Trials@uspto.gov
`Tel: 571-272-7822
`
`
`
`Paper 10
` Entered: October 14, 2014
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NOVEN PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG AND LTS LOHMANN THERAPIE-SYSTEME AG,
`Patent Owners.
`____________
`
`Case IPR2014-00549
`Patent 6,316,023 B1
`_____________
`
`
`Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and
`SCOTT E. KAMHOLZ, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`Tel: 571-272-7822
`
`
`
`Paper 10
` Entered: October 14, 2014
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`NOVEN PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`NOVARTIS AG AND LTS LOHMANN THERAPIE-SYSTEME AG,
`Patent Owners.
`____________
`
`Case IPR2014-00549
`Patent 6,316,023 B1
`_____________
`
`
`Before FRANCISCO C. PRATS, ERICA A. FRANKLIN, and
`SCOTT E. KAMHOLZ, Administrative Patent Judges.
`
`FRANKLIN, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`IPR2014-00549
`Patent 6,316,023 B1
`
`
`I.
`
`INTRODUCTION
`
`Noven Pharmaceuticals, Inc. (“Petitioner”) filed a Petition to institute
`
`an inter partes review of claims 1, 2, 4, 5, 7, and 8 of U.S. Patent No.
`
`6,316,023 B1 (Ex. 1001, “the ’023 patent”). Paper 1 (“Pet.”). Novartis AG
`
`and LTS Lohmann Therapie-Systeme AG (collectively, “Patent Owner”),
`
`filed a Preliminary Response to the Petition. Paper 7 (“Prelim. Resp.”).
`
`We have jurisdiction under 35 U.S.C. § 314, which provides that an
`
`inter partes review may not be instituted “unless . . . there is a reasonable
`
`likelihood that the petitioner would prevail with respect to at least 1 of the
`
`claims challenged in the petition.” Upon considering the Petition and
`
`Preliminary Response, we determine that Petitioner has shown a reasonable
`
`likelihood that it would prevail in showing the unpatentability of claims 1, 2,
`
`4, 5, 7, and 8 of the ’023 patent. Accordingly, we institute an inter partes
`
`review of those claims.
`
`A. Related Proceedings
`
`According to Petitioner and Patent Owner, the ’023 patent is involved
`
`in various district court actions, including two actions involving the parties
`
`to this proceeding, titled: Novartis Pharm. Corp. v. Noven Pharm. Inc., 1:13-
`
`cv-00527 (D. Del.); and Novartis Pharm. Corp. v. Noven Pharm. Inc., 1:14-
`
`cv-00111 (D. Del.). Pet. 1–2; Paper 6 at 2.
`
`Additionally, Petitioner has filed a petition for inter partes review of
`
`related U.S. Patent No. 6,335,031. IPR2014-00550, Paper 1.
`
`
`
`
`
`
`
`
`
`2
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`IPR2014-00549
`Patent 6,316,023 B1
`
`
`B. The ’023 Patent (Ex. 1001)
`
`The ’023 patent is directed to a pharmaceutical composition
`
`comprising (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methylphenyl
`
`carbamate (“compound A”; “rivastigmine”; “S-enantiomer of RA7”) in the
`
`form of a free base or acid addition salt, along with an antioxidant, and a
`
`diluent or carrier. Ex. 1001, 1:7–47. “Compound A is useful in inhibiting
`
`acetylcholinesterase in the central nervous system, e.g. for the treatment of
`
`Alzheimer’s disease.” Id. at 1:15–17. A transdermal composition
`
`comprising compound A in the form of a free base or acid addition salt, two
`
`polymers, and a plasticizer is disclosed in the prior art. Id. at 1:18–22. The
`
`inventors of the ’023 patent explained that the composition of the prior art
`
`“is susceptible to degradation, particularly in the presence of oxygen.” Id. at
`
`1:23–25. The ’023 patent states:
`
`The present applicant has found that stable pharmaceu-
`tical compositions comprising compound A can now be
`obtained, which show insignificant degradation of
`compound A over a prolonged time period, e.g. 2 years,
`as indicated by standard tests, e.g. stress tests.
`
`In one aspect, the invention provides a pharmaceutical
`composition comprising Compound A in free base or
`acid addition salt form and an anti-oxidant.
`
`The pharmaceutical compositions of the present
`invention show a reduction in degradation by-products in
`stress stability tests.
`
`Id. at 1:30–39.
`
`
`
`
`
`
`
`3
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`IPR2014-00549
`Patent 6,316,023 B1
`
`
`C. Illustrative Claims
`
`Independent claims 1 and 7 of the ’023 patent are illustrative of the
`
`claims at issue:
`
`A pharmaceutical composition comprising 1 to 40
`1.
