"Express Mail" mailing label number ______________ _
`
`Date of Deposit ___________ __ __ _ __ _ __ _ _
`
`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. I.IO on the date indicated above and is addressed to the Commissioner for Patents, P.O.
`Box 1450, Alexandria, VA 22313-1450.
`
`Printed Name
`
`Signature
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`First Applicant:
`
`Title:
`
`NIYIKIZA Clet
`
`I
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.:
`
`X-14173B
`
`I
`
`PRELIMINARY AMENDMENT
`
`Commissioner for Patents
`P.O. 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.
`
`Sandoz Inc.
`Exhibit 1002-00001
`
`Teva – Fresenius
`Exhibit 1002-00001
`
`

`
`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/USOI/14860, filed 15
`June 200 l, 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 fluorouraeil,
`as manufactured by Glaxo; 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 Sodium Disodium (ALIMTA), as manufactured by Eli Lilly & Co.
`
`- 2 -
`
`Sandoz Inc.
`Exhibit 1002-00002
`
`Teva – Fresenius
`Exhibit 1002-00002
`
`

`
`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 µg and 1000 µg 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 ofpemetrexed disodium in combination with between 350 µg
`
`and lOOOµg of folic acid, daily, until administration of pemetrexed dis odium 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 500µg to about
`
`1500µg of vitamin B12 is administered.
`
`32. (New)
`
`The improved method of Claim 31 wherein about 1000 µg of vitamin
`
`B12 is administered.
`
`- 3 -
`
`Sandoz Inc.
`Exhibit 1002-00003
`
`Teva – Fresenius
`Exhibit 1002-00003
`
`

`
`Docket No. X-14173B
`
`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 µg and 1000 µg 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 ofpemetrexed disodium in combination with between 350 µg
`
`and IOOOµg of folic acid, daily, until administration of pemetrexed dis odium is discontinued,
`
`and a methylmalonic acid lowering agent selected from the group consisting of vitamin B12,
`
`- 4 -
`
`Sandoz Inc.
`Exhibit 1002-00004
`
`Teva – Fresenius
`Exhibit 1002-00004
`
`

`
`Docket No. X-14173B
`
`hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-
`
`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 every 1680 hours, until
`
`administration of pemetrexed disodium is discontinued.
`
`- 5 -
`
`Sandoz Inc.
`Exhibit 1002-00005
`
`Teva – Fresenius
`Exhibit 1002-00005
`
`

`
`Docket No. X-14173B
`
`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
`29(a)
`
`29(b)
`
`29(b)
`
`29(c)
`
`29(c)
`
`29(c)
`
`29(c)
`
`Basis at
`Page 13, line 21to25.
`
`Page 7, lines 5-8;
`Originally filed Claim 7.
`
`Element
`"administration of between 350µg and IOOOµg of folic
`acid, daily beginning approximately 1 to 3 weeks
`before treatment with pemetrexed disodium"
`"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"
`"administration of pemetrexed disodium in
`combination with"
`"between 350 µg and IOOOµg of folic acid, daily, until
`administration of pemetrexed dis odium is
`discontinued"
`Page 7, lines 5-8;
`"a methylmalonic acid lowering agent selected from
`the group consisting of vitamin B12, hydroxocobalamin, Originally filed Claim 7.
`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
`
`Page 7, lines 25-26.
`
`Page 5, lines 20-21;
`Originally filed Claim 4.
`Page 13, line 21to25;
`Page 14, line 3.
`
`Page 7, lines 26-27.
`
`- 6 -
`
`Sandoz Inc.
`Exhibit 1002-00006
`
`Teva – Fresenius
`Exhibit 1002-00006
`
`

