clonazepam, or a salt thereof.
`
`71
`
`16.
`
`The method of Claim 15, wherein the the mood
`
`stabilizer is carbamazapine, oxcarbamazapine,
`
`zonisamide, lamotragine, topiramate, gabapentin,
`
`levetiracetam or clonazepam, or a salt thereof.
`
`301 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`72
`
`ABSTRACT
`
`The pharmaceutical composition of the present
`
`invention comprises a carbostyril derivative which is a
`
`dopamine-serotonin system stabilizer and a mood
`
`stabilizer in a pharmaceutically acceptable carrier.
`
`The carbostyril derivative may be aripiprazole or a
`
`metabolite thereof. The mood stabilizer may include
`
`but is not limited to lithium, valproic acid,
`
`divalproex sodium, carbamazapine, oxcarbamazapine,
`
`zonisamide, lamotragine, topiramate, gabapentin,
`
`levetiracetam or clonazepam. These compositions are
`
`used to treat patients with mood disorders,
`
`particularly bipolar disorder with or without psychotic
`
`features, mania or mixed episodes. Methods are
`
`provided for separate administration of a carbostyril
`
`derivative and a mood stabilizer to a patient with a
`
`mood disorder.
`
`302 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Q81665
`Tetsuro KIKUCHI, et al.
`CARBOSTYRIL DERIVATIVES AND MOOD ...
`Filing Date: Non•mber 14, 2005
`Gordon Kit 202-293-7060
`I of8
`
`1/8
`
`(%) A8.1311'JI/\ 'v'88011'J83HJ.
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`303 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Q81665
`Tetsuro KIKUCHI, el al.
`CARBOSTYRIL DERIVATIVES AND MOOD ...
`Filing Date: November 14, 2005
`Gordon Kit 202-293-7060
`2 of8
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`304 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Q81665
`Tetsuro KIKUCHI, et al.
`CARBOSTYRIL DERIVATIVES AND MOOD ...
`Filing Date: November 14, 2005
`Gordon Kit 202-293-7060
`3 of8
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`
`305 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Q81665
`Tetsuro KIKUCHI, et al.
`CARBOSTYRIL DE RIVA TJVES AND MOOD ...
`Filing Date: No,·ember 14, 2005
`Gordon Kit 202-293-7060
`4of8
`
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`306 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Q81665
`Tetsuro KIKUCHI. et al.
`CARBOSTYRIL DERIVATIVES AND MOOD ...
`Filing Date: November 14, 2005
`Gordon Kit 202-293-7060
`5 of8
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`
`307 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`5.--~~~~~~~~~~~~~~~~~~~~~~~~---,
`
`FIG.6
`
`205r
`
`2.9171
`
`0.833
`
`-1.25
`
`-3.333
`
`~
`
`/
`
`I
`
`-2.25
`
`-5.5
`
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`I
`
`°'Cl:?'!(') ;;l
`OO:::>v;
`..., a= ;ti i:::
`ooooao; 0
`=oo
`7't.1Vl7'
`;:;·!it~;;;;;
`~~~~
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`:I:
`,:,,. ~ o--
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`
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`
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`
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`
`I I
`
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`
`I
`
`"""-~--~~~ -·
`
`)
`
`5
`
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`-7.5 ----.---r--..-----.----.---..------.----.---.----' -12
`3.6
`7.19
`0
`10.79 14.39 17.98 21.58 25.18
`28.77 32.37 35.97
`TIME (min.)
`
`308 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`..
`
`Q81665
`Tctsuro KIKUCHI, et al.
`CARBOSTYRIL DERIVATIVES AND MOOD ...
`Filing Date: No•·ember 14, 2005
`Gordon Kit 202-293-7060
`7 of8
`
`7/8
`
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`
`309 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`t
`
`\
`\
`
`•
`
`-
`
`Tetsuro KIKUCHI el I
`CARBOSTYRIL 0 a ·
`QS 1665
`Filing Date: i'o\·e.!i!:IrVl~T!~~.? AND MOOD ...
`Gordon Kil 202-293-7060, -
`::.
`8 of8
`
`8/8
`
`FIG.8
`
`,._I
`
`o
`
`/
`
`DM-1458
`
`Cl
`
`HO
`
`Cl
`I
`N~(CH2)4Q ~ N 0
`'--'
`H
`
`H03S
`
`Cl
`
`Cl
`
`3A4/206
`
`3A4/2D6
`
`H
`
`3A4
`
`H
`
`7
`
`~
`
`7
`
`0
`
`H
`
`-....::
`
`N o
`
`H
`
`Cl ~
`GI _-)=C" ~ Cl
`Cl
`Cl
`u~~N(CH>),o~rr'>o HQ,S_-·)=(-N"
`DM-1454 i
`/
`H ~ \__JN(CH2)4Q
`~ ~ ~-...;;::
`Cl
`Cl
`-
`/'.
