"prress Mail" mailing label number
`
`Date of Deposit
`
` Printed Name
`
`I hereby certify that this paper or fee is being deposited With the United States Postal Service "Express Mail Post Office to
`Addressee" service under 37 C.F.R. 1.10 on the date indicated above and is addressed to the Commissioner for Patents, PO.
`Box 1450, Alexandria: VA 22313-1450,
`
`Si- lature
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`First Applicant:
`N IYIKIZA Clet
`
`Title:
`NOVEL AN TlF OLATE COMBINATION THERAPIES
`
`
`
`
`Docket No:
`X—14173B
`
`PRELIMINARY AMENDMENT
`
`Commissioner for Patents
`PO. BOX 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`Introductory Comments
`
`Please amend the accompanying application as follows:
`
`Amendments to the Specification are reflected on page 2 of this paper.
`
`Amendments to the Claims are reflected in the listing of claims, which begins on page 3 of
`
`this paper.
`
`Remarks/Arguments begin on page 6 of this paper.
`
`ACCORD EX 1002
`
`ACCORD EX 1002
`
`

`

`Docket No. X—14173B
`
`Amendments to the Specification
`
`At page 1, line 2, please insert the following replacement paragraph:
`
`This application is a divisional of Application No. 11/288,807, filed 29 November 2005,
`
`which is a divisional of Application No. 10/297,821 filed 05 December 2002, now Patent
`
`Number 7,053,065, which claims priority under 35 USC 371, for PCT/US01/14860, filed 15
`
`June 2001, which claims the priority of U.S. provisional applications No. 60/215,310, filed
`
`30 June 2000, No. 60/235,859, filed 27 September 2000, and No. 60/284,448, filed 18 April
`
`2001.
`
`Please replace paragraph [0024], at page 6, lines 6-16, with the following
`
`amended paragraph:
`
`[0024] The terms "antifolate" and "antifolate drug" refer to a chemical compound which
`
`inhibits at least one key folate-requiring enzyme of the thymidine or purine biosynthetic
`
`pathways, preferably thymidylate synthase ("TS"), dihydrofolate reductase ("DHFR"), or
`
`glycinamide ribonucleotide formyltransferase ("GARFT"), by competing with reduced folates
`
`for binding sites of these enzymes. Preferred examples of antifolates include 5—Huereuraeil;
`
`as—manufaetured—by461aaee;—Tomudex®, as manufactured by Zeneca; Methotrexate®, as
`
`manufactured by Lederle; Lometrexol®,
`
`as manufactured by Tularik; pyrido[2,3-
`
`d]pyrimidine derivatives described by Taylor et al in U.S. Pat. Nos. 4,684,653, 4,833,145,
`
`4,902,796, 4,871,743, and 4,882,334; derivatives described by Akimoto in U.S. Pat. No.
`
`4,997,838; thymidylate synthase inhibitors as found in EPO application 239,362; and most
`
`preferred, Pemetrexed Sedium—Disodium (ALIMTA), as manufactured by Eli Lilly & Co.
`
`

`

`Docket No. X—14173B
`
`Amendments to the Claims
`
`This listing of claims will replace all prior versions and listings of claims in the application.
`
`Listing of Claims:
`
`Claims 1—28. Cancelled
`
`29. (New)
`
`An improved method for administering pemetrexed disodium to a
`
`patient in need of chemotherapeutic treatment, wherein the improvement comprises:
`
`a)
`
`administration of between 350 ug and 1000 ug of folic acid, daily beginning
`
`approximately 1 to 3 weeks before treatment with pemetrexed disodium;
`
`b)
`
`administration of a methylmalonic acid lowering agent selected from the
`
`group consisting of vitamin B12, hydroxocobalamin, cyano-10-chlorocobalamin,
`
`aquocobalamin perchlorate, aquo-lO-chlorocobalamin perchlorate, azidocobalamin,
`
`chlorocobalamin and cobalamin, wherein the methylmalonic acid lowering agent is
`
`administered from about 1 to about 3 weeks prior to the first administration of pemetrexed
`
`disodium; and
`
`c)
`
`administration of pemetrexed disodium in combination with between 350 ug
`
`and 1000ug of folic acid, daily, until administration of pemetrexed disodium is discontinued,
`
`and a methylmalonic acid lowering agent selected from the group consisting of vitamin B12,
`
`hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-
`
`chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin and cobalamin, wherein the
`
`methylmalonic acid lowering agent administration is repeated from about every 6 weeks to
`
`about every 12 weeks, until administration of pemetrexed disodium is discontinued.
`
`30. (New)
`
`The improved method of Claim 29 wherein the methylmalonic acid
`
`lowering agent is vitamin B12.
`
`31. (New)
`
`The improved method of Claim 30 wherein about 500 ug to about
`
`1500ug of vitamin B12 is administered.
`
`32. (New)
`
`The improved method of Claim 31 wherein about 1000 pg of vitamin
`
`B12 is administered.
`
`

