 has been joined with this proceeding.
`
`
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`
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`Response to p. 1 ¶ 1: The testimony cited by Patent Owners demonstrates
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`neither that bond strength is theoretical nor “that a POSA would not have
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`reasonably predicted that rivastigmine would undergo oxidative degradation”
`
`based on its structure as Patent Owners assert. (Paper 44 at 1.) Dr. Schöneich
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`testified that the bond dissociation energies reported in Carey & Sundberg
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`(“C&S”) (Ex. 1007) are “absolute values” and are “independent of the
`
`measurement.” (Ex. 1048 at 23:8-14, discussing ¶13 of Dr. Schöneich’s Reply
`
`Declaration (Ex. 1032), which reproduces bond dissociation energy values from
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`C&S (Ex. 1007 at 683).) As Dr. Schöneich testified, the bond dissociation energy
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`(i.e., bond strength) for a particular bond in a molecule is an inherent property of
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`the molecule based on its chemical structure. (Ex. 1025 at 58:13-21.) Because
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`rivastigmine has three structural features immediately adjacent to a particular
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`carbon-hydrogen (“C-H”) bond, a POSA would have immediately identified this
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`bond as especially weak and particularly susceptible to oxidation. (Ex. 1011 ¶¶ 12,
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`55; Ex. 1025 at 48:2-49:13, 73:17-76:22; Ex. 1032 ¶¶ 14-15.)
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`Response to p. 1 ¶ 2: The testimony cited by Patent Owners does not
`
`demonstrate “that a POSA would not have reasonably predicted that rivastigmine
`
`would undergo oxidative degradation” based on its structure as Patent Owners
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`assert. (Paper 44 at 1.) Dr. Schöneich did not testify that C&S “provides only
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`relative reactivities, not absolute reactivities of aromatic hydrocarbons” as Patent
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`
`
`1
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`
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`Owners assert. (Id., emphasis added.) It was Patent Owners’ questioning that
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`related only to a single table in C&S that shows the relative reactivities of aromatic
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`hydrocarbons. These relative reactivities are important to demonstrate that a C-H
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`bond at a benzylic position, that is also a tertiary position (as in rivastigmine), is 67
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`times more reactive to oxygen than a C-H bond in a benzylic position alone. (Ex.
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`1032 ¶ 13, citing Ex. 1007 at 693.) Patent Owners further mischaracterize Dr.
`
`Schöneich’s testimony, because he also testified that C&S provides the absolute
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`bond strengths of tertiary and benzylic C-H bonds in the table of bond dissociation
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`energies and states that “Benzylic, allylic, and tertiary positions are especially
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`susceptible to oxidation.” (Ex. 1032 ¶¶ 8, 10, 11, citing Ex. 1007 at 683, 693.)
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`This testimony demonstrates that a POSA would have reasonably predicted that
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`rivastigmine would undergo oxidative degradation based on its chemical structure
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`because the POSA would have recognized that a particular C-H bond in
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`rivastigmine is especially weak and therefore susceptible to oxidation.
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`Response to p. 2 ¶ 1: The testimony cited by Patent Owners does not
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`demonstrate that “a POSA would not have reasonably predicted from its structure
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`that rivastigmine would undergo oxidative degradation . . . or require an
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`antioxidant” as Patent Owners assert. (Paper 44 at 2.) Dr. Schöneich testified that
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`a POSA would understand that “oxidation reactions usually occur significantly
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`slower” in the dry state. (Ex. 1048 at 70:7-20, see also Ex. 1032 ¶ 48) Thus, a
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`
`
`2
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`
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`POSA would have understood that an antioxidant may not be necessary even for an
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`oxidation-sensitive drug when is it formulated as a dry dosage form. (Ex. 1048 at
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`69:18-70:2, quoting Ex. 1032 ¶ 48.)
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`
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`Response to p. 2 ¶ 2, p. 5 ¶ 1, p. 12 ¶ 1: Patent Owners’ assertions that Dr.
