(10) International Publication Number (43) International Publication Date WO 2013/ A3 20 June 2013 ( ) W P O P C T

Transcription

1 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2013/ A3 20 June 2013 ( ) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 48/00 ( ) A61K 31/7088 ( ) kind of national protection available): AE, AG, AL, AM, A61K 31/7105 ( ) A61P 35/00 ( ) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 12/ HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 December 2012 ( ) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/570, December ( ) US (84) Designated States (unless otherwise indicated, for every 61/652, May 2012 ( ) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicants: THE BOARD OF REGENTS OF THE UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, UNIVERSITY OF TEXAS SYSTEM [US/US]; 201 W. TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 7th Street, Austin, TX (US). DANA-FARBER EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, CANCER INSTITUTE, INC. [US/US]; 450 Brookline MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Avenue, Boston, MA (US). TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (72) Inventors: MULLER, Florian, L.; Holcombe Blvd., ML, MR, NE, SN, TD, TG). Unit 1958, Houston, TX (US). FLETCHER-SAN- Published: ANIKONE, Eliot; Holcombe Blvd., Unit 1958, Hou ston, TX (US). COLLA, Simona; Holcombe with international search report (Art. 21(3)) Blvd., Unit 1958, Houston, TX (US). with sequence listing part of description (Rule 5.2(a)) AQUILANTI, Elisa; Holcombe Blvd., Unit 1958, (88) Date of publication of the international search report: Houston, TX (US). DEPINHO, Ronald; H ol 26 September 2013 combe Blvd.,unit 194, Houston, TX (US). (74) Agent: BYRD, Marshall, P.; Parker Highlander PLLC, 1120 S. Capital Of Texas Highway, Building One, Suite 200, Austin, TX (US). < o o (57) Abstract: Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis, such as an enolase in - hibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS. - (54) Title: COLLATERAL GENE INACTIVATION BIOMARKERS AND TARGETS FOR CANCER THERAPY S

2 A. CLASSIFICATION OF SUBJECT MATTER A61K 48/00( )i, A61K 31/7105( )i, A61K 31/7088( )i, A61P 35/00( )i According to International Patent Classification (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) A61K 48/00; A61K 39/395; C12Q 1/00; A61K 3 1/7105; A61K 9/00; A61F 2/06; A61K ; A61K 38/00; C07D 471/04; C12N 15/10; C07K 14/00; C12N 15/00; A61K 38/17; A61K 31/437; C12Q 1/68; A61K 31/7088; A61P 35/00 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Korean utility models and applications for utility models Japanese utility models and applications for utility models Electronic data base consulted during the international search (name of data base and, where practicable, search terms used) ekompass(kipo internal) & Keywords: cancer, heterozygous, housekeeping gene, functionally redundant, DOCUMENTS CONSIDERED TO BE RELEVANT Category' Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. WO A2 (VARIAGENICS, INC.) 24 September ,14-41,43-61 See claims 1, 3, 4, 16, 24, 31, 32, 41, 43, 57, 59, 71, 72, 83, 86, 103,,63-71, , 111, and 112. DRAPER, N. et al., "Mutations in the genes encoding llb-hydroxysteroid 1-11,14-41,43-61 dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause,63-71,73-76 cortisone reductase deficiency", Nature Genetics, 2003, Vol. 34, No. 4, pp See the whole document. US A l (MARTIN, S. et al.) 28 May ,14-41,43-61 See claims 1, 3, and 4.,63-71,73-76 WO A2 (INDIANA UNIVERSITY) 09 October ,14-41,43-61 See claim 1.,63-71,73-76 US A l (HUANG, L. et al.) 29 July ,14-41,43-61 See abstract and claim 1.,63-71,73-76 US A l (NAKAMURA, Y. et al.) 09 July ,14-41,43-61 See claim 1 and table 5.,63-71,73-76 Further documents are listed in the continuation of Box C. See patent family annex. Special categories of cited documents: "T" later document published after the international filing date or priority document defining the general state of the art which is not considered date and not in conflict with the application but cited to understand to be of particular relevance the principle or theory underlying the invention earlier application or patent but published on or after the international "X" document of particular relevance: the claimed invention cannot be filing date considered novel or cannot be considered to involve an inventive document which may throw doubts on priority claim(s) or which is step when the document is taken alone cited to establish the publication date of citation or other "Y" document of particular relevance: the claimed invention cannot be special reason (as specified) considered to involve an inventive step when the document is document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents,such combination means being obvious to a person skilled in the art document published prior to the international filing date but later "&" document member of the same patent family than the priority date claimed Date of the actual completion of the international search Date of mailing of the international search report 26 June 2013 ( ) 26 June 2013 ( ) Name and mailing address of the ISA/KR Authorized officer * *» Korean Intellectual Property Office 1 Cheongsa-ro, Seo-gu, Daejeon Metropolitan City, CHOI, Sung Hee ¾ , Republic of Korea Facsimile No Telephone No * Form PCT/ISA/210 (second sheet) (July 2009)

3 C (Continuation). DOCUMENTS CONSIDERED TO BE RELEVANT Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A WO A l (DANA-FARBER CANCER INSTITUTE, INC.) 31 December ,14-41,43-61 See claim 1 and table 1.,63-71,73-76 A WO A l (ONCOTHERAPY SCIENCE, INC.) 28 August ,14-41,43-61 See abstract; and claims 1 and 2.,63-71,73-76 A US A l (POPOWSKI, Y.) 31 December ,14-41,43-61 See claims 1 and 27.,63-71,73-76 Form PCT/ISA/210 (continuation of second sheet) (July 2009)

4 Box No. II 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 17(2)(a) for the following reasons: Claims Nos.: 12-13, 42, 72 because they relate to subject matter not required to be searched by this Authority, namely: Claims 12-13, 42, and 72 pertain to methods for treatment of the human body by therapy and thus relate to a subject matter which this International Searching Authority is not required, under Article 17(2)(a)(i) of the PCT and Rule 39. l(iv) of the Regulations under the PCT, to search. Claims Nos.: 62 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: Claim 62 refers to claim 62 itself. Hence, claim 62 does not meet the requirements of PCT Article