UNITED STA IBS p A IBNT AND TRADEMARK OFFICE
`
`UNITED STA TES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria., Virginia 22313-1450
`www.uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`13/372,426
`
`02/13/2012
`
`Matvey E. LUKASHEV
`
`2159.3210002/JMC/MRG/U-S
`
`5998
`
`53644
`7590
`05/03/2012
`SIBRNE, KESSLER, GOLDSIBIN & FOX, P.L.L.C.
`1100 NEW YORK A VE., N.W.
`WASHINGTON, DC 20005
`
`EXAMINER
`
`ULM,JOHND
`
`ART UNIT
`
`PAPER NUMBER
`
`1649
`
`MAIL DATE
`
`DELIVERY MODE
`
`05/03/2012
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`PTOL-90A (Rev. 04/07)
`
`Page 1 of 11
`
`Biogen Exhibit 2018
`Mylan v. Biogen
`IPR2018-01403
`
`

`

`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`13/372,426
`
`Examiner
`
`LUKASHEV ET AL.
`
`Art Unit
`
`1649
`JOHN ULM
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address -(cid:173)
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE ;J. MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1 )IZI Responsive to communication(s) filed on 14 February 2012.
`2a)O This action is FINAL.
`2b)IZI This action is non-final.
`3)0 An election was made by the applicant in response to a restriction requirement set forth during the interview on
`__ ; the restriction requirement and election have been incorporated into this action.
`4)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 G.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`5)1Zl Claim(s) 18-36 is/are pending in the application.
`5a) Of the above claim(s) __ is/are withdrawn from consideration.
`6)0 Claim(s) __ is/are allowed.
`7)1Zl Claim(s) 18-36 is/are rejected.
`8)0 Claim(s) __ is/are objected to.
`9)0 Claim(s) __ are subject to restriction and/or election requirement.
`
`Application Papers
`
`10)0 The specification is objected to by the Examiner.
`11 )0 The drawing(s) filed on __ is/are: a)O accepted or b)O objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`12)0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.
`
`Priority under 35 U.S.C. § 119
`
`13)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)O All b)O Some * c)O None of:
`1.0 Certified copies of the priority documents have been received.
`2.0 Certified copies of the priority documents have been received in Application No. __ .
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`*Seethe attached detailed Office action for a list of the certified copies not received.
`
`Attachment{s)
`1) 0 Notice of References Cited (PTO-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PTO-948)
`3) [8J Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 02/13112 x 6.
`
`4) 0 Interview Summary (PTO-413)
`Paper No(s)/Mail Date. __ .
`5) 0 Notice of Informal Patent Application
`6) 0 Other: __ .
`
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 03-11)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20120502
`
`Page 2 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 2
`
`DETAILED ACTION
`
`1)
`
`Claims 18 to 36 are pending in the instant application. Claims 1 to 17
`
`have been canceled and claims 18 to 36 added as requested by Applicant in the
`
`preliminary amendment filed concurrently with the instant application.
`
`Information Disclosure Statement
`
`2)
`
`The six information disclosure statements (I OS) submitted on 14 February
`
`of 2012 are in compliance with the provisions of 37 CFR 1.97 and have been
`
`considered by the examiner.
`
`3)
`
`Applicant is advised that M.P.E.P. 609.02(A)(2) states that "[t]he examiner
`
`will consider information which has been considered by the Office in a parent
`
`application when examining: (A) a continuation application filed under 37 CFR 1.53(b),
`
`(B) a divisional application filed under 37 CFR 1.53(b), or (C) a continuation- in-part
`
`application filed under 37 CFR 1.53(b). A listing of the information need not be
`
`resubmitted in the continuing application unless the applicant desires the information to
`
`be printed on the patent". Therefore, Applicant is hereby assured that information which
`
`has been considered by the Office in any parent of the instant application has been
`
`considered by the examiner in the instant application. However, if applicant desires the
`
`information to be printed on the patent they must submit an information disclosure
`
`statement in accordance with 37 CFR 1.98.