`

`Docket No. X—l4l73B
`
`33. (New)
`
`The improved method of Claim 29 wherein the methylmalonic acid
`
`lowering agent is administered by an intramuscular injection, orally, or as a parenteral.
`
`34. (New)
`
`The improved method of Claim 33 wherein the methylmalonic acid
`
`lowering agent is administered by an intramuscular injection.
`
`35. (New)
`
`The improved method of Claim 34 wherein the methylmalonic acid
`
`lowering agent administration is repeated about every 9 weeks, until administration of
`
`pemetrexed disodium is discontinued.
`
`36. (New)
`
`The improved method of Claim 32 wherein vitamin B12 is
`
`administered by an intramuscular injection, orally, or as a parenteral.
`
`37. (New)
`
`The improved method of Claim 36 wherein vitamin B12 is
`
`administered by an intramuscular injection.
`
`38. (New)
`
`The improved method of Claim 37 wherein the methylmalonic acid
`
`lowering agent administration is repeated about every 9 weeks, until administration of
`
`pemetrexed disodium is discontinued.
`
`39. (New)
`
`An improved method for administering pemetrexed disodium to a
`
`patient in need of chemotherapeutic treatment, wherein the improvement comprises:
`
`a)
`
`administration of between 350 ug and 1000 ug of folic acid, daily beginning
`
`approximately 1 to 3 weeks before treatment with pemetrexed disodium;
`
`b)
`
`administration of a methylmalonic acid lowering agent selected from the
`
`group consisting of vitamin B12, hydroxocobalamin, cyano-10-chlorocobalamin,
`
`aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin,
`
`chlorocobalamin and cobalamin, wherein the methylmalonic acid lowering agent is
`
`administered from about 1 to about 3 weeks prior to the first administration of pemetrexed
`
`disodium; and
`
`c)
`
`administration of pemetrexed disodium in combination with between 350 ug
`
`and 1000ug of folic acid, daily, until administration of pemetrexed disodium is discontinued,
`
`and a methylmalonic acid lowering agent selected from the group consisting of vitamin B12,
`
`

`

`Docket No. X—l4l73B
`
`hydroxocobalamin, cyano-lO-chlorocobalamin, aquocobalamin perchlorate, aquo-lO-
`
`chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin and cobalamin, wherein the
`
`methylmalonic acid lowering agent is administered by an intramuscular injection and wherein
`
`administration is repeated from about every 24 hours to about everyl680 hours, until
`
`administration of pemetrexed disodium is discontinued.
`
`

