PCT /US2005/041904
`
`wo 2006/055809
`
`Figure 31
`
`Figure 31A
`
`s..
`C1l
`.Q
`E
`::s :z
`
`66
`22
`200
`Antibody Concentration [nM]
`
`Figure 31B
`
`0 ..,..
`><
`0
`G)
`
`(l -0
`
`s..
`C1l
`.Q
`E
`::s :z
`
`66
`22
`200
`Antibody Concentration [nM]
`
`Figure 31A and B: Inhibition of Tumor Cell Proliferation. 2 x 104 DU4475 cells
`were serum starved overnight following treatment with desferrioxamine, then
`incubated with various an1ount of 18Fl (shadowed bar) or isotype control IgG
`(opened bar) in the presence of VEGF-A (A) or PlGF (B). After 2 days incubation,
`total cell number was determined using a Coulter cell counter. The results are shown
`as mean value with standard error.
`
`32/33
`
`SUN - IPR2017-01929, Ex. 1010, p. 251 of 494
`
`

`

`PCT IUS2005/041904
`
`wo 2006/055809
`
`Figure 32
`
`Figure 32A
`
`2.4
`
`2.0
`
`--- IMC-18F1
`-!:r- MF1
`
`li5 1.6
`-.::1'
`c
`1.2
`ci
`
`0.8
`
`0.4
`
`0.0
`0.0001
`
`0.001
`0.01
`0.1
`Antibody, J.lQ/ml
`
`Figure32B
`
`1.4
`
`1.2
`
`--- IMC-18F1
`-!:r- MF1
`
`Figure 32C
`
`1.0
`
`c
`It)
`-.::1' 0.8
`c
`ci 0.6
`0.4
`
`0.2
`
`0.0
`
`0.0001
`
`0.001
`0.01
`0.1
`Antibody, J.lQ/ml
`
`--IMC-18F1
`
`-!:r-1C11
`
`2.0
`
`1.8
`
`1.6
`
`1.4
`c
`10 1.2
`-.::1'
`c:i 1.0
`ci 0.8
`0.6
`
`0.4
`
`0.2
`
`0.0
`0.0001
`
`0.001
`0.01
`0.1
`Antibody, J.lQ/.ml
`
`Figure 32A, B, and C: Specificity of 18F1 and Anti-mouse VEGFR-1 Antibody
`MFL 18F1 has binding activity with immobilized recombinant human VEGFR-1 (A)
`but not with mouse VEGFR-1 (B) and human VEGFR-2 (C) as compared to positive
`control MF1 or VEGFR-2 specific antibody 1C11. Anti-mouse VEGFR-1 antibody
`MFI did not bind to immobilized recombinant human VEGFR-l(A). 18Fl was used
`as a positive control in solid phase binding assay.
`
`33/33
`
`SUN - IPR2017-01929, Ex. 1010, p. 252 of 494
`
`

`

`Case PAT050279-US-CNT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`IN REAPPLICATION OF
`
`Hiestand, Peter C. et al.
`
`APPLICATION NO: 13/149468
`
`FILED: May 31, 2011
`
`Art Unit: 1629
`
`Examiner:
`
`FOR: DOSAGE REGIMEN OF AN S1P RECEPTOR AGONIST
`
`MS: Amendment
`Commissioner for Patents
`PO Box 1450
`Alexandria, VA 22313-1450
`
`SUPPLEMENTAL INFORMATION DISCLOSURE STATEMENT
`
`Sir:
`
`In accordance with 37 C.F.R. §1.56, applicants wish to call the Examiner's attention to the
`
`references cited on the attached form(s) PTO/SB/08A/B.
`
`Copies of the references are enclosed herewith.
`
`The Examiner is requested to consider the foregoing information in relation to this application
`
`and indicate that each reference was considered by returning a copy of the initialed
`
`PTO/SB/08A/B form(s).
`
`Please charge Deposit Account No. 19-0134 in the name of Novartis in the amount of $180 for
`
`payment of the fee pursuant to 37 CFR §1.17(p) for the submission of an Information Disclosure
`
`Statement under 37 CFR §1.97(c). The Commissioner is hereby authorized to charge any
`
`additional fees 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
`+1 862 7783785
`
`Date: tJ ;I Cf /; ~
`
`SUN - IPR2017-01929, Ex. 1010, p. 253 of 494
`
`