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`Schöneich’s “structural theory is unproven” (Paper 44 at 2, 5-6) is not supported
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`by the testimony cited by Patent Owners. Dr. Schöneich testified that a POSA
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`would have immediately recognized that rivastigmine was particularly susceptible
`
`to oxidation due to the presence of three structural features2 immediately adjacent
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`to a C-H bond that a POSA would understand to cause that bond to be especially
`
`weak and therefore readily oxidized. (Ex. 1025 at 48:2-49:13; Ex. 1011 ¶¶ 12, 53-
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`55; Ex. 1032 ¶¶ 7-15) The support for Dr. Schöneich’s opinion is drawn from a
`
`standard textbook, Carey & Sundberg (Ex. 1007), which identifies these same
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`structural features as causing adjacent C-H bonds to be “especially weak” and
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`therefore prone to oxidation. (Ex. 1032 ¶¶ 7-15; Ex. 1025 at 58:3-68:15.)
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`In addition, Dr. Schöneich provided nicotine as an example of a drug with
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`2 Patent Owners mischaracterize Dr. Schöneich’s’ opinion by reciting only two of
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`the three structural features identified by Dr. Schöneich that a POSA would have
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`recognized as causing a particular C-H bond in rivastigmine to be especially weak
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`and therefore particularly susceptible to oxidation. (Ex. 1011 ¶¶ 12, 55; Ex. 1025
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`at 48:2-49:13, 73:17-76:22; Ex. 1032 ¶¶ 14-15.)
`
`
`
`3
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`
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`the same three key structural features as rivastigmine that was known to undergo
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`oxidation at the subject C-H bond and was known to oxidatively degrade in
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`pharmaceutical formulations including transdermal patches. (Ex. 1025 at 84:17-
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`89:20; Ex. 1026 at 452:1-5, 563:3-7; Ex. 1032 ¶¶ 46, 56-59.)
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`
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`Response to p. 2 ¶ 3: Patent Owners’ conclusion that “theoretical
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`‘susceptibility’ to oxidative degradation does not correlate with the pharmaceutical
`
`reality” (Paper 44 at 2-3) is not supported by the cited testimony. It was not
`
`merely an “assertion” of Dr. Schöneich’s that the benzylic position is “especially
`
`susceptible to oxidation.” Rather, Dr. Schöneich’s testimony is supported by, and
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`indeed quoted from, a standard chemistry textbook, Carey & Sundberg. (Ex. 1007
`
`at 693.) Dextromethorphan was reported to be only “moderately stable” and had
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`been observed to oxidatively degrade. (Ex. 1019 at 308; Ex. 1032 at 61.)
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`
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`Response to p. 3 ¶ 1 and p. 4 ¶ 1: Patent Owners incorrectly assert that Dr.
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`Schöneich mischaracterized the teachings of Boccardi 1994 (Ex. 2050) and
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`Boccardi 1989 (Ex. 1019). As Dr. Schöneich testified, Boccardi 1989 states that
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`dextromethorphan is only “moderately stable” and investigated the degradation of
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`dextromethorphan they had previously observed and assumed was due to the
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`presence of trace amounts of iron in glassware. (Ex. 1048 at 113:13-114:17; see
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`also Ex. 1032 ¶ 61; Ex. 1019 at 308.) Boccardi 1994 states that the product of
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`oxidative degradation (i.e., 10-ketodextromethorphan), was found in trace amounts
`
`
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`4
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`
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`during preformulation of an antitussive syrup. (Ex. 2050, Boccardi, at 433.) These
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`teachings are consistent with Dr. Schöneich’s opinion that dextromethorphan
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`(which has just one of the structural features—a benzylic C-H bond—found in
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`rivastigmine) was known to undergo oxidative degradation.
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`
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`Response to p. 3 ¶ 2:
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` Patent Owners incorrectly assert that Dr.
`
`Schöneich mischaracterized the teachings of Boccardi 1989. Dr. Schöneich
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`disagreed with Dr. Klibanov’s characterization of Boccardi 1989, because
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`Boccardi 1989 does not state that dextromethorphan will “only” degrade under the
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`accelerated conditions described in the article as Dr. Klibanov contended. (Ex.
