UNITED STA 1ES p A 1ENT AND TRADEMARK OFFICE
`
`UNITED STATES 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.
`
`12/303,765
`
`12/08/2008
`
`Peter C. Hiestand
`
`50279-US-PCT
`
`9401
`
`7590
`
`06114/2011
`
`1095
`NOV ARTIS
`CORPORATEIN1ELLECTUALPROPERTY
`ONE HEALTH PLAZA 10112
`EAST HANOVER, NJ 07936-1080
`
`EXAMINER
`
`SPIVACK, PHYLLIS G
`
`ART UNIT
`
`PAPER NUMBER
`
`1629
`
`MAIL DATE
`
`DELIVERY MODE
`
`06/14/2011
`
`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)
`
`SUN - IPR2017-01929, Ex. 1009, p. 1 of 204
`
`

`

`Application No.
`
`Applicant(s)
`
`Notice of Abandonment
`
`12/303,765
`Examiner
`
`HIESTAND ET AL.
`Art Unit
`
`1629
`PHYLLIS SPIVACK
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address--
`
`This application is abandoned in view of:
`
`1. ~Applicant's failure to timely file a proper reply to the Office letter mailed on 29 November 2010.
`(a) D A reply was received on __ (with a Certificate of Mailing or Transmission dated __ ), which is after the expiration of the
`period for reply (including a total extension of time of __ month(s)) which expired on __ .
`(b) D A proposed reply was received on __ , but it does not constitute a proper reply under 37 CFR 1.113 (a) to the final rejection.
`(A proper reply under 37 CFR 1.113 to a final rejection consists only of: (1) a timely filed amendment which places the
`application in condition for allowance; (2) a timely filed Notice of Appeal (with appeal fee); or (3) a timely filed Request for
`Continued Examination (RCE) in compliance with 37 CFR 1.114).
`(c) D A reply was received on __ but it does not constitute a proper reply, or a bona fide attempt at a proper reply, to the non(cid:173)
`final rejection. See 37 CFR 1.85(a) and 1.111. (See explanation in box 7 below).
`
`(d) ~ No reply has been received.
`
`2. D Applicant's failure to timely pay the required issue fee and publication fee, if applicable, within the statutory period of three months
`from the mailing date of the Notice of Allowance (PTOL-85).
`(a) D The issue fee and publication fee, if applicable, was received on __ (with a Certificate of Mailing or Transmission dated
`__ ),which is after the expiration of the statutory period for payment of the issue fee (and publication fee) set in the Notice of
`Allowance (PTOL-85).
`(b) D The submitted fee of$ __ is insufficient. A balance of$ __ is due.
`The issue fee required by 37 CFR 1.18 is $ __ . The publication fee, if required by 37 CFR 1.18(d), is$ __ .
`(c) D The issue fee and publication fee, if applicable, has not been received.
`
`3.0 Applicant's failure to timely file corrected drawings as required by, and within the three-month period set in, the Notice of
`Allowability (PT0-37).
`(a) D Proposed corrected drawings were received on __ (with a Certificate of Mailing or Transmission dated __ ), which is
`after the expiration of the period for reply.
`(b) D No corrected drawings have been received.
`
`4. D The letter of express abandonment which is signed by the attorney or agent of record, the assignee of the entire interest, or all of
`the applicants.
`
`5. D The letter of express abandonment which is signed by an attorney or agent (acting in a representative capacity under 37 CFR
`1.34(a)) upon the filing of a continuing application.
`
`6. D The decision by the Board of Patent Appeals and Interference rendered on __ and because the period for seeking court review
`of the decision has expired and there are no allowed claims.
`
`7. ~The reason(s) below:
`
`On May 31, 2011 Applicants' representative, Karen DeBenedictis, filed a request for a continuation of application S.N.
`12/303,765.
`
`/Phyllis G. Spivack/
`Primary Examiner, Art Unit 1629
`
`Petitions to revive under 37 CFR 1.137(a) or (b), or requests to withdraw the holding of abandonment under 37 CFR 1.181, should be promptly filed to
`minimize any negative effects on patent term.
`U.S. Patent and Trademark Off1ce
`PTOL-1432 (Rev. 04·01)
`
`Notice of Abandonment
`
`Part of Paper No. 20110613
`
`SUN - IPR2017-01929, Ex. 1009, p. 2 of 204
`
`