`

`Docket No. X—l4l73B
`
`Remarks
`
`Applicants submit this paper and request entry of the amendments herein.
`
`The Specification has been amended to recite specific reference to earlier-filed
`
`applications from which this application claims priority. The Specification has also been
`
`amended to correct an obvious error in the name of the compound “Alimta,” which is found
`
`on page 6, line 16. The name has been corrected to read “pemetrexed disodium.” Support
`
`for the correction can be found at least on page 2, lines 6-7, where the correct name of the
`
`compound is recited.
`
`Claims 1—28 have been cancelled, and new Claims 29—39 have been introduced.
`
`Support for new Claim 29-39 is generally found in the specification, at least on page 5, line
`
`20 to page 6, line 5; page 6, line 19 to page 7, line 4; page 7, lines 5-8, and 18-27; page 12,
`
`lines 19-29; page 13, line 21 to page 14, line 6; as well as in the claims as originally filed.
`
`Support for the improved combination can be found at least on page 13, line 21 to page 14,
`
`line 6; as well as on page 16, lines 3-9, and Table 1. More specifically, support for each
`
`element of Claims 29—39 is listed in the table below.
`
`Claim
`
`Element
`
`Basis at
`
`29(3)
`
`“administration of between 350ug and lOOOug of folic
`acid, daily beginning approximately 1 to 3 weeks
`before treatment with . emetrexed disodium”
`
`Page 13, line 21 to 25.
`
`29(b)
`
`Page 7, lines 5—8;
`Originally filed Claim 7.
`
`“administration of a methylmalonic acid lowering
`agent selected from the group consisting of vitamin
`B12, hydroxocobalamin, cyano- l 0-chlorocobalamin,
`aquocobalamin perchlorate, aquo-lO-chlorocobalamin
`perchlorate, azidocobalamin, chlorocobalamin and
`cobalamin”
`
`
`
`
`
`29(b)
`
`29(c)
`
`29(0)
`
`29(c)
`
`“wherein the methylmalonic acid lowering agent is
`administered from about 1 to about 3 weeks prior to the
`
`first administration of pemetrexed disodium”
`
`Page 7, lines 25-26.
`
`“administration of pemetrexed disodium in
`combination with”
`
`“between 350 Hg and lOOOug of folic acid, daily, until
`administration of pemetrexed disodium is
`discontinued”
`
`Page 5, lines 20-21;
`Oriinall
`filed Claim 4.
`
`Page 13, line 21 to 25;
`Page 14, line 3.
`
`Page 7, lines 5-8;
`“a methylmalonic acid lowering agent selected from
`the group consisting of vitamin B12, hydroxocobalamin, Originally filed Claim 7.
`cyano— lO—chlorocobalamin, aquocobalamin
`perchlorate, aquo- lO-chlorocobalamin perchlorate,
`azidocobalamin, chlorocobalamin and cobalamin”
`
`29(c)
`
`“wherein the methylmalonic acid lowering agent
`administration is reeated from about eve
`6 weeks to
`
`Page 7, lines 26-27.
`
`
`
`

`

`Docket No. X—14173B
`
`about every 12 weeks, until administration of
`oemetrexed disodium is discontinued”
`
`30
`
`31
`
`32
`
`“meth lmalonic acid lowering a ent is vitamin B12
`
`Pae 6, lines 20-21.
`
`“about 500 g to about 1500 g of vitamin B12”
`
`Page 7, lines 18-19.
`
`“about 1000 pg of vitamin B12”
`
` Claim 29; and
`
`
`
`Page 7, lines 24—25;
`Page 12, lines 21-24;
`Page 13, lines 27—28;
`Pae 14, lines 3—4.
`
`Page 7, lines 9-13.
`
`Page 7, lines 11-13, and
`18—25;
`
`Page 12, lines 21-24;
`Page 13, lines 27—30;
`Page 14, lines 3—6.
`Page 7, lines 26-27;
`Page 12, lines 23—24;
`Page 13, lines 29—30;
`Pae 14, lines 5—6.
`See basis for elements of
`
`
`
`33/36
`
`“administered by an intramuscular injection, orally, or
`as a oarenteral”
`
`34/37
`
`“administered by an intramuscular injection”
`
`“methylmalonic acid lowering agent administration is
`repeated about every 9 weeks, until administration of
`pemetrexed disodium is discontinued”
`
`35/38
`
`39
`
`Pae 7, lines 18-22.
`
`Applicants respectfully assert that no new matter has been introduced as a result of
`
`amendment of the Claims. Applicants request prompt consideration and allowance of the
`
`claimed subject matter. If a telephone interview would be of assistance in advancing
`
`prosecution of the subject application, Applicants’ undersigned attorney invites the Examiner
`
`to telephone her at the number provided.
`
`Respectfully submitted,
`
`/Manisha A. Desai/
`
`Manisha A. Desai, Ph.D.
`
`Attorney for Applicant
`Registration No. 43,585
`Phone: (317) 433—5333
`
`Eli Lilly and Company
`Patent Division
`PO. Box 6288
`
`Indianapolis, Indiana 46206—6288
`
`July 11, 2007
`
`