`
`1048 at 96:6-15 quoting Ex. 1032 ¶ 61) As Dr. Schöneich testified, Boccardi 1989
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`used accelerated conditions to study oxidative degradation of dextromethorphan
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`that they had previously observed and assumed was due to trace amounts of iron in
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`glassware. (Ex. 1048 at 113:13-114:17; see also Ex. 1032 ¶ 61; Ex. 1019 at 308.)
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`That iron ions (Fe(III)), a common initiator of oxidation, was required under the
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`accelerated conditions for oxidation to occur does not mean that dextromethorphan
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`oxidation only occurs under the accelerated conditions (which included conditions
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`like irradiation). Boccardi 1989 clearly states that the accelerated conditions were
`
`used “[i]n an effort to define the role of trace metals in these reactions,” i.e., the
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`previously observed degradation reactions. (Ex. 1019 at 308; Ex. 1032 ¶ 61.)
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`Thus, Dr. Schöneich’s testimony is consistent with the teachings of Boccardi 1989.
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`5
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`
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`Response to p. 4 ¶ 2 and p. 6 ¶ 1: Patent Owners mischaracterize Dr.
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`Schöneich’s testimony. Dr. Schöneich cited literature demonstrating that nicotine
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`(a real-world pharmaceutical compound), which has the same three key structural
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`features as rivastigmine, was known to undergo oxidative degradation including in
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`transdermal patch formulations. (Ex. 1048 at 50:17-51:2, Ex. 1011 ¶¶ 48-49, 56-
`
`58; Ex. 1032 ¶¶ 56-59.)
`
`Patent Owners’ statement concerning the so-called “real-world” compounds
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`is misleading. Dr. Schöneich and Patent Owners’ expert, Dr. Klibanov, both
`
`testified that a POSA would not draw any conclusions regarding the oxidative
`
`stability of a drug compound that is formulated in a commercial product without an
`
`antioxidant because the formulator could have taken steps other than adding an
`
`antioxidant to prevent oxidation. (Ex. 1032 ¶ 42-45; Ex. 1025 at 91:8-92:2; Ex.
`
`1026 at 551:9–552:16, 553:1-6.) Dr. Klibanov and Dr. Schöneich thus agreed that
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`a POSA would not draw any conclusions regarding a compound’s susceptibility to
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`oxidation from Dr. Klibanov’s so-called “real-world” examples. (Id.)
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`
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`Response to p. 6 ¶ 2, p. 10 ¶ 2: The testimony cited by Patent Owners is
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`consistent with Dr. Schöneich’s previous testimony that all of Dr. Klibanov’s
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`“real-world” examples were formulated in a dry dosage form, as a salt, or both,
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`which a POSA would understand to reduce oxidation. (Ex. 1032 ¶¶ 47-48, Ex.
`
`1025 at 91:8-92:2). Dr. Klibanov never contests that formulation of his “real-
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`
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`6
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`world” compounds as salts (in liquid or solid form) would have been understood
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`by a POSA to reduce oxidation.
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`
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`Response to p. 7 ¶ 1: Patent Owners’ assertions that “theoretical
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`‘susceptibility’ to oxidative degradation does not correlate with pharmaceutical
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`realities and that it is the structure of the molecule as a whole that determines
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`stability” are not supported by the cited testimony. Dr. Schöneich explained that
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`Dr. Klibanov’s so-called “real world” compounds were formulated as either a solid
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`dosage form, as a salt, or both, which are measures that a POSA would understand
`
`to reduce oxidation so that an antioxidant may not be necessary. (Ex. 1048 at
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`69:18-71:12, 72:8-16, 103:22-104:10, Ex. 1032 ¶¶ 47-48.)