`

`CASE PAT050279-US-PCT
`
`FILING BY "EXPRESS MAIL" UNDER 37 CFR 1.10
`
`Express Mail Label Number
`
`Date of Deposit
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`IN RE PCT NATIONAL STAGE APPLICATION OF
`
`Art Unit: 1614
`
`Hiestand, Peter C. et al.
`
`Examiner: Spivack, Phyllis G
`
`INTERNATIONAL APPLICATION NO: PCT/EP07/005597
`
`FILED: June 25, 2007
`
`U.S. APPLICATION NO: 12/303765
`
`35 USC §371 DATE: December 08,2008
`
`FOR: S1P Receptor Modulators for Treating Multiple Sclerosis
`
`Commissioner for Patents
`PO Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`PETITION FOR EXTENSION OF TIME
`
`The Office Action of November 29, 2010 has a shortened statutory time set to expire on
`
`February 28, 2011. A three-month extension is hereby requested pursuant to 37 CFR
`
`§1.136(a).
`
`The response to said Office Action is a request for filing a continued application of the
`
`above-identified application.
`
`Please charge Deposit Account No. 19-0134 in the name of Novartis in the amount of
`
`$111 0 for payment of the extension fee. The Commissioner is hereby authorized to charge any
`
`additional fees under 37 CFR §1.17 which may be required, or credit any overpayment, to
`
`Account No. 19-0134 in the name of Novartis.
`
`Novartis Pharmaceuticals Corporation
`One Health Plaza, Bldg. 101
`East Hanover, NJ 07936
`(862) 77§::37f_5
`/
`
`Date: $ j:?/ // j
`
`Karen DeBenedictis
`Attorney for Applicant
`Reg. No. 32,977
`
`SUN - IPR2017-01929, Ex. 1009, p. 3 of 204
`
`

`

`Electronic Patent Application Fee Transmittal
`
`Application Number:
`
`Filing Date:
`
`12303765
`
`08-Dec-2008
`
`Title of Invention:
`
`S1 PRECEPTOR MODULATORS FOR TREATING MULTIPLE SCLEROSIS
`
`First Named Inventor/Applicant Name:
`
`Peter C. Hiestand
`
`Filer:
`
`Karen DeBenedictis/Denise Cooper
`
`Attorney Docket Number:
`
`50279-US-PCT
`
`Filed as Large Entity
`
`U.S. National Stage under 35 USC 371 Filing Fees
`
`Description
`
`Fee Code
`
`Quantity
`
`Amount
`
`Sub-Total in
`USD($)
`
`Basic Filing:
`
`Pages:
`
`Claims:
`
`Miscellaneous-Filing:
`
`Petition:
`
`Patent-Appeals-and-Interference:
`
`Post-Allowance-and-Post-Issuance:
`
`Extension-of-Time:
`
`Extension- 3 months with $0 paid
`
`1253
`
`1
`
`1110
`
`1110
`
`SUN - IPR2017-01929, Ex. 1009, p. 4 of 204
`
`

`

`Description
`
`Fee Code
`
`Quantity
`
`Amount
`
`Sub-Total in
`USD($)
`
`Miscellaneous:
`
`Total in USD ($)
`
`1110
`
`SUN - IPR2017-01929, Ex. 1009, p. 5 of 204
`
`

