`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Control No: Unassigned
`
`Examiner: Unassigned
`
`Art Unit: Unassigned
`
`
`In the Reexamination of:
`Harold Kohn
`
`
`Patent No. RE38,551
`
`Issue Date: Jul. 6, 2004
`
`Title: ANTICONVULSANT
`ENANTIOMERIC AMINO ACID
`DERIVATIVES
`
`
`
`REQUEST FOR EX PARTE REEXAMINATION
`OF U.S. PATENT NO. RE38,551
`UNDER 35 U.S.C. §§ 301-307 AND 37 C.F.R. § 1.510 et. seq.
`
`
`Mail Stop Ex Parte Reexam
`Central Reexamination Unit
`United States Patent &Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Commissioner:
`
`
`This is a request for ex parte reexamination pursuant to 37 C.F.R.
`
`§ 1.510 of claims 1-13 of U.S. Patent No. RE 38,551 ( the
`
`.
`
`This reexamination should be consolidated under 37 C.F.R. § 42.122(a) with
`
`co-pending inter partes review of the same
`
` Argentum
`
`Pharms. Inc v. Research Corporation Techs., IPR2016-00204 (petition filed
`
`Nov. 23, 2015; institution decision due May 25, 2016).
`
`
`
`-1-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.1
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`
`
`TABLE OF CONTENTS
`
`EXHIBIT LIST ............................................................................................................................... 4
`
`I. RELATED PROCEEDINGS ................................................................................................... 7
`
`II.
`
`NT ............................................................................................. 7
`
`III. SUMMARY OF PRIOR AND PENDING PROCEEDINGS INVOLVING THE
` ..................................................................................................................... 9
`
`A. Original Prosecution
`
` ..................................................................................10
`
` Patent Owner Admits that Claims 39-
`B. PTE Request
`Read on Lacosamide ..............................................................................................12
`
`C. District Court Litigation Patent Owner Admits that R3 Group of Claim 44
` ...........................................................................14
`
`D.
`
`E.
`
` Obviousness-
`IPR2014-01126
`Was Never Presented or Considered......................................................................15
`
` Obviousness-
`IPR2016-00204
`Was Never Presented or Considered......................................................................17
`
`IV. SUMMARY OF SUBSTANTIAL NEW QUESTION OF PATENTABILITY AND
`PROPOSED REJECTIONS.............................................................................................. 19
`
`V. DETAILED EXPLANATION OF SUBSTANTIAL NEW QUESTION OF
`PATENTABILITY ........................................................................................................... 20
`
`A.
`
`B.
`
` ...............................20
`
`methoxymethyl is an ether ...........................25
`
`VI. PROPOSED GROUNDS OF REJECTION ........................................................................ 29
`
`A. Claim Construction ....................................................................................................29
`
`1.
`
`2.
`
`to
`
` .........................29
`
`-limiting
`because the body of the claim contains all the required components ........31
`
`B. Law of Obviousness-Type Double Patenting ............................................................33
`
`C. Ground 1: Claims 1-
`
` .................................................................37
`
`differ from Claims 43-
`1. Claims 1-
`patent only at the R and R1 substituents and stereochemistry ...................38
`
`2. The differences between Claims 1-
`
`-
` ............................................................40
`
`
`
`-2-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.2
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`3.
`
`4. Claims 11-
`
`D. Ground 2: Claims 1-
`
`............................................................................................46
`
` ..................................................................................51
`
`........................................................................53
`
`1. LeGall is prior art under 35 U.S.C. § 102(b) ..................................................54
`
`-
`2. Claims 1-9 of the
`patent only at the R and R1 substituents and stereochemistry ...................60
`
`3. The differences between Claims 1-
`
`-
`w of LeGall ..............................61
`
`4.
`
`5. Claims 11-
`
` ..............................................................65
`
`laim
` .....................................................66
`
`VII. CLAIM CHARTS IN SUPPORT OF PROPOSED REJECTIONS .................................. 68
`
`VIII. CONCLUSION ................................................................................................................. 80
`
`
`
`
`
`
`
`-3-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.3
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`Ex. #
`
`1001 U.