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`That the so-called “real-world” pharmaceutical compounds were formulated
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`without an antioxidant does not demonstrate that these compounds are oxidatively
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`stable or that the structure of the molecule as a whole determines stability as Patent
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`Owners contend. Dr. Schöneich and Patent Owners’ expert, Dr. Klibanov, both
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`testified that a POSA would not draw any conclusions regarding the oxidative
`
`stability of a drug compound that is formulated in a commercial product without an
`
`antioxidant because the formulator could have taken steps other than adding an
`
`antioxidant to prevent oxidation. (Ex. 1032 ¶ 42-45; Ex. 1025 at 91:8-92:2; Ex.
`
`1026 at 551:9–552:16, 553:1-6.) Dr. Klibanov and Dr. Schöneich thus agreed that
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`a POSA would not draw any conclusions regarding a compound’s susceptibility to
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`7
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`
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`oxidation from Dr. Klibanov’s so-called “real-world” examples. (Id.)
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`
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`Response to p. 8 ¶¶ 1-2: Patent Owners incorrectly assert that “the absence
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`of any indication of oxidative instability in the PDR . . . suggests that those
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`compounds were not known to undergo oxidative degradation under
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`pharmaceutically relevant conditions.” (Paper 44 at 8, 9.) Patent Owners’
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`assertion conflicts with Dr. Schöneich’s testimony and with the testimony of Patent
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`Owners’ expert, Dr. Klibanov. Dr. Klibanov and Dr. Schöneich agreed that a
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`POSA would not draw any conclusions regarding a compound’s susceptibility to
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`oxidation from Dr. Klibanov’s so-called “real-world” examples from the PDR.
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`(Ex. 1032 ¶¶ 42-45; Ex. 1025 at 91:8-92:2; Ex. 1026 at 551:9–552:16, 553:1-6.)
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`
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`The excerpt of 21 CFR § 201.57 (Ex. 2060) does not contradict any of Dr.
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`Schöneich’s opinions as Patent Owners assert (Paper 44 at 9). There is no expert
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`testimony concerning the relevance of this document to either parties’ positions in
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`this proceeding or the meaning of the text cited by Patent Owners. Patent Owners
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`introduced the document for the first time during Dr. Schöneich’s deposition, and
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`Dr. Schöneich’s only admission was that Patent Owners’ counsel read a sentence
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`from the document correctly (Ex. 1048 at 58:19-63:16).
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`
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`Response to p. 9 ¶ 1: The cited testimony at Ex. 1048, 13:18-14:20 does
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`not contradict Dr. Schöneich’s opinion that a POSA would have recognized that
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`oxidation of rivastigmine is similar to the oxidation of olefins (alkenes). Dr.
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`
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`8
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`
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`Schöneich explained that rivastigmine “is a substituted alkene” and a “special form
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`of an alkene.” (Ex. 1048 at 12:5-9 (emphasis added), 13:23-14:2.) Dr. Schöneich
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`testified that a POSA would have recognized that the oxidation of rivastigmine
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`(and that of nicotine) is similar to the well-known oxidation of alkenes (olefins)
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`because like alkenes, rivastigmine (and nicotine) contains a C-H bond adjacent to a
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`carbon-carbon double bond. (Ex. 1032 ¶¶ 31, 57-8, Ex. 1048 at 12:25-13:15.)
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`
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`Response to p. 9 ¶ 2: Patent Owners mischaracterize Dr. Schöneich’s
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`testimony. Dr. Schöneich stated that an unsubstituted olefin (alkene) cannot form
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`an N-oxide. (Ex. 1048 at 15:12-15.) However, Dr. Schöneich testified that
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`rivastigmine would be considered a substituted olefin (alkene). (Id., 10:24-12:24.)
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`Patent Owners assertion that “it is now known that when rivastigmine
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`oxidizes, it forms an N-oxide” is unsupported attorney argument that is not
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`supported by any testimony in this proceeding. Patent Owners’ sole basis for this
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`statement is a single-page excerpt of a Novartis document (Ex. 2059) produced for
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`the first time at Dr. Schöneich’s deposition (see Ex. 1048 at 16:18-18:20). Patent
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`Owners’ expert, Dr. Klibanov, does not address this document in his declaration.3
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`An N-oxide degradation product further supports Dr. Schöneich’s opinions
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`regarding the predictability of rivastigmine’s oxidation because an N-oxide is one
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`of the rivastigmine degradation products shown in Appendix A to Dr. Schöneich’s
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`3 Petitioners have requested that the Board exclude this document. (Paper 47.)