`

`Case PAT050279-US-CNT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`IN REAPPLICATION OF
`
`Hiestand, Peter C. et al.
`
`APPLICATION NO: 13/149468
`
`FILED: May 31, 2011
`
`Art Unit: 1629
`
`Examiner:
`
`FOR: DOSAGE REGIMEN OF AN S1P RECEPTOR AGONIST
`
`MS: Amendment
`Commissioner for Patents
`PO Box 1450
`Alexandria, VA 22313-1450
`
`SUPPLEMENTAL INFORMATION DISCLOSURE STATEMENT
`
`Sir:
`
`In accordance with 37 C.F.R. §1.56, applicants wish to call the Examiner's attention to the
`
`references cited on the attached form(s) PTO/SB/08A/B.
`
`Copies of the references are enclosed herewith.
`
`The Examiner is requested to consider the foregoing information in relation to this application
`
`and indicate that each reference was considered by returning a copy of the initialed
`
`PTO/SB/08A/B form(s).
`
`Please charge Deposit Account No. 19-0134 in the name of Novartis in the amount of $180 for
`
`payment of the fee pursuant to 37 CFR §1.17(p) for the submission of an Information Disclosure
`
`Statement under 37 CFR §1.97(c). The Commissioner is hereby authorized to charge any
`
`additional fees 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
`+1 862 7783785
`
`Date: tJ ;I Cf /; ~
`
`SUN - IPR2017-01929, Ex. 1010, p. 254 of 494
`
`

`

`PTO/SBIOSa (07-09)
`Approved for use through 07/31/2012. OMS 0651-0031
`U.S. Patent and Trademark Offace; U.S. DEPARTMENT OF COMMERCE
`Under the PapeiWOrk Reduction Act of 1995, no persons are reauired to resPOnd to a collection of information unless it contains a valid OMS control number.
`
`Substitute for form 1449/PTO
`
`INFORMATION DISCLOSURE
`STATEMENT BY APPLICANT
`(Use as many sheets as necessary)
`
`Sheet
`
`I
`
`1
`
`I of I
`
`1
`
`Complete if Known
`Application Number
`13/149468
`May 31,2011
`Filing Date
`First Named Inventor
`Hiestand Peter C. et al.
`Art unit
`1629
`Examiner Name
`Attomev DockefNumber
`
`PAT050279-US-CNT
`
`Examiner
`Initials*
`
`Cite
`No.'
`
`Document Number
`Number-Kind Code21
`... ""•"""
`
`U.S. PATENT DOCUMENTS
`Publication Date
`Name of Patentee or
`Applicant of Cited Document
`MM-00-YYYY
`
`Pages, Columns, lines, Where
`Relevant Passages or Relevant
`Fi!lures Aopear
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`
`US-
`us-
`
`Examiner
`Initials*
`
`Cite
`No.1
`
`Foreign Patent Document
`
`Country Code3 Number" Kind Code5 ,,.,...,
`
`FOREIGN PATENT DOCUMENTS
`Publication Date
`Name of Patentee or
`Applicant of Cited Document
`MM-DD-YYYY
`
`Pages, Columns, lines,
`Where Relevant Passages or
`Relevant Figures Appear
`
`RU2199339C2
`
`02-27-2003
`
`TEKH; 000 BID
`
`I Examiner
`~ignature
`
`Date
`Considered
`*EXAMINER: Initial if reference considered, whether or not citation is in conformance with MPEP 609. Draw a line through citation if not in conformance
`and not considered. Include copy of this form with the next communication to applicant. 1 Applicant's unique citation designation number (optional). 2
`See Kind Codes of USPTO Patent Documents at www.uspto.gov or MPEP 901.04. 3 Enter Office that issued the document, by the two-letter code (WIPO
`Standard ST.3}. 4 For Japanese patent documents, the indication of the year of the reign of the Emperor must precede the serial number of the patent
`document. 5 Kind of document by the appropriate symbols as indicated on the document under WIPO Standard ST.16 if possible. 6 Applicant is to place
`a check mark here if English language Translation is attached.
`This collection of information is required by 37 CFR 1.97 and 1.98. The information is required to obtain or retain a benefit by the public which is to file
`(and by the USPTO to process} an application. Confidentiality is governed by 35 U.S.C. 122 and 37 CFR 1.14. This collection is estimated to take 2
`hours to complete, including gathering, preparing, and submitting the completed application form to the USPTO. Time will vary depending upon the
`individual case. Any comments on the amount of time you require to complete this form and/or suggestions for reducing this burden, should be sent to the
`Chief Information Officer, U.S. Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450. DO NOT SEND FEES OR COMPLETED
`FORMS TO THIS ADDRESS. SEND TO: Commissioner for Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`If you need assistance in completing the form, call 1-800-PT0-9199 (1-800-786-9199) and select option 2.
`
`-re
`0
`0
`0
`0
`0
`0
`
`SUN - IPR2017-01929, Ex. 1010, p. 255 of 494
`
`