`
`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`Page 3 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 3
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set
`forth in section 102 of this title, if the differences between the subject matter sought to be patented and
`the prior art are such that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the invention was made.
`
`The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied for establishing a background for determining
`
`obviousness under 35 U.S.C. 103(a) are summarized as follows:
`
`1.
`2.
`3.
`4.
`
`Determining the scope and contents of the prior art.
`Ascertaining the differences between the prior art and the claims at issue.
`Resolving the level of ordinary skill in the pertinent art.
`Considering objective evidence present in the application indicating
`obviousness or nonobviousness.
`
`4)
`
`Claims 18 to 36 are rejected under 35 U.S.C. 103(a) as being
`
`unpatentable over the Joshi et al. patent publication (US 2003/0018072 A 1 ). These
`
`claims are drawn to a method of treating multiple sclerosis in an individual suffering
`
`therefrom by the daily oral administration thereto of dimethyl fumarate or diethyl
`
`fumarate at a rate of 480 mg per day.
`
`The Joshi et al. patent publication has been cited because it fairly taught the oral
`
`administration of dialkyl fumarates to a subject suffering from an auto immune disease.
`
`The text in paragraph [024] therein expressly identified dimethyl fumarate, methyl ethyl
`
`fumarate and diethyl fumarate as preferred embodiments of the dialkyl fumarates
`
`discussed therein. Further, the text in paragraphs [003], [014] and [030] specifically
`
`identified multiple sclerosis as one of the autoimmune diseases to be treated by the oral
`
`administration of dialkyl fumarates. The Joshi et al. patent publication does not
`
`anticipate the instant claims because it did not disclose the specific treatment protocol
`
`recited therein.
`
`Page 4 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 4
`
`However, given the disclosure by Joshi et al. that multiple sclerosis can be
`
`effectively treated by the oral administration of dimethyl fumarate or diethyl fumarate to
`
`an individual suffering therefrom, one of ordinary skill in the art would have found it
`
`prima facie obvious to have engaged in that routine experimentation needed to
`
`determine the optimal effective protocol for such treatment. Merely determining the
`
`optimal conditions for practicing a prior art process, in the absence of unexpected
`
`results, does not constitute a patentable inventive contribution. See M.P.E.P. 2144.05
`
`11.
`
`In addition, the only in vivo method of treatment that is described in the
`
`specification involves the mouse experimental autoimmune encephalitis (EAE) model,
`
`which is an entirely artificial condition that mimics only certain pathological
`
`manifestations of MS and is causally unrelated thereto. In discussing a primate-based
`
`EAE system, the abstract of the 't Hart et al. publication (The Lancet Neurology
`
`3(10) :588-597, Oct. 2004, cited by Applicant) states that "[t]he many, highly specific,
`
`biological therapies for immune-based diseases create a need for valid preclinical
`
`animal models", and that "[t]he wide immunological gap between human beings and
`
`laboratory mouse and rat models makes many disease models in these species invalid".
`
`The concluding paragraph on page 569 oft' Hart et al. further advises that "[a]lthough
`
`many features of the MS immunopathogenesis have been elegantly modeled in inbred
`
`strains of rats and mice, successful therapeutic interventions in these models have
`
`shown limited predictive value for clinical success". This reference shows that one of
`
`ordinary skill in this art would not reasonably conclude that the in vivo treatment
`
`Page 5 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 5
`
`protocols described in the working examples of the instant specification, which employ a
`
`mouse EAE model system and from which the parameters of the claims method have
`
`been derived, can be expected to be predictive of the optimal conditions for the
`
`treatment of MS in humans by the oral administration of dimethyl fumarate or diethyl
`
`fumarate thereto.
`
`5)
`
`Claims 18 to 36 are rejected under 35 U.S.C. 103(a) as being
`
`unpatentable over the Schimrigh et al. publication (Euro. J. Neural. 13(6):604-610, Jun.
