Attorney Docket Number 03956.054600.2
`
`PATENT APPLICATION
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`GILEAD PHARMASSET LLC
`
`Divisional of
`Application No.: 12/783,680
`
`Filed: Concurrently Herewith
`
`For: NUCLEOSIDE
`PHOSPHORAMIDATES
`
`)
`
`)
`
`)
`
`)
`
`)
`
`)
`
`Examiner: Unassigned
`
`Group Art Unit: Unassigned
`
`January 10, 2013
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-14 50
`
`Sir:
`
`PRELIMINARY AMENDMENT
`
`Prior to examination on the merits, please amend the application as follows.
`
`1
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`Attorney Docket No. 03956.054600.2
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`Amendments to the Specification:
`
`Please amend the paragraph following the subheading "Priority Claim" and before the
`
`subheading "Field of the Invention" on page 1 as follows:
`
`--The righ-t of)9riority is elaimed toThis application is a divisional of U.S. Application
`
`No. 12/783,680, filed May 20, 2010, which claims priority under 35 U.S.C. § 119(e) to U.S.
`
`Provisional Patent Application Nos. 61/179,923, filed May 20, 2009, and 61/319,513, filed
`
`March 31, 2010, all the subjeet matter of which are [[is]] incorporated by reference in their[[ its]]
`
`entiret[[y]]ies. --
`
`Please amend the sentence on p. 27, lns. 11-12 as follows:
`
`-- In a fourth aspect of the seventh embodiment, the protecting compound is tert-butyl[[(cid:173)
`
`]]dimethyl[[-]]silyl[[-]]_chloride. --
`
`Please amend the first sentence on p. 52, lns. 1-2 as follows:
`--The ratio of two diastereomers Sp:Rp was 9.65[[/]]J based on 31P NMR (162 MHz,
`
`DMSO-d6, 8-0.31 (Sp), -0.47_(Ep). --
`
`Please amend the scheme preceding Example 11 on p. 56, lns. 23-24 as follows:
`y
`NO
`2 1BuMgCI. THF.. 0
`
`H
`0
`'f'Nyo
`0 N~
`HO~ ~ +
`He>'
`~
`3
`
`y
`~
`<?Ph 0~ I
`Oy< ,P, ;;>
`
`= OPh
`, J ..... ~CPO N~
`fn II 0
`
`H
`0
`'f'Nyo
`
`YJN 0
`y
`~
`QPh
`i> ~oyN
`.
`!('~~ ~ 'o
`\_V ~
`0
`HO, F
`
`0
`
`H
`
`0
`
`:
`
`o
`
`y
`<{Ph ~N02
`~
`oyA ,.P ..... ~
`II
`N
`II 0
`O HO
`
`2
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`Attorney Docket No. 03956.054600.2
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`Please amend the scheme for Example 15 on p. 59 as follows:
`
`0
`
`(Nil
`IIOtlA"
`
`HO~··
`
`\.F
`
`3
`
`I
`Pyridine
`
`/
`
`~0
`o~···'' co
`o-O•p-0
`8 tt 0
`
`lj"H
`
`I NH
`~
`
`0
`
`THF/H 20
`
`(?
`+Ji-CI \__ 1
`~i-ol/o,~~o Levulinic anhydride
`
`0
`
`\.___}__
`
`Ho"",.
`
`\.F
`
`9
`
`OH
`
`~2
`Oo-P·'N~ o ~~I
`~2
`
`o o..A..,
`
`OH
`
`Q o·t''j:'~
`
`0
`0
`8 (Sp-isomer)
`
`tBuMgCl/THF
`
`3
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`Attorney Docket No. 03956.054600.2
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`Amendments to the Claims:
`
`The following listing of the claims replaces all prior versions and listings.
`
`1.-81. (Cancelled).
`
`82.
`
`(New): A compound represented by the formula (4):
`
`0
`
`{;c
`H
`*!? ~OyN 0
`\.____L,.
`0
`HN-- P-O
`~
`I" OPh
`HO-
`
`0
`
`,''
`
`\ .