`~ /J N\__JN(CH2)4Q
`DM-1451 i
`DM-1460
`t
`HO_)=(_ " ~
`Cl
`Cl
`~N\__JN(CH2)4Q
`59 i
`Aripiprazole )=( ~
`14
`(OPC-14597) ~rfl.J(CH>),Q~NAO
`DM-
`Cl
`3A4/206
`'--'
`3A4/2D0 )=(Cl " ~
`I
`*
`~N\._JN(CH,j,O~O
`~ H
`3A4 .
`OPC-14857
`~ h N'--'NH ~
`HOOC(H2C)3Q~~o
`
`I
`C
`
`Cl
`
`7
`
`'--'
`
`DM-1452
`
`~~(CH>),Q,(J()_O
`
`OH
`
`H
`
`Clv=CI
`-r--...
`DCPP
`
`HOOC(H,C),oW.o
`H
`OPC-3373
`
`OPC-39:2
`
`\
`C
`I
`Cl
`HO~N"NH
`'--' ~ Cl
`
`DM-1431 \
`
`Cl
`
`GluO~NJH
`
`Glucuronide of DM-1431
`
`Cl
`Cl
`H03S~N=NH
`Sulfale of DM-1 431
`
`310 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`(U) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property
`Organization
`International Bureau
`
`•
`
`!RID ID I lllH Dllllll Ii llllllBlllHll llD llllDI lllllllllmllll
`
`( 43) International Publication Date
`9 December 2004 (09.12.2004)
`
`PCT
`
`(10) International Publication Number
`WO 2004/105682 A3
`
`(51) International Patent Classilication7:
`31119, 311519
`
`A61K 31/47,
`
`(21) International Application Number:
`PCT/US2004/013308
`
`(22) International Filing Date:
`
`19 May 2004 (19.05.2004)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`(30) Priority Data:
`60/473,378
`
`English
`
`English
`
`23 May 2003 (23.05.2003) US
`
`(71) Applicant (for all designated States except US): OT(cid:173)
`SUKA PHARMACEUTICAL CO., LTD.
`[JP/JP];
`9, Kanda-Tsukasacho 2-chome, Chiyoda-ku, Tokyo
`101-8535 (JP).
`
`iiiiiiii
`
`(72) Inventors; and
`(75) Inventors/Applicants (for US only): KIKUCHI, Tetsuro
`[JP/JP); 157-13, Kawauchicho Komatsunishi, Tokushima(cid:173)
`shi, Tokushima 771-0104 (JP). IWAMOTO, Taro [JP/US];
`36 Boundinot Street, Princeton, NJ 08540 (US). HIROSE,
`Tsuyoshi [JP/JP]; 8-9-502, Sakoichibancho, Tokushima(cid:173)
`shi, Tokushima 770-0021 (JP).
`
`(74) Agents: KIT, Gordon et al.; Sughrue Mion, PLLC, 2100
`Pennsylvania Ave., N.W., Suite 800, Washington, DC
`20037-3213 (US).
`
`(81) Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN,
`CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI,
`GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE,
`KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD,
`MG, MK, MN, MW, MX, MZ, NA, NI, NO, NZ, OM, PG,
`PH, PL, Pf, RO, RU, SC, SD, SE, SG, SK, SL, SY, TJ, TM,
`TN, TR, TI, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM,
`zw.
`
`(84) Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM,
`ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM),
`European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI,
`FR, GB, GR, HU, IE, IT, LU, MC, NL, PL, PT, RO, SE, SI,
`SK, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
`GW, ML, MR, NE, SN, TD, TG).
`
`Published:
`with international search repon
`
`[Continued on next page]
`
`-iiiiiiii
`!!!!!!!! == -iiiiiiii = iiiiiiii -
`- ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~-
`
`(54) Title: CARBOSTYRIL DERIVATIVES AND MOOD STABILIZERS FOR TREATING MOOD DISORDERS
`
`!!!!!!!!
`iiiiiiii
`
`iiiiiiii ----
`
`N
`QC
`
`210
`
`~
`
`w a: i w a.
`
`~
`
`8
`
`3
`
`0
`
`-3
`
`-6
`
`..g
`
`>
`::s.
`
`3.92"
`
`-225
`
`~
`~ ::i;:
`-5.5 ~
`8
`::i;: a:
`w
`j;
`
`-6.75
`
`10
`
`-12 ~-~-.....---.---.---.---.....---.--.---..----' -12
`0
`3.6
`7.19
`10.79 14.39 17.98 21.58 25.18 2/J.77 32..31 35.97
`TIME{mln.)