`
`
`
`Exhibit Name
`
`
`
`1002 Declaration of Dr. Binghe Wang from IPR2016-00204
`
`1003 Declaration of Dr. Clayton Heathcock from IPR2014-01126
`
`1004
`
`1005
`
`Joint Statement of Uncontested Facts, UCB, Inc. v. Accord
`Healthcare Inc., 1:13-cv-01206 (D. Del. Oct. 26, 2015)
`
`
`
`1006 Excerpt from U.S. Patent Application No. 08/818,688
`
`1007 District Court Claim Construction Opinion
`
`1008 Philippe LeGall, 2-Substituted-2-acetamido-N-benzylacetamides.
`Synthesis, Spectroscopic and Anticonvulsant Properties (Dec.
`
`
`1009
`
`
`
`1010 Choi et al., Trimethylsilyl Halides: Effective Reagents for the
`Synthesis of -Halo Amino Acid Derivatives, Tet. Lett., Vol.
`
`
`1011 Purdie et al., The Alkylation of Sugars, J.A.C.S.Vol. 83, pg. 1021
`
`
`1012 Kohn et al., Preparation and Anticonvulsant Activity of a Series of
`Functionalized -Heteroatom-Substituted Amino Acids, J. Med.
`
`
`1013 Silverman, R. B., The Organic Chemistry of Drug Design and
`Drug Action
`
`
`1014 Development of New Stereoisomeric Drugs, U.S. F.D.A., May 1,
`1992
`
`1015 Cortes et al., Effect of Structural Modification of the Hydantoin
`Ring on Anticonvulsant Activity, J. Med. Chem., Vol. 28, pg. 601
`
`
`
`
`-4-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.4
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`1016 LeGall et al., Synthesis of Functionalized Non-Natural Amino Acid
`Derivatives via Amidoalkylation Transformations, Int. J. Peptide
`
`
`-
`1017 Kohn
`Heterocyclic -Acetamido-N-benzylacetamide Derivatives, J. Med.
`Chem. Vol. 36, pg. 3350 (1993)
`
`1018 Kohn et al., Preparation and Anticonvulsant Activity of a Series of
`Functionalized -Aromatic and -Heteroaromatic Amino Acids, J.
`Med. Chem. Vol. 33, pg. 919 (1990)
`
`1019
`
`
`
`1020 Patent Term Extension Request in U.S. Patent No. 5,654,301
`
`1021 FDA Guideline for Industry, November 1994
`
`1022 Schmidt, R., Dose-Finding Studies in Clinical Drug Development,
`Eur. J. Clin. Pharmacol, Vol. 34, pg. 15 (1988)
`
`Isbell, H. S., The Optical Rotation of the Various Asymmetric
`Carbon Atoms in the Hexose and Pentose Sugars, B. S. Jour.
`Research, Vol. 5, pg. 1041 (1929)
`
`1023
`
`1024
`
`Physicochemical Properties in Relation to Biologic Action,
`(Delgado J. N. & Remers W. A., eds. 1991) (Wilson)
`
`1025 Thornber, C. W., Isosterism and Molecular Modification in Drug
`Design, Chem. Soc. Rev., Vol. 8(4) (1979)
`
`1026 Reissue Declaration in Reissue of U.S. Patent No. 5,773,475
`
`1027 Subpoena directed to The University of Houston
`
`1028 Texas Public Information Act Requests and Responses
`
`1029 Zhou et al., Decisions under Uncertainty: the Fuzzy Compromise
`Decision Support Problem, Eng. Opt. Vol. 20, pg. 21 (1992)
`
`1030 Mistree et al., A Decsion-Based Perspective for the Design of
`Methods for Systems Design, (1989)
`
`1031 Mistree et al., A Decision-based Approach to Concurrent Design,
`Concurrent Engineering: Contemporary Issues and Modern Design
`Tools, (Parsaei, H. R. & Sullivan W. G. Eds. 1993)
`
`
`
`-5-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.5
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`1032
`
`Ingram W. T., Concerning Periodic Points in Mappings of
`Continua, J. Am. Math. Soc., Vol. 104(2) (1988)
`
`1033 Mattson, Current Challenges in the Treatment of Epilepsy,
`Neurology, Vol. 44(suppl. 5), pg. 84 (1994)
`
`1034 Löscher et al., New Avenues for Anti-Epileptic Drug Discovery and
`Development, Nature Reviews: Drug Discovery, Vol. 12, pg. 12
`(2013)
`
`1035 Cohen authorized amendment in U.S. Patent Application No.