`weight percent of (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-
`methylphenyl carbamate in the form of a free base or acid
`addition salt, 0.01 to 0.5 weight percent of an antioxidant, and a
`diluent or carrier, wherein the weight percents are based on the
`total weight of the pharmaceutical composition.
`
`Ex. 1001, 8:17–20.
`
`
`A transdermal device comprising a pharmaceutical
`7.
`composition comprising 1 to 40 weight percent of (S)-N-ethyl-
`3-[(1-dimethylamino)ethyl]-N-methylphenyl carbamate in the
`form of a free base or acid addition salt, 0.01 to 0.5 weight
`percent of an antioxidant, and a diluent or carrier, wherein the
`weight percents are based on
`the
`total weight of
`the
`pharmaceutical composition.
`
`Id. at 8:44–50.
`
`
`D. The Prior Art
`
`Petitioner relies on the following prior art:
`
`Enz
`
`UK Patent Application GB 2,203,040 A,
`published Oct. 12, 1988 (“Enz”)
`
`Handbook Handbook of Pharmaceutical Excipients (A.
`Wade & P.J. Weller eds., 2d ed. 1994)
`(“the Handbook”)
`
`Sasaki
`
`Ebert
`
`JP Patent Application 59-184121, published
`Oct. 19, 1984 (“Sasaki”)
`
`WO 95/24172, published Sept. 14, 1995
`(“Ebert”)
`
`Ex. 1002
`
`Ex. 1003
`
`Ex. 1005
`
`
`Ex. 1006
`
`
`
`
`
`4
`
`
`
`IPR2014-00549
`Patent 6,316,023 B1
`
`Kissel
`
`EP Patent Application 0155229A2, published
`Sept. 18, 1985 (“Kissel”)
`
`Rosin
`
`Elmalem
`
`US 4,948,807, issued Aug. 14, 1990
`(“Rosin”)
`
`Antagonism of Morphine-Induced
`Respiratory Depression by Novel
`Anticholinesterase Agents, 30
`NEUROPHARMACOLOGY. 1059-1064 (1991)
`(“Elmalem”)
`
`Ex. 1007
`
`Ex. 1008
`
`Ex. 1009
`
`Petitioner also relies on declarations of Dr. Agis Kydonieus
`
`(Ex. 1010) and Dr. Christian Schöneich (Ex. 1011).
`
`
`
`E. The Asserted Grounds
`
`Petitioner challenges claims 1, 2, 4, 5, 7, and 8 of the ’023 patent on
`
`the following grounds:
`
`Reference(s)
`
`Enz and the Handbook, optionally in
`view of Rosin and/or Elmalem and/or
`Ebert
`Enz and the Handbook, and/or Rosin,
`and/or Ebert
`Enz and the Handbook and/or Ebert
`
`Enz, the Handbook, and Ebert or
`Kissel
`Enz and Sasaki
`
`Basis
`
`Claims
`
`§ 103(a) 1, 7
`
`§ 103(a) 2
`
`§ 103(a) 4, 5
`
`§ 103(a) 8
`
`§ 103(a) 1, 2, 4, 5, and 7
`
`Enz, Sasaki, and Ebert or Kissel
`
`§ 103(a) 8
`
`
`
`
`
`
`
`
`
`5
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`IPR2014-00549
`Patent 6,316,023 B1
`
`
`35 U.S.C. § 315(a)
`
`Patent Owner asserts that 35 U.S.C. § 315(a) bars the Petition.
`
`II.
`
`Prelim. Resp. 1. 35 U.S.C. § 315(a) states, in part:
`
`
`INTER PARTES REVIEW BARRED BY CIVIL
`(1)
`ACTION.—An inter partes review may not be instituted if,
`before the date on which the petition for such a review is filed,
`the petitioner or real party in interest filed a civil action
`challenging the validity of a claim of the patent.
`
`
`
`Patent Owner asserts that Petitioner “effectively” filed a civil action
`
`challenging the validity of a claim of the ’023 patent before the date of its
`
`petition by filing with the U.S. Food and Drug Administration (“FDA”) a
`
`certification pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(IV) (“Paragraph IV
`
`certification”) challenging the validity of the ‘023 patent. Id. at 1–2.