`

`Please type a plus sign (+) inside this box
`I]
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`Approved for use through 9/30/98. 0MB 0651-0032
`Patent and Trademark Office‘ US DEPARTMENT OF COMMERCE
`
`PTO/SB/01 (8-96) (MODIFIED)
`
`Attorne Docket Number
`
`X-14173
`
`DECLARATION FOR
`
`First Named Inventor
`
`CletNi
`
`ikiza
`
`UTILITY OR DESIGN
`
`COMPLETE IF KNOWN
`
`PATENT APPLICATION
`
`Declaration Submitted with Initial Filing
`
`Finn Date _
`Grou . Art Unit —
`
`As 3 below named Inventor, I hereby declare that:
`
`My residence post office address and citizenship are as stated below next to my name.
`
`I believe I am the original. first and sole Inventor (if only one name is listed below) or an original, first and joint inventor (if plural names are listed
`below of the sub'ect matter which is claimed and for which a atent is sou-ht on the Invention entitled:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`the specrfication of which
`[:I is attached hereto
`OR
`X was filed on
`(MM/DD/YYYY)
`
`15 June 2001
`
`as United States Application Number or PCT International
`
`Application
`Number
`
`PCT/USO1/14860
`
`and was amended on
`(MM/DDIYYYY)
`
`(if applicable).
`
`ll hereby state that l have reviewed and understand the contents of the above—identified specification, including the claims, as amended by any
`amendment specifically referred to above.
`
`I acknowledge the duty to disclose information which is material to patentability as defined in Title 37 Code of Federal Regulations. § 1.56.
`
`I hereby claim foreign priority benefits under Title 35, United States Code § 119(a)—(d) or § 365(b) of any foreign application(s) for patent or
`Inventor’s certificate, or 5 365(3) of any PCT international application which designated at least one country other than the United States of
`America, listed below and have also identified below, by checking the box. any foreign application for patent or inventor's certificate, or of any
`PCT international a Iication havin a filinc date before that ofthe a «Iication on which oriorit
`is claimed
`Prior Foreign Application
`Country
`Foreign Filing Date
`Priority
`Number 5
`MMIDD/YYYY
`Not Claimed
`
`Certified Copy Attached
`YES
`No
`
`E] Additional foreign application numbers are listed on a supplemental priority sheet attached hereto.
`
`
`
`I hereb claim the benefit under Title 35, United States Code § 119(e) of an United States urovisional a. Iications 5 listed below
`A -llcation Number 5
`“
`60/215,310
`60/235,859
`60/284,448
`
`30 June 2000
`27 September 2000
`18 April 2001
`
`E] Additional provisional application
`numbers are listed on a supplemental
`priority sheet attached hereto.
`
`
`
`[Page 1]
`
`