`08/818,688
`
`1036 File History of U.S. Patent Appl. No. 08/818,688
`
`1037 FDA Orange Book for Vimpat®
`
`1038 Excerpts from Trial Transcript of Dr. Harold Kohn Testimony,
`UCB, Inc. v. Accord Healthcare Inc., 1:13-cv-01206 (D. Del. Nov.
`10, 2015)
`
`1039 Excerpts from Trial Transcript of Dr. William Roush Testimony,
`UCB, Inc. v. Accord Healthcare Inc., 1:13-cv-01206 (D. Del. Nov.
`10 and 12, 2015)
`
`,
`1040 Excerpts from Trial Transcript
`UCB, Inc. v. Accord Healthcare Inc., 1:13-cv-01206 (D. Del. Nov.
`9, 2015)
`
`1041 Excerpts from Trial Transcript of Dr. Clayton Heathcock, UCB,
`Inc. v. Accord Healthcare Inc., 1:13-cv-01206 (D. Del. Nov. 9,
`2015)
`
`
`
`-6-
`
`
`
`
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.6
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`Third Party Requester
`
`requests ex parte reexamination
`
`under 35 U.S.C. §§ 301-307 of all claims (claims 1-13) of U.S. Patent No.
`
`the
`
` The Patent Owner is purportedly
`
`Research Corporation Technologies,
`
`
`
`I.
`
`RELATED PROCEEDINGS
`
`A
`
` in the
`
`Office. On November 23, 2015, a petition for inter partes review of the
`
`The petition was accorded case number IPR2016-00204. Patent Owner filed
`
`a preliminary response on February 25, 2016. A decision from the PTAB on
`
`whether to institute the IPR is due no later than May 25, 2015 (i.e., 3 months
`
`from the preliminary response).
`
`II.
`
`NT
`
`is the third in a series of patents owned by RCT and
`
`naming Dr. Harold Kohn as an inventor, each patent expiring later than the
`
`last, whose claims cover lacosamide: U.S. Patent No. 5,378,729
`
`729
`
` (Ex. 1009); U.S. Patent No. 5,654,301
`
` (Ex.
`
`1019); and
`
` (Ex. 1001).
`
`
`
` Patent Application No.
`
`
`
`-7-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.7
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
` 1997, and which
`
`claims priority to U.S. Provisional Application No. 60/013,522 filed on
`
`March 15, 1996 (the earliest possible effective date).
`
`Claim 1 is the sole independent cla
`
` Claim 1 reads:
`
`1. A compound in the R configuration having the
`
`formula:
`
`wherein
`
`Ar is phenyl which is unsubstituted or substituted
`
`
`
`with at least one halo group;
`
`Q is lower alkoxy, and
`
`Q1 is methyl.
`
`Claims 2-9 are compound claims depending directly or indirectly from
`
`claim 1.
`
`according to claim 1 which is (R)-N-Benzyl 2-Acetamido-3-
`
`methoxypropion-
`
` The structure of lacosamide is shown below
`
`(wherein Ar is benzyl, Q is methoxymethyl, and Q1 is methyl):
`
`
`
`-8-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.8
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`Lacosamide
`
`
`
`Claim 10 recites
`
` therapeutic composition comprising an
`
`anticonvulsant effective amount of a compound according to any one of
`
`claims 1-9 and a
`
`
`
`Claims 11-13 are method claims. Claim 11 reads:
`
`11. A method of treating central nervous system
`
`disorders in an animal comprising administering to said
`
`animal in need thereof an anticonvulsant effective
`
`amount of a compound according to any one of claims 1-
`
`9.
`
`Claim 12 dep
`
`
`
`
`
`is a
`
`III. SUMMARY OF PRIOR AND PENDING PROCEEDINGS
`
`ATENT
`
`
`
`,
`
`which the Patent Owner failed to correct during original prosecution. Later,
`
`when seeking a patent term extension from the PTO under 35 U.S.C. § 156,
`
`
`
`-9-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.9
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`the Patent Owner made statements to the PTO that were directly contrary to
`
`earlier mistaken understanding and reasons for allowing the
`
`. During litigation before a Federal District Court, the Patent
`
`Owner again made statements that confirm that the Examiner
`
`
`
`understanding was a mistake. This history is explained below.