`

`Electronic Acknowledgement Receipt
`
`EFSID:
`
`Application Number:
`
`10198772
`
`12303765
`
`International Application Number:
`
`Confirmation Number:
`
`9401
`
`Title of Invention:
`
`S1 PRECEPTOR MODULATORS FOR TREATING MULTIPLE SCLEROSIS
`
`First Named Inventor/Applicant Name:
`
`Peter C. Hiestand
`
`Customer Number:
`
`01095
`
`Filer:
`
`Karen DeBenedictis/Denise Cooper
`
`Filer Authorized By:
`
`Karen DeBenedictis
`
`Attorney Docket Number:
`
`50279-US-PCT
`
`Receipt Date:
`
`Filing Date:
`
`TimeStamp:
`
`31-MAY-2011
`
`08-DEC-2008
`
`16:55:22
`
`Application Type:
`
`U.S. National Stage under 35 USC 371
`
`Payment information:
`
`Submitted with Payment
`
`Payment Type
`
`Payment was successfully received in RAM
`
`RAM confirmation Number
`
`Deposit Account
`
`Authorized User
`
`yes
`
`Deposit Account
`
`$1110
`
`4054
`
`190134
`
`The Director of the USPTO is hereby authorized to charge indicated fees and credit any overpayment as follows:
`
`Charge any Additional Fees required under 37 C.F.R. 1.492 (National application filing, search, and examination fees)
`
`Charge any Additional Fees required under 37 C.F.R. Section 1.17 (Patent application and reexamination processing fees)
`
`SUN - IPR2017-01929, Ex. 1009, p. 6 of 204
`
`

`

`Charge any Additional Fees required under 37 C.F.R. Section 1.19 (Document supply fees)
`
`Charge any Additional Fees required under 37 C.F.R. Section 1.20 (Post Issuance fees)
`
`Charge any Additional Fees required under 37 C.F.R. Section 1.21 (Miscellaneous fees and charges)
`
`File Listing:
`
`Document
`Number
`
`Document Description
`
`File Name
`
`File Size( Bytes)/
`Message Digest
`
`Multi
`Part /.zip
`
`Pages
`(ifappl.)
`
`33432
`
`1
`
`Extension of Time
`
`50279_Ext.pdf
`
`no
`
`1
`
`Warnings:
`
`Information:
`
`Ocbeb0db6dc632a778e30d2db6fde0e5c1
`Oe7df
`
`30465
`
`2
`
`Fee Worksheet (PT0-875)
`
`fee-info. pdf
`
`no
`
`2
`
`54afa82a8c17aedd0a9c131 Oa78a56cd 1 aS
`8165
`
`Warnings:
`
`Information:
`
`Total Files Size (in bytes)
`
`63897
`
`This Acknowledgement Receipt evidences receipt on the noted date by the USPTO of the indicated documents,
`characterized by the applicant, and including page counts, where applicable. It serves as evidence of receipt similar to a
`Post Card, as described in MPEP 503.
`
`New A~~lications Under 35 U.S.C. 111
`If a new application is being filed and the application includes the necessary components for a filing date (see 37 CFR
`1.53(b)-(d) and MPEP 506), a Filing Receipt (37 CFR 1.54) will be issued in due course and the date shown on this
`Acknowledgement Receipt will establish the filing date of the application.
`
`National Stage of an International A~~lication under 35 U.S.C. 371
`If a timely submission to enter the national stage of an international application is compliant with the conditions of 35
`U.S.C. 371 and other applicable requirements a Form PCT/DO/E0/903 indicating acceptance of the application as a
`national stage submission under 35 U.S.C. 371 will be issued in addition to the Filing Receipt, in due course.
`
`New International A~~lication Filed with the USPTO as a Receiving Office
`If a new international application is being filed and the international application includes the necessary components for
`an international filing date (see PCT Article 11 and MPEP 181 0), a Notification of the International Application Number
`and of the International Filing Date (Form PCT/R0/1 OS) will be issued in due course, subject to prescriptions concerning
`national security, and the date shown on this Acknowledgement Receipt will establish the international filing date of
`the application.
`
`SUN - IPR2017-01929, Ex. 1009, p. 7 of 204
`
`