`

`Please type a plus sign (+) inside this box
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`Patent and Trademark Office' US. DEPARTMENT OF COMMERCE
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`
`DECLARATION
`I hereby claim the benefit under Title 35, United States Code §120 of any United States application(s), or § 365(c) of any PCT international
`application designating the United States of America, listed below and, insofar as the subject matter of each of the claims of this application is not
`disclosed in the prior United States or PCT international application in the manner provided by the first paragraph of Title 35, United States Code §
`112, I acknowledge the duty to disclose information which is material to patentability as defined in Title 37, Code of Federal Regulations § 1 56
`which became available between the filin- date of the nor ao lication and the national or PCT international filin- date of this a nlicatlon.
`
`U.S. Parent
`A- olication Number
`
`PCT Parent
`Number
`
`Parent Filing Date
`MM/DDIYYYY
`
`Parent Patent Number
`ifa- olicable
`
`E] Additional US. or PCT international application numbers are listed on a supplemental priority sheet attached hereto.
`As a named inventor, I hereby appoint the following registered practitioner(s) to prosecute this application and to transact all business in the Patent
`and Trademark Office connected therewith:
`
`
`
`Re. No.
`Attorne Name
`Re- No
`Attorne Narne
`Paul J. Koivunleml
`45,263
`Arvie J. Anderson
`— _
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Brian P. Barrett
`Michael T. Bates
`Roer S. Ben amln
`Ga M. Birch
`William R. Boudreaux
`Steven P. Caltrider
`Paul R. Cantrell
`John Cleveland
`Charles E. Cohen
`Donald L. Comeollo
`Gre-o A. Cox
`Paula K, Davis
`John C. Demeter
`Manisha A. Desai
`Paul J. Ga Io
`Francis 0. Ginah
`Janet A. Gon-ola
`Am E. Hamilton
`James A. Hoffmann
`Danica Hostettler
`Frederick D. Hunter
`Thomas E. Jackson
`Soonhee Jan-
`Charles Jo ner
`Gerald P. Keleher
`James J. Kelle
`
`39,597
`34,121
`27,025
`48,881
`35,796
`36,467
`36,470
`50,697
`34,565
`30,741
`47,504
`47,517
`30,167
`43,585
`36,808
`44,712
`48,436
`33,894
`50,221
`51,820
`26,915
`33,064
`44,802
`30,466
`43,707
`41,888
`
`
`
`
`
`
`KMLee
`James P. Leeds
`Nelsen L Lentz
`Elizabeth A. McGraw
`Doulas K. Norman
`Arleen Palmber-
`Thomas G. Plant
`Edward Prein
`Grant E. Reed
`James J Sales
`Michael J. Sa les
`DaVid M. Stemerlck
`Mark J. Stewart
`Robert D. Titus
`Robert C. Tucker
`Tina M. Tucker
`MaCharri Vorndran-Jones
`Gilbert T. Vo
`Thomas D. Webster
`Lawrence T. Welch
`Alexander Wilson
`Ma Ann Wiskerchen
`Dan L. Wood
`
`
`
`47,744
`35,241
`38,537
`44,646
`33,267
`40,422
`35.784
`37,212
`41,264
`33,773
`32,295
`40,187
`43,936
`40,206
`45,165
`47,145
`36,711
`43,972
`39.872
`29,487
`45,782
`45,511
`48,613
`
`
`
`
`
`|:] Additional registered practitioner(s) named on a supplemental sheet attached hereto.
`Direct all correspondence to
`
`M ELl LILLY AND COMPANY
`ATTN: Elizabeth A. McGraw
`Patent Division, PO. Box 6288
`46206-6288
`INDIANAPOLIS murmu-
`“— Telehone
`317 277-7443 E- 317 276-3861
`I hereby declare that all statements made herein of my own knowledge are true and that all statements made on information and belief are
`believed to be true; and further that these statements were made with the knowledge that willful false statements and the like so made are
`punishable by fine or imprisonment, or both, under Section 1001 of Title 18 of the United States Code and that such willful false statements may
`'eo-ardize the validit of the a lication or an atent issued thereon.
`
`Name of Sole or First Inventor:
`Given
`
`D A Petition has been filed for this unsigned inventor
`Family
`Ni
`ikiza
`
`N
`5—...—
`Inventor‘s Signature g'!W .
`
`92 W0 V- $20092
`
`6802 Antietam Place
`Address
`Post Office Address SAME AS ABOVE
`CI
`Indianapolis
`E
`
`WEI.“ 46278 _us
`
`Additional Inventors are being named on supplement sheet(s) attached hereto.
`
`

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`E, A Petition has been filed for this unsigned inventor
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`
`
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`e..Jr.
`Name
`Name ‘4 A?
`Inventor’
`,
`'
`‘ I
`,
`”flak-AME Bam- 4.1m
`
`
`Win-m:-
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`8015 Ha
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`
`M—E-M_
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`Name of Additional Joint Inventor, if any:
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`{:1 A Petition has been filed for this unsigned inventor
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`-——-—-——-
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`’1’!” Name
`Name
`e.-.Jr.
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`WM-
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`Post Office Address SAME AS ABOVE
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`Ancaster
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`LSG 1G4
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`Name
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`and Tradetmrt. (mm RS. Department <1! Commerce, FRO. Beg 1:530. Nemndm‘ VA zmta» um :39 N0? SEN!) FEES (3R CthLETEB FOR‘MS 3°51} YHES
`mnfiesgt 355m 113: Cemmtssiom 6:: Patents, H3. am: “53, Aiexandm, VA 223t3~t 453,
`
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`
`