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`9
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`
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`Declaration (Ex. 1011 at A11; Ex. 1048 at 19:14-20:21). Dr. Schöneich predicted
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`that oxidation at the subject carbon-hydrogen bond would result in the formation of
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`the N-oxide. (Ex. 1011 ¶¶ A1, A3, A11.)
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`
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`Response to p. 10 ¶ 1: Patent Owners incorrectly assert that testimony at
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`Ex. 1048, 92:5-15 and 110:21-111:12 contradicts Dr. Schöneich’s prior testimony
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`(Ex. 1025 at 96:10-18). Dr. Schöneich’s prior testimony is consistent with the
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`testimony cited by Patent Owners. Dr. Schöneich previously testified that a POSA
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`would have immediately recognized that rivastigmine, due to the presence of three
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`adjacent functional groups, would be “particularly susceptible” and “prone to
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`oxidation” because it contains an “especially weak,” and “readily-cleaved C-H
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`bond.” (See, e.g., Ex. 1025 at 48:2-49:13; Ex. 1011 ¶¶ 12, 55.)
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`
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`Patent Owners incorrectly assert that Dr. Schöneich stated in his previous
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`testimony that a POSA would need to conduct testing to determine whether
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`rivastigmine oxidatively degrades. In fact, Dr. Schöneich testified that although a
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`POSA can determine if a compound like rivastigmine is prone to oxidative
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`degradation by examination of its chemical structure, such degradation depends
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`upon the environment (e.g., whether oxygen, initiators, or antioxidants are
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`present). (Ex. 1025 at 94:21-95:6, 95:24-96:6, see also id. at 79:16-80:24.)
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`
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`Response to p. 11 ¶¶ 1-2: Patent Owners mischaracterize Dr. Schöneich’s
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`testimony. Patent Owners incorrectly assert that Dr. Schöneich testified that
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`10
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`
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`formulation of a compound in a dry dosage form establishes that is susceptible to
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`oxidation or that measures were taken to avoid oxidation. Dr. Schöneich testified
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`that the so-called “real world examples” selected by Dr. Klibanov from the PDR
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`were formulated as a dry dosage form, as a salt, or both. (Ex. 1032 ¶ 47.) Dr.
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`Schöneich further testified that a POSA would know that oxidation is usually
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`reduced in the dry state so that an antioxidant may not be necessary even for an
`
`oxidation-sensitive drug. (Ex. 1032 ¶¶ 47-48; Ex. 1025 at 79:16-80:14, 186:11-
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`186:24; Ex. 1016 at 92). The quote from Ex. 2021 cited by Patent Owners is
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`consistent with Dr. Schöneich’s testimony because it states that oxidation can
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`occur in the solid state only “to some extent.” (Ex. 2021 at 80).
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`
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`Response to p. 12 ¶ 1: Patent Owners incorrectly assert that Dr.
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`Schöneich’s testimony is unsupported. Regarding Dr. Klibanov’s so-called “real-
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`world” compounds, Dr. Schöneich testified that they were formulated as either a
`
`solid dosage form, as a salt, or both, which are measures that a POSA would
`
`understand to reduce oxidation so that an antioxidant may not be necessary. (Ex.
`
`1048 at 69:18-71:12, 72:8-16, 103:22-104:10, Ex. 1032 ¶¶ 47-48.) Dr. Schöneich
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`never testified that alternative measures (other than formulation in a dry dosage
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`form or as a salt) were in fact taken. Rather, Dr. Schöneich and Patent Owners’
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`expert, Dr. Klibanov, testified that a POSA would not draw any conclusions
`
`regarding the susceptibility to oxidation of a compound in a commercial
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`
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`11
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`
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`formulation without an antioxidant (i.e., the “real-world” compounds) because the
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`formulator could take steps other than adding an antioxidant to prevent oxidation.