`
`A. Original Prosecution
`
`
`
`
`
`Disclosed in the
`
`Patent
`
`-filed, earlier-expiring patent. Accordingly, under
`
`RCT. The
`
`the doctrine of obviousness-type double patenting, the Examiner should
`
`have considered whether the
`
`-filed, later-expiring patent claims in
`
`application (which issued as
`
`
`
`The prosecution history
`
`reveals that the Examiner
`
`allowed the claims to issue over
`
`chemistry mistake.
`
`In her Notice of Allowability for the
`
`, the Examiner
`
`identified the
`
` (Ex. 1036, File
`
`History 08/818,688, at p. 158.) The Examiner nonetheless allowed the
`
`claims to issue because she concluded that t
`
`
`
`-10-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.10
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`that the substituents R2 or R3 of claims 39-
`
`teach or
`
`suggest lacosamide ether group (i.e., the methoxymethyl group):
`
`allowance: Instant claims are directed [to] anticonvulsant
`
`enantiomeric amino acid derivatives in the method of treating
`
`CNS disorders. The closest prior arts are Cohen (US
`
`5,654,301) and Anderson et al. (J. Am. Chem. Soc., 1967).
`
`Cohen teach [sic] structurally similar compounds as claimed
`
`herein for similar pharmaceutical method. The difference
`
`between the reference and herein claimed compounds is the
`
`definition of R2, R3 in the reference. The reference never teach
`
`or suggest [sic] R2, R3 to be an ether, as against ether in herein
`
`claims
`
`(Ex. 1036, File History 08/818,688, p. 158.)1
`
`This was a mistake.
`
`patent provides that R2 or R3
`
` 1:54-60); dependent
`
`claim 42 specifies that R2 or R3
`
`id. at 3:40); and, dependent claim 44 further specifies that
`
`the electron donating group is methoxy (id. at 4:30). Thus, claim 44 of the
`
` patent discloses that one of R2 and R3 is hydrogen, and the other is
`
`
`1 Emphasis is added to all quotes throughout this request, unless otherwise
`noted.
`
`
`
`-11-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.11
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`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`methoxymethyl. Furthermore, claim 45 specifies that n is 1. This
`
`combination of substituents results in the following structure:
`
`
`
`Methoxymethyl, shown above in red, is an ether. An ether is a
`
`functional group characterized by a C-O-C linkage, an oxygen bonded to
`
`two carbons. (Ex. 1003, Heathcock, ¶ 68.)
`
`defines methoxymethyl as the substituent at R2 or R3, which is an ether. (Ex.
`
`1003, Heathcock, ¶ 68.) Therefore, the Examiner made a mistake in
`
`concluding
`
`R2, R3 to be an ether. The
`
`original patent issued as a result of this mistake.
`
`B.
`
`PTE Request Patent Owner Admits that Claims 39-
`45 of the
` Read on Lacosamide
`
`In 2008, after the
`
` patent issued, Patent Owner filed a request with
`
`the PTO, under 35 U.S.C. § 156, for an extension of patent term
`
`patent. (Ex. 1020, PTE Request.) In that request for patent term extension,
`
`Patent Owner affirmatively told
`
` approved product and claim the active ingredient of the final
`
`
`
`-12-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.12
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`approved
`
`(Ex. 1020, PTE Request, p. 5.) Specifically,
`
`the Patent Owner stated:
`
`U.S. Patent No. 5,654,301 claims the approved product,
`
`VIMPAT® injection. More specifically, claims 39-45 read on
`
`the approved product and claim the active ingredient of the
`
`final approved product lacosamide, claim 46 reads on the
`
`approved product and claims a composition comprising
`
`lacosamide, and claim 47 reads on methods that comprise
`
`using lacosamide for treatment of CNS (i.e. central nervous
`
`system) disorders.
`
`(Id.)
