PATENT COOPERATION TREATY PCT INTERNATIONAL PRELIMINARY REPORT ON PATENTABILITY (Chapter I of the Patent Cooperation Treaty) (PCT Rule 44bis) Applicant's or agent's fle reference FOR FURTHER ACTION See Hem 4 below Jop110923, Tntemational application No. Taemational filing date (day’montivvenr) Priority date (dayrmonthivear) PTICN2011/081324 [26 October 2011 (26.10.2011) [27 October 2010 (27.10.2010) Tnvemational Patent Classification Git edition unless older edition indicated) [See relevant information in Form PCT/ISAI237 Npplicant [ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD. 1, "This international pretiminary report on patentability (Chapter I) is issued by the International Bureau on behalf of the Intemational Searching Authority under Rulle 4 bis.1(@) This REPORT consists of a total of 6 sheets, including this cover sheet In the atached sheets, any reference to the writen opinion of the International Searching Authority should be read as a reference to the international preliminary report on patentability (Chapter |) instead 3, This report contains indications relating o the following items: RQ wnot Basi ofthe report Box No. Non-esablishment of opinion with regard to novel, inventive sep and indus torte Box No.1 Lack of nity of invention Bea nov Reason statement under Ale 35@) with regard wo novel inventive tp or Indust aplcigy, claon ane cplanaios sopping ah sateen Box No. VIL eran defects inthe iteration pion Box No, VIL ‘ain observations on the international application 4, ‘The International Bureau will communicate this report to designated Offices in accordance with Rules 44bis:3(¢) and 93bis.1 but not, except where the applicant makes an express request under Article 23(2), before the expiration of 30 months from the priority date (Rule 44bis 2, Date of fssance of dhs report 20 April 2013 (30.04.2013) Authorized officer The Intemational Bureau of WIPO 34, chemin des Colombettes 1211 Geneva 20, Switzerland Lingfei Bai Facsimile No, +41 22 338 82 70 e-mail: px02.pet@wipo.int Form PCTABVS7S (January 2004)PATENT COOPERATION TREATY ome INTERNATIONAL SEARCHING AUTHORITY Te kg PCT 2% a WRITTEN OPINION OF THLE INTERNATIONAL SEARCHING AUTHORITY erate dH.) Davot mag (dew’monthivear) 49+ 01.2012 Saat ga TS Scan 0P110923 ‘See paragraph 2 below Ina appa Tara gar daa a eT PCT/CN2011/081324 26.10.2011 27.10.2010 ateratonal Patent Clasiicaton IPC) or bth mana clasicaton and PC C07D401/1482006.01) 4 pane ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD. 1. This pinion contains indications eating othe following ms Box No.1 Basis of the opinion Box No. Priotty Bon No. Ill Nonstablishment of opinion with rear to novel Box No, Retsoned satemeat under Role 43.14) with Box No. VI Certain documents cited Box No. VIL Cetin defects i he international ppticaion O00 XOOOR ox No, VII Certain observations on the ftrnatioal aplication FURTHER ACTION In than this one toe the IPEA andthe chosen IPE fas ified the Feri this Inerstional Searching Authity wil a be so consiere PCTISA Fc fart opin ee Form PCTISA20, Jor before the expiration of 2 mond fo 2. Fartcr details sce notes o Favra PCTISA/20. ato novelty, inventive sep or indi pplicabiiyitations ar explanations supporting sch alee If 8 demand for intentional preliminary examination i made, this opinion willbe considers to be a writen opinion of the nana Preliminary Examining Authority CTPEA") excep tha this does ot apply where the applicant sexes an Author ater a rea wer Roe 850) that writen opinions of 1 this opinion i, as povided above, considered 1 be a ite opinion ofthe PEA, the applica i avted w sant the PEA writen rpiytogehcr where appropri, with amendments, before the expation of 8 ts from the dat of mailing of Form init dat, whichever expires le, Nam and mang advss ofthe SAIN ats of complstuon of opinion Fecsmile No, Tatras oer Telephone No. Forni PCTIASA297 (omer set) (Ape 2007)WRITTEN OPINION OF TI Taieratal appaion No INTERNATIONAL SEARCHING AUTHORITY PCT/CN2011/081324 BoxNo.T Basia his opinion 1. _Widhegard oe ngage. hs opinion as been established onthe bass of EX) tenets aplication in he ngage in wich ws fil ‘rslaton Frise forthe purposes of iteration seaech (Roles 12a) and 23.10), which she kinguage of This opinion hasbeen established taking into account the retifea Aor nder Re 91 Rk 43546 18) rg vious mistake sured by ce noted to this 3. With regu to any muleotde andor amin aid sequence dls inte immatoslapston and nessary tthe lined Ibreain ts opbuon hase nabsed one fs 2 eof omer Ly seus iting format ot matia LO