`

`PTO/SB/96 (8—96) (MODIFIED)
`Approved for use through 9/30/98, OMB 0651—0027
`Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`
`CERTIFICATE UNDER 37 CFR 3.731b!
`
`First Applicant: NIYIKIZA Clet
`
`Entitled: NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.: X—14173B
`
`ELI LILLY AND COMPANY, an Indiana Corporation
`(Name of Assignee)
`(Type of Assignee, e.g. corporation, partnership, university, government agency, etc.)
`certifies that it is the assignee of the entire right, title and interest in the patent application identified above by virtue of
`either:
`
`A.
`
`[ X] An assignment from the inventor(s) of the patent application identified above.
`
`[X] The assignment was recorded in the Patent and Trademark Office at Reel 014132, Frame 0597.
`[
`] The assignment is being submitted separately for recordation; a copy of this assignment is attached.
`
`B. [
`
`] A chain of title from the inventor(s), of the patent application identified above, to the current assignee as shown
`below:
`
`OR
`
`1.
`
`To:
`From:
`The document was recorded in the Patent and Trademark Office at
`
`Reel
`
`, Frame
`
`, or for which a copy thereof is attached.
`
`To:
`From:
`The document was recorded in the Patent and Trademark Office at
`
`
`
`Reel
`
`, Frame
`
`, or for which a copy thereof is attached.
`
`
`To:
`From:
`The document was recorded in the Patent and Trademark Office at
`
`Reel
`
`, Frame
`
`, or for which a copy thereof is attached.
`
`[
`
`]
`
`Additional documents in the chain of title are listed on a supplemental sheet.
`
`[
`
`] Copies of assignments or other documents in the chain of title are attached.
`
`The undersigned (whose title is supplied below) is empowered to sign this certificate on behalf of the assignee.
`
`I hereby declare that all statements made herein of my own knowledge are true, and that all statements made on
`information and belief are believed to be true; and further, that these statements are made with the knowledge that willful
`false statements, and the like so made, are punishable by fine or imprisonment, or both, under Section 1001, Title 18 of the
`United States Code, and that such willful false statements may jeopardize the validity of the application or any patent
`issuing thereon.
`
`July 11, 2007
`Date
`
`/Manisha A. Desai/
`Manisha A. Desai
`Patent Counsel
`Send to: Commissioner for Patents, PO. Box 1450, Alexandria, VA 22313—1450
`
`

`

`
`CERTIFICATION OF FACSIMILE TRANSMISSION
`
`I hereby certify that this paper is being facsimile transmitted to the Patent and Trademark Office on the date shown below.
`
`
`Type or print name of person signing certification
`
`Date
`Signature
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADEIVLARK OFFICE
`
`
`NIYIKIZA Clet
`
`
`
` First Applicant:
`
`
`
`For:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.:
`
`X—l4l73B
`
`AMENDMENT AND PETITION TO CORRECT
`
`INVENTORSHIP UNDER 37 C.F.R. 1.481b!
`
`Commissioner for Patents
`PO. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`1. Amendment and Petition
`
`This amendment and petition is to delete the names of the following persons originally
`
`named as inventors and who are not the inventors of the invention now being claimed: Paolo Paoletti,
`
`of Indianapolis, Indiana, and James Jacob Rusthoven, of Ancaster, Canada.
`
`2. Claims Now On File
`
`The claims in this application are as follows:
`
`New claims 29—39 filed on July 11, 2007
`
`3. Diligence
`
`This amendment and petition is being filed diligently after discovery that any
`
`claims for which the above named inventors who are being deleted are now no longer the
`
`inventors of the subject matter being claimed.
`
`

`

`Docket No. X—l4l73B
`
`4. Fee Payment
`
`Please charge $130.00,
`
`the surcharge required by §l.l7(i), and charge any
`
`additional fees which may be required by this or any other related paper, or credit any
`I
`
`overpayment to Deposit Account No. 05—0840,
`
`in the name of Eli Lilly and Company.
`
`enclose an original and two copies of this paper.
`
`Respectfully submitted,
`
`/Manisha A. Desai/
`
`Manisha A. Desai, Ph.D.
`
`Attorney for Applicant
`Registration No. 43,585
`Telephone: (317) 433—5333
`
`Eli Lilly and Company
`Patent Division
`PO. Box 6288
`
`Indianapolis, Indiana 46206—6288
`
`July 11, 2007
`
`