`

`UNITED STA 1ES p A 1ENT AND TRADEMARK OFFICE
`
`UNITED STATES 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.
`
`12/303,765
`
`12/08/2008
`
`Peter C. Hiestand
`
`50279-US-PCT
`
`9401
`
`7590
`
`11/29/2010
`
`1095
`NOV ARTIS
`CORPORATEIN1ELLECTUALPROPERTY
`ONE HEALTH PLAZA 10112
`EAST HANOVER, NJ 07936-1080
`
`EXAMINER
`
`SPIVACK, PHYLLIS G
`
`ART UNIT
`
`PAPER NUMBER
`
`1614
`
`MAIL DATE
`
`DELIVERY MODE
`
`11/29/2010
`
`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)
`
`SUN - IPR2017-01929, Ex. 1009, p. 8 of 204
`
`

`

`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`12/303,765
`
`Examiner
`
`HIESTAND ET AL.
`
`Art Unit
`
`1614
`Phyllis G. Spivack
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE~ 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)[8J Responsive to communication(s) filed on 14 September 2010.
`2a)0 This action is FINAL.
`2b)[8J This action is non-final.
`3)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 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`4)[8J Claim(s) 4-14 is/are pending in the application.
`4a) Of the above claim(s) 10. 11.13 and 14 is/are withdrawn from consideration.
`5)0 Claim(s) __ is/are allowed.
`6)[8J Claim(s) 4-9 and 12 is/are rejected.
`7)0 Claim(s) __ is/are objected to.
`8)0 Claim(s) __ are subject to restriction and/or election requirement.
`
`Application Papers
`
`9)0 The specification is objected to by the Examiner.
`10)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).
`11 )0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PT0-152.
`
`Priority under 35 U.S.C. § 119
`
`12)[8J Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)IZ! 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.[8J 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)).
`*See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`1) [8J Notice of References Cited (PT0-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PT0-948)
`3) [8Jinformation Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 12/8/08.
`
`4) 0
`
`Interview Summary (PT0-413)
`Paper No(s)/Mail Date. __ .
`5) 0 Notice of Informal Patent Application
`6) 0 Other: __ .
`
`U.S. Patent and Trademark Off1ce
`PTOL-326 (Rev. 08-06)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20101120
`
`SUN - IPR2017-01929, Ex. 1009, p. 9 of 204
`
`

`

`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 2
`
`Applicants' Preliminary Amendment filed December 8, 2008 is acknowledged.
`
`Updated priority information and a new Abstract are noted. New claims 12-14 are
`
`presented. Claims 1-3 are canceled. Accordingly, claims 4-14 are pending.
`
`An Information Disclosure Statement filed December 8, 2008 is further
`
`acknowledged and has been considered.
`
`In response to a Species Requirement, Applicants elected the compound 2-
`
`amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol (also referred to as "FTY720"), in free
`
`form or in a pharmaceutically acceptable salt or hydrate form, as the species of S1 P
`
`receptor modulator. Applicants further elected multiple sclerosis (MS) as the species of
`
`demyelinating disease. Because Applicants did not distinctly and specifically point out
`
`the supposed errors in the restriction requirement, the election has been treated as an
`
`election without traverse (MPEP § 818.03(a)).
`
`Thus the subject matter initially under consideration is drawn to methods for
`
`preventing, inhibiting or treating neo-angiogenesis associated with a demyelinating
`
`disease in a subject in need thereof, comprising administering to said subject a
`
`therapeutically effective amount of an S1 P receptor modulator, wherein the
`
`demyelinating disease is multiple sclerosis, and, wherein the S1 Preceptor modulator or
`
`agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane, 1 ,3-diol, 2-amino-2-[4-(3-
`
`benzyloxyphenoxy)-2-chlorophenyl]ethyl-1 ,3-propane-diol, and a pharmaceutical
`
`combination comprising a) a first agent which is a SIP receptor modulator, i.e., FTY 720,
`
`in free form or in pharmaceutically acceptable salt form, and b) a VEGF-receptor
`
`antagonist, claims 4-9 and 12. Those methods drawn to treating neo-angiogenesis
`
`SUN - IPR2017-01929, Ex. 1009, p. 10 of 204
`
`