`

`Electronic Patent Application Fee Transmittal
`
`Application Number:
`
`Filing Date:
`
`13149468
`
`31-May-2011
`
`Title of Invention:
`
`S1 PRECEPTOR MODULATORS FOR TREATING MUTIPLE SCLEROSIS
`
`First Named Inventor/Applicant Name:
`
`Peter C. Hiestand
`
`Filer:
`
`Karen DeBenedictis/Denise Cooper
`
`Attorney Docket Number:
`
`PAT050279-US-CNT
`
`Filed as Large Entity
`
`Utility under 35 USC 111 (a) 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:
`
`SUN - IPR2017-01929, Ex. 1010, p. 256 of 494
`
`

`

`Description
`
`Fee Code
`
`Quantity
`
`Amount
`
`Sub-Total in
`USD($)
`
`Miscellaneous:
`
`Submission- Information Disclosure Stmt
`
`1806
`
`1
`
`180
`
`180
`
`Total in USD ($)
`
`180
`
`SUN - IPR2017-01929, Ex. 1010, p. 257 of 494
`
`

`

`Electronic Acknowledgement Receipt
`
`EFSID:
`
`Application Number:
`
`12546461
`
`13149468
`
`International Application Number:
`
`Confirmation Number:
`
`1536
`
`Title of Invention:
`
`S1 PRECEPTOR MODULATORS FOR TREATING MUTIPLE SCLEROSIS
`
`First Named Inventor/Applicant Name:
`
`Peter C. Hiestand
`
`Customer Number:
`
`1095
`
`Filer:
`
`Karen DeBenedictis/Denise Cooper
`
`Filer Authorized By:
`
`Karen DeBenedictis
`
`Attorney Docket Number:
`
`PAT050279-US-CNT
`
`Receipt Date:
`
`Filing Date:
`
`TimeStamp:
`
`16-APR-2012
`
`31-MAY-2011
`
`12:17:36
`
`Application Type:
`
`Utility under 35 USC 111 (a)
`
`Payment information:
`
`Submitted with Payment
`
`Payment Type
`
`Payment was successfully received in RAM
`
`RAM confirmation Number
`
`Deposit Account
`
`Authorized User
`
`yes
`
`Deposit Account
`
`$180
`
`10438
`
`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. Section 1.21 (Miscellaneous fees and charges)
`
`SUN - IPR2017-01929, Ex. 1010, p. 258 of 494
`
`