`
`•
`
`0
`
`-;..F
`
`wherein P* represents a chiral phosphorus atom and wherein the compound is at least
`
`97% of the Sp stereoisomer represented by the formula (Sp-4):
`
`(4)
`
`0
`
`0
`
`,''
`
`{;c
`hrn,J' o~N °
`
`\ .
`
`I " PhO
`
`'
`
`HO-
`
`0
`
`•
`
`-;..F
`
`and not more than 3% of the Rp stereoisomer represented by the formula (Rp-4):
`
`83.
`
`(New): The compound according to claim 82, wherein the compound is at least
`
`98% of the Sp stereoisomer represented by the formula (Sp-4) and not more than 2% of the Rp
`
`stereoisomer represented by the formula (Rp-4).
`
`84.
`
`(New): The compound according to claim 82, wherein the compound is at least
`
`99% of the Sp stereoisomer represented by the formula (Sp-4) and not more than 1% of the Rp
`
`stereoisomer represented by the formula (Rp-4).
`
`4
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`Attorney Docket No. 03956.054600.2
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`85.
`
`(New): A pharmaceutical composition comprising the compound according to
`
`claim 82 and a pharmaceutically acceptable medium.
`
`86.
`
`(New): A pharmaceutical composition comprising the compound according to
`
`claim 83 and a pharmaceutically acceptable medium.
`
`87.
`
`(New): A pharmaceutical composition comprising the compound according to
`
`claim 84 and a pharmaceutically acceptable medium.
`
`88.
`
`(New): A method of treating a hepatitis C virus infection in a human comprising
`
`administering to the human an effective amount of the compound according to claim 82.
`
`89.
`
`(New): The method according to claim 88 further comprising administering to the
`
`human another antiviral agent.
`
`90.
`
`(New): A method of treating a hepatitis C virus infection in a human comprising
`
`administering to the human an effective amount of the compound according to claim 83.
`
`91.
`
`(New): The method according to claim 90 further comprising administering to the
`
`human another antiviral agent.
`
`92.
`
`(New): A method of treating a hepatitis C virus infection in a human comprising
`
`administering to the human an effective amount of the compound according to claim 84.
`
`93.
`
`(New): The method according to claim 92 further comprising administering to the
`
`human another antiviral agent.
`
`5
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`Attorney Docket No. 03956.054600.2
`
`This application is a divisional of U.S. Patent Application No. 12/783,680 filed
`
`REMARKS
`
`May 20, 2010.
`
`Pages 1, 27, 52, 56 and 59 of the specification are presently amended. Page 1 is
`
`amended to reflect the continuity information for the present application. Pages 27 and 52 are
`
`amended to correct clerical errors that would have been readily apparent as such to a person
`
`having ordinary skill in the art. Pages 56 and 59 are amended to clarify the stereochemistry of
`
`certain compounds depicted in the chemical reaction schemes on those pages.
`
`A clean version of the amendment provided above to the scheme found on p. 56,
`
`lns. 23-24 is as follows:
`H OYN
`y
`0
`H
`yNyo
`= OPh
`~OyNJO
`y
`NO
`: .i .... ~0 N~
`<fPh ~ 2 1BuMgCI, THF., o
`~
`o'IT'· .P, ~
`~N 011 0
`II 00 II
`H
`N
`H 0
`
`0
`
`,·
`00
`
`0
`
`~
`F
`
`HO ~ +
`HO F
`3
`
`0
`
`8 (Sp-isomer)
`
`The scheme preceding Example 11 on p. 56 is amended as shown above to clearly
`
`indicate the stereochemistry at the phosphorous atoms (P) of the phosphoramidate reagent (8, Sp-
`
`isomer) and the final product (Sp-4). Support for these amendments can be found, for example, at
`
`p. 7, lns. 3-4, which depicts the structure of the product (Sp-4), as well as at p. 56, ln. 26 through
`
`p. 57, ln. 10, which indicate that the reagent used in the process illustrated by the amended
`
`scheme is (S)-2-[ (S)-( 4-nitro-phenoxy)-phenoxy-phoshorylamino] propionic acid isopropyl ester
`
`(8, Sp-isomer).