`

`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 3
`
`associated with demyelinating diseases in a subject in need thereof other than multiple
`
`sclerosis and S1 Preceptor modulators or agonists other than FTY720, as well as
`
`claims 10, 11, 13 and 14, are presently withdrawn from consideration by the Examiner,
`
`37 CFR 1 .142(b ), as drawn to non-elected inventions. Re-affirmation of the elections is
`
`requested when Applicants respond to this Office Action.
`
`The abstract of the disclosure is objected to because the subject matter under
`
`consideration excludes methods of prevention. Correction is required. See MPEP
`
`§ 608.01 (b).
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`Claims 4 and 5 are rejected under 35 U.S.C. 112, second paragraph, as being
`
`indefinite for failing to particularly point out and distinctly claim the subject matter which
`
`Applicants regard as the invention.
`
`Claim 4 recites the limitation "medicament." There is insufficient antecedent
`
`basis for this limitation in independent claim 7 from which claim 4 depends.
`
`Claim 5, drawn to a pharmaceutical composition, does not properly further limit
`
`the subject matter of claim 7 which is drawn to a method of treatment.
`
`Correction is required.
`
`The following is a quotation of the first paragraph of 35 U .S.C. 112:
`
`The specification shall contain a written description of the invention, and of the manner and process of
`making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the
`art to which it pertains, or with which it is most nearly connected, to make and use the same and shall
`set forth the best mode contemplated by the inventor of carrying out his invention.
`
`SUN - IPR2017-01929, Ex. 1009, p. 11 of 204
`
`

`

`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 4
`
`Claims 4-9 and 12 are rejected under 35 U.S.C. 112, first paragraph, as
`
`containing subject matter which was not described in the specification in such a way as
`
`to enable one skilled in the art to which it pertains, or with which it is most nearly
`
`connected, to practice the invention. The claims are directed to treating, preventing or
`
`inhibiting neo-angiogenesis associated with the demyelinating disease multiple
`
`sclerosis. On page 13 of the specification, the administration of Compound A, a S1 P
`
`receptor modulator, is described as blocking disease-associated neo-angiogenesis, as
`
`well as inhibiting the relapse phases of multiple sclerosis in an animal assay. The
`
`present specification does not reasonably provide enablement for methods of
`
`prevention, within the full scope of the claims.
`
`To be enabling, the specification must teach those skilled in the art how to make
`
`and use the full scope of the claimed invention without undue experimentation. In re
`
`Wright, 999 F.2d 1557, 1561 (Fed. Cir., 1993). Explaining what is meant by "undue
`
`experimentation," the Federal Circuit has stated that:
`
`The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or
`
`if the specification in question provides a reasonable amount of guidance with respect to the direction in which
`
`experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed
`
`invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
`
`The factors that may be considered in determining whether a disclosure would
`
`require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC
`
`1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547,
`
`SUN - IPR2017-01929, Ex. 1009, p. 12 of 204
`
`