`
`The Patent Owner
`
` statement above confirms that the methoxymethyl
`
`group of lacosamide is
`
` claims 39-45
`
`could not otherwise read on the approved product lacosamide. Patent
`
`Owner submitted a claim chart to support this assertion. (Ex. 1020, PTE
`
`Request, pp. 5-7.) That claim chart is consistent with the analysis above. In
`
`the claim chart, Patent Owner represented that
`
`carbon atom is bonded to a hydrogen and a -CH2OCH3 group (a lower alkyl
`
`substituted with a methoxy group), thus satisfying the
`
`
`
`requirement that one of R2 and R3 be a hydrogen while the other of R2 and
`
`R3
`
`Ex. 1020,
`
`PTE Request, p. 6.) This admission confirms that the methoxymethyl group
`
`
`
`-13-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.13
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`of lacosamide is an ether (having a C-O-C linkage) and that lacosamide is
`
`covered by claims 39-45 of
`
`.
`
`The above admissions by the Patent Owner can be used in this
`
`reexamination. See MPEP § 2258 ([a]dmission by the patent owner of
`
`record in the file can
`
`to determine the scope and content of the prior
`
`art in conjunction with patents and printed publications in a prior art
`
`rejection, whether such admissions result from patents or printed
`
`publications or from some other source ).
`
`C. District Court Litigation
`R3
`Methoxymethyl
`
` Patent Owner Admits that
`
`Patent Owner is a party in co-pending Federal District Court litigation
`
`styled UCB, Inc., et al. v. Accord Healthcare, Inc., et al., Civil Action No.
`
`13-1206-LPS (D. Del.). In that litigation, the Patent Owner made the
`
`following admission
`
`For purposes of this litigation, claim 44 of U.S.
`
`Patent No. 5,654,301 (the
`
`) defines a genus of compounds with
`
`a methoxymethyl group at R3.
`
`(Ex. 1004, Joint Statement, ¶ 88.)
`
`The above statement by the Patent Owner again confirms, this time
`
`explicitly, that the R3
`
`methoxymethyl. This admission by the Patent Owner can be used in this
`
`reexamination. See MPEP § 2258: ( [a]n admission by the patent owner of
`
`
`
`-14-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.14
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`record in the file or in a court record may be utilized in combination with a
`
`patent or printed publication ). Such admissions may be utilized to
`
`determine the scope and content of the prior art in conjunction with patents
`
`and printed publications in a prior art rejection, whether such admissions
`
`result from patents or printed publications or from some other source.
`
`Id.
`
`D.
`
`IPR2014-01126 Obviousness-Type Double Patenting
`Never Presented or
`
`Considered
`
`On July 10, 2014, a petition for inter partes review IPR2014-01126
`
`
`
`The First IPR
`
`Petition presented three grounds of unpatentability, none of which involved
`
`obviousness-
`
`the three
`
`grounds presented in the First IPR Petition were: (1) statutory anticipation
`
`under 35 U.S.C. §
`
`statutory anticipation under 35
`
`U.S.C. § 102 by LeGall,2 and (3) statutory obviousness under 35 U.S.C.
`
`§ 103 over LeGall an
`
`The PTAB denied the First IPR
`
`Petition on January 9, 2015.
`
`patent), the PTAB denied the petition because a person of ordinary skill
`
`at once envisage[d] each species with the genus of
`
`
`2 Philippe LeGall, 2-Substituted-2-acetamido-N-benzylacetamides.
`Synthesis, Spectroscopic and Anticonvulsant Properties (Dec. 1987)
`
`
`
`
`-15-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.15
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`compounds
`
`anticipate lacosamide.
`
`(Decision, pp. 8-9.)
`
`whether
`
`,
`
`including methoxymethyl, and did not address whether methoxymethyl is an
`
`ether. (Id. at p. 7.) For the second ground (anticipation by LeGall), the
`
`§ 102(b) because no evidence was presented that LeGall was publicly
`
`patent. (Id. at pp. 12-13.)3 Likewise, the third ground (obviousness over
`
`was denied for the same reason as the second
`
`ground. (Id. at p. 14.) Accordingly, in IPR2014-01126, the Board never
`
`addressed
`
`define a methoxymethyl at
`
`the R2 or R3 position, nor whether methoxymethyl is an ether, nor whether
`
`those claims render obvious (under either statutory § 103 obviousness or
`
`obviousness-type double patenting)
`
`
`
`In any event, even if the same exact double-patenting question were
`
`presented in the inter partes review (which it was not), the Director does not
`
`
`3 Subsequent to this decision, Patent Owner admitted in the District Court
`litigation
`
`the meaning of 35 U.S.C. §
`Statement of Uncontested Facts, at ¶ 87.)
`
`ed
`
`(Ex. 1004,
`
`
`
`-16-
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`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.16
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`regard an inter partes review petition as a basis to deny the existence of a
`
`SNQ for purposes of reexamination. See Control No. 96/000,071, SNQ
`
`Determination mailed Aug. 14, 2014 (finding SNQ based on exact same art
`
`and claim charts taken directly from a prior IPR).
`
`E.
`
`IPR2016-00204 Obviousness-Type Double Patenting
`Never Presented or
`
`Considered
`
`On November 23, 2015, a petition for inter partes review IPR2016-
`
`00204
`
`
`
`The
`
`Second IPR Petition also does not present any double patenting ground
`
`Instead, the Second IPR Petition presents only statutory anticipation under
`
`35 U.S.C. § 102 by LeGall, and statutory obviousness under § 103 over
`
`co
`
`4 Kohn 1991,5 Silverman,6
`
`
`4 Choi et al., Trimethylsilyl Halides: Effective Reagents for the Synthesis of
`-Halo Amino Acid Derivatives, Tet. Lett., Vol. 36(39), pg. 7011 (1995)
`
`5 Kohn et al., Preparation and Anticonvulsant Activity of a Series of
`-Heteroatom-Substituted Amino Acids, J. Med. Chem. Vol.
`
`34, pg. 2444 (1991)
`6 Silverman, R. B., The Organic Chemistry of Drug Design and Drug
`Action, Academic Press (1992)
`
`
`
`
`-17-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.17
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`and Cortes.7 Accordingly, in IPR2016-00204, the question of double
`
`was never presented to the Board. The Board
`
`has not yet decided whether to institute IPR2016-00204 based on the
`
`grounds presented in the Second IPR Petition.
`
`In any event, even if the same exact double-patenting question were
`
`presented in the inter partes review (which it was not), the Director does not
`
`regard an inter partes review petition as a basis to deny the existence of a
`
`SNQ for purposes of reexamination. See Control No. 96/000,071, SNQ
`
`Determination mailed Aug. 14, 2014 (finding SNQ based on exact same art
`
`and claim charts taken directly from a prior IPR).
`
`
`7 Cortes et al., Effect of Structural Modification of the Hydantoin Ring on
`Anticonvulsant Activity, J. Med. Chem., Vol. 28, pg. 601 (1985)
`(Ex. 1015).
`
`
`
`-18-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.18
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`IV. SUMMARY OF SUBSTANTIAL NEW QUESTION OF
`PATENTABILITY AND PROPOSED REJECTIONS
`
`The instant request sets forth the following Substantial New Question of
`
`Patentability
`
`for claims 1-
`
`:
`
`SNQ
`Reference
`
`SNQ Reference is Presented in a
`New Light
`
`atent
`(Ex. 1019)
`raises an
`SNQ for
`claims 1-13,
`alone or as
`evidenced by
`LeGall (Ex.
`1008).
`
` was
`Although the
`considered during original
` later
`examination, Patent Owner
`admissions to both the PTO (Ex. 1020)
`and District Court (Ex. 1004) confirm
`that the Examiner misunderstood that
`Claim 44 of the
`does
`indeed contain an ether
`(methoxymethyl) at the R3 position.
`
`New
`Technological
`Teaching
`
`The compound of
`Claim 44 of the
`
`contains an ether
`(methoxymethyl)
`at the R3 position.
`
`LeGall was never considered during
`examination or reissue. LeGall
`discloses a compound with an ether
`(methoxymethyl) at the R3 position, as
`Dr. Kohn admitted under oath to the
`District Court (Ex. 1038). Moreover,
`Patent Owner has admitted that LeGall
`is prior art (Ex. 1004, Joint Statement
`of Uncontested Facts, ¶86(ee) and
`¶87.).
`
`
`
`
`
`-19-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.19
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`Based on the above SNQ, Requester proposes two grounds of rejection,
`
`each of which asserts unpatentability of claims 1-13 under the doctrine of
`
`obviousness-
`
`8:
`
`Ground Claims
`
`Basis
`
`Reference(s)
`
`1
`
`2
`
`1-13
`
`OTDP
`
`1-13
`
`OTDP
`
`Kohn 1991
`
`LeGall
`
`
`V. DETAILED EXPLANATION OF SUBSTANTIAL NEW
`QUESTION OF PATENTABILITY
`
`A.
`
`patent (Claim 44) contains an ether
`(methoxymethyl)
`
`-13
`
`. The
`
`1 patent is an earlier-filed, earlier-
`
`both of which are owned by RCT. Specifically,
`
`-
`
`GATT patent that enjoyed a 17-year term, expiring on August 5, 2014. By
`
`contrast, t
`
`551 patent will not expire until March 17, 2022. (Ex. 1037,
`
`FDA Orange Book.) Accordingly, unless the claims of the
`
`are
`
`novel and nonobvious over the claims of the
`
`RCT will
`
`have received
`
`wise extension
`
`f
`
`
`8 See MPEP §
`he issue of double patenting, over prior art patents
`or non-prior art patents, is appropriate for consideration in reexamination
`under 35 U.S.C. 302, both as a basis for ordering reexamination under 35
`
`U.S.C. 304 and during subsequent examination on the merits.
`
`
`
`-20-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.20
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`approximately 7 ½ years. See MPEP § 804 (citing In re Schneller, 397 F.2d
`
`350, 354 (CCPA 1968)).
`
` SNQ for claims 1-
`
`because,
`
`misunderstanding during prosecution, claims 39-
`
`45 of th
`
`do indeed
`
`a methoxymethyl group)
`
`at the R2 or R3 position.
`
`by a C-O-C
`
`linkage (an oxygen bonded to two carbons); and methoxymethyl
`
`(-CH2OCH3) contains such a C-O-C linkage. (Ex. 1003, Heathcock, ¶ 68.)
`
`The expert declaration of Dr. Heathcock, submitted herewith as an exhibit,
`
`explains in more detail
`
`and why methoxymethyl is
`
`indeed an ether. (Ex. 1003, Heathcock, ¶¶ 65-73.)
`
`Furthermore,
`
`admissions, both to the PTO and to the
`
`District Court, confirm
`
`
`
`and contain a methoxymethyl group. These admissions by the Patent Owner
`
` a
`
`. See MPEP § 2258 (discussing
`
`appropriate use of patent owner admissions in reexamination). Specifically,
`
`the Patent Owner told the PTO, when requesting a patent term extension of
`
`
`
`-45
`
`read on the approved
`
`product and claim the
`
`and that lacosamide
`
`-CH2OCH3
`
`
`
`-21-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.21
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`
`
`. (Ex. 1020,
`
`PTE Request, pp. 5-6.) Second, in the pending District Court litigation, the
`
`claim 44 of the 301 patent defines a genus of
`
`compounds with a methoxymethyl group at R3
`
`(Ex. 1004, Statement of
`
`Uncontested Facts, ¶ 88.) Together, the above statements by the Patent
`
`confirm
`
`reason for
`
`allowing
`
` was a mistake.
`
`The following discussion maps the
`
`the single element
`
`that the Examiner apparently
`
`believed was missing in the prior art:
`
`Q is lower alkoxy as recited in Claim 1
`
`w
`
`-carbon) of an amino acid, claims 39-
`
`define a su
`
`wherein the substituent is a lower alkoxy.
`
`
`
` at the
`
`-carbon)
`
`patent is an independent claim that recites the general formula:
`
`(Ex. 1019,
`
`Claim 39.)
`
`
`
`
`
`-22-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.22
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`2 and R3 is hydrogen and the
`
`(Ex. 1019,
`
`Claim 40.) Through additional dependency, claim 42 further
`
`2 and R3 is methyl substituted with an electron
`
`(Ex. 1019,
`
`Claim 42.) Claim 43 specifies that
`
`at R2 and R3
`
`lower alkoxy Ex. 1019,
`
`Claim 43.)
`
`Furthermore, claim 44
`
`
`
`Ex. 1019,
`
`Claim 43). Thus,
`
`2 and R3 is hydrogen, and
`
`the other is methoxymethyl, as depicted below:
`
`
`
`As seen above, the methoxymethyl substituent has the chemical
`
`formula -CH2OCH3. Methoxymethyl thus contains 2 carbon atoms (one
`
`carbon atom in addition to the one carbon atom in the methylene
`
`bridge -CH2-)
`
`551 patent that
`
`
`
`-23-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.23
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`the alkoxy contain 1-3 carbon atoms, and it meets the requirement of claim
`
`4
`
`551 that Q is methoxy. See also Ex. 1020, PTE Request, p. 6
`
`-CH2OCH3 group
`
`a lower alkyl
`
`substituted with a methoxy group ).