`
`A clean version of the amendment provided above to the scheme on p. 59 is as
`
`follows:
`
`6
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`Attorney Docket No. 03956.054600.2
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`0 (Nil
`HotlA0
`
`HO~··
`
`~F
`
`3
`
`I
`Pyridine
`
`/
`
`c~~~
`+Ji-CI \__ I
`~i-ol/o,~~o
`
`0
`
`Levulinic anhydride
`
`~
`Hd ..
`
`~F
`
`9
`
`tBuMgCl/THF
`
`THF/H 20
`
`The scheme provided for Example 15 on p. 59 is amended as shown above to
`
`clarify the stereochemistry of certain compounds depicted in the scheme. Support for these
`
`amendments can be found, for example, at p. 59, ln. 1, which describes Example 15 as the
`
`"Preparation of Sp-4"; p. 7, lns. 3-4, which depicts the structure of (Sp-4); and pp. 60, ln. 1
`
`7
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`Attorney Docket No. 03956.054600.2
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`through 62, ln. 20, which describe the reagents and intermediates involved in the synthesis of
`
`(Sp-4) from the compound (3a) as depicted in the scheme on p. 59.
`
`Claims 1-81 are cancelled. Claims 82-93 are new. Upon entry of the present
`
`claim amendments, claims 82-93 will be pending.
`
`Support for new claims 82-84 is found, for example, on pages 46-48 (Example 4) and 69-
`
`62 (Example 15). Support for new claims 85-87 is found, for example, in original claim 40 and
`
`on pages 20-23. Support for new claims 88-92 is found, for example, in original claims 41 and
`
`42 and on pages 23-26.
`
`It is believed that no new matter is presented by the foregoing amendments.
`
`Applicants' undersigned attorneys may be reached in their New York office by
`
`telephone at (212) 218-2100. All correspondence should be directed to the address given below.
`
`Respectfully submitted,
`
`I Alicia A. Russo/
`Alicia A. Russo
`Registration No.: 46,192
`
`Erin J.D. Austin
`Registration No.: 66,532
`
`Attorneys for Applicants
`
`FITZPATRICK, CELLA, HARPER & SCINTO
`1290 Avenue of the Americas
`New York, New York 10104
`Facsimile: (212) 218-2200
`
`8
`
`FCHS WS 8463967v3.doc
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`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.
`
`13/738,425
`
`01110/2013
`
`Bruce Ross
`
`03956.054600.2
`
`3029
`
`104538
`7590
`04/04/2013
`Fitzpatrick Cella Harper & Scinto (Gilead)
`1290 A venue of the Americas
`New York, NY 10104
`
`EXAMINER
`
`WANG, ZHENGFU
`
`ART UNIT
`
`PAPER NUMBER
`
`1623
`
`MAIL DATE
`
`DELIVERY MODE
`
`04/04/2013
`
`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)
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`Office Action Summary
`
`Application No.
`
`13/738,425
`
`Examiner
`
`Applicant(s)
`
`ROSS ET AL.
`
`Art Unit
`
`1623
`ZHENGFU WANG
`-- 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) 82-93 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) 82-93 is/are rejected.
`8)0 Claim(s) __ is/are objected to.
`9)0 Claim(s) __ are subject to restriction and/or election requirement.
`
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway
`program at a participating intellectual property office for the corresponding application. For more information, please see
`htto:/iwww.us..Qto.aov/oatents/init events/gQh/index.jsQ or send an inquiry to PPHfeedback@us.Qto.qov.
`
`Application Papers
`
`1 0)0 The specification is objected to by the Examiner.
`11 )[8] The drawing(s) filed on 10 Januarv 2013 is/are: a)[8] 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).
`
`Priority under 35 U.S.C. § 119
`
`12)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) [8] Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date 1110/2013. 3/20/2013.
`
`U.S. Patent and Trademark Off1ce
`PTOL-326 (Rev. 09·12)
`
`3) 0 Interview Summary (PT0-413)
`Paper No(s)/Mail Date. __ .
`4) 0 Other: __ .
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20130315
`
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`Application/Control Number: 13/738,425
`Art Unit: 1623
`
`Page 2
`
`DETAILED ACTION
`
`The preliminary amendment filed on January 10, 2013, in which claims 1-81 are
`
`cancelled, and claims 82-93 are newly added, is acknowledged.