`

`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 5
`
`the court recited eight factors to consider when assessing whether or not a disclosure
`
`would require undue experimentation. These factors are:
`
`1) the quantity of experimentation necessary
`
`2) the amount of direction or guidance provided
`
`3) the presence or absence of working examples
`
`4) the nature of the invention
`
`5) the state of the art
`
`6) the relative skill of those in the art
`
`7) the predictability of the art and
`
`8) the breadth of the claims.
`
`These factors are always applied against the background understanding that
`
`scope of enablement varies inversely with the degree of unpredictability involved. In re
`
`Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping
`
`that in mind, the Wands factors are relevant to the instant fact situation for the following
`
`reasons:
`
`The nature of the invention. state of the prior art. relative skill of those in the art
`and the predictability of the art
`
`The invention encompasses prevention of multiple sclerosis. The relative skill of
`
`those in the art is high, generally that of an M.D. or Ph.D. with expertise in the area of
`
`neurology. However, that factor is outweighed by the unpredictable nature of MS, as
`
`indicated by Miller et al., Current Neuroloq. Neurosci. Reports.
`
`SUN - IPR2017-01929, Ex. 1009, p. 13 of 204
`
`

`

`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 6
`
`According to Miller, which is cited for evidentiary purposes only, multiple sclerosis
`
`is a complex demyelinating disease with an unpredictable course. See the Abstract and
`
`Introduction. As such, one skilled in the art would not readily accept an assertion that
`
`multiple sclerosis would be prevented following administration of FTY720.
`
`In cases involving unpredictable factors, such as the instant claims drawn to
`
`physiological activity, the scope of enablement varies inversely with the degree of
`
`unpredictability of the factors involved. One skilled in the chemical or biological arts
`
`cannot always reasonably predict how different chemical compounds might behave
`
`under varying circumstances. See Ex parte Sudilovsky 21 USPQ2d 1701.
`
`The amount of direction or guidance provided and the presence or absence of
`
`working examples
`
`A clinical trial is described on page 13 wherein 20 patients with relapsing-
`
`remitting MS receive Compound A in a scheduled regimen. No therapeutic outcome is
`
`noted. There are no working examples drawn to a prevention modality in which a
`
`claimed compound is shown to be clinically effective. Such an assertion is beyond the
`
`scope of the instantly claimed invention.
`
`The quantity of experimentation necessary
`
`Absent reasonable a priori expectations of success for preventing multiple
`
`sclerosis, one skilled in the neurology art would have had to test extensively numerous
`
`laboratory models of MS using various dosages and dosing regimens to discover which
`
`is effective. Since each prospective embodiment, as well as future embodiments as the
`
`SUN - IPR2017-01929, Ex. 1009, p. 14 of 204
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`

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`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 7
`
`art progresses, would have to be empirically tested, undue experimentation would be
`
`required to practice the invention as it is claimed in its current scope. The specification
`
`provides inadequate guidance to do otherwise.
`
`Due to the known unpredictability of the art, and in the absence of experimental
`
`evidence commensurate in scope with the claims, the skilled artisan would not accept
`
`the assertion that administering one of the claimed compounds, e.g., FTY720, would
`
`result in the prevention of multiple sclerosis. The instant claims do not comply with the
`
`enablement requirements of 35 U.S.C. 112, first paragraph, since to practice the
`
`claimed invention would require a person of ordinary skill in the art to engage in undue
`
`experimentation with no assurance of success.
`
`The following is a quotation of 35 U.S.C. 1 03(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`(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.
`
`Claim 6 is rejected under 35 U.S.C. 1 03(a) as being unpatentable over HLA, T.,
`
`FASEB Journal.
`
`Hla teaches FTY 720 to be an S1 P agonist and a potent inhibitor ofVEGF-
`
`induced vascular permeability in vivo. In the control of vascular permeability, S1 P
`
`receptor agonism may be useful. Since the S1 Preceptor is strongly induced in tumor
`
`vessels, suppression of its expression by local injection of siRNA in vivo resulted in
`
`SUN - IPR2017-01929, Ex. 1009, p. 15 of 204
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`