`

`File Listing:
`
`Document
`Number
`
`Document Description
`
`File Name
`
`File Size( Bytes)/
`Message Digest
`
`Multi
`Part /.zip
`
`Pages
`(ifappl.)
`
`40981
`
`1
`
`Foreign Reference
`
`15-RU2199339-abstract.pdf
`
`no
`
`1
`
`6d 172b 70b289fcc3f7 3 55 3 55 85 37f2878064
`6834
`
`Warnings:
`
`Information:
`
`2
`
`Warnings:
`
`Information:
`
`50279-IDS.pdf
`
`yes
`
`2
`
`110493
`
`dcf72d3d17fa0091 a95bf23fbedea6f0f0465
`958
`
`Multipart Description/PDF files in .zip description
`
`Document Description
`
`Start
`
`End
`
`Transmittal Letter
`
`Information Disclosure Statement (IDS) Form (SBOS)
`
`1
`
`2
`
`1
`
`2
`
`30482
`
`3
`
`Fee Worksheet (SB06)
`
`fee-info. pdf
`
`no
`
`2
`
`2e9d06a9df16f834b2bdaf514249e5fd6299
`bbbf
`
`Warnings:
`
`Information:
`
`Total Files Size (in bytes)
`
`181956
`
`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
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`
`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
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`the application.
`
`SUN - IPR2017-01929, Ex. 1010, p. 259 of 494
`
`

`

`With regard to other embodiments of the claimed invention, a medication for slowing
`inhibiting or
`
`treating Primary(cid:173)
`
`progression of a demyelinating disease and
`
`for
`
`progressive multiple sclerosis, comprising an irrununomodulator is known from the prior art {see
`
`RU 2199339 C2 27.02.2003) (03).
`
`Bibliographic data: RU.2199339 (C2)- 2003a02~27
`
`-+ Report data error
`
`Q Print
`
`METHOD FOR TREATING fvlUL TIPLE SCLEROSIS
`
`Paye hrmknmrk
`
`RU2·199339 (C?i - METHOD FOR TREATING MULT!Pi F SCLFROS!S
`
`BP..RBAS 1 M; TOTOLJAN r~ P..; SKOROMETS P.. A; SMIRr~OV M ~oJ; ZHIVOTOVSKAJA M L; JP..KOVLEVA V S :':
`
`TEKH; 000 BIO :_
`
`Classification:
`
`- intematiOil<ll: AMIGKU; (IPC1-7): ,1\,61 K38/20
`
`- Emopean:
`
`AI)IJiicatiOIIIIIIIIlber: RU2001 01 04'~29 20010223
`
`Priority mmlhel!s.): RU2001 0104929 20010223
`
`.e.bstr~ct of RU2199339 (C2}
`
`i
`Translate tl1is tel-1 into
`[_?_~r:::1"r' ___________________________ .,:J ~~-- .",., .. ,..,.,:~.,,::-'·:-,,.,:·:-,,,,,,,,
`
`FIELD medicine, neurology SUBSTM'<GE: during tr:e stage of exacerbation patients witl1 tY:ultip!e sclerosis sr10uld be intravenously
`injected by drops wi!r1 r1uman interleukin-2 (h-IL-2) preparation, for example, ronco!eukin, attr1e dosage of not less than 1 min IU once per
`7d. Tt1e mett10d enables to considerabiV shorten tr1erapy terms in patients w;H1 multiple sclerosis at the background of pronounced immune
`deficiency-, decrease the number of relapses and prolong labor capacity- period in patients with multiple sclerosis. EFFECT: higher efficiennt
`oftl1erapy. 1 cl, 2 ex, 2 tbl
`
`SUN - IPR2017-01929, Ex. 1010, p. 260 of 494
`
`