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`(Ex. 1032 ¶ 42-45; Ex. 1025 at 91:8-92:2; Ex. 1026 at 551:9–552:16, 553:1-6.)
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`
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`Response to p. 12 ¶ 2: Patent Owners incorrectly assert that Dr.
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`Schöneich’s testimony is unsupported. Dr. Schöneich did not admit that “he did
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`not cite any document” as Patent Owners contend. To the contrary, Dr. Schöneich
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`testified that he cited to Dr. Klibanov’s Declaration describing the mechanism of
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`carbamate hydrolysis by base catalysis. (Ex. 1048 at 102:9-103:2; see also Ex.
`
`1032 ¶ 29 citing ¶ 92 of Dr. Klibanov’s Declaration (Ex. 2012).) Dr. Schöneich’s
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`statement that a POSA would have recognized that the presence of the basic
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`tertiary amines in one molecule [of physostigmine] would facilitate hydrolysis of
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`the carbamate group on other [physostigmine] molecules” was supported by Dr.
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`Schöneich’s citation to Patent Owners’ expert declaration.
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`
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`Response to p. 12 ¶ 3: Patent Owners draw incorrect conclusions from Dr.
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`Schöneich’s testimony where he stated that dosage form is significant. Dr.
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`Schöneich testified that a POSA would understand that oxidation reactions can be
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`reduced or prevented when a compound is formulated in a dry dosage form. (Ex.
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`1032 ¶ 48.) Dr. Schöneich did not testify that a POSA would not be informed by
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`oxidative degradation of rivastigmine in oral and injectable formulations. To the
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`contrary, Dr. Schöneich testified that the susceptibility of a compound to oxidation
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`
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`12
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`
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`is an inherent property of the molecule based on its chemical structure and that
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`inherent susceptibility is present in any formulation including transdermal
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`formulations (Ex. 1032 ¶ 26; Ex. 1025 at 80:15-24.) Thus, a POSA would have
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`considered disclosure of oxidative degradation in oral and injectable formulations
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`to be relevant to transdermal formulations.
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`
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`Response to p. 13 ¶¶ 1-2: Patent Owners incorrectly assert that Dr.
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`Schöneich mischaracterized Dr. Klibanov’s opinions. Dr. Schöneich testified that
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`Dr. Klibanov applied functional group chemistry when Dr. Klibanov made general
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`predictions regarding the susceptibility of monomethyl carbamates to hydrolysis
`
`and the resistance of dialkyl carbamates to hydrolysis. (Ex. 1032 ¶¶ 6, 27-28.)
`
`
`
`That these functional groups were studied experimentally since the 1930s
`
`and the known reactivity of monomethyl carbamates was based on past
`
`experimentation does not change the fact that Dr. Klibanov made general
`
`predictions about the stability of molecules based only on the presence of these
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`functional groups (i.e., applied functional group chemistry). As Dr. Schöneich
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`stated, the utility of functional group chemistry is that a particular functional group
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`will have a known reactivity regardless of the structure of the rest of the molecule.
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`(Ex. 1032 ¶ 24; Ex. 1038 at 167; Ex. 1047 at 46.) Thus, Dr. Schöneich correctly
`
`stated that Dr. Klibanov applied functional group chemistry when discussing the
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`reactivity of carbamates in violation of his notion that the whole molecule (and not
`
`
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`13
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`
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`the presence of functional groups) determines stability. (Ex. 1032 ¶¶ 27-28.)
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`
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`Response to p. 14 ¶ 1: Patent Owners incorrectly assert that Dr. Schöneich
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`mischaracterized Dr. Klibanov’s opinions. Dr. Schöneich stated that the only
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`support relied upon by Dr. Klibanov for his assertion that the “whole molecule”
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`determines stability was a single sentence in the ’548 patent concerning the
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`hydrolytic degradation of physostigmine. (Ex. 1032 ¶ 27.) That Dr. Klibanov also
`
`stated that “[t]he following numerous real-world examples further demonstrate that
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`point” (Ex. 2012 ¶ 132) does not refute Dr. Schöneich’s statements because Dr.