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`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 8
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`decreased microvessel density, decreased vascular stabilization and attenuated tumor
`
`growth. Hla suggests modulation of S1 P signaling in the vascular system may provide
`
`a way of regulating angiogenesis and vascular formation.
`
`A kit is no more than a conventional type of packaging.
`
`One skilled in the art would have been motivated to combine FTY 720 and a
`
`VEGF-receptor antagonist together in a pharmaceutical formulation. Such would have
`
`been obvious in the absence of evidence to the contrary because FTY 720 is an
`
`inhibitor of VEGF-induced vascular permeability. Thus the combination of FTY 720 with
`
`another antagonist of VEGF would have reasonably provided an additive effect when
`
`seeking a means of regulating angiogenesis and vascular formation.
`
`Claims 4, 5, 7-9 and 12 are rejected under 35 U.S.C. 1 03(a) as being
`
`unpatentable over Kovarik et al., WO 2006/058316, in view of HLA, T., FASEB Journal.
`
`Kovarik teaches the administration of the compound 2-amino-2-[2-(4-
`
`octylphenyl)ethyl]propane-1,3-diol, FTY720, to treat autoimmune diseases of which
`
`multiple sclerosis is specifically recited. See page 14, lines 7-8. All types of multiple
`
`sclerosis are reasonably encompassed in Kovarik's teaching. The elected specie, 2-
`
`amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, FTY 720, is described as a preferred
`
`embodiment on page 13, lines 3-7.
`
`With respect to an intermittent dosing regimen (claim 9), it is not inventive to
`
`discover an optimum dosing regimen by routine experimentation when general
`
`conditions of a claim are disclosed in the prior art. See In re Aller, 220 F.2d 454, 456,
`
`105 USPQ 233, 235 (CCPA 1955) and MPEP §2144.05(11). The medical arts recognize
`
`SUN - IPR2017-01929, Ex. 1009, p. 16 of 204
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`

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`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 9
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`that drug therapy may be optimized by designing regimens that account for the
`
`concentration of a drug, for example, to achieve a desired pharmacological response.
`
`Factors such as weight, age, gender, renal and hepatic status, inter alia, are always
`
`considered. Therefore, the determination of the optimum characterization of the
`
`composition, dosing regimen and dosage amounts would have been a matter well within
`
`the purview of one of ordinary skill in the art, at the time of the invention, through no
`
`more than routine experimentation.
`
`Kovarik does not disclose combination therapy. However, the teachings of Hla,
`
`as set forth supra, suggest beneficial combination therapy in order to achieve an
`
`additive effect when seeking a means of regulating angiogenesis and vascular
`
`formation.
`
`No claim is allowed.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Phyllis G. Spivack whose telephone number is 571-272-
`
`0585. The Examiner can normally be reached on 10:30 AM-7 PM.
`
`If attempts to reach the Examiner by telephone are unsuccessful after one
`
`business day, the Examiner's supervisor, Ardin Marschel, can be reached on 591-272-
`
`0718. The fax phone number for the organization where this application or proceeding
`
`is assigned is 571-273-8300.
`
`SUN - IPR2017-01929, Ex. 1009, p. 17 of 204
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`

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`Application/Control Number: 12/303,765
`Art Unit: 1614
`
`Page 10
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`Information regarding the status of an application may be obtained from the
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`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.
`
`November 20, 2010
`
`/Phyllis G. Spivack/
`Primary Examiner, Art Unit 1614
`
`SUN - IPR2017-01929, Ex. 1009, p. 18 of 204
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`