`
`Claims 82-93 are pending in the instant application and are examined on the
`
`merits herein.
`
`Priority
`
`This application is a divisional application of US application No. 12/783,680 filed
`
`on May 20, 2010, which claims benefit of provisional application Nos. 61/179,923 filed
`
`on May 20, 2009 and 61/319,513 filed on March 31, 2010.
`
`Information Disclosure Statement
`
`The information disclosure statements (I OS), dated January 10, 2013 and March
`
`20, 2013, comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609.
`
`Accordingly, they have been placed in the application file and the information therein
`
`has been considered as to the merits.
`
`Claim Rejections - 35 USC § 103
`
`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.
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`Application/Control Number: 13/738,425
`Art Unit: 1623
`
`Page 3
`
`Patentability shall not be negatived by the manner in which the invention was made.
`
`This application currently names joint inventors. In considering patentability of
`
`the claims under 35 U.S.C. 1 03(a), the examiner presumes that the subject matter of
`
`the various claims was commonly owned at the time any inventions covered therein
`
`were made absent any evidence to the contrary. Applicant is advised of the obligation
`
`under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was
`
`not commonly owned at the time a later invention was made in order for the examiner to
`
`consider the applicability of 35 U.S.C. 1 03(c) and potential 35 U.S.C. 1 02(e), (f) or (g)
`
`prior art under 35 U.S.C. 1 03(a).
`
`Claims 82-93 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over Sofia (2"d International Workshop on HCV-Resistance and New Compounds,
`
`October 31,2007, cited by Applicant in IDS dated January 10, 2013).
`
`Sofia teaches a phosphoramidate prodrug of formula
`
`wherein R3 is isopropyl group (page 8), which is a mixture of Sp and Rp stereoisomers.
`
`The dislcosed phosphoramidate prodrug is a potent therapeutic agents for treating HCV
`
`infection (pages 1-13).
`
`Sofia does not expressly teach wherein the Sp stereosiomer is at least 97%, 98%
`
`or 99% and Rp stereoisomer is not more than 3%, 2%, or 1 %. Sofia does not expressly
`
`teach that the compound is in a pharmaceutical composition form.
`
`It would have been obvious to one of ordinary skill in the art at the time the
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`Application/Control Number: 13/738,425
`Art Unit: 1623
`
`Page 4
`
`invention was made to separate the mixture of Sp and Rp stereoisomers and formulate
`
`it into a pharmaceutical composition for treating HCV infection.
`
`One having ordinary skill in the art at the time the invention was made would
`
`have been motivated to separate the mixture of Sp and Rp stereoisomers and formulate
`
`it into a pharmaceutical composition for treating HCV infection because the disclosed
`
`phosphoramidate prodrug containing a mixture of Sp and Rp isomers is known to have
`
`potential therapeutic effect and usefulness in treating HCV infection, and separation the
`
`two isomers of a known therapeutic drug and identifying the therapeutic potency of each
`
`isomer are well known in the art. One of ordinary skill in the art would have reasonably
`
`expected the success because separating the isomers of the known therapeutic agents
`
`and identifying the potency of each isomer and formulate into a pharmaceutical
`
`composition is well within the ordinary and routine level of one skilled in the art.
`
`Thus, the claimed invention as a whole is prima facie obvious over Sofia.
`
`Double Patenting
`
`The nonstatutory double patenting rejection is based on a judicially created doctrine
`grounded in public policy (a policy reflected in the statute) so as to prevent the
`unjustified or improper timewise extension of the "right to exclude" granted by a
`patent and to prevent possible harassment by multiple assignees. A nonstatutory
`obviousness-type double patenting rejection is appropriate where the conflicting
`claims are not identical, but at least one examined application claim is not
`patentably distinct from the reference claim(s) because the examined application
`claim is either anticipated by, or would have been obvious over, the reference
`claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In
`re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759
`F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214
`USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);
`and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
`A timely filed terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321 (d)
`may be used to overcome an actual or provisional rejection based on a
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`Application/Control Number: 13/738,425
`Art Unit: 1623
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`Page 5
`
`nonstatutory double patenting ground provided the conflicting application or patent
`either is shown to be commonly owned with this application, or claims an invention
`made as a result of activities undertaken within the scope of a joint research
`agreement.