`
`According to Patent Owner, upon receiving notice of the Paragraph IV
`
`certification, Patent Owner was forced to bring a civil action to defend the
`
`’023 patent. Id. at 2. Patent Owner asserts that the Federal Circuit “has
`
`characterized the Paragraph IV filer, rather than the patent owner, as the
`
`party who initiates the challenge to patent validity.” Id. (citing In re
`
`Rosuvastatin Calcium Patent Litig., 703 F.3d 511, 515 (Fed. Cir. 2012) and
`
`In re Ciprofloxacin Hydrochloride Antitrust Litig., 544 F.3d 1323, 1334
`
`(Fed. Cir. 2008)). Thus, Patent Owner asserts that although Patent Owner
`
`filed the civil action, Petitioner’s Paragraph IV certification “effectively
`
`constituted the filing of a civil action.” Id. at 4.
`
`
`
`We disagree with Patent Owner. When the statute refers to filing a
`
`civil action, it refers to filing a complaint with a court to commence a civil
`
`action. See, e.g., Baldwin Cnty. Welcome Ctr. v. Brown, 466 U.S. 147, 149
`
`
`
`6
`
`
`
`IPR2014-00549
`Patent 6,316,023 B1
`
`(1984) (a civil action is brought upon filing a complaint with a court); Ariosa
`
`Diagnostics v. Isis Innovation Ltd, Case IPR2012-00022, slip op. at 4
`
`(PTAB Feb. 12, 2013)(Paper 20) (citing Baldwin, 466 U.S. at 149).
`
`Petitioner’s initiating a challenge to patent validity by filing of a Paragraph
`
`IV certification with the FDA did not involve filing of a complaint with a
`
`court. Thus, Petitioner’s action does not bar institution on the present
`
`Petition under 35 U.S.C. 315(a).
`
`
`
`III. ANALYSIS
`
`A. Claim Construction
`
`In an inter partes review, the Board interprets claim terms in an
`
`unexpired patent according to the broadest reasonable construction in light
`
`of the specification of the patent in which they appear. 37 C.F.R.
`
`§ 42.100(b). Under that standard, and absent any special definitions, we
`
`give claim terms their ordinary and customary meaning, as would be
`
`understood by one of ordinary skill in the art at the time of the invention.
`
`In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Any
`
`special definitions for claim terms must be set forth with reasonable clarity,
`
`deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed.
`
`Cir. 1994).
`
`Petitioner proposes constructions for the claim terms “pharmaceutical
`
`composition,” “antioxidant,” “diluent or carrier,” and “transdermal device.”
`
`Pet. 7–8. Patent Owner has not proposed constructions for these terms. We
`
`have determined that express construction of these terms is not necessary at
`
`this time.
`
`
`
`7
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`
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`IPR2014-00549
`Patent 6,316,023 B1
`
`
`Petitioner also proposes that we construe the term “(S)-N-ethyl-3-[(1-
`
`dimethylamino)ethyl]-N-methylphenyl carbamate” as referring to
`
`rivastigmine, i.e., the S-enantiomer of a racemic mixture known as RA7. Id.
`
`at 8. Patent Owner agrees with this characterization, and further clarifies
`
`that the racemate, RA7, is N-ethyl-3-{(1-dimethylamino)ethyl}-N-methyl-
`
`phenyl-carbamate HCl. Prelim. Resp. 9. Upon consideration of the record,
`
`we determine that the agreed-upon construction is consistent with the plain
`
`and ordinary meaning in the context of the specification. We adopt the
`
`agreed-upon construction.
`
`Additionally, Petitioner proposes that we construe the term
`
`“comprising” as “embrac[ing] compositions containing both rivastigmine
`
`and its enantiomer, including compositions containing racemic RA7.” Pet. 9.
`
`Patent Owner asserts that although the term “comprising” indicates that “the
`
`challenged claims can encompass some amount of (R)-enantiomer, that
`
`amount cannot be equal to or greater than the amount of (S)-enantiomer.”
`
`Prelim. Resp. 10. We note, however, that Enz, which Petitioner relies upon
`
`for each ground in the Petition, discloses a pharmaceutical composition
`
`containing rivastigmine, i.e., the S-enantiomer. Ex. 1002, Abstract. In other
`
`words, based upon our review of the Petition, the grounds presented do not
`
`rely on a disclosure of a composition comprising the racemate RA7 to meet
`
`the limitation in the claims specifically reciting the S-enantiomer.
`
`Accordingly, for purposes of this decision, we determine that no express
`
`claim construction is necessary for the claim term “comprising.”
`
`
`
`
`
`8
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`IPR2014-00549
`Patent 6,316,023 B1
`
`
`B. Obviousness of Claims 1 and 7 over Enz (Ex. 1002) and
`the Handbook (Ex. 1003), Optionally in View of Rosin (Ex. 1008 )
`and/or Elmalem (Ex. 1009) and /or Ebert (Ex. 1006)
`
`Petitioner contends that claims 1 and 7 are unpatentable over the
`
`
`
`combination of Enz and the Handbook, optionally in view of Rosin and/or
`
`Elmalem and /or Ebert. Pet. 21–32.
`
`1.
`
`Enz
`
`Enz discloses compositions for systemic transdermal administration
`
`containing (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methyl-phenyl
`
`carbamate of formula I
`
`
`
`
`
`in free base or acid addition salt form. Ex. 1002, 2.
`
`Enz explains that the racemic mixture (±)-N-ethyl-3-[1-
`
`dimethylamino)ethyl]-N-methyl-phenyl-carbamate in the form of its
`
`hydrochloride is known as RA7. Id. at 3. Enz teaches that (S)-N-ethyl-3-
`
`[(1-dimethylamino)ethyl]-N-methyl-phenyl-carbamate in free base may be
`
`prepared from the racemate by separation of the enantiomers in accordance
`
`with known methods. Id. The acid addition salts may be prepared from the
`
`free base according to a known manner. Id. Enz teaches that Compound A,
`
`the compound of formula I in form of its hydrogen tartrate, is “slightly
`
`superior than” the racemic mixture. Id. at 6.
`
`Additionally, Enz discloses providing “a pharmaceutical composition
`
`comprising a compound according to the invention in association with at
`
`
`
`9
`
`
`
`IPR2014-00549
`Patent 6,316,023 B1
`
`least one pharmaceutical carrier or diluent.” Id. at 10. In Example 2, Enz
`
`discloses a preparation of a transdermal composition comprising 20% of
`
`compound A, 30% of a hydrophilic polymer, e.g., Eudragit E 100, 44% of a
`
`non-swellable acrylate polymer, e.g., Durotack 280-2416, and 6% of a
`
`plasticizer, e.g., Brij 97. Id. at 20. The composition is spread on top of an
`
`aluminized foil to produce a film that is allowed to dry. Id. Thereafter, the
`
`aluminum foil is cut into patches. Id.
`
`2.
`
`The Handbook
`
`The Handbook lists pharmaceutical excipients and provides a
`
`description of each excipient, including nonproprietary and chemical names,
`
`structural formula, functional category, applications in pharmaceutical
`
`formulation or technology, and in some cases, the normal usage
`
`concentration range. Ex. 1003, 5. The Handbook identifies several
`
`excipients as antioxidants, including alpha tocopherol, normally used in the
`
`concentration range of 0.001–0.05%. Id. at 5–7.
`
`3.
`
`Rosin
`
`Rosin discloses phenyl carbamates that inhibit acetylcholinesterase in
`
`the mammalian brain after systemic administration, e.g., orally or
`
`parenterally. Ex. 1008, 4:16–20. Preferred compounds of the invention
`
`include N-ethyl, N-methyl-3[(1-dimethylamino)ethyl]phenyl carbamate, i.e.,
`
`RA7. Id. at 5:40–45; 12:56–60; 14:17–19. The compounds may be
`
`combined “with a physiologically acceptable vehicle, carrier, excipient,
`
`binder, preservative, stabilizer, flavor, etc., in a unit dosage form as called
`
`for by accepted pharmaceutical practice.” Id. at 7:19–24. The compositions
`
`may be formulated as tablets, capsules or elixirs for oral administration or in
`
`sterile solutions or suspensions for parenteral administration. Id. at 7:15–19.
`
`
`
`10
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`
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`IPR2014-00549
`Patent 6,316,023 B1
`
`Rosin states:
`
` Sterile compositions for injection can be formulated
`according to conventional pharmaceutical practice by
`dissolving or suspending the active substance in a vehicle
`such as water for injection. Buffers, preservatives,
`antioxidants and the like can be incorporated as required.
` Preferred antioxidants for use with the compounds of
`the present invention include sodium metabisulphite
`and ascorbic acid.
`
`Id. at 7:45–50.
`
`4.
`
`Elmalem
`
`Elmalem is a journal article discussing a study comparing the effects
`
`of three anticholinesterase agents, including RA7, with those of
`
`physostigmine on the respiratory depression induced by morphine in rabbits.
`
`Ex. 1009 at 1059. Elmalem explains that each of these four drugs was
`
`“made up freshly in sterile saline, which include an equal weight of sodium
`
`metabisulphite, to prevent oxidation.” Id. at 1060.
`
`5.
`
`Ebert
`
`Ebert discloses a drug-containing adhesive composite transdermal
`
`delivery device comprising a substantially drug impermeable proximal
`
`release liner and a method for making the device. Ex. 1006, Abstract. Ebert
`
`explains that although its disclosure specifically refers to nicotine as the
`
`active drug, “any other liquid drug contained in an active gel which can be
`
`transdermally or transmucosally delivered may be substituted in place of
`
`nicotine.” Id. at 15:30–35. With respect to nicotine, Ebert explains that a
`
`“trait of nicotine that can be problematic is its tendency to oxidize readily in
`
`the presence of light and air.” Id. at 21:18–20. Ebert teaches that “[d]uring
`
`fabrication of nicotine patches, oxidation is controlled by addition of an
`
`antioxidant to the active gel,” wherein BHT is a preferred antioxidant. Id. at
`
`
`
`11
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`IPR2014-00549
`Patent 6,316,023 B1
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`21:23–26. Ebert teaches mixing BHT with nicotine preferably in the range
`
`of about 0.01–1.0% w/w. Id. at 21:26–28.
`
`6.
`
`Analysis
`
`Petitioner asserts that Enz teaches a composition that meets every
`
`limitation of claims 1 and 7, except the addition of an antioxidant. Pet. 21.
`
`Specifically, Petitioner asserts that Enz discloses in Example 2 a
`
`pharmaceutical composition, e.g., a transdermal device, comprising 20
`
`weight percent of hydrogen tartrate salt of rivastigmine, i.e., 1 to 40 weight
`
`percent of (S)-N-ethyl-3-[(1-dimethylamino)ethyl]-N-methyl-phenyl-
`
`carbamate, Eudragit E 100 (a hydrophilic polymer) and Durotack 280-2416
`
`(an acrylic adhesive), i.e., a diluent or carrier, and Brij 97 (a plasticizer). Id.
`
`at 20–21. At this time, Patent Owner has not disputed that Enz discloses
`
`these limitations of claims 1 and 7. See Prelim. Resp. 1–22. Based on the
`
`information presented at this stage of the proceeding, Petitioner has shown
`
`sufficiently that Enz teaches each limitation of claims 1 and 7, except the
`
`addition of an antioxidant.
`
`According to Petitioner, at the time of the invention, a person of
`
`ordinary skill in the art who endeavored to formulate rivastigmine into a
`
`transdermal patch, as taught by Enz, would have investigated the stability of
`
`the drug. Pet. 22–23; Ex. 1010 ¶ 23. Petitioner asserts that each of Elmalem
`
`and Rosin teach or suggest the addition of an antioxidant to compositions
`
`comprising RA7. Pet. 23 (citing Ex. 1009 at 2, Ex. 1010 ¶ 58; Ex. 1008 at
`
`7:45–53). Petitioner asserts that a person of ordinary skill in the art would
`
`have understood from these references that RA7 was susceptible to oxidation
`
`and “would have known that there would be little or no difference between
`
`rivastigmine and RA7 with respect to oxidation.” Id. (citing Ex. 1010 ¶ 29).
`
`
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`12
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`IPR2014-00549
`Patent 6,316,023 B1
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`Further, Petitioner asserts that in investigating the stability of
`
`rivastigmine, a person of ordinary skill in the art “would have reasonably
`
`expected, based on the molecular structure of the drug, that rivastigmine
`
`would be susceptible to oxidative degradation.” Id. at 25 (citing Ex. 1010 ¶
`
`58; Ex. 1011¶¶ 52–59). In particular, Petitioner submits the declaration of
`
`Dr. Christian Schӧneich, as supporting the position that a person of ordinary
`
`skill in the art would have recognized the similarities between the structure
`
`of rivastigmine and nicotine and “would have expected that rivastigmine
`
`would be susceptible to oxidative degradation at the benzylic C-H bond and
`
`adjacent tertiary amine via similar mechanisms as nicotine and to roughly
`
`the same extent as nicotine.” Id. 26–27 (citing Ex. 1011 ¶ 59).
`
`In this vein, Petitioner asserts that “Ebert taught that nicotine was
`
`known to readily oxidize in the presence of light and air, and that adding an
`
`antioxidant … could reduce that oxidation.” Pet. 27 (citing Ex. 1006 at 21).
`
`Therefore, according to Petitioner, a person of ordinary skill in the art would
`
`have had reason to combine rivastigmine with an antioxidant to protect
`
`against degradation based on the teachings of Rosin, Elmalem, and Ebert.
`
`Id. (citing Ex. 1010 ¶ 58; Ex. 1011 ¶ 61). Moreover, Petitioner asserts that
`
`these teachings would have provided a person of ordinary skill a reasonable
`
`expectation of successfully protecting rivastigmine against oxidative
`
`degradation by adding an antioxidant to the composition. Id. (citing Ex.
`
`1006 at 21; Ex. 1010 ¶ 58; Ex. 1011 ¶ 50; Ex. 1008 at 5:44–45, 14:17–19,
`
`7:45–53).
`
`Based on the information presented in the Petition, we are persuaded
`
`that Petitioner has established a reasonable likelihood of showing that it
`
`would have been obvious to a person of ordinary skill in the art at the time
`
`
`
`13
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`IPR2014-00549
`Patent 6,316,023 B1
`
`of the invention to combine an antioxidant with the pharmaceutical
`
`composition disclosed by Enz. Specifically, on this record, Petitioner has
`
`shown sufficiently that each of Rosin and Elmalem suggests combining an
`
`antioxidant with the racemate, RA7, may be useful. Ex. 1008 at 7:45–50;
`
`Ex. 1009 at 1059. Elmalem discloses adding an antioxidant to prevent
`
`oxidation of various compounds, including RA7. Petitioner provided
`
`testimony that a person of ordinary skill in the art at the time of the invention
`
`would have considered the prior art teaching and/or suggestion to add an
`
`antioxidant to RA7 to be applicable also to its S-enantiomer, rivastigmine.
`
`Pet. 22–23 (citing Ex. 1011 ¶¶ 29, 54).
`
`Further, Petitioner provided testimony discussing the chemical
`
`structure of rivastigmine and explanation why a person of ordinary skill in
`
`the art would have understood from its structure that rivastigmine was
`
`susceptible to oxidation. Pet. 25 (citing Ex. 1010 ¶ 58; Ex. 1011¶¶ 52–59).
`
`Moreover, this discussion involved a comparison of similar features present
`
`in the chemical structures of rivastigmine and nicotine, a drug known to be
`
`susceptible to oxidation, wherein such oxidation is controlled by the addition
`
`of an antioxidant. Id. 26–27 (citing Ex. 1011 ¶ 59; Ex. 1006 at 21). Thus,
`
`on the current record, Petitioner has articulated sound reasoning with
`
`rational underpinning to support a motivation for combining the teachings of
`
`the prior art. See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006), cited with
`
`approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417–18 (2007).
`
`Petitioner also asserts that a person of ordinary skill in the art easily
`
`would have determined the optimal antioxidant and its concentration by
`
`referencing the Handbook and by routine experimentation. Pet. 28.
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`Moreover, Petitioner asserts that the antioxidant range of 0.01 to 0.5 weight
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`percent of the composition recited in claims 1 and 7 overlaps the antioxidant
`
`ranges taught in the prior art. Id. Therefore, Petitioner asserts that it would
`
`have been obvious for a person of ordinary skill in the art at the time the
`
`invention was made to have modified the transdermal device in Enz to
`
`include an antioxidant in the amounts specified in the Handbook, which
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`would have yielded the inventions of claims 1 and 7. Id.
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`Based on the information presented in the Petition, we are persuaded
`
`that Petitioner has made a sufficient showing of obviousness with respect to
`
`the weight percent range of antioxidant recited in claims 1 and 7,
`
`considering the recited range overlaps the ranges disclosed in the Handbook.
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`See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie
`
`case of obviousness typically exists when the ranges of a claimed
`
`composition overlap the ranges disclosed in the prior art.”); Ex. 1003 at 5–
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`23.
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`In sum, we are persuaded that Petitioner has made a sufficient
`
`showing, on the current record, that the combination of Enz, the Handbook,
`
`Rosin, Elmalem, and Ebert teaches or suggests the inventions of claims 1
`
`and 7 of the ’023 patent. Accordingly, we determine that Petitioner has
`
`established a reasonable likelihood of prevailing on its assertion that claims
`
`1 and 7 would have been obvious over the combination of Enz, the
`
`Handbook, Rosin, Elmalem, and Ebert under 35 U.S.C. § 103(a).
`
`C. Obviousness of Claim 2 over Enz (Ex. 1002) and
`the Handbook (Ex. 1003) and/or Rosin (Ex. 1008 )
`and /or Ebert (Ex. 1006)
`
`Petitioner contends that claim 2 is rendered obvious by the
`
`
`
`combination of Enz and the Handbook and/or Rosin and/or Ebert. Pet. 32–
`
`34. Claim 2 depends from claim 1 and further recites “wherein the
`
`
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`antioxidant is selected from the group consisting of tocopherol, esters of
`
`tocopherol, ascorbic acid, esters of ascorbic acid, butylhydroxytoluene,
`
`butylhydroxyanisole, propyl gallate, and combinations thereof.” Petitioner
`
`asserts that a person of ordinary skill in the art would have been motivated to
`
`modify Enz’s transdermal patch by adding an antioxidant for the reasons
`
`discussed regarding Ground 1. Pet. 32. Additionally, Petitioner asserts that
`
`many of the antioxidants recited in claim 2 are listed in the Handbook. Id.
`
`(citing Ex. 1003 at 3–23). According to Petitioner a person of ordinary skill
`
`in the art at the time of the invention would have been motivated to select
`
`one of these known antioxidants listed in the Handbook because inclusion in
`
`the Handbook indicates approved use in pharmaceuticals. Id. (citing
`
`Ex. 1010 ¶ 61).
`
`
`
`Further, Petitioner asserts that Rosin provides motivation with a
`
`reasonable expectation of success to select ascorbic acid as an antioxidant.
`
`Id. at 32–33. Rosin teaches that preferred antioxidants for use with
`
`compounds of its invention, e.g., RA7, include ascorbic acid. Ex. 1008 at
`
`7:51–53. Additionally, Petitioner asserts that Ebert provides motivation with
`
`a reasonable expectation of success to select BHT, BHA, and tocopherol by
`
`teaching the use of these antioxidants to prevent degradation of nicotine in
`
`transdermal devices. Pet. 33 (citing Ex. 1006 at 21).
`
`For the same reasons discussed regarding the ground involving the
`
`combination of Enz, the Handbook, Rosin, Elmalem, and Ebert, we are
`
`persuaded, based on the information presented in the Petition, that Petitioner
`
`has made a sufficient showing that the combination of Enz, the Handbook,
`
`Rosin, and Ebert would have provided a reason to a person of ordinary skill
`
`in the art at the time of the invention to add an antioxidant to the
`
`
`
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`IPR2014-00549
`Patent 6,316,023 B1
`
`composition disclosed by Enz. Further, Petitioner has shown sufficiently,
`
`based on the evidence presently before us, that a person of ordinary skill in
`
`the art would have found it obvious to select one of the recited antioxidants
`
`in claim 2 that is listed in the Handbook, and/or specifically disclosed in
`
`Rosin or Ebert. Petitioner persuades us, on the current record, that doing so
`
`would have amounted to combining a familiar element according to a known
`
`method to yield no more than a predictable result. See KSR Int’l Co., 550
`
`U.S. at 416.
`
`Accordingly, we determine that Petitioner has established a
`
`reasonable likelihood of prevailing on its assertion that claim 2 would have
`
`been obvious over the combination of Enz, the Handbook, Rosin, and Ebert
`
`under 35 U.S.C. § 103(a).
`
`D. Obviousness of Claims 4 and 5 over Enz (Ex. 1002) and
`the Handbook (Ex. 1003) and/or Ebert (Ex. 1006)
`
`Petitioner contends that claims 4 and 5 are rendered obvious by the
`
`combination of Enz and the Handbook and/or Ebert. Pet. 34–36. Claim 4
`
`depends from claim 1 and further recites “wherein the antioxidant is present
`
`in an amount of from 0.05 to 0.2 weight percent.” Claim 5 recites, “wherein
`
`the antioxidant is present in an amount of from 0.1 to 0.15 weight percent.”
`
`Petitioner asserts that a person of ordinary skill in the art would have been
`
`motivated to modify Enz’s transdermal patch by adding an antioxidant for
`
`the reasons discussed regarding Ground 1. Pet. 34. Additionally, Petitioner
`
`asserts that the antioxidant concentration ranges recited in claims 4 and 5
`
`overlap with the ranges disclosed in the Handbook and in Ebert. Id.; Ex.
`
`1003 at 5–23; Ex. 1006 at 21.
`
`
`
`17
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`IPR2014-00549
`Patent 6,316,023 B1
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`
`For the same reasons discussed regarding claim 1, we are persuaded,
`
`based on the information presented in the Petition, that Petitioner has made a
`
`sufficient showing that a person of ordinary skill in the art at the time of the
`
`invention would have been motivated to add an antioxidant to the
`
`composition disclosed by Enz. Further, Petitioner has shown sufficiently, on
`
`the current record, that the weight percent range of antioxidant recited in
`
`claims 4 and 5 would have been obvious, considering the recited ranges
`
`overlap the ranges disclosed in the Handbook. See In re Peterson, 315 F.3d
`
`at 1329.