`
`Dependent claim 45
`
`further specifies that n is 1. The
`
`resulting structure is depicted below:
`
`The selection of the R and R1 substituents
`
`
`
`is addressed in the proposed grounds of rejection below. For purposes of the
`
`patent cl
`
`due to any supposed novelty or
`
`nonobviousness of the R and R1 substituents. Instead the Examiner allowed
`
`because of
`
`definition of R2, R3 in the
`
`reference
`
`(Ex. 1036, File History 08/818,688, at p.158.). As shown above,
`
`however, the Examiner was mistaken with respect to the R2, R3 groups in the
`
`, which clearly do define a methoxymethyl group, exactly as
`
`
`
`-24-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.24
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`. Therefore, the Director should find that a SNQ
`
`has been raised
`
`.
`
`B.
`
`methoxymethyl is an ether
`
`The SNQ discussed above with respect to
`
`evidenced by LeGall (Ex. 1008). The status of LeGall as prior art is
`
`discussed in detail in Proposed Ground 2 below. For purposes of this SNQ,
`
`however, it suffices to simply point out that Patent Owner has admitted in
`
`District Court litigation that the LeGall thesis was publicly accessible more
`
`than one year before the earliest priority date for
`
`§
`
` (Ex. 1004, Joint Statement of Uncontested Facts, p. 19, ¶87.)
`
`This explicit admission was made by Patent Owner in a court record
`
`therefore
`
`ilized in combination with a patent or printed
`
`publication when ordering reexamination. MPEP § 2258.
`
`Moreover this admission by the Patent Owner was made after the PTAB
`
`denied an earlier IPR petition (the First IPR Petition, filed in IPR2014-
`
`01126) finding insufficient evidence presented in that petition to show that
`
`LeGall was publicly accessible in order
`
`under § 102(b). Whereas Patent Owner during IPR2014-01126 disputed
`
`
`
`-25-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.25
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`whether LeGall was prior art, Patent Owner later admitted otherwise during
`
`the District Court litigation.
`
`The reason for
`
` about-face is that new evidence of
`
`was discovered in the District Court litigation
`
`that forced Patent Owner to admit that LeGall in fact is prior art. See Ex.
`
`1040
`
`, p. 44
`
`IPR2014-01126], at
`
`In the course of this case, we got
`
`
`
`
`
`LeGall
`
` constitutes a
`
` 102(b) (Ex. 1004,
`
`Joint Statement, p. 19, ¶87), together with additional evidence presented
`
`below in Proposed Ground 2 that LeGall was publicly accessible more than
`
`one year before the earliest effective date, is new information relative to any
`
`
`
`reasonable examiner would
`
`consider important in deciding whether or not the claims are patentable.
`
`Importantly, LeGall confirms that the
`
`is an ether. LeGall discloses a compound (107e) that contains a
`
`methoxymethyl (-CH2OCH3) at the R3
`
` (which is
`
`the R position of compound 107), shown below in the red box:
`
`
`
`-26-
`
`ARGENTUM PHARMACEUTICALS LLC
`IPR2016-00204 - Exhibit 1045 p.26
`
`

`

`Request for Ex Parte Reexamination
`
`
`U.S. Patent No. RE38,551
`
`Ex. 1008, LeGall, p. 137, Tbl. 36 (red box
`added).
`
`(methoxymethyl colored
`red)
`
`
`In the District Court litigation, Dr. Harold Kohn (the named inventor of
`
` and thesis advisor to Mr. Philippe LeGall) was asked about
`
`compound 107e of LeGall. Under oath, Dr. Kohn admitted that
`
`the -CH2OCH3 group of compound 107e in LeGall is an ether:
`
`Q. Dr. Kohn, you have the LeGall thesis, I
`
`DTX-2019 in your binder. Maybe we can
`
`put it on the screen.
`
`. . .
`
`Q. And if you could look at page 137 of that
`
`thesis, this is the chart of compounds in the 107
`
`s