`

`Notice of References Cited
`
`Application/Control No.
`
`12/303,765
`
`Examiner
`
`Phyllis G. Spivack
`
`U.S. PATENT DOCUMENTS
`
`Applicant(s)/Patent Under
`Reexamination
`HIESTAND ET AL.
`
`Art Unit
`
`1614
`
`Page 1 of 1
`
`*
`
`Document Number
`Country Code-Number-Kind Code
`
`Date
`MM-YYYY
`
`Name
`
`Classification
`
`A
`
`US-
`
`US-
`B
`c US-
`D US-
`E US-
`US-
`
`F
`
`G
`
`H
`
`I
`
`J
`
`K
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`L
`M US-
`
`*
`
`Document Number
`Country Code-Number-Kind Code
`
`Date
`MM-YYYY
`
`Country
`
`Name
`
`Classification
`
`FOREIGN PATENT DOCUMENTS
`
`N
`
`0
`
`p
`
`Q
`
`R
`s
`T
`
`*
`
`NON-PATENT DOCUMENTS
`
`Include as applicable: Author, Title Date, Publisher, Edition or Volume, Pertinent Pages)
`
`u Miller et al., Neural. & Neurosci. Reports, (September, 201 0), 1 0(5), pp. 397-406.
`
`v Hla, T., FASEB Journal, (March 6, 2006), 20(4), Part 1, A20.
`
`w
`
`X
`
`*A copy of th1s reference IS not bemg furnished w1th th1s Off1ce act1on. (See MPEP § 707.05(a).)
`Dates in MM-YYYY format are publication dates. Classifications may be US or foreign.
`
`U.S. Patent and Trademark Office
`PT0-892 (Rev. 01-2001)
`
`Notice of References Cited
`
`Part of Paper No. 20101120
`
`SUN - IPR2017-01929, Ex. 1009, p. 19 of 204
`
`

`

`Search Notes
`
`I IIIII
`
`Application/Control No.
`
`12/303,765
`Examiner
`
`Applicant(s)/Patent under
`Reexamination
`
`HIESTAND ET AL.
`Art Unit
`
`Phyllis G. Spivack
`
`1614
`
`SEARCHED
`
`SEARCH NOTES
`(INCLUDING SEARCH STRATEGY)
`
`Class
`
`Subclass
`
`Date
`
`Examiner
`
`DATE
`
`EXMR
`
`PALM inventors search
`
`11/20/2010
`
`PS
`
`STN & inventors search
`
`11/15/2010
`
`PS
`
`INTERFERENCE SEARCHED
`
`Class
`
`Subclass
`
`Date
`
`Examiner
`
`U.S. Patent and Trademark Office
`
`Part of Paper No. 20101120
`
`SUN - IPR2017-01929, Ex. 1009, p. 20 of 204
`
`

`

`UNI1ED STATES PATENT AND TRADEMARK OFFICE
`
`BIB DATA SHEET
`
`Page 1 of 1
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www.uspto.gov
`
`CONFIRMATION NO. 9401
`
`SERIAL NUMBER
`
`12/303,765
`
`FILING or 371 (c)
`DATE
`12/08/2008
`RULE
`
`CLASS
`
`514
`
`GROUP ART UNIT ATTORNEY DOCKET
`NO.
`1614
`50279-US-PCT
`
`APPLICANTS
`Peter C. Hiestand, Allschwil, SWITZERLAND;
`Christian Schnell, Hesingue, FRANCE;
`** CONTINUING DATA *************************
`This application is a 371 of PCT/EP07/05597 06/25/2007
`** FOREIGN APPLICATIONS *************************
`UNITED KINGDOM 0612721.1 06/27/2006
`** IF REQUIRED, FOREIGN FILING LICENSE GRANTED **
`03/19/2010
`
`0 Metafter
`Allowance
`
`STATE OR
`COUNTRY
`
`SHEETS
`DRAWINGS
`
`TOTAL
`CLAIMS
`
`INDEPENDENT
`CLAIMS
`
`SWITZERLAND
`
`0
`
`11
`
`2
`
`~Yes DNa
`Foreign Priority claimed
`35 USC t t9(a-d) conditions met ~Yes 0 No
`Verified and
`/PHYLLIS G
`SPIVACK/
`Examiner's Signature
`
`Initials
`
`Acknowledged
`ADDRESS
`NOV ARTIS
`CORPORATE INTELLECTUAL PROPERTY
`ONE HEALTH PLAZA 101/2
`EAST HANOVER, NJ 07936-1080
`UNITED STATES
`TITLE
`S1 PRECEPTOR MODULATORS FOR TREATING MULTIP