`
`141.e't
`
`\C "' = ~
`= (57) Abstract: The phannaceutical composition of the present invention comprises a carbostyril derivative which is a dopamine-sero-
`~
`= tonin system stabilizer and a mood stabilizer in a pharmaceutically acceptable carrier. The carbostyri) derivative may be aripiprazole
`N or a metabolite thereof. The mood stabilizer may include but is not limited to lithium, va1proic acid, diva1proex sodium, carbamaza-
`0 pine, oxcarbamazapine, zonisamide, lamotragine, topiramate, gabapentin, levetiracetam or clonazepam. These compositions are
`
`::;..,.. used to treat patients with mood disorders, particularly bipolar disorder with or without psychotic features, mania or mixed episodes.
`_..,. Methods are provided for separate administration of a carbostyril derivative and a mood stabilizer to a patient with a mood disorder.
`
`311 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`'
`
`w o 200411 os6s2 A3
`
`1 mu11m1mH1111~m um um1uirn m~mnnm11111111111n11111n~ mm on
`
`(88) Date of publication of the international search report:
`12 May2005
`
`For two-letter codes and other abbreviations, refer to the "Guid(cid:173)
`ance Notes on Codes and Abbreviations" appearing at the begin(cid:173)
`ning of each regular issue of the PCT Gazette.
`
`312 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`..
`
`INTERNATIONAL SEARCH REPORT
`
`International application No.
`
`PCT/US04/ 13308
`
`A.
`CLASSIFICATION OF SUBJECT MATIER
`: A61K 31/47; A61K 31/19; A61K 31/519
`IPC(l)
`:
`USCL
`5141310
`Accordinl!. to International Patent Classification m>M or to both national classification and IPC
`B.
`FIELDS SEARCHED
`Minimum documentation searched (classification system followed by classification symbols)
`U.S. : 514/310; 514/557; 5141299
`
`Documentation searched other than mininmm documentation to the extent that such documents are included in the fields searched
`
`Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
`CAPLUS; MEDLINE; EA.ST
`
`c.
`DOCUMENTS CONSIDERED TO BE RELEVANT
`Category*
`Citation of document, with indication, where appropriate, of the relevant passages
`x
`WO 02/087590 Al (ORTHO-MCNEIL PHARMACEUTICAL, INC.) 7 November 2002
`(07.111.2002 page 4, lines 17-21; page 5 lines 5-10, 31-32; page 8, lines 4-11.
`x
`US 2003/0109546 Al (FENTON) 12 June 2003 (12.06.2003). see entire document, page
`-
`2 [0013]; [0017; [0032.
`p
`
`Relevant to claim No.
`1-5, 12-16
`
`1-5, 12-16
`
`x
`-
`p
`
`y
`
`y
`
`y
`
`y
`
`WO 03/066039 Al (ABBOT LABORATORIES) 14 August 2003 (14.08.2003), page 5,
`lines 33-35; page 16 lines 40-42; pae 15, lines 10-13.
`
`1-5, 12-16
`
`WO 00/59489 A2 (SEPRACOR, INC.) 12 October 2000 (12.10.2000), page 4, lines 7-12;
`pae 6, lines 14-18; pae 7, lines 5-10/
`WO 99/62522 Al (ELI LILLY AND COMPANY) 9 December 1999 (09.12.1999), page
`3, line 6-page 4; line 30, pae 7, line 12-17.
`GORDON et al. Mood Stabilization and weight loss with Topi.nunate, American Journal
`
`of Psychiatry, June 1999, Vol. 156, No. 6, pages 968-969, see pages l and 2.
`
`WO 97/35584 Al (ELI LILLY AND COMPANY) 2 October 1997 (02.10.1997), see page
`2, lines 9-15, and lines 34-36
`
`1-5, 12-16
`
`1-5, 12-16
`
`1-5, 12-16
`
`1-5, 12-16
`
`·~ Further documents are listed in the continuation of Box C. D
`•
`•A•
`
`Special categories of cited clocumcnta:
`
`documait defining !he general state of the art which Is not CODSidcred to be
`of particular relevance
`earlier application or patent publlshed on or aftec the intemadooal filing date
`document which may throw doubts on priority claim(&) or which ls cited to
`establish lhe publication date of another citation or other special reason {as
`specified)
`
`"B"
`
`"L"
`
`"T"
`
`"X"
`
`•y•
`
`See patent family annex.
`la!er document published after !he international filing date or priority
`date and not in conflict with lhe application but cited to undcnuand the
`princ!ple or theory underlying lhe invention
`document or panlcular relevance; Iba claimed invention cannot be
`considered DO\ICI or cannot be considered to involve an inventive step
`when the document is taken alone
`
`document oC panicular relevance; the clabned invention cannot be
`considered to Involve an inventive step when the document is
`combined wllh one or more other such documents, such cambination
`being obvious to a person skilled In the art
`
`·Be
`
`document member of lhc same patent famll)•
`
`Date onur ~~r mn~onal search report
`
`Aulborizodoffi= r¥- ~ f7
`
`Sreeni Padmanabhan
`
`•
`
`Telephone No. 571-272-1600
`
`"0"
`
`document referring to an oml disclmure, use, exhibition or other means
`
`"P"
`
`docmnent published prior to the International fding date but later than the
`priority date claimed
`
`Date of the actual completion of the international search
`
`OS December 2004 (05.12.2004)
`Name and mailing address of the ISA/US
`Mail Stop PCT, Attn: ISA/US
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`Facsimile No. (703) 305-3230
`Form PCT/ISA/210 (second sheet) (July 1998)
`
`313 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`INTERNATIONAL SEARCH REPORT
`
`PCT/US04/13308
`
`C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT
`
`Categoty.