`

`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Case PAT050279-US-CNT
`
`IN REAPPLICATION OF
`Hiestand, Peter C. et al.
`APPLICATION NO: 13/149468
`FILED: May 31, 2011
`FOR: DOSAGE REGIMEN OF AN S1 P RECEPTOR AGONIST
`
`Art Unit: 1629
`Examiner:
`
`Commissioner for Patents
`PO Box 1450
`Alexandria, VA 22313-1450
`
`INFORMATION DISCLOSURE STATEMENT
`
`Sir:
`
`This paper is being filed:
`
`00
`
`supplemental to the Information Disclosure Statements filed May 31, 2011 and
`
`December 30, 2011.
`
`Please charge Deposit Account No. 19-0134 in the name of Novartis in the amount of $180 for
`payment of the fee pursuant to 37 CFR §1.17(p) for the submission of an Information Disclosure
`Statement under 37 CFR §1.97(c). The Commissioner is hereby authorized to charge any
`additional fees which may be required, or credit any overpayment, to Account No. 19-0134 in
`the name of Novartis.
`
`In accordance with 37 C.F.R. §1.56, applicants wish to call the Examiner's attention to the
`references cited on the attached form(s) PTO/SB/08A/B.
`
`~ Copies of the references are enclosed herewith.
`
`The Examiner is requested to consider the foregoing information in relation to this application
`and indicate that each reference was considered by returning a copy of the initialed
`PTO/SB/08A/B form(s).
`
`Novartis Pharmaceuticals Corporation
`One Health Plaza, Bldg. 101
`East Hanover, NJ 07936
`+1 862 7.7837,.5
`Date:y)// jj;L
`
`>
`
`ren DeBenedictis
`Attorney for Applicant
`Reg. No. 32,977
`
`SUN - IPR2017-01929, Ex. 1010, p. 261 of 494
`
`

`

`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.
`
`131149,468
`
`05/3112011
`
`Peter C. Hiestand
`
`PAT050279-US-CNT
`
`1536
`
`7590
`
`04/03/2012
`
`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
`
`04/03/2012
`
`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)
`
`SUN - IPR2017-01929, Ex. 1010, p. 262 of 494
`
`