`

`"Express Mail" mailing label number
`
`
`
`Date of Deposit
`
`
`
` Printed Name
`
`I hereby certify that this paper or fee is being deposited With the United States Postal Service "Express Mail Post Office to
`Addressee" service under 37 C.F.R. 1.10 on the date indicated above and is addressed to the Commissioner for Patents, PO.
`Box 1450, Alexandria, VA 22313-1450.
`
`Si - ature
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADER/LARK OFFICE
`
`
`NIYIKIZA Clet
`First Applicant:
`
`
`Title:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`
`Docket No:
`X—l4l73B
`
`
`
`
`INFORlVLATION DISCLOSURE STATEMENT
`
`Commissioner for Patents
`PO. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`As a means of complying with the duty of disclosure, Applicants submit an
`
`"Information Disclosure Citation In An Application" on a Form PTO-1449 (modified) for
`
`consideration by the Examiner. As permitted by 37 C.F.R. §l.98(d), Applicants refer to
`
`application Serial No. 11/288,807,
`
`filed November 29, 2005,
`
`for copies of the listed
`
`documents.
`
`Since this Statement
`
`is being filed in accordance with 37 C.F.R.
`
`l.97(b),
`
`Applicants submit that no additional fee is required.
`
`Applicants request consideration of this information.
`
`Respectfully submitted,
`
`/Manisha A. Desai/
`
`Manisha A. Desai, Ph.D.
`
`Attorney for Applicant
`Registration No. 43,585
`Telephone: (317) 433—5333
`
`Eli Lilly and Company
`Patent Division
`PO. Box 6288
`
`Indianapolis, Indiana 46206—6288
`
`July 11, 2007
`
`

`

`FORM PTO 1449 (modified)
`
`Atty. Docket No.
`X-14173B
`
`Serial No
`
`Sheet 1 of2
`
`INFORMATION DISCLOSURE CITATION
`IN AN APPLICATION
`
`Flrst Apphcant
`NIYIKIZA C161
`
`Examiner
`Initials*
`
`Document Number
`Number—Kind Code2 (if known)
`
`_
`
`Publication Date
`MM—DD—YYYY
`
`Name of Patentee or
`Applicant of Cited Document
`
`Pages, Columns, Lines,
`Where Relevant Pages
`or Relevant Figures
`
`U.S. PATENT DOCUMENTS
`
`L S 6,207,651
`Allen, et al.
`3/27/2001
`
`
`L S 6,297,224
`
`10/2/2001
`
`Allen, et al.
`
`Allen, et al.
`3/4/2003
`S 6,528,496
`
`
`S 03/02163 50
`
`11/20/2003
`
`Allen, et al.
`
`Allen, et al.
`12/4/2003
`S 03/0225030
`
`
`Thompson, Robert E.
`01/1960
`S 2,920,015
`
`
`Pitman, Bradford D.
`01/2004
`S 2004/0005311 A1
`
`
`S 5,344,932
`
`09/1994
`
`Taylor, Edward C.
`
`Niyikiza, et a1.
`05/2006
`S 7,053,065
`
`
`
`
`
`
`
`Pages, Columns, Lines, Where
`Relevant Passages or Relevant
`Figures Appear
`
`Examiner
`Initials*
`
`I
`
`FOREIGN PATENT DOCUMENTS
`Foreign Patent Document
`Name of Patentee or
`Applicant of Cited
`Document
`
`Country Code3 -Number 4'
`Kind Code5 (if known)
`
`Publication Date
`MM-DD-YYYY
`
`_—_—Si_ ature
`*EXAMINER: Initial if reference considered, whether or not citation is in conformance with MPEP 609. Draw line through citation if not in conformance and not considered. Include copy of
`this form with next communication to applicant
`1Applicant’s unique citation designation number (optional). 2 See Kinds Codes of USPTO Patent Documents at wwwnsntonov or MPEP 901.04. 3Enter Office that issued the document, by the
`two-letter code (WIPO Stande ST.3). 4For Japanese patent documents, the indication of the year of the reign of the Emperor must precede the serial number of the patent document 5Kind of
`document by the appropriate symbols as indicated on the document under WIPO Stande ST. 16 ifpossible. 6Applicant is to place a check mark here if English language Translation is attached.
`Burden Hours Statement: This form is estimated to take 2.0 hours to complete. Time will vary depending upon the needs of the individual case.
`Any comments on the amount of time you are required to complete this form should be sent to the Chief Information Officer, U.S. Patent and Trademark Office, Washington, DC 20231. DO
`NOT SEND FEES OR COMPLETED FORMS TO THIS ADDRESS. SEND TO: Commissioner for Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`