`
`2006, cited by Applicant). As indicated above, these claims are drawn to a method of
`
`treating multiple sclerosis in an individual suffering therefrom by the daily oral
`
`administration thereto of dimethyl fumarate or diethyl fumarate at a rate of 480 mg per
`
`day. The Schimrigh et al. publication is cited because it described the successful
`
`clinical treatment of human subjects suffering from multiple sclerosis by the
`
`administration of fumaric acid esters, which include dimethyl fumarate, methyl ethyl
`
`fumarate and diethyl fumarate, to those subjects. The Schimrigh et al. publication does
`
`not anticipate the instant claims because it did not disclose the specific treatment
`
`protocol recited therein. However, as indicated above, one of ordinary skill in the art
`
`would have found it prima facie obvious to have engaged in that routine experimentation
`
`needed to determine the optimal effective protocol for such treatment. Merely
`
`determining the optimal conditions for practicing a prior art process, in the absence of
`
`unexpected results, does not constitute a patentable inventive contribution.
`
`6)
`
`In a preliminary amendment filed of 14 February of 2012 in the instant
`
`application, Applicant has extensively traversed the above rejections as they have been
`
`Page 6 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 6
`
`applied to identical claims 18 to 36 in application number 12/526,296 essentially on the
`
`premise that the claimed method produces particularly advantageous and unexpected
`
`results as applied to individuals suffering from relapsing-remitting multiple sclerosis
`
`(RRMS). The unexpected and advantageous results demonstrated for the claimed
`
`method relative to the other embodiments that are disclosed in the instant specification
`
`are not in dispute. However, neither those unexpected and allegedly advantageous
`
`results nor the particular combination now claimed are described in the specification as
`
`filed. In fact, the demonstration that the now claimed combination is operable in not
`
`unexpected. It is Applicant's discovery, subsequent to the filing of the instant
`
`application, that the majority of embodiments described in the specification are
`
`inoperative that is unexpected. The fact that dimethyl fumarate, methyl ethyl fumarate
`
`and diethyl fumarate can be successfully employed to treat MS was not unexpected as
`
`of the filing date of the instant application.
`
`The instant specification teaches the treatment of a plurality of neurological
`
`diseases including those listed in paragraphs [0104] to [0106] therein, which states that
`
`"neurological diseases suitable for the methods described herein include
`
`neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's
`
`disease, Alzheimer's disease, and Huntington's disease", "MS", "acute haemorrhagic
`
`leucoencephalomyelitis, Hurst's disease, acute disseminated encephalomyelitis, optic
`
`neuritis, Devic's disease, spinal cord lesions, acute necrotizing myelitis, transverse
`
`myelitis, chronic progressive myelopathy, progressive multifocal leukoencephalopathy
`
`(PML), radiation myelopathy, HTLV-1 associated myelopathy, monophasic isolated
`
`Page 7 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 7
`
`demyelination, central pontine myelinolysis, and leucodystrophy (e.g.,
`
`adrenoleucodystrophy, metachromatic leucodystrophy, Krabbe's disease, Canavan's
`
`disease, Alexander's disease, Pelizaeus-Merbacher disease, vanishing white matter
`
`disease, oculodentodigital syndrome, Zellweger's syndrome), chronic inflammatory
`
`demyelinating polyneuropathy (CIDP), acute inflammatory demyelinating
`
`polyneuropathy (AIDP), Leber's optic atrophy," "Charcot-Marie-Tooth disease",
`
`"polyneuritis and mitochondrial disorders with demyelination". Nowhere does the
`
`instant specification, as filed, disclose a particular advantage to applying the method
`
`described therein to RRMS.
`
`In addition, with respect to dimethyl fumarate (DMF) or monomethyl fumarate
`
`(MMF), the text in paragraph [0116] of the specification taught that "an effective amount
`
`can range from 1 mg/kg to 50 mg/kg (e.g., from 2.5 mg/kg to 20 mg/kg or from 2.5
`
`mg/kg to 15 mg/kg)" and that "an effective dose of DMF or MMF to be administered to a
`
`subject orally can be from about 0.1 g to 1 g per pay, 200 mg to about 800 mg per day
`
`(e.g., from about 240 mg to about 720 mg per day; or from about 480 mg to about 720
`
`mg per day; or about 720 mg per day)". Again, the specification, as filed, fails to
`
`demonstrate any particular advantage to be realized from the administration of a
`
`dosage of 480 mg per day of DMF or methyl ethyl fumarate (MEF) to an individual
`
`suffering from RRMS. Applicant's subsequent discovery that the vast majority of
`
`dosages described in the specification are inoperative is the only unexpected result that
`
`is supported by the evidence of record, and those embodiments are not the subject of
`
`the instant claims.