`
`Docket No. X-14173B
`
`about every 12 weeks, until administration of
`pemetrexed disodium is discontinued"
`"methylmalonic acid lowering agent is vitamin B12
`"about 500µg to about 1500ug of vitamin B12"
`"about 1000 µg of vitamin B12"
`
`30
`31
`32
`
`33/36
`
`34/37
`
`"administered by an intramuscular injection, orally, or
`as a parenteral"
`"administered by an intramuscular injection"
`
`35/38
`
`"methylmalonic acid lowering agent administration is
`repeated about every 9 weeks, until administration of
`pemetrexed disodium is discontinued"
`
`39
`
`Page 6, lines 20-21.
`Page 7, lines 18-19.
`Page 7, lines 24-25;
`Page 12, lines 21-24;
`Page 13, lines 27-28;
`Page 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;
`Page 14, lines 5-6.
`See basis for elements of
`Claim 29; and
`Page 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.
`
`Eli Lilly and Company
`Patent Division
`P.O. Box 6288
`Indianapolis, Indiana 46206-6288
`
`July 11, 2007
`
`Respectfully submitted,
`
`/Manisha A. Desai/
`Manisha A. Desai, Ph.D.
`Attorney for Applicant
`Registration No. 43,585
`Phone: (317) 433-5333
`
`- 7 -
`
`Sandoz Inc.
`Exhibit 1002-00007
`
`Teva – Fresenius
`Exhibit 1002-00007
`
`

`
`61ease type a plus sign (+) inside this box
`
`[::J
`
`DECLARATION FOR
`UTILITY OR DESIGN
`PATENT APPLICATION
`
`6 Deci•rahoo S"bm'""' w;th tom,; Fm,.
`
`Declaration Submitted after Initial Filing
`
`Approved for use through 9/30/98. OMB 0651-0032
`Patent and Trademark Office· U.S DEPARTMENT OF COMMERCE
`
`PTO/SB/01 (8-96) (MODIFIED)
`
`Attorney Docket Number
`
`X-14173
`
`First Named Inventor
`
`Clet Niyikiza
`
`COMPLETE IF KNOWN
`
`Application Number
`
`Filing Date
`
`Group Art Unit
`
`Examiner Name
`
`As a below named Inventor, I hereby declare that:
`
`My residence, post offi~e _address,_ and citizensh_ip ~re as stated below next to my_ n_a_n:i_e. __
`
`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 subject matter which is claimed and for which a oaten! is souQht on the Invention entitled:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`the spec1ficat1on of which
`D is attached hereto
`OR
`(:] was filed on
`(MM/DD/YYYY)
`
`Application
`Number
`
`I
`
`PCT/US01/14860
`
`I as United States Application Number or PCT International
`I 15 June 2001
`I (if applicable).
`I and was amended on
`I
`
`(MM/DD/YYYY)
`
`JI hereby state that I 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§ 365(a) 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 aoolication havinQ a filinQ date before that of the a Jolication on which priority is claimed
`Foreign Filing Date
`Priority
`Country
`Prior Foreign Application
`IMM/DD/YYYYI
`Not Claimed
`Number(s)
`
`Certified Copy Attached
`YES
`NO
`D
`D
`D
`D
`D
`D
`D
`D
`D
`D
`D
`D
`
`D
`D
`D
`D
`D
`D
`
`D Additional foreign application numbers are listed on a supplemental priority sheet attached hereto.
`I herebv claim the benefit under Title 35, United States Code Ii 119(e) of any United States Provisional appllcat1ons(s) listed below
`Filing Date IMM/DD/YYYYl
`Application Number(s)
`D Additional provisional application
`30 June 2000
`60/215,310
`27 September 2000
`60/235,859
`18 April 2001
`60/284,448
`
`numbers are listed on a supplemental
`priority sheet attached hereto.
`
`[Page 1]
`
`Sandoz Inc.
`Exhibit 1002-00008
`
`Teva – Fresenius
`Exhibit 1002-00008
`
`

`
`cilease type a plus sign (+) inside this box [:']
`
`PTO/SB/01 (8-96) (MODIFIED)
`
`Approved for use through 9130198. OMB 0651-0032
`Patent and Trademark Office· U S DEPARTMENT OF COMMERCE
`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 appl1cat1on 1s 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 1s material to patentab11ity as defined 1n Title 37, Code of Federal Regulations § 1 56
`which became available between the filina date of the prior application and the national or PCT international filina date of this aoolicat1on.
`PCT Parent
`Parent Filing Date
`Parent Patent Number
`U.S. Parent
`(if aoolicable)
`(MM/DDNYYY)
`Number
`Application Number
`
`0 Additional U.S. or PCT international application numbers are listed on a supplemental priority sheet attached hereto.
`As a named inventor, I hereby appoint the following registered pract1t1oner(s) to prosecute this application and to transact all business in the Patent
`and Trademark Office connected therewith:
`
`Attornev Name
`Arvie J. Anderson
`Lynn D. Apeh:iren
`Robert A Armitaae
`Brian P. Barrett
`Michael T. Bates
`Roaer S. Ben1am1n
`Garv M. Birch
`William R. Boudreaux
`Steven P. Caltrider
`Paul R. Cantrell
`John Cleveland
`Charles E. Cohen
`Donald L. Comeaho
`Greaorv A. Cox
`Paula K. Davis
`John C. Demeter
`Manisha A. Desai
`Paul J. Gaylo
`Francis 0. Ginah
`Janet A. Gonaola
`Amv E. Hamilton
`James A. Hoffmann
`Danica Hostettler
`Frederick D. Hunter
`Thomas E. Jackson
`Soonhee Jana
`Charles Joyner
`Gerald P. Keleher
`James J. Kelley
`
`Ren. No.
`45,263
`45,341
`27,417
`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
`
`Attornev Name
`Paul J. Koivuniem1
`Thomas LaGrandeur
`Robert E. Lee
`Kirby Lee
`James P. Leeds
`Nelsen L Lentz
`Elizabeth A. McGraw
`Doualas K. Norman
`Arleen Palmbera
`Thomas G. Plant
`Edward Prein
`Grant E. Reed
`James J Sales
`Michael J. Savles
`David M. Stemenck
`Mark J. Stewart
`Robert D. Titus
`Robert C. Tucker
`Tina M. Tucker
`MaCharri Vorndran-Jones
`Gilbert T. Voy
`Thomas D. Webster
`Lawrence T. Welch
`Alexander Wilson
`MarvAnn Wiskerchen
`Dan L. Wood
`
`Rea. No.
`31,533
`51,026
`27,919
`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
`
`D Additional registered practitioner(s) named on a supplemental sheet attached hereto.
`I
`Direct all correspondence to
`ELI LILLY AND COMPANY
`Name
`ATTN: Elizabeth A. McGraw
`Address
`Patent Division, P.O. Box 6288
`Address
`I 46206-6288
`IZIP
`State
`INDIANAPOLIS
`City
`I
`I Fax
`I <317l 276-3861
`I 1317> 277-7443
`I Telephone
`Country
`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
`jeopardize the validitv of the application or any patent issued thereon.
`
`I INDIANA
`
`I Clet
`
`Name
`
`e.o. Jr.
`
`I D A Petition has been filed for this unsigned inventor
`I Family I Niyikiza
`l Suffix I
`I Middle
`I
`Name of Sole or First Inventor:
`Given
`~//
`Name
`'
`N"n'IA -
`I Date I o2. '7 ;vo //. :lco;<.
`I / /,'~/A hJ') ~/J?l ,;_./'1
`I
`Inventor's Signature
`j Citizenship I US
`I Country l us
`_,
`):..:.'_ystate
`Residence: City 1 lndiana'polrs/
`I 6802 Antietam Ptace
`Address
`Post Office Address I SAME AS ABOVE
`I State I IN I Zip
`I Indianapolis
`146278
`City
`rXl Additional inventors are being named on supplement sheet(s) attached hereto.
`
`!IN
`
`l Country
`
`!us
`
`[Page 2]
`
`Sandoz Inc.
`Exhibit 1002-00009
`
`Teva – Fresenius
`Exhibit 1002-00009
`
`

`
`cilease type a plus sign (+) inside this box tJ
`
`Approved for use through 9/30/98. OMB 0651-0032
`Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
`DECLARATION
`
`I
`
`PTO/SB/01 (8-96) (MODIFIED)
`
`Name of Additional Joint Inventor, if any:
`
`LJ A Petition has been filed for this unsigned inventor
`
`Given
`Name
`
`Middle
`Name
`
`Family
`Name
`
`Paoletti
`
`IN
`
`Country
`
`us
`
`Suffix
`e .. Jr.
`~).<!__. '"1, 2.002...
`Citizenship
`IT
`
`Date
`
`Address
`
`8015 Ha
`
`ard Drive
`
`Post Office Address SAME AS ABOVE
`Indianapolis
`
`Ci
`
`Name of Additional Joint Inventor, if any:
`
`James
`
`Given
`Name
`Inventor's
`Si nature
`
`Residence:
`Post Office Address 15 Lovers Lane
`
`State
`
`IN
`
`Zi
`
`46240
`
`Count
`
`us
`
`LJ A Petition has been filed for this unsigned inventor
`Jacob
`
`Family Rusthoven
`Name
`
`Middle
`Name
`
`State Ontario Count CA
`
`Date
`
`Post Office Address SAME AS ABOVE
`An caster
`state Ontario Zip
`
`Ci
`
`L9G 1G4
`
`Country
`
`CA
`
`Name of Additional Joint Inventor, if any: CJ A Petition has been filed for this unsigned inventor
`.....
`I Family
`I Suffix I
`
`Middle
`Name
`
`I
`
`Name
`
`I
`
`I State
`
`I
`
`I Countrv I
`
`e.g.
`Jr.
`
`I Date I
`I Citizenship I
`
`Given
`Name
`
`Inventor's
`Signature
`
`Residence: City I
`
`Post Office Address
`Post Office Address SAME AS ABOVE
`City I
`
`I State I
`
`I Zip
`
`I
`
`I Country
`
`I
`
`Name of Additional Joint Inventor, if any:
`
`Given
`Name
`Inventor's
`Signature
`
`Residence: City I
`
`Post Office Address
`
`c=J A Petition has been filed for this unsigned inventor
`I Family
`I Suffix I
`
`Middle I
`
`Name
`
`Name
`
`I
`
`e.Q. Jr.
`
`I Date I
`J Citizenship I
`
`I State
`
`I
`
`I Country I
`
`Post Office Address SAME AS ABOVE
`
`City I
`
`I State I
`
`I Zip I
`
`I Country
`
`I
`
`(Page 3)
`
`Sandoz Inc.
`Exhibit 1002-00010
`
`Teva – Fresenius
`Exhibit 1002-00010
`
`

`
`PTo.<SBi!'\O ( 1;!,;J;;_!
`App;::>"*<'.i l\)I' :.$<.> lhfoog1:! 11/30/'<!.t,'<15, OMB 0051-!l>::'-35
`l!.R f'al:er<! ~ml ir<>dema•k G#i<.-.:i; U.S. OSPARiMH!T OF COMMERCE
`Um.1<;1 the Papwworl< RerJuctim1 Act Gf tllSS, no l}effl<J>1s af" mqu<;e<l t<"< 1<>'0lX>f>li it) a ooll<>~~ion cf i>>forma\iti,1 !Imm;~ ii ui~p!ay"-" valid OMS '"~nlml numMr.
`
`POWER OF ATTORNF5Y TO PRosgclJTE .APPl_,ICATJONS BEFORF~ THE USPTO
`
`I hereby appoint:
`
`n
`LJ Practitioner(s} nanWd below (If more than ten pal~nt pra<~!iikmers are to tie named, thefl a customer num.ber must be used}:
`Nalne
`Registmoon Number
`
`0 Practitiooors associated with the Gu:stnma Number: I 25885
`
`OR
`
`=1
`
`as aiiomoy(s) or agent{s} to represent tlie ur\ders~ before lhe Untted States Patent and Traoo1narn Office {US PTO) in connection with
`any and all patent appHcatlons assigned Q!tl to the unders!gnoo accoming tn the. USPTO assignment records or a$ignmen! documents
`attact~ to this iorm in accordance with :17 CFR 3.13(b).
`
`Assignee Name and Address:
`Eli Lilly and Company
`Patent Division
`PO Box 6288
`Indianapolis, Indiana 46206-6288
`
`A copy of this form, together with a statement under 3.7 CFR 3.73(b) (Form PTOJSSl96 or equivalent} Is
`required ta be filed in eaeh app!icat!on in which this form is used. The statement under 37 CFR 3.73(b)
`may be completed by one of the practitioner& appointed io this form if the appointed practitioner is
`authorized to act on behalf of t:he assignee, and must identify the application in which this Power of
`Attornev is to be filed.
`
`StGNA11JR.E of A:sssi-gnee of Record
`The im!ividilil:l WhQSe signature a.u_d ti Ile lS sup11Hed hel1J1:1r iii ;mthoifr~rl !o ad mi lx::halfofthe a~sign~
`
`Name
`
`r->ri~
`
`Do._uglas K Norman
`-
`Signature 1t·hi •,7,~ ·1 ?~ ( .. 7 it' f\ .. '{i,.,.,
`/ ,., /i ...
`'
`)
`·' •t.i
`I !,· l ti-y ;'.>..;J..( <'·l.<>'I
`1 Oeput/Gene;ai'l:counse!, General Patent Counsel
`317A33-1651
`-ilta •ltuo111at1<m 1s req<<fmd lO ol:ilmn or reta:n a :ien-en~ t1y ma poolic wtncn 1$ w me {aM oy ~'!'.!
`"t ;.;9 0..-l>W.:tKJll <st in!Oml&tl<l!l l:5 '"11>Jlffi(I r>y ,>l ,_,,..." 1.<fi Gi!.!! 1.3'1
`tl..'>PTO lt> Pf°''"'~ss) a<'< applit::atiu". Conf~nfulilty is g<l'ii>med b>t <i~ IJ.S.C. t22 ;!;'..ct 'St Cf:R t. M. Tnls c~OOll" ~ ;;.<o<itt"""'d II> m~* ~ minute>< I'<> '"'"'"»>!<mo,
`in<.:h>ding 91.i!.OOrln;J, preparing, and su~Tiltti.-.g t1m cro1pit<!o'<l ai>~iiCB!lon form lo Ille IJSPTO. r;,,w wi~ Y>lry de:[Je.-.di•ig "l"'"l Ill» i1Kl!vld1m! ~- An)' rommel'l'!s
`M tne llffi(<~lrt ill lJme y<>u requi~ ~ oomp:fete thi« If,,.,., "~ suooMtrons m Nlrlili::i"!l ttul> t'l.!«ien. 1ID..'>uid oo :<>M! k> Ow Cf\.'<sf lnfarmatlt>fl on~, t.1.$.. P~t
`Md Ttad<lm·~'~ OU~:e. U.S. !)apartment of C"mmerc,., f'.0. l3<.i;1145tl. ,'\!exa~til'l, VA r.~JH--14$0_ !X) Nor SF.NO F.EES OR COMPLETED FORMS TO TH!S
`."-DORESS. SEl<IO TO: Commissioner fur Pa.toots,. P.O. Boll 'f450, Afaxandna, VA 22313-1450.
`
`Date
`
`Teleplio!'ie
`
`Sandoz Inc.
`Exhibit 1002-00011
`
`Teva – Fresenius
`Exhibit 1002-00011
`
`

`
`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 3.73(b)
`
`First Applicant: NIYIKIZA Clet
`
`Entitled: NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.: X-14173B
`
`ELI LILLY AND COMP ANY, an Indiana Corporation
`(Name of Assignee)
`(Type of Assignee, e.g. corporation, partnership, university, goverrnnent 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.
`
`2.
`
`3.
`
`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, P.O. Box 1450, Alexandria, VA 22313-1450
`
`Sandoz Inc.
`Exhibit 1002-00012
`
`Teva – Fresenius
`Exhibit 1002-00012
`
`

`
`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
`
`Signature
`
`Date
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`First Applicant:
`
`NIYIKIZA Clet
`
`For:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.:
`
`X-14173B
`
`AMENDMENT AND PETITION TO CORRECT
`INVENTORSHIP UNDER 37 C.F.R. 1.48(b)
`
`Commissioner for Patents
`P.O. 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.
`
`Sandoz Inc.
`Exhibit 1002-00013
`
`Teva – Fresenius
`Exhibit 1002-00013
`
`

`
`Docket No. X-14173B
`
`-2-
`
`4. Fee Payment
`Please charge $130.00, the surcharge required by § 1.17(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
`P.O. Box 6288
`Indianapolis, Indiana 46206-6288
`
`July 11, 2007
`
`Sandoz Inc.
`Exhibit 1002-00014
`
`Teva – Fresenius
`Exhibit 1002-00014
`
`

`
`"Express Mail" mailing label number ______________ _
`
`Date of Deposit ___ __ __ __ _____ __ ___ __ _
`
`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. I.IO on the date indicated above and is addressed to the Commissioner for Patents, P.O.
`Box 1450, Alexandria, VA 22313-1450.
`
`Printed Name
`
`Signature
`
`PATENT APPLICATION
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`First Applicant:
`
`NIYIKIZA Clet
`
`Title:
`
`NOVEL ANTIFOLATE COMBINATION THERAPIES
`
`Docket No.:
`
`X-14173B
`
`I
`
`INFORMATION DISCLOSURE STATEMENT
`
`Commissioner for Patents
`P.O. 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 PT0-1449 (modified) for
`consideration by the Examiner. As permitted by 37 C.F.R. §1.98(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. 1.97(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
`P.O. Box 6288
`Indianapolis, Indiana 46206-6288
`
`July 11, 2007
`
`Sandoz Inc.
`Exhibit 1002-00015
`
`Teva – Fresenius
`Exhibit 1002-00015
`
`

`
`FORM PTO 1449 (modified)
`
`INFORMATION DISCLOSURE CITATION
`IN AN APPLICATION
`
`Atty. Docket No.
`X-14173B
`First Applicant
`NIYIKIZA Clet
`Filing Date
`
`Sheet 1 of2
`
`I Serial No
`
`I Group
`
`Examiner
`Initials*
`
`Cite
`No. l
`
`Document Number
`Number-Kind Code2 (if known)
`
`U.S. PATENT DOCUMENTS
`Pages, Columns, Lines,
`Publication Date
`Name of Patentee or
`MM-DD-YYYY
`Applicant of Cited Document Where Relevant Pages
`or Relevant Figures
`Appear
`
`AA
`
`AB
`
`AC
`
`AD
`
`AE
`
`AF
`
`AG
`
`AH
`
`Al
`
`AJ
`
`us 5,405,839
`
`us 5,431,925
`
`us 5,563,126
`
`us 5,736,402
`
`us 6,207,651
`
`us 6,297,224
`
`us 6,528,496
`
`us 03/0216350
`
`us 03/0225030
`
`us 2,920,015
`
`41 11/1995
`
`Tetsuo, et al.
`
`07/00/1995
`
`Ohmori, et al.
`
`10/8/1996
`
`417/1998
`
`3/27/2001
`
`10/2/2001
`
`3/4/2003
`
`Allen, et al.
`
`Francis, et al.
`
`Allen, et al.
`
`Allen, et al.
`
`Allen, et al.
`
`11/20/2003
`
`Allen, et al.
`
`12/4/2003
`
`01/1960
`
`Allen, et al.
`
`Thompson, Robert E.
`
`AK
`
`US 2004/0005311 Al
`
`01/2004
`
`Pitman, Bradford D.
`
`AL
`
`us 5,344,932
`
`AM
`
`us 7,053,065
`
`09/1994
`
`05/2006
`
`Taylor, Edward C.
`
`Niyikiza, et al.
`
`Examiner
`Initials*
`
`Cite
`No. 1
`
`BA
`
`FOREIGN PATENT DOCUMENTS
`Foreign Patent Document
`Name of Patentee or
`Applicant of Cited
`Country Code3 -Number 4-
`Document
`Kind Code5 (if known)
`EP 0 546 870
`
`Publication Date
`MM-DD-YYYY
`6/16/1993
`
`EPO
`
`Pages, Columns, Lines, Where
`Relevant Passages or Relevant
`Figures Appear
`
`T6
`
`Examiner
`Signature
`*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 ofUSPTO Patent Documents at W»V1v.us11to.i!ov or MPEP 901.04. 3Enter Office that issued the document, by the
`two-letter code (WIPO Standard 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 if possible. 6 Applicant is to place a check markhere 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
`
`I
`
`Sandoz Inc.
`Exhibit 1002-00016
`
`Teva – Fresenius
`Exhibit 1002-00016
`
`

`
`Sheet 2 of