`

`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`13/149,468
`
`Examiner
`
`HIESTAND ET AL.
`
`Art Unit
`
`1629
`PHYLLIS G. SPIVACK
`-- The MAILING DATE 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 ;2 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 t. t 36(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. § t33).
`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 t .704(b).
`
`Status
`1 )0 Responsive to communication(s) filed on __ .
`2a)0 This action is FINAL.
`2b)[8] 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 C. D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`5)[8] Claim(s) 12-21 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)[8] Claim(s) 12-21 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
`
`1 0)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 PT0-152.
`
`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)).
`*See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment{s)
`1) 0 Notice of References Cited (PT0-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PT0-948)
`3) [8] Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 5131111:9/29111.
`
`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. 03·11)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20120324
`
`SUN - IPR2017-01929, Ex. 1010, p. 263 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 2
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`Applicants' Preliminary Amendment file May 31, 2011 is acknowledged. Claims
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`1-11 are canceled. New claims 12-21 are presented and represent all of the claims
`
`under consideration. A new Abstract and updated priority information are noted.
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`Information Disclosure Statements filed May 31, 2011 and September 29, 2011
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`are further acknowledged and have been reviewed. The reference to Dr. Maschkowskij
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`cited on the Information Disclosure Statement filed September 29, 2011 is not present
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`in the instant file or in the parent application.
`
`The abstract of the disclosure is objected to because the subject matter under
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`consideration is limited to administration of the compound 2-amino-2-[2-(4-
`
`octylphenyl)ethyl]propane-1 ,3-propane-1 ,3-diol, or a pharmaceutically acceptable salt
`
`thereof. The subject matter under consideration excludes prevention of neo-
`
`angiogenesis associated with a demyelinating disease. The terms depicted in formula
`
`X, i.e., Z, R1x. R2Z and R3z are not defined. Correction is required. See MPEP
`
`§ 608.01 (b).
`
`Claims 18 and 19 are objected to under 37 CFR 1.75 as being substantial
`
`duplicates. When two claims in an application are duplicates or else are so close in
`
`content that they both cover the same thing, despite a slight difference in wording, it is
`
`proper after allowing one claim to object to the other as being a substantial duplicate of
`
`the allowed claim. See MPEP § 706.03(k).
`
`SUN - IPR2017-01929, Ex. 1010, p. 264 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 3
`
`Applicants are advised that should claim 18 be found allowable, claim 19 will be
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`objected to under 37 CFR 1.75 as being a substantial duplicate thereof.
`
`The disclosure is objected to for the following informality:
`
`On page 12 of the specification, line 22, 2-amino-2-[2-(4-
`
`octylphenyl)ethyl]propane-1 ,3-propane-1 ,3-diol is misspelled.
`
`Appropriate correction is required.
`
`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 1 02 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.
`
`Claims12-21 are rejected under 35 U.S.C. 1 03(a) as being unpatentable over
`
`Virley, D.J., Journal of the American Society for Experimental NeuroTherapeutics, in
`
`view of LaMontagne. et al., Cancer Research, and further in view of Kovarik et al., WO
`
`06/058316.
`
`Virley teaches the administration of 2-amino-2-[2-(4-octylphenyl)ethyl]propane-
`
`1 ,3-propane-1 ,3-diol, also known as FTY720, which is a sphingosine-1-phosphate
`
`receptor modulator, for the treatment of multiple sclerosis (MS). Virley distinguishes
`
`between the categories of relapsing-remitting MS and primary progressive MS. See the
`
`introduction on page 638, as well as the discussion of experimental models forMS on
`
`SUN - IPR2017-01929, Ex. 1010, p. 265 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 4
`
`page 640. In order to provide predictive indices for clinical application, experimental
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`autoimmune encephalomyelitis (EAE) models are discussed.
`
`Due to the majority of MS patients presenting relapsing-remitting symptoms before progressing onto a
`chronic phase, a number of animal models of EAE have been designed to simulate the more dynamic
`clinical and pathological features of relapsing-remitting MS. One such model, using the Biozzi AB/H
`mouse, involves the inoculation of homologous spinal cord homogenate (or more specifically MOG
`peptide) in adjuvant without the additional use of Bordetella pertussis toxin, and reproducibly induces a
`chronic relapsing-remitting demyelinating disease. The dynamic chronicity of symptoms is expressed as
`an acute induction of disease (loss of tail tone and hindlimb paralysis), followed by reduced severity