`Effective January 1, 1994, a registered attorney or agent of record may sign a
`terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply
`with 37 CFR 3.73(b).
`
`Claims 82-93 are rejected on the ground of nonstatutory obviousness-type
`
`double patenting as being unpatentable over claims 1-14 of US 7964580.
`
`Claims 82-93 of the instant application are drawn to a compound represented by
`
`formula (4):
`
`wherein the Sp stereosiomer is at least
`
`97%, 98% or 99%, a pharmaceutical composition comprising the above compound and
`
`a method of using the compound for treating HCV infection.
`
`Claim 1 of US 7964580 discloses the compound (S)-2{[(2R,3R,4R,5R)-5-(2,4-
`
`Dioxo-3 ,4-di hydro-2 H-pyri midi n-1 -yl)-4-fl uoro-3-hydroxy-4-methyl-tetrahydrofu ran-2-yl-
`
`methoxy]-phenoxy-phosphorylamino}-propionic acid isopropyl ester or a stereoisomer
`
`thereof. Claims 2-5 are drawn to a composition and a method for treating HCV infection
`
`using the compound of claim 1. Claim 8 of US 7964580 discloses the compound of (S)-
`
`isopropyl 2-( (S)-( ( (2 R,3 R,4R,5 R)-5-(2,4- Dioxo-3,4-di hydropyri midin-1 (2H)-yl)-4-fluoro-3-
`
`hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino) propanoate,
`
`which is the same as the compound of the instant claim 82. Claim 9 of US 7964580
`
`teaches a composition comprising the compound. Claims 11 and 12 of US 7964580
`
`disclose a method of treating HCV infection by administering the compound of claim 8.
`
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`Application/Control Number: 13/738,425
`Art Unit: 1623
`
`Page 6
`
`Claims 6 and 13 of US 7964580 teach a process for preparing the compound
`
`( S)-2-{[ (2 R, 3 R ,4 R ,5 R)-5-(2 ,4-dioxo-3 ,4-di hydro-2 H-pyri midi n-1 -yl)-4-fl uoro-3-hydroxy-4-
`
`methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid
`
`isopropyl ester (i.e. instant formula (4)) or a stereoisomer thereof, said process
`
`comprising: reacting a compound 4"
`
`~":
`
`r:*"-=:.~ .... )
`~:; .. ~.)~-::..~-··):
`.·.
`'
`,
`'"'·<::('"'''-·~·,···.~~--··X
`,., .. ._.(, ......... ~;
`~
`
`I
`
`, wherein X' is a leaving group,
`
`with a nucleoside analog 5'
`
`. The specification of US7964580
`
`teaches a method of making the compound
`
`,, .. x::)
`,,,,,,r··'""'' ~··'·}c--,
`·--..."[..,. .. ·
`:
`
`by reacting phenyl
`
`dichlorophosphate with isopropyl alanate (column 458-463).
`
`Therefore, claims 82-93 of the instant application are anticipated by claims 8-13
`
`and obvious over claims 1-7 and 14 of US 7964580.
`
`Conclusion
`
`In view of the rejections to the pending claims set forth above, no claim is
`
`allowed.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to ZHENGFU WANG whose telephone number is
`
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`Application/Control Number: 13/738,425
`Art Unit: 1623
`
`Page 7
`
`(571 )270-7470. The examiner can normally be reached on Monday-Friday, 8:30AM-
`
`5:00PM.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Shaojia Anna Jiang can be reached on (571 )272-0627. 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.
`
`/SHAOJIA ANNA JIANG/
`Supervisory Patent Examiner, Art Unit 1623
`
`/ZHENGFU WANG/
`Examiner, Art Unit 1623
`
`IPR2018-00125
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`J}~ THE UNITED STATES PA._TEl',.ff i\ND TEJ\DEh'lA.RK i)FFICE
`
`In rt.~ Application of
`
`GILEl>,J) PH.:\R\L\SSFT LLC
`
`i\pptkation No.: 13/738,425
`
`hied: January 10,, 2013
`
`For NUCLEOSIDE
`PHC)SPI-10RAM1DATES
`
`C\•mrnh~ioner f(_;r Pat<:~n.ts
`P.O. Box 1450
`l\kxandria,
`/\ 22313--1450
`
`Unmp Art Unit: 1623
`
`ConJinn~Uon r----lo.: 3029
`
`)
`
`)
`
`}\1ay 15,2013
`
`n::quired, or credit any ov.;:rpayment, to n~.:TJoSit Account 50-3939.