`
`Page 8 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 8
`
`It is a matter of law that a claimed invention must be patentable as of the
`
`effective filing date of the application containing that claim. Applicant may not rely upon
`
`subsequent discoveries made by themselves or others to complete the claimed
`
`invention. In the decision In re Lundberg, 117 USPQ 190, 1958, the CCPA held that
`
`"advantages which are not disclosed in application cannot be urged as basis for
`
`allowing claims". This rejection is not in conflict with the decision in in re Chu, 66 F.3d
`
`292, 298-99, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995). The claimed subject matter
`
`at issue in in re Chu (US Patent 5,567,394, Chu et al.) was distinguished from the most
`
`closely related prior art by the placement of a catalyst at a particular position in an
`
`apparatus for controlling emissions of a fossil fuel fired boiler. Evidence provided by
`
`Applicant demonstrated addition undisclosed advantages that inherently result from that
`
`placement. Whereas the Chu et al. application did not disclose certain unexpected
`
`results obtained thereby, it clearly disclosed the criticality of placing the catalyst at the
`
`particular position recited in the claims and the subsequently demonstrated advantages
`
`were inherent to that element. In the present case, the instant specification does not
`
`disclose the criticality of the limitations of the now claimed treatment protocol nor does it
`
`identify the claimed combination as being particularly advantageous, which
`
`distinguishes the current fact pattern from that which was addressed by the court in in re
`
`Chu. Applicant's discovery that the majority of embodiments disclosed in the
`
`specification are inoperative hardly supports the patentability of those few embodiments
`
`that have been subsequently discovered by Applicant to be operable.
`
`Response to Arguments
`
`Page 9 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 9
`
`7)
`
`Applicant's arguments filed 14 February of 2012, as well as the declaration
`
`by Katherine Dawson under 37 CFR 1.132 that was executed on 13 October of 2011,
`
`have been fully considered but they are not persuasive essentially for those reasons
`
`given above.
`
`Double Patenting
`
`35 U.S.C. 101 reads as follows:
`
`Whoever invents or discovers any new and useful process, machine, manufacture, or composition of
`matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the
`conditions and requirements of this title.
`
`A rejection based on double patenting of the "same invention" type finds its
`
`support in the language of 35 U.S.C. 101 which states that "whoever invents or
`
`discovers any new and useful process ... may obtain _g patent therefor ... " (Emphasis
`
`added). Thus, the term "same invention," in this context, means an invention drawn to
`
`identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re
`
`Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164
`
`USPQ 619 (CCPA 1970).
`
`A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by
`
`canceling or amending the conflicting claims so they are no longer coextensive in
`
`scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection
`
`based upon 35 U.S.C. 101.
`
`8)
`
`Claims 18 to 36 are provisionally rejected under 35 U.S.C. 101 as claiming
`
`the same invention as that of claims 18 to 36 of copending Application No. 12/526,296.
`
`This is a provisional double patenting rejection since the conflicting claims have not in
`
`fact been patented.
`
`Page 10 of 11
`
`

`

`Application/Control Number: 13/372,426
`Art Unit: 1649
`
`Page 1 O
`
`Conclusion
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to JOHN ULM whose telephone number is (571 )272-0880.
`
`The examiner can normally be reached on 9:00AM to 5:30PM.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Jeffrey Stucker can be reached on (571) 272-0911. The fax phone number
`
`for the organization where this application or proceeding is assigned is 571 -273-8300.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
`
`you have questions on access to the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a
`
`USPTO Customer Service Representative or access to the automated information
`
`system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
`
`/John D. Ulm/
`Primary Examiner, Art Unit 1649
`
`Page 11 of 11
`
`