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`Klibanov provides no support or citation, nor does he explain how his “real-world”
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`examples support the notion. (Ex. 2012 ¶ 132.) The only support that Dr.
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`Klibanov provided in his prior testimony is his citation to the ’548 patent (Ex. 2012
`
`¶ 83 (footnote 16)). Thus, Dr. Schöneich did not mischaracterize Dr. Klibanov’s
`
`opinion when he stated that the ’548 patent was the only support cited by Dr.
`
`Klibanov for his whole molecule determines stability notion.
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`
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`Response to p. 15 ¶ 1: Patent Owners incorrectly assert that Dr. Schöneich
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`mischaracterized Dr. Klibanov’s opinions when he stated that opinions in Dr.
`
`Klibanov’s Declaration are inconsistent with his prior testimony. Dr. Klibanov
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`unequivocally testified that a POSA would not draw any conclusions regarding the
`
`susceptibility to oxidation of a compound formulated in a commercial formulation
`
`without an antioxidant (i.e., the “real-world” compounds) because the formulator
`
`
`
`14
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`
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`could take steps other than adding an antioxidant to prevent oxidation. (Ex. 1026
`
`at 551:9–552:16, 553:1-6.) As Dr. Schöneich explained, testimony in Dr.
`
`Klibanov’s Declaration contradicts this previous testimony. Specifically,
`
`regarding his “real-world” pharmaceutical compounds, Dr. Klibanov stated that
`
`“[i]n the absence of any teaching or suggestion to the contrary, a POSA would
`
`expect that the drugs in these formulations do not undergo oxidative degradation
`
`under pharmaceutically relevant conditions” (Ex. 2012, FN 15). That Dr. Klibanov
`
`also stated that he was not aware of literature reporting the oxidative degradation
`
`of these compounds does not change the fact that Dr. Klibanov’s statement in his
`
`declaration is inconsistent with his prior testimony.
`
`
`
`Response to p. 15 ¶ 2: Patent Owners incorrectly state that Dr. Schöneich
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`mischaracterized Dr. Klibanov’s opinions regarding the structural features that a
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`POSA would recognize as making rivastigmine susceptible to oxidation. By
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`taking one sentence out of context, Patent Owners mischaracterize Dr. Schöneich’s
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`testimony. The cited paragraph of Dr. Schöneich’s Reply Declaration states that
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`several compounds relied on by Dr. Klibanov do not have the three structural
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`features found in rivastigmine that a POSA would have recognized as causing
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`rivastigmine to be susceptible to oxidative degradation and that Dr. Klibanov
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`admitted that one or more of those structural features were missing from these
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`compounds. (Ex. 1032 ¶ 50.)
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`15
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`Dated: May 12, 2015
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`Respectfully submitted,
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`/Michael K. Levy/
`Steven J. Lee (Reg. No. 31,272)
`Michael K. Levy (Reg. No. 40,699)
`KENYON & KENYON LLP
`One Broadway
`New York, NY 10004-1007
`Tel: 212-425-7200
`Fax: 212-425-5288
`
`Counsel for Petitioner Noven Pharmaceuticals,
`Inc.
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`16
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`CERTIFICATE OF SERVICE
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` I
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` certify pursuant to 37 C.F.R. §42.6(e) that a copy of the foregoing
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`Petitioners’ Response to Patent Owners’ Motion for Observations on Cross-
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`Examination of Dr. Schöneich was served electronically on May 12, 2015 to
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`counsel for Patent Owners at the following email address:
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`/Michael K. Levy/
`Michael K. Levy (Reg. No. 40,699)
`KENYON & KENYON LLP
`One Broadway
`New York, NY 10004-1007
`Tel: 212-425-7200
`Fax: 212-425-5288
`Counsel for Petitioner Noven Pharmaceuticals,
`Inc.
`
`ExelonPatchIPR@fchs.com.
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`Dated: May 12, 2015
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