`(remission) and then a relapse disease episode. The development of clinical signs in this model are
`preceded by a loss in weight, whereas remission periods are associated with an increase in body weight,
`implicating changes in weight as surrogate markers of disease status. Reductions in the degree of
`inflammation and evidence for remyelination are thought to reflect the remission period in this EAE model,
`whereas relapses are thought to be indicative of an amplified inflammatory response, gliosis and
`demyelination within the CNS.
`
`In particular, Virley teaches the oral administration of FTY720 in a Lewis rat EAE
`
`model demonstrates a dramatic reduction in clinical severity, mortality and the infiltration
`
`of leukocytes into the CNS. Proinflammatory cytokines such as IL-2,
`
`IL-6, and IFN's were markedly suppressed in the CNS following prophylactic FTY720
`
`treatment relative to saline treatment. The mechanistic effect of FTY720 on
`
`reducing lymphocyte trafficking and CNS inflammation within EAE, was further studied
`
`with contrast-enhanced MRI, using superparamagnetic iron-oxide nanoparticles to track
`
`macrophage infiltration. The oral administration of FTY720 was shown to significantly
`
`reduce the magnitude and extent of cellular infiltration into the CNS of EAE-sensitized
`
`rats. These effects with FTY720 treatment corresponded to reductions in lesion
`
`burden and blood brain barrier disruption assessed by MRI signatures and a marked
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`reduction in neurological disability during the acute and relapsing phase of the model.
`
`Therapeutic administration of FTY720 at the point of relapse also significantly
`
`suppressed further progression of clinical signs, providing compelling evidence for this
`
`SUN - IPR2017-01929, Ex. 1010, p. 266 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 5
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`agent as a potential therapeutic agent for MS. Data from a phase II clinical trial with
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`FTY720, confirmed a relapse reduction rate of more than 50% in 281 relapsing-remit-
`
`ting MS patients for 6 months of treatment, relative to placebo. Inflammatory disease
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`activity, as visualized by gadolinium-enhanced T1-weighted MR imaging was shown to
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`be dramatically reduced by up to 80%, after 6 months of oral, once a day, treatment.
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`Progressive disease activity in the form of new T2 MRI lesions was also demonstrated
`
`to be reduced by more than 60% after FTY720 treatment. The onset of effect was
`
`demonstrated as early as 2 months following treatment, and MS patients showed no
`
`significant adverse events over the 6-month trial duration relative to placebo. See page
`
`644.
`
`Virley fails to teach the required dosage of 0.5 mg, as well as methods of
`
`inhibiting or treating a neo-angiogenesis association with MS.
`
`However, LaMontagne teaches FTY720 to be an anti-angiogenic agent. The
`
`compound becomes phosphorylated in vivo and interacts with spingosine-1-phosphate
`
`(S1 P) receptors. The effect is on vascular permeability, an important aspect of
`
`angiogenesis. See the Abstract.
`
`Kovarik teaches dosage regimens involving S1 P receptor agonists, of which
`
`FTY720 is clearly encompassed. Maintenance dosages are disclosed on page 15, line
`
`9, as required by all of the present claims. Specifically, on line 16, page 17, a daily
`
`dose of 0.5 mg is taught for the treatment of autoimmune diseases, of which MS is
`
`recited as an example, on lines 7-8 on page 14.
`
`SUN - IPR2017-01929, Ex. 1010, p. 267 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 6
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`Therefore, in view of the teachings of Virley, LaMontagne and Kovarik, one
`
`skilled in the neurology art would have been motivated to administer FTY720 with a
`
`reasonable expectation of success in inhibiting neo-angiogenesis associated multiple
`
`sclerosis, in alleviating relapses in MS and slowing the progression of MS. Such would
`
`have been obvious because FTY720 is a known anti-angiogenic agent that has been
`
`taught for use in the treatment of autoimmune diseases such as multiple sclerosis, at a
`
`dosage of 0.5 mg. According to Virley, FTY720 significantly reduced- by more than
`
`60% - progressive disease activity after treatment. FTY720 administration resulted in a
`
`relapse reduction rate of more than 50% in 281 relapsing-remitting MS patients.
`
`No claim is allowed.
`
`Foster et al., US 2006/0046979, is cited to show further the state of the art.
`
`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 from 10:30 to 7 PM.
`
`If attempts to reach the Examiner by telephone are unsuccessful after one
`
`business day, the Examiner's supervisor, Jeff Lundgren, can be reached 571-272-5541.
`
`The fax phone number for the organization where this application or proceeding is
`
`assigned is 571-273-8300.
`
`SUN - IPR2017-01929, Ex. 1010, p. 268 of 494
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`

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`Application/Control Number: 13/149,468
`Art Unit: 1629
`
`Page 7
`
`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).
`
`March 24, 2012
`
`/Phyllis G. Spivack/
`Primary Examiner, Art Unit 1629
`
`SUN - IPR2017-01929, Ex. 1010, p. 269 of 494
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`SUN - IPR2017-01929, Ex. 1010,