`
`A
`
`Citation of document, with jndicetion where appropriate, of the relevant passages
`
`Relevant to claim No.
`
`BALD:ESSARINI et al. Hospital Use of Antipsychotic Agents in 1989 and 1993: Stable
`Dosing with Decreased Length of Stay, American Journal of Psychiatry, July 1995. Vol.
`152, No. 7, pages 1038-1044, seepaes 1-8.
`
`1-5, 12-16
`
`Form PCTnSA/210 (second sheet) (July 1998)
`
`314 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`INTERNATIONAL SEARCH REPORT
`
`International application No.
`
`I
`
`PCT/US04/133f- 8
`~~-----..-------i
`Box No. II Observations where certain claims were found unsearchable (Continuation of item 2 of first
`sheet)
`This international search report bas not been established in respect of certain claims under Article 17(2)(a) for the following
`reasons:
`
`1. D Claims Nos.:
`
`because they relate to subject matter not required to be searched by this Authority, namely:
`
`2. D Claims Nos.:
`
`because they relate to parts of the international application that do not comply with the prescribed requirements to
`such an extent that no meaningful international search can be carried out, specifically:
`
`3. ~
`Claims Nos.: 6-11
`because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule
`
`6.4(a).
`Box No. m Observations where unity of invention is lacking (Continuation of item 3 of first sheet)
`
`This International Searching Authority found multiple inventions in this international application. as follows:
`
`1. D
`2. D
`3. D
`
`As all required additional search fees were timely paid by the applicant, this international search report covers all
`searchable claims.
`As all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite
`payment of any additional fee.
`As only some of the required additional search fees were timely paid by the applicant, this international search
`report covers only those claims for which fees were paid, specifically claims Nos.:
`
`4. D No required additional search fees were timely paid by the applicant. Consequently, this international search report
`
`is restricted to the invention first mentioned in the claims; it is covered by claims Nos.:
`
`Remark on Protest 0
`D No protest accompanied the payment of additional search fees.
`
`The additional search fees were accompanied by the applicant's protest.
`
`Fonn PCT/ISA/210 (continllation of first sheet(2)) (January 2004)
`
`315 of 1328
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`
`

`
`10/5 56 600
`JC14 Rgc'd rc~~/?TO 14 NOV 2005
`
`PATENT APPLICATION
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re application of
`
`Tetsuro KIKUCHI, et al.
`
`Appln. No.: Based on PCT/US2004/013308
`
`Docket No: QS 1665
`
`Confirmation No.: Unknown
`
`Group Art Unit: Unknown
`
`Filed: November 14, 2005
`
`Examiner: Unknown
`
`For:
`
`CARBOSTYRIL DERIVATIVES AND MOOD STABILIZERS FOR TREATING
`MOOD DISORDERS
`
`INFORMATION DISCLOSURE STATEMENT
`UNDER 37 C.F.R. §§ 1.97 and 1.98
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`In accordance with the duty of disclosure under 37 C.F.R. § 1.56, Applicant hereby
`
`notifies the U.S. Patent and Trademark Office of the documents which are listed on the attached
`
`PTO/SB/08 A & B (modified) form and/or listed herein and which the Examiner may deem
`
`material to patentability of the claims of the above-identified application.
`
`One copy of each of the listed documents is submitted herewith, along with a copy of the
`
`corresponding Communication from a Foreign Patent Office, except for the following: U.S.
`
`patents and/or U.S. patent publications; and co-pending non-provisional U.S. applications filed
`
`after June 30, 2003.
`
`The present Information Disclosure Statement is being filed: (1) No later than three
`
`months from the application's filing date; (2) Before the mailing date of the first Office Action
`
`316 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`-
`
`10/556600
`JC14 Rec'd PCT/PTO 14 NOV 2005
`
`INFORMATION DISCLOSURE STATEMENT
`U.S. Appln. No.: Based on PCT/US2004/013308
`
`on the merits (whichever is later); or (3) Before the mailing date of the first Office Action after
`
`filing a request for continued examination (RCE) under§ 1.114, and therefore, no Statement
`
`under 37 C.F.R. § 1.97(e) or fee under 37 C.F.R. § 1.17(p) is required.
`
`The submission of the listed documents is not intended as an admission that any such
`
`document constitutes prior art against the claims of the present application. Applicant does not
`
`waive any right to take any action that would be appropriate to antedate or otherwise remove any
`
`listed document as a competent reference against the claims of the present application.
`
`The USPTO is directed and authorized to charge all required fees, except for the Issue
`
`Fee and the Publication Fee, to Deposit Account No. 19-4880. Please also credit any
`
`overpayments to said Deposit Account. A duplicate copy of this paper is attached.
`
`SUGHRUE MION, PLLC
`Telephone: (202) 293-7060
`Facsimile: (202) 293-7860
`WASHINGTON OFFICE
`
`23373
`
`CUSTOMER NUMBER
`
`Date: November 14, 2005
`
`2
`
`317 of 1328
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`
`

`
`-
`
`Substitute for Form 1449 A & B/PTO
`
`INFORMATION DISCLOSURE
`STATE1\1ENT BY APPLICANT
`
`(use as many sheets as necessary)
`
`Sheet
`
`I I
`
`I or I 2
`
`14 NOV 2005_
`
`MODIFIED PTOISBI08 A & B (06-03)
`Complete if Known
`Application Number
`Based 011. PCT /US2004/013 308 _
`Unknl~ / I'.) I') n h 11 I I
`Confirmation Number
`November I4,-2005 -
`Filing Date
`First Named Inventor
`Tetsuro KIKUCHI
`Art Unit
`Unknown
`Examiner Name
`Unknown
`Attorney Docket Number Q81665
`
`Document Number
`
`U.S. PATENT DOCUMENTS
`
`Examiner
`Initials*
`
`Cite
`No. 1
`
`Number
`
`us 2003/0109546
`us 5,006,528
`us 2002/0173513
`us 2003/0027817
`us 2001/0023254
`us
`
`Kind
`Code1
`(if known)
`Al
`
`Al
`Al
`Al
`
`Publication Date
`MM-DD-YYYY
`
`Name of Patentee or Applicant of Cited Document
`
`06-12-2003
`04-09-1991
`11-21-2002
`02-06-2003
`09-20-2001
`
`Wavne S. Fenton
`Yasuo Oshiro, et al.
`Shaun Jordan, et al.
`Gary Dennis Tollefson
`Susan L. McEJroy
`
`Examiner
`Initials*
`
`Cite
`No.1
`
`FOREIGN PATENT DOCUMENTS
`Foreign Patent Document
`Kind Code3
`(if known)
`
`Publication Date
`MM-DD-YYYY
`
`Name of Patentee or
`Applicant of Cited Document
`
`Translation•
`
`Country
`Code3
`
`Number•
`
`WO
`
`WO
`WO
`WO
`WO
`
`EP
`
`WO
`
`WO
`
`EP
`
`02/087590
`
`03/066039
`00159489
`99/62522
`97/35584
`
`0367141
`
`02/060423
`
`03/026659
`
`0966967
`
`Al
`
`Al
`A2
`Al
`Al
`
`A2
`
`A2
`
`Al
`
`A2
`
`11-07-2002
`
`08-14-2003
`10-12-2000
`12-09-1999
`10-02-1997
`
`05-09-1990
`
`08-08-2002
`
`04-03-2003
`
`12-29-1999
`
`ORTHO-MCNEIL
`PHARMACEUTICAL, INC.
`ABBOTT LABO RA TORIES
`SEPRACOR INC.
`ELI LILLY AND COMPANY
`ELI LILLY AND COMPANY
`OTSUKA PHARMACEUTICAL
`CO., LTD.
`OTSUKA PHARMACEUTICAL
`CO., LTD.
`OTSUKA PHARMACEUTICAL
`CO., LTD.
`ELI LILLY AND COMP ANY
`
`Examiner
`Initials*
`
`Cite
`No. 1
`
`NON PATENT LITERATURE DOCUMENTS
`Include name of the author (in CAPITAL LETTERS}, title or the article (when appropriate), title or the item (book, magazine,
`journal, serial, symposium, catalog, etc.), date, page(s}, volume-issue number(s), publisher, city, and/or country where published.
`GORDON et al., Mood Stabilization and weight loss with Topiramate, American Journal of Psychiatry,
`June 1999, Vol. 156, No. 6, pages 968-969, see pages I and 2.
`BALDESSARINI et al, Hospital Use of Antipsychotic Agents in 1989 and 1993: Stable Dosing with
`Decreased Length of Stay, American Journal of Psychiatry, July 1995, Vol. 152, No. 7, pages I 038-1044,
`see pages 1-8.
`JACOBSEN et al., Risperidone in the Treatment of Affective Illness and Obsessive-Compulsive Disorder,
`Journal of Clinical Psychiatry, September 1995, Vol. 56, No. 9, oo. 423-429
`WEISLER et al., Adjunctive Use ofOlanzapine in Mood Disorders: Five Case Reports, Annals of Clinical
`Psvchiatrv, 1997, Vol. 9, No. 4, oo-259-262
`
`Translation•
`
`Examiner Signature
`
`Date Considered
`
`•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 fonn with ne.<1 communication to applicant.
`
`'Applicant's unique citation designation number (optional). 'See Kind Codes ofUSPTO Patent Documents at www.uspto.gov, MPEP 901.04 or in t11e comment box of this document. 'Enter
`Office that issued the document, by the two-letter code {WIPO Standard ST. 3). 'For Japanese patent documents, the indication of the year of the reign of the Emperor must precede the serial
`number of the patent document. 'Kind of document by the appropriate symbols as indicated on the document under WIPO Standard ST. 16 if possible. 6 Applicant is to indicate here if English
`language Translation is attached.
`
`318 of 1328
`
`Alkermes, Ex. 1076
`
`

`
`Substitute for Form 1449 A & B/PTO
`
`INFORMATION DISCLOSURE
`STATEi\.1ENT BY APPLICANT
`
`(use as many sheets as necessary)
`
`Sheet
`
`12
`
`I of I 2
`
`JC14 Rec'd PCT!PTO 14 NOV 2005
`
`MODIFIED PTO/SB/08 A & B (06-03)
`
`Complete if Kn~v!.l.. -- -
`- - -
`Unkno~l I I _., lo") f'i h I J r r
`Application Number
`Confirmation Number
`UnknO\Vn
`Filing Date
`November 14, 2005
`Tetsuro KIKUCHI
`First Named Inventor
`Art Unit
`Unknown
`Examiner Name
`Unknown
`Attorney Docket Number Q81665
`
`Document Number
`
`U.S. PATENT DOCUMENTS
`
`Examiner
`Initials*
`
`Cite
`No. 1
`
`Number
`
`us
`us
`us
`
`Kind
`Code2
`(if known)
`
`Publication Date
`MM-DD-YYYY
`
`Name of Patentee or Applicant of Cited Document
`
`Examiner
`Initials*
`
`Cite
`No.'
`
`FOREIGN PATENT DOCUMENTS
`Foreign Patent Document
`Kind Code5
`(if known)
`
`Publication Date
`MM-DD-YYYY
`
`Name of Patentee or
`Applicant of Cited Document
`
`Translation•
`
`Country
`Code3
`
`Number4
`
`Examiner
`Initials*
`
`Cite
`No. 1
`
`NON PA TENT LITERATURE DOCUMENTS
`Include name of the author (in CAPITAL LETTERS), tille of the article (when appropriate), title of the item (book, magazine,
`journal, serial, sym1>osium, catalog, etc.), date, page(s), •·olume-issue number(s), publisher, city, and/or country where published.
`MCELROY et al., Clozapine in the Treatment of Psychotic Mood Disorders, Schizoaffective Disorder, and
`Schizophrenia, J. Cl in. Psychiatry, October 1991, Vol. 52, No. I 0, DD. 411-414
`CITROME et al., Pharmacokinetics and Safety of Aripiprazole and Concomitant Mood Stabilizers, 2002,
`Vol. 5, Sunni. I, page Sl87 (P.4.E. 035)
`MOELLER et al., Treatment ofBioolar Disorder, J. Clin. Psvchiatrv, 2003, Vol. 64, Sunni. 6, DD. 9-17
`KOW A TCH et al., The Use of Mood Stablizers and Atypical Anti psychotics in Children and Adolescents
`with Bipolar Disorders, CNS Spectrums, April 2003, Vol. 8, No. 4, DD. 273-280
`
`Translation•
`
`Examiner Signature
`
`Date Considered
`
`•EXAMINER: Initial if reference considered, whether or not citation is in confommnce with MPEP 609. Draw line through citation if not in conformance and not considered. Include copy of
`thls form \\'lth ne.\t communication to applicanl.
`
`1 Applicant's unique citation designation number (optional). 'See Kind Codes of USPTO Patent Documents at www.uspto.gov, MPEP 901.04 or in the comment box of this document 'Enter
`Office Iha! issued the document, by the two-letter code (WIPO Standard ST. 3). 'For Japanese paten! documents, the indication of the year of the reign of the Emperor must precede the serial
`number of the patem document. 'Kind of document by the appropriate symbols as indicated on the document under WIPO Standard ST. 16 if possible. 6 Applicant is to indicate here if English
`language Translation is attached.
`
`319 of 1328
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`
`

`
`vJ \ bb 1- o'O
`
`• (ll) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) World Intellectual Property Organization
`Intemationa1 Bureau
`
`•
`
`1m111111mmm111111111111R111m1m1111D11DIDD
`
`(43) loternational Publication Date
`7 November 2002 (07.11.2002)
`
`PCT
`
`(10) lotematiooal PubUcatioo Number
`WO 02/087590 Al
`
`(51) loteroatiooal Patent Classificatloo7: A61K 31/5513,
`3USl9, 31135, A61P 25118
`
`(21) loteroatiooal Application Number: PCTIUS02/12997
`
`(22) loteroatiooal Yaliog Date:
`
`23 April 2002 (23.04.2002)
`
`(25) Filing Language:
`
`(26) Publication Language:
`
`English
`
`English
`
`(30) Priority Data:
`601286,765
`60/301,661
`
`26 April 2001 (26.04.2001) us
`28 June 2001 (28.06.2001) US
`
`(71) Applicant: ORrHO-MCNEIL PHARMACEUTICAL,
`INC. [US/US]; U.S. Route #202, Raritan, NJ 08869-0602
`(US).
`
`(81) Designated States (naJJonaJ): AH, AG, AL. AM, AT, AU,
`AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR. CU,
`CZ. DE. DK. DM, DZ, EC, EE, F.S, Fl, GB, OD, OE, GH.
`GM, HR. HU, ID, Il,, IN, IS, JP, KB. KG, KP. KR. KZ. LC.
`LK, LR, l.S, LT, LU, LV, MA, MD, MG, MK, MN, MW,
`MX. MZ. NO, NZ, OM, PH. PL. PT, RO, RU, SD, SE, SG,
`·SI. SK, SL, TJ, TM, TN, TR, TT, 1Z, UA, UG, UZ. VN,
`YU, ZA, ZM, ZW.
`
`(84) Designated States (regional): ARIPO patent (OH, GM,
`KE, l.S, MW, Mz, SD, SL, SZ, Tz, UG, ZM, ZW),
`Bmasian patent (AM, AZ. BY. KO, KZ. MD, RU, TJ, TM),
`European patent (AT, BE, CH, CY, DE. DK. F.S, Fl, FR,
`GB, GR, IE., IT, LU, MC, NL, PT, SE,, TR), OAPI patent
`(BF. BJ, CF, CG, CI, CM, GA. GN, GQ, GW, ML, MR,
`NH, SN, TD, TG).
`
`Published:
`with international search report
`before the expiration of the lime limit for amending the
`claims and to be republished in the evenl of receipt of
`amendmel'lls
`
`For twcr/e/ler codes and other abbreviations, refer to the "Guid(cid:173)
`ance Notes on Codes and Abbreviations" appearing at the begin(cid:173)
`ning of each regular issue of the FCT Gazette.
`
`-
`-
`iiiiiii
`
`(72) loveotor: FENTON, Wayne. S.; 11602 Parle Edge Drive.
`Rockville, MD 208S2 (US).
`
`: : (74) Agents: .JOHNSON, Philip, S. et al.; Johnson & Johnson.
`
`;;;;;;;;;;;;;;
`
`(US).
`
`e:;:; ---
`= One Johnson & Johnson Plaza, New Btunswick, NJ 08933
`= !!!!!!!! == ---
`------== = --~
`
`,-4 <
`= O'\ -n
`--N
`= TIVES AND ATYPICAL ANTIPSYCHCJilCS
`0
`
`l""-(cid:173)
`QO
`=~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
`(54) Title: TREA1MENTOFPSYCHanc DISORDERSCOMPRISINOCO-THERAPYWTrH ANTICONVULSANTDERIVA-
`
`:::;;..... (57) Abstract: Treatment of psychotic disorders such as schizophrenia, schizophreniform and schizoaffective disorders comprising
`.-... co-therapy with an anticonvulsant derivative and atypical antipsychotic.
`
`320 of 1328
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`

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`PCT/USOl/12997
`
`TREATMENT OF PSYCHOTIC DISORDERS COMPRISING CO-THERAPY WITH
`ANTICONVULSANT DERIVATIVES AND ATYPICAL ANTIPSYCHOTICS
`
`5
`
`10
`
`CROSS REFERENCE TO RELATED APPLICATION
`This application claims priority from United States provisional application Serial
`No. 60/286,765, filed April 26, 2001 and United States provisional application Serial
`No. 601301.661. filed June 28, 2001, the contents of which are hereby incorporated by
`reference.
`
`BACKGROUND OF THE INVENTION
`Compounds of Formula (I):
`
`Rs_(xyCH20S02NHR1
`.
`
`. r-< ~R2
`
`15
`
`25
`
`R3
`R4
`{I)
`are structurally novel antiepileptic compounds that are highly effective
`anticonwlsants in animal tests (MARYANOFF. B.E, NORTEY. S.0., GARDOCKI,
`J.F., SHANK, R.P. AND DODGSON, S.P. J. Med. Chem. 1987, 30, 880-887;
`MARYANOFF, B.E., COSTANZO, M.J., SHANK, R.P., SCHUPSKY, J.J., ORTEGON.
`M.E., AND VAUGHT J.L. Bioorg. M_ed. Chem. Lett. 1993. 3, 2653-2656; SHANK, R.P.,
`GARDOCKI, J.F., VAUGHT, J.L., DAVIS. C.B .• SCHUPSKY, J.J .• RAFFA. R.B.,
`DODGSON, S.J., NORTEY, S.O., MARYANOFF, B.E. Epilepsia 1994. 35, 450-460;
`20 MARYANOFF BE, COSTANZO MJ, NORTEY SO, GRECO MN, SHANK RP,
`SCHUPSKY JJ, ORTEGON MP, VAUGHT JL J. Med. Chem. 1998, 41, 1315-1343).
`These compounds are covered by three US Patents: No.4,513,006, No.5,242,942,
`and No.5,384,327. One of these compounds 2,3:4,5-bis-0-(1-methylethylidene)-B-D(cid:173)
`fructopyranose sulfamate known as topiramate has been demonstrated in clinical trials
`of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating
`simple and complex partial seizures and secondarily generalized seizures (E.
`FAUGHT, B.J. WILDER, R.E. RAMSEY, R.A. REIFE, L D. KRAMER, G.W.
`PLEDGER, R.M. KARIM el al., Epilepsia 1995, 36 (S4), 33; S.K. SACHDEO. R.C.
`SACHDEO, R.A. REIFE, P. LIM and G. PLEDGER. Epilepsia 1995, 36 (S4). 33; T.A.
`30 GLAUSER, Epilepsia 1999, 40 (S5), S71-80; R.C. SACHDEO, Clin. Pharmacokinet.
`1998, 34, 335-346), and is currently marketed for ttie treatment of seizures in patients
`with simple and complex partial epilepsy and seizures In patients with primary or
`
`1
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`321 of 1328
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`secondary generalized seizures in the United States, Europe and most other markets
`throughout the world.
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`Compounds of Formula (I) were initially found to possess antlconwlsant
`actMty in the traditional maximal electroshock seizure (MES) test in mice (SHANK,
`R.P., GARDOCKI, J.F., VAUGHT, J.L. DAVIS, C.B., SCHUPSKY, J.J., RAFFA. R.B.,
`DODGSON, S.J., NORTEY. S.O., and MARYANOFF, B.E., Ep11epsia 1994, 35, 450-
`460}. Subsequent studies revealed that Compounds of Fonnula I were also highly
`effective in the MES test in rats. Topiramate was also found to effectively block
`seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA, T.
`KANDA, A. ISHll, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M. SASA, Eur. J.
`Pharmacol. 1994, 254 ... 83-89), and in an animal model of kindled epilepsy {A.
`WAUQUIER and S. ZHOU, Epilepsy Res. 1996, 24. 73-77).
`
`More recenUy, Shank, RP in U.S. Patent No. 5,753,693 disdoses the use of
`compounds of formula (I) for the treatment of bipolar disorder. van Kammen, DP in
`WIPO publication WO 00/32183 disdoses the use of compounds of formula (I) for the
`treatment of schizophrenia.
`
`Psychotic disorders are those that are predominantly characterized by
`psychosis. Psychotic disorders include schizophrenia, schizophreniform disorder,
`schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic
`disorder. psychotic disorder as a result of a general medical condition, substance(cid:173)
`induced psychotic disorder, and psychotic disorder not otherwise specified (Diagnostic
`and Statistical Manual of Mental Disorders, Ed. 41t1, American Psychiatric Association,
`Washington, DC 1994; Kaplan & Sadock's Comprehensive Textbook of Psychiatry,
`Seventh Edition, Volume I, Lippincott Williams & Wilkins: Philadelphia, pp. 825, 2000).
`
`According to the American Psychiatric Association, the term •psychoticn means
`grossly impaired in reality testing. Gross impairment in reality testing is defined as
`existing when individuals incorrectly evaluate the accuracy of their perceptions and
`thoughts, and make incorrect inferences about external reality, even in the face of
`contrary evidence. The term "psychotic" is also appropriate when behavior is so
`disorganized that it is reasonable to infer that reality testing is grossly disturbed, for
`example, when there is markedly incoherent speech without apparent awareness by
`the person that the speech is not understandable, or when agitated, inattentive, and
`
`2
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`disoriented behavior is observed in the phencyclidine psychotic disorder (Diagnostic
`and Statistical Manual of ~ental Disorders. Ed. 4°', American Psychiatric Association.
`Washington, DC 1994; Kaplan & Sadock's Comprehensive Textbook of Psychiatry,
`Seventh Edition. Volume I, Lippincott Williams & Wilkins: Philadelphia, pp. 825, 2000).
`
`s
`
`· ·
`
`--. .10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`Schizophrenia is a group of illnesses that are phenomenologically and
`etiologically heterogeneous and which are characterized by perturbati