`
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`

`i\Homey Docket l-Jo. 0395tdl54600.2
`
`' '
`. :l
`.
`'
`.
`l
`1· · r t
`.
`.• 'l
`·1·l
`1H.~ to! O\'dng lSl (h tt1e clanns Js f>rOVh ~.:x1 lor r K' :~x.mnmer s conve1w:nci'.:;
`.
`.
`•
`
`~--
`
`OPh
`
`Hd
`
`( 4)
`
`tO.
`
`(Pn~:viously Prcscni~::cl): The cornpound according to clnirn 82, \Vh{cl\sin th;;;
`
`cornprrtmd 13 at least 99'/J ofthe ::-'r st.;;reoisoni~r reptes.::~nled by the t!nmula (Sp-4) and not more
`thnn 1 ~:(,of t!w K' ster .. xlisonJer repi\~sent;,~d by· th~ f~•rmul8 (Rp~4).
`
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`

`.c\tlorney Docket J ... Jo. 03956.054600.2
`
`8:-'.
`
`(Pteviously Prestcnted): "\ pharnJ<Ctceutical comp~:'Sition ~ornprising Hlf-' compound
`
`~tccording to \.'!~un1 82 and a phann::Kel.rtkally accqnabk~ medintrJ.
`
`86.
`
`(Previm.wly Pn:scntedt .A. pharma;x~mkai C(ll!lposHion compri~>lng the compn1.1nd
`
`according to claim 83 and u pharma~cuth .. 'aHy ac~;.·eptabh .. ' rnediurn.
`
`8S.
`
`(f\.;~viously Prestnted): /\ rnethod of treating n l1epatitis C virus intb~tion in a
`
`lnnnan (;ornprising adminlst.er1ng to tht· hurnan an effecti '/e an:1(Hmt of the corr1pound rH:eording
`
`tn claim 8L
`
`89.
`
`'~0.
`
`(Prevhmsly· Present•~d): ;\method of tn:ating a hGpatitis C virus inn.:ction in a
`
`to claitn 83.
`
`91.
`
`u)
`
`~Previously Prt'S<..~ni..;.'d;; A method r•ftrcating a hii;patHicl C virus infection in a
`
`9.3,
`
`(Previously Prt~S(~nkcll: The rn<".';thod dccording to clnim 92 further cornprising
`
`;Hhnini8teri.ng to th':: hu:man ;uwther anti\'iral agent
`
`3
`
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`Attorney Dockeli··.Jo. 03956.0546002
`
`Clain1s 82-93 arc pending in the instant (tppJi;;;ntion.
`
`iJH.~ tbnn u! u
`
`, '-Vherein R is isoprop}l (pag';:< 8), \Vhich is a mhd.W\.'
`
`of Sv and Rp skn~'oisorners and which is a potent th<.:rnpcutic agent f~:n tre:xting HCV inf'c:ctions.
`
`4
`
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`:\ttc,rnc~y [)ock~et }·Jo, 0395<S.054600~2
`
`The Applicant respectfully tr<n:en:it.'S the § l 03(ai rejection a'-' tht:: Ollie;;;' tkils to
`
`norH1bvious <:xver SoHa bus\;d on wwxpcc:ted results.
`
`HI
`
`not sutlicknL by irsd.f~ to <;::stab !ish alwirnafade case •Jf obviousness. fv1PEP § 2144.08
`
`In
`
`to select the claimed spi.,'C:ies from Ht<:: Jbdo~;~~d genus. ld ln nus regard, the express tead:dngs
`
`in the cit-:.'d rei~:l\':ncef::;), <J5 well as the level of predictabiLity in ihe art ~;hould b;; .:.·onsiderecL ld.
`
`5
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`Attorney l)ocket No. 03')56.054600.2
`
`.. l
`.
`l
`.
`. ~ ,,
`. . '
`.
`.. ll
`' '
`.
`l
`,")ccorH.'t L1.e Appltc~ml respec.Uu y m.li.'lHJ.H tnat Sona onuis .;: e.ments ott K'
`
`•
`
`('l
`
`.
`
`pending c.lairn::>, and ftrrth.;;:r tha:t the O:tlh::e's rmsupport.;;d :;wsertions regarding whal v,-as
`
`"knov;n" an: in.:mt11cleru to supply the rnissing lirnitatkms.
`
`teach or suggesr a.! I of the limitatkms in a cbim .. CFMT Iw:~. 1'. Yf.ddzq.l Intern Cmp., 349 F.3d
`
`1333, 1342 {Fed. Cir. 20lH); !n re Ochiai, 71 .F.3d 1565, 1572 (F!i.'i.-L Cir, 1995). Additionally,
`
`unquestiormbk dr:rnonstmtion as to defy disputo;:." l\fPEP § 2 !44.03 (citing In re "·lhten. 424
`
`F.2d 1088, l09l (CCPA 1970).1
`
`•)f any trf the rnc~rnbers of the disdo:wd genus of compounds, nor does it teach or suggest that c•11e
`
`IPR2018-00125
`
`Page 22 of 58
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`

`

`Atlonwy Docket l~·(-,. 03956.054600.2
`
`] ' I
`I'. 1
`J 1 d
`i'' 1
`,,
`. f' , ·t
`,
`f,
`' J J, ',
`.
`.
`l
`per onnmg ~'U('.l scparano.ns. /V1umona .. y, :<:>:.L.<.a c n~s nol osc OS\:.' or sug&,_:,est \''hl11.:n, r. ~.::rc h::.r, en
`
`.
`
`.
`
`ilK~ Rp and Sp sl..ereolsmncrs of any cornpound \vithin the disdosed g;~'nus would be the rrwre
`
`,
`.
`·[.
`.\
`·1
`• ·j
`. , ) .
`',
`f'
`'
`.
`j
`j.
`j
`,
`+'
`poU .. 'nt or hlc t\vo. n 1acL gl 'f('· t 1.: level o unpn.·mctutn sty 1.n Lk art, t 1e App Jc,mt suhnuts LE!t
`,. I
`.
`
`of any compound blli.ng yvithin thf:' gerws in Sot1n "''iou.ld be the nwre potent against HCV.
`
`Third., ''obvious to try'' is only an npprnprh1te conskk:ration \NIK're one ';vou1d
`
`h.:.rvt: been able to chc,ose fh.m1 a flnite number of identitkd, pn;dictabh.' sdutions \Vith a
`
`rrurnber of icL::ntifi{.'d, predictable soluth.n1s .ti:>r obtaining th.:' isolated Sp and Rr sten:.::>lsorners of
`
`the cmnpounrb ~~n.cornpass~:d by the genus in Sofi<:t. Fu1th,:::r, vvhether one skiHed in the an r:nighl
`
`IPR2018-00125
`
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`

`pn.csently c:lairned cornpounds w;:•uld have be10.~n predictahk
`
`Rl''4
`,)pwi~""'''" ---------·.···-············~"""'Q:::L':~~ ............... ~ ............. ,., ..
`
`·····""
`
`8
`
`IPR2018-00125
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`

`..... (/\Li~:hL:\J~~l!i.:iQL ............. .
`i~Ji~ia A .. r~uS80
`
`Erin J.D. Austin
`Registration No.: 66,532
`
`FITZPATJ:\.ICK, CELl../\, HARPER&. SC!NT()
`1290 A Vt;'llth;.' of th('; /\.nR'rkas
`1'·-S<..~'N \'od-e Ntw ~{,Jrk 10104
`Facsintile: {212) 218-2200
`
`9
`
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`

`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`104538
`
`e
`
`2013-05-20
`
`Fitzpatrick Cella Harper & Scinto (Gilead)
`1290 A venue of the Americas
`New York. NY 10104
`
`UNITED STATES DEPARTMENT OF COMMERCE
`U.S. Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria. Virginia 22313-1450
`www.uspto.gov
`
`PaperNo.
`
`Application No.:
`
`13/738,425
`
`Date Mailed:
`
`2013-05-20
`
`First Named Inventor:
`
`Ross, Bruce,
`
`Examiner:
`
`WANG, ZHENGFU
`
`Attorney Docket No.:
`
`03956.054600.2
`
`Art Unit:
`
`1623
`
`Confirmation No.:
`
`3029
`
`Filing Date:
`
`2013-01-10
`
`Please find attached an Office communication concerning this application or proceeding.
`
`PT0-90c (Rev.OS-06)
`
`Commissioner for Patents
`
`IPR2018-00125
`
`Page 26 of 58
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`

`Notice of Non-Compliant Amendment
`(37 CFR 1.121)
`
`Application No.
`13/738,425
`
`Applicant(s)
`ROSS ET AL.
`
`Art Unit
`2600
`
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address--
`
`The amendment document filed on 15 Mav. 2013 is considered non-compliant because it has failed to meet the
`requirements of 37 CFR 1.121 or 1 .4. In order for the amendment document to be compliant, correction of the following
`item(s) is required.
`
`THE FOLLOWING MARKED (X) ITEM(S) CAUSE THE AMENDMENT DOCUMENT TO BE NON-COMPLIANT:
`D 1. Amendments to the specification:
`D A. Amended paragraph(s) do not include markings.
`D B. New paragraph(s) should not be underlined.
`D C. Other
`.
`D 2. Abstract:
`D A. Not presented on a separate sheet. 37 CFR 1.72.
`D B. Other
`.
`D 3. Amendments to the drawings:
`D A. The drawings are not properly identified in the top margin as "Replacement Sheet," "New Sheet," or
`"Annotated Sheet" as required by 37 CFR 1.121(d).
`D B. The practice of submitting proposed drawing correction has been eliminated. Replacement drawings
`showing amended figures, without markings, in compliance with 37 CFR 1 .84 are required.
`D C. Other __
`[8J 4. Amendments to the claims:
`[8J A. A complete listing of all of the claims is not present.
`D B. The listing of claims does not include the text of all pending claims (including withdrawn claims)
`1Z1 C. Each claim has not been provided with the proper status identifier, and as such, the individual status
`of each claim cannot be identified. Note: the status of every claim must be indicated after its claim
`number by using one of the following status identifiers: (Original), (Currently amended), (Canceled),
`(Previously presented), (New), (Not entered), (Withdrawn) and (Withdrawn-currently amended).
`D D. The claims of this amendment paper have not been presented in ascending numerical order.
`D E. Other: __
`D 5. Other (e.g., the amendment is unsigned or not signed in accordance with 37 CFR 1.4): For further explanation
`of the amendment format required by 37 CFR 1.121, see MPEP § 714.
`
`TIME PERIODS FOR FILING A REPLY TO THIS NOTICE:
`1. Applicant is given no new time period if the non-compliant amendment is an after-final amendment or an
`amendment filed after allowance, or a drawing submission (only) If applicant wishes to resubmit the non-compliant
`after-final amendment with corrections, the entire corrected amendment must be resubmitted.
`
`2. Applicant is given one month, or thirty (30) days, whichever is longer, from the mail date of this notice to supply the
`correction, if the non-compliant amendment is one of the following: a preliminary amendment, a non-final amendment
`(including a submission for a request for continued examination (RCE) under 37 CFR 1.114), a supplemental
`amendment filed within a suspension period under 37 CFR 1.1 03(a) or (c), and an amendment filed in response to a
`Quayle action. If any of above boxes 1 to 4 are checked, the correction required is only the corrected section of the
`non-compliant amendment in compliance with 37 CFR 1 .121.
`
`Extensions of time are available under 37 CFR 1.136(a) Q.!J.)y if the non-compliant amendment is a non-final
`amendment or an amendment filed in response to a Quayle action.
`Failure to timely respond to this notice will result in:
`Abandonment of the application if the non-compliant amendment is a non-final amendment or an amendment
`filed in re