conser tine of lingamishing [1 conain ite ineraionl pplication as id [Etomite bgp hs Anthro he purposes fers 4 [1] traction, ne ca ht ethane versio copy of cubes Hing and ub) ating ets es ftenshed the required statements hatte information in the subsequent or aoa copies i mt fo tha nthe pation as filed or des not go beyond the application as ils, appropri, wee ished 5. Additional comment: Forni PCTISAL237 (ou No. CApil 2007)a TreatoaT appicaion No INTERNATIONAL SEARCHING AUTHORITY PCT/CN2011/081324 BoxNe, V__Reasoned statement under Rule 435121()() with regard to novelty inventive dp oF industrial apy: ilations and explanations supporting such statement 1 Statemea Novelty (8) chim 1-10 ves cis No Inventive step 1S) chim: 1-10 ves Cian No Indosial applicailiy TA) hing 1 ves cis No ‘Graton and explanations 2.1 Reference is made to the following documents: D1: WO2010054056A2 (TEVA PHARMACEUTICALS INDUSTRIES LTD.) 14 May 2010 (14.05.2010) D2: WO2007015871A1 (NOVARTIS AG) 08 February 2007 (08.02.2007) D3: WO2007015870A2 (NOVARTIS AG) 08 February 2007 (08.02.2007) 2.1 Novelty Claim 1 of the present application sets forth a Nilotinib hydrochloride crystal with X-ray diffraction pattern data as depicted in table 1, D1 discloses a series of crystals of Nilotinib hydrochloride (see claims 1-39 and figs. 1-24). The X-ray diffraction pattern of the crystal of Nilotinib hydrochloride disclosed by D1 is different from the x-ray diffraction pattern of the Nilotinib hydrochloride crystal of claim 1, Therefore, the Nilotinib hydrochloride crystal Form PCTISAI237 (Box No. V} (Apail 2007),a TreatoaT appicaion No INTERNATIONAL SEARCHING AUTHORITY PCT/CN2011/081324 BoxNe, VReasoned statement under Rule 435121()(0 with regard to novelty, inventive dp oF industrial apply: ilations and explanations supporting such statement disclosed by Dl is different from the Nilotinib hydrochloride crystal disclosed by claim 1. D2 also discloses a series of crystals of Nilotinib hydrochloride (see claims 1-17 and figs. 1-8). The X-ray diffraction pattern of the crystal of Nilotinib hydrochloride disclosed by D2 is different from the X-ray diffraction pattern of the Nilotinib hydrochloride crystal of claim 1. Therefore, the Nilotinib hydrochloride crystal disclosed by D2 is different from the Nilotinib hydrochloride crystal disclosed by claim 1. D3 also discloses a series of crystals of Nilotinib hydrochloride (see claims 1- 64 and figs. 1-25). The X-ray diffraction pattern of the crystal of Nilotinib hydrochloride disclosed by D3 is different from the X-ray diffraction pattern of the Nilotinib hydrochloride crystal of claim 1. Therefore, the Nilotinib hydrochloride crystal disclosed by D3 is different from the Nilotinib hydrochloride crystal disclosed by claim 1. Therefore, claim 1 is novel with respect to D1-D3 and satisfy the criteria set out in PCT Article 33(2). Claims 2-10 set forth a preparation method of the crystal of claim 1. On the basis of the above analysis, the crystal of claim 1 is novel. Therefore, claims 2-10 are novel in the sense of PCT Article 33(2). 2.2 Inventive step Claim 1 of the present application sets forth a Nilotinib hydrochloride crystal with X-ray diffraction pattern data as depicted in table 1. Dl is the closest prior art document, and discloses a series of crystals of Nilotinib hydrochloride (see claims 1-39 and figs. 1-24). The X-ray diffraction pattern of the crystal of Nilotinib hydrochloride disclosed by D1 is or PCTISAPDST (Box No. V) (Apail2007)WRITTEN OPINION OF THE TreatoaT appicaion No INTERNATIONAL SEARCHING AUTHORITY PCT/CN2011/081324 BoxNe, VReasoned statement under Rule 435121()(0 with regard to novelty, inventive dp oF industrial apply: ilations and explanations supporting such statement different from the X-ray diffraction pattern of the Nilotinib hydrochloride crystal of claim 1. The prior art documents also do not give the corresponding technical teaching of obtaining the crystalline form of claim 1. Therefore, claim 1 is not obvious on the basis of the prior art documents. Claim 1 involves an inventive step and satisfies the criteria set out in PCT Article 33(3). Claims 2-10 set forth a preparation method of the crystal of claim 1, Because claim 1 involves an inventive step, claims 2- 10 also involve an inventive step and satisfy the criteria set out in PCT Article 33(3). 2.3 Industrial applicability Claims 1-10 can be made or used in industry. Therefore, claims 1-10 are industrially applicable under PCT article 33(4). Form PCTISAI237 (Box No. V} (Apail 2007),