`

`Initialsi<
`
`No. 1
`
`NON PATENT LITERATURE DOCUMENTS
`Include name of the author (in CAPITAL LETTERS), title of the article (when appropriate), title of the item
`(book, magazine, journal, serial, symposium, catalog, etc.), date, page(s), volume—issue number(s) publisher,
`c1t and/or count where nublished.
`
`Sheet 2 of2
`
`Calvert H.: "Folate status and the safety profile of antifolates", Seminars in
`Oncology, 2002, 29/2 Suppl. 5, pp. 3-7, XP008005755
`
`Calvert H.: "Future directions in the development of pemetrexed", Seminars
`in Oncology, 2002, 29/2 Suppl. 5, pp. 54-61, XP008005744
`
`CA
`
`CB
`
`CC
`
`CD
`
`CE
`
`CF
`
`Westerhof, et a1: "Carrier-and receptor-mediated transport of folate
`antagonists targeting folate-dependent enzymes: correlates of molecularstructure
`and biological activity", Mol. Pharmacology, 1995, 48(3), pp. 459-
`71, XP008005762
`Worzalla, et a]: "Role of folic acid in modulating the toxicity and efficacy of
`the multitargeted antifolate, LY231514", Anticancer Research (1998), 18(5A),
`
`pp. 3235-3239, XP008005757
`Hanauske, et a1: "Pemetrexed disodium: A novel antifolate clinically active
`against multiple solid tumors", Oncologist, Alphamed Press, US, Vol. 4, No.
`6, 2001, pp. 363-373, XP008005751
`Bunn, et al: "Vitamin B 12 and folate reduce toxicity of Alimta (pemetrexed
`disodium, LY 231514, MTA), a novel antifolate/antimetabolite",
`Program/Proceedings - American Society of Clinical Oncology, the Society,
`US, Vol. 76A, No. 20, 2001, oa_e 300, XPOO8005885
`Dierkes, et al., Supplementation with Vitamin B 12 Decreases Homocystein
`and Methylmalonic Acid but Also Serum Folate in Patients with End-Stage
`Renal Disease. Metabolism. May 1999. Vol. 48, No. 5, pages 631-635. See:
`abstract.
`
`
`
`CG
`
`-- Arsenyan et al. (Abstract: Onkol. Nauchn., (1978) 12(10);49_54
`-- John, et al. (Cancer 2000, 88: 1807-13)
`
`CJ
`
`Poydock et al., "Growth-inhibiting effect of hydroxocobaltniin and L-ascorbic acid on
`two solid tumors in mce", IRCS Medical _Science, Vol. 12, No. 9, pp. 813 (1984).
`The Cecil Reference, TEXTBOOK of MEDICINE, 2lst Edition (2000). Chapter 198. pps.
`CK
`1060-1074.
`
`
`Examiner
`Si 3 ature
`*EXAMINER: Initial if reference considered, whether or not citation is in conformance with MPEP 609. Draw line through citation if not in conformance and not considered. Include copy of
`this form with next communication to applicant
`1Applicant’s unique citation designation number (optional). 2 See Kinds Codes of USPTO Patent Documents at www.usnt0.trov or MPEP 901.04. 3Enter Office that issued the document, by the
`two-letter code (WIPO Stande ST.3). 4For Japanese patent documents, the indication of the year of the reign of the Emperor must precede the serial number of the patent document 5Kind of
`document by the appropriate symbols as indicated on the document under WIPO Standard ST. 16 ifpossible. 6Applicant is to place a check mark here if English language Translation is attached.
`Burden Hours Statement: This form is estimated to take 2.0 hours to complete. Time will vary depending upon the needs of the individual case.
`Any comments on the amount of time you are required to complete this form should be sent to the Chief Information Officer, U.S. Patent and Trademark Office, Washington, DC 20231. DO
`NOT SEND FEES OR COMPLETED FORMS TO THIS ADDRESS. SEND TO: Commissioner for Patents, P.O. Box 1450, Alexandria, VA 22313-1450.
`
`Date Considered
`
`

`

`Electronic Patent Application Fee Transmittal
`
`Filing Date:
`
`
`
`—--m-
`
`Title of Invention:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`First Named Inventor/Applicant Name:
`
`Clet Niyikiza
`
`Manisha Arvind Desai/Lisa Capps
`
`Miscellaneous-Filing:
`
`Patent-Appeals-and-lnterference:
`
`

`

`Post -A| Iowance-and-Post-Issu ance:
`
`1000
`
`Extension-of-Time:
`
`Miscellaneous:
`
`was?"
`
`Total in USD ($)
`
`

`

`International Application Number: —
`
`Title of Invention:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`
`
`First Named Inventor/Applicant Name:
`
`Payment information: