(19) World Intellectual Property Organization (12) INTERNATIONAL APPLICA International Bureau (43) International Publication Date 13 July 2006 (13.07.2006) ‘TION PUBLISHED UNDER THE PATENT COOPERATION TRE: \TY (PCT) (10) International Publication Number WO 2006/074230 A3 «) an 2) es) 26) 30) am am m 7) 2006/074230 3 Ill International Patent Classification: CO7D 495/04 (2006.01) International Application Number PCT/US2006/000186 International Filing Date: 6 January 2006 (06.01.2006) Filing Language: inglish Publication Language: lish Priority Data: 601642,166 6 January 2008 (06.01.2008) US Applicant Yor all designated States except BB, US): TEVA. _GYOGYSZERGYAR —_ZARTKORUEN MUKODO RESZVENYTARSASAG [HU/HU]; Palla ‘dt 13, H-4042 Debrecen (HU) ficunt (for BB only): TEVA PHARMACEUTICALS, \, INC. [US/US]; 1090 H ORSHAM ROAD, Po.box. 1090, North Wales, Pennsylvania 19454-1090 (US), Inventors; and Inventors/Applicants (for US only): KOVACS, Lase zlo, Zsolt (HUAIU}; Jeriko U. 14, ViilS0, H-4032 Debrecen (HU). SZABO, Csaba [HU/HU]; Tozser U. 1, 180831 Debrecen (HU), MOLNARNE, Erika, Magyar [HUMTU]; Boszormenyi Ut 91 Iv/l3, 11-4032 Debrecen (HU), KOVACSNE-MEZEL, Adrienne [HU/HU]; 252 Karoli Gaspar Street, H-4032 Debecen (HU). SINGER, ‘Claude [TLL]; 8% David Elazat, 44358 Kfar Saba (IL). ARONHIME, Judith (IL/IL]; Rebov Harav Maor lose 5a, 76217 Rehovot (IL). (74) Agents: BRAINARD, Charles R. et al; KENYON & KENYON LLP, One Broadway, New York, New York 10004-1050 (US). (BL) Designated States (unless otherwise indicated, for every Kind of national protection available): AB, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH,CN, CO, CR, CU, DK, DM, DZ, EC, BE, BG, BS, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, 18, JP, KE, KG, KM, KN, KP, KR, KZ, LC, LK, LR, LS,11, LU, 1) LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI (84) Designated States (unless otherwise indicated, for every Kind of regional protection available: ARIPO (BW, GM, KE, LS, MW, MZ, NA, SD, SL, 8Z, TZ, UG, 7M, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TI, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, BS, FI, FR, GB, GR, HU, TE, 1S, IT, LT, LU, LV, MC, NL, PL, PT, RO, GN, GQ, GW, ML, MR, NE, SN, TD, TG). PL SI, SK, TR), OAPI (BE, BJ, CR, CG,CI,CM, GA, Published: — with international search report (88) Date of publication ofthe international search repor 28 December 2006 Fortwo-leiercodes and other abbreviations, refer tothe “Guid- ‘ance Notes on Codes and Abbreviations” appearing atthe begin ning of each regular issue of the PCT Gazete. © (54) Tule: METHOD OF MAKING DORZOL AMIDE HYDROCHLORIDE B (57) Abstrnct Processes for he preparation of drzalamie hydrochloride and an intermediate of Formula (IV), ae providedINTERNATIONAL SEARCH REPORT Intemational appllcation No PcT/us2006/000186 , CLASSIFICATION OF SUBJECT MATTER INV. C07D495/04 Accord ntemational Patent Classifaatlon (PO) oro bot nallonal caseclon and °C FIELDS SEARCHED co7D Timurs documentation searched (aasatialon spaanTolowed by Csslionlon sympa) ‘Docamantaon searched othr Tan minkvum gosumentalon io he sala al GG) Gooumanis are GUN Tha Tels SeaTNeG EPO-Internal loins dala base Sonaulod Gung he Waralonal ear ars Gala basa and, white pracicasoarh wre used (. DOCUMENTS CONSIDERED TO BE RELEVANT Categone (tation of document, wih ination, where approplat, othe evant passages eovant claim Ne, x Us 5 157 129 A (BLACKLOCK ET AL) 1-3,5,6, 20 October 1992 (1992-10-20) 9,10 cited in the application column 8, line 25 - line 43 A column 10, line 7 - line 22 35-52 A Us 2003/220509 Al (LOSADA PABLO GARCIA ET 1-34, AL) 27 November 2003 (2003-11-27) 53-94 cited in the application paragraph [0016] A example 8 35-52 A US 4 797 413 A (BALDWIN ET AL) 1-34, 10 January 1989 (1989-01-10) 53-94 cited in the application example 6 Furor documents ar istedin the continuation of Box [x] see pate family anno. *Sparial clepories of tod doaumens *A* document detning the general sat of he a which not ‘onaoted to boo! paula eens arlargosurent bl pushed on or afer he Inentona fing date docurantwhien may throw doubts on prorty clas) ich chet etalsn the pubcalon ele anoter ‘aon or oer spec teason (es spened) 0° document refering to an ora dscsue, use, exhbton or ‘the means “document pushed pi the inerntional fing date but Ter tha the print dele ano “7 tr document pubtshed ae the trterational ing date ‘rps ate an nl nce th fa hadi Unrsand he neo hey "x aocuront of pariclarretovance; to clams ivenon at be eonaered novel or eannol be consort inventive sop won the docu stake alone “y docament of parr celevance: the claimed invention ‘anncl bo snetderedto vole an ivanve step when the ‘document combined win one or ore siber ach coed ‘ents, such combinalon boing evs fo person sklod ine at *a¢ docamant ero he same patent fay ‘Dio oho ached eorelaton ha Wiemaonal soarch 7 August 2006 ‘ale of ang othe Tomalional seach repo 16/08/2006 Tame ane rang adress ofthe ISAT uropsan Patent Office, P15, $878 Patentan 2 INL 2200 4 Pwe “Tal (ate 70) 940-2040, Tx 81 51 opon Fae (331-70) 40-3016 “aorzedofiosr Bakboord, J Faas BETTE fran BON EID)Tntraonal application No. INTERNATIONAL SEARCH REPORT PCT/US2006/000186 Box Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet) ‘This international Search Report has not been established In respect of certain claims under Article 47(2)(a) forthe following reasons: 1. 1 cteims nos. because they relate to subject mater not raqured to be searched by this Authory, namely: 2. [] ciaims nos.: ‘because they relate to parts of the Intemational Application that do not comply withthe prescribed requirements to euch ‘an extent that no meaningful International Search can be carried au, specicaly 3. [] claims Nos because they are dependent claims and are not crated in accordance with the second and third sentences of Aule 64a. Box ll Observations where unity of invention is lacking (Continuation of item 3 of first sheet) ‘Tris international Searching Authority found multiple invention inthis international application, as follows: see additional sheet 1. [jy] Asaltrequired adetional search fees wero timely paid by the applicant, tis International Search leport covers all ‘searchatle claims. ‘As all searchable claims could be searched without effort justiyng an addtional foe, this Authority eid not invite payment ‘of any adaitonal fe. 3. [7] As only some of the required addonal search foes were timely pal by the applicant, his Interational Search Ropert LJ covers only those claims for which feos were paid, specifically ams Nos, 4. [Ll nerequted esto soar os wer pad he pean Consegety, bs nenatoral Search pa a Nae ane es en ey Pe coca Copeeriee Romark on Protest ‘The addtional search fees were accompanied by the applicants protest. [No protest accompanied the payment of adational search fees. x Form PCT/SA/210 (continuation of frst sheet (2)) (January 2004)International Applicaton No. PCT/US2006 /000186 FURTHER INFORMATION CONTINUED FROM PCTIISA/ 210 This International Searching Authority found multiple (groups of) inventions in this international apptication, as follows: 1. claims: 1-34, 53-94 Proce: for the synthesis of dorzolamide salt 2, claims: 35-52 Process of purifying dorzolamide saltINTERNATIONAL SEARCH REPORT Information on patent family membsre Intemational application No PCT/uS2006/000186 Patent document Publsation Ptent family Publication cited in search report dae members) ate Us 5157129 A 20-10-1992 CA 2040604 Al 19-10-1991 EP 0453288 AL 23-10-1991 oP 4224581 A 13-08-1992 Us 2003220509 Al 27-11-2003 AT 269338 T 15-07-2004 AU 8595801 A 22-03-2002 CA 2436185 AL 14-03-2002 DE 60103921 D1 22-07-2004 DE 60103921 T2 30-06-2005 EP 1329453 AL 23-07-2003 Wo 0220529 Al 14-03-2002 ES 2223907 T3 01-03-2005 ES 2177415 AL 01-12-2002 JP 2004508375 T 18-03-2004 Us 4797413 A 10-01-1989 NONE Fann POTENT sal fara ss ROR)