`
`Accordingly, we determine that Petitioner has established a
`
`reasonable likelihood of prevailing on its assertion that claims 4 and 5 are
`
`rendered obvious by the combination of Enz, the Handbook, and Ebert under
`
`35 U.S.C. § 103(a).
`
`E. Obviousness of Claim 8 over Enz (Ex. 1002),
`the Handbook (Ex. 1003), and Ebert (Ex. 1006) or Kissel (Ex. 1007)
`
`Petitioner contends that claim 8 is rendered obvious by the
`
`combination of Enz, the Handbook, and Ebert or Kissel. Pet. 36–37.
`
`Claim 8 depends from claim 7 and further recites “further comprising an
`
`antioxidant; a backing layer providing support for the pharmaceutical
`
`composition; an adhesive for contacting and fixing the pharmaceutical
`
`composition to the backing layer; and a release liner releasably contacting
`
`said adhesive.”
`
`1.
`
`Kissel
`
`Kissel discloses pharmaceutical compositions for the transdermal
`
`systemic administration of an active agent. Ex. 1007, Abstract. Kissel
`
`teaches that pharmaceutical compositions for the sustained transdermal
`
`
`
`18
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`IPR2014-00549
`Patent 6,316,023 B1
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`administration of drugs may include a solid drug reservoir having a backing
`
`member impermeable to the drug on one side and a protective peel strip on
`
`the other side that is taken off before use. Id. at 2.
`
`2.
`
`Analysis
`
`Petitioner asserts that a person of ordinary skill in the art would have
`
`been motivated to modify Enz’s transdermal patch by adding an antioxidant
`
`for the reasons discussed regarding Ground 1. Pet. 36. Additionally,
`
`Petitioner asserts that Enz discloses that its composition comprises an
`
`aluminum foil, i.e., a backing layer providing support for the composition,
`
`and Durotack, an adhesive. Id.; Ex. 1002 20 (Ex. 2). Petitioner asserts that
`
`Ebert and Kissel each teach that a release liner was a common component of
`
`transdermal patches, as it protects the composition prior to use and provides
`
`convenient packaging. Id. at 36–37; Ex. 1006, Abstract; Ex. 1007 at 2.
`
`Thus, Petitioner asserts that a person of ordinary skill in the art at the time of
`
`the invention would have been motivated to include a release liner on Enz’s
`
`transdermal patch. Id.
`
`For the same reasons discussed regarding claim 7, we are persuaded,
`
`on the current record, that Petitioner has made a sufficient showing that a
`
`person of ordinary skill in the art at the time of the invention would have
`
`been motivated to add an antioxidant to the composition disclosed by Enz.
`
`Further, based on the current record, Petitioner has shown sufficiently that it
`
`would have been obvious to a person of ordinary skill in the art to add a
`
`release liner, as taught by each of Ebert and Kissel, to the transdermal patch
`
`disclosed by Enz. On the current record, doing so would have amounted to
`
`combining a familiar element according to a known method to yield no more
`
`than a predictable result. See KSR Int’l Co., 550 U.S. at 416.
`
`
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`19
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`IPR2014-00549
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`
`Accordingly, we determine that Petitioner has established a
`
`reasonable likelihood of prevailing on its assertion that claim 8 is rendered
`
`obvious by the combination of Enz, the Handbook and Ebert or Kissel.
`
`F. Obviousness of Claims 1, 2, 4, 5, and 7 over
`Enz (Ex. 1002) and Sasaki (Ex. 1005)
`
`
`Petitioner contends that claims 1, 2, 4, 5, and 7 are rendered obvious
`
`by the combination of Enz and Sasaki. Pet. 37–43.
`
` 1.
`
`Sasaki
`
`
`
`Sasaki discloses an acrylic adhesive plaster comprising tocopherol and
`
`a drug. Ex. 1005 at 1. Sasaki teaches that the therapeutic effect of a
`
`preparation comprising a drug blended with a plaster comprising an acrylic
`
`adhesive substance tends to be greatly reduced due to the breakdown and
`
`dissipation of the drug when the adhesive substance is stored for a long time.
`
`Ex. 1005 at 1. Sasaki explains that breakdown of the drug in such a
`
`composition especially occurs when the drug is a phenolic hydroxyl group-
`
`containing compound, and amine compound, or the like. Id. Sasaki teaches
`
`that if a tocopherol is blended in a plaster comprising a drug and an acrylic
`
`adhesive substance, “the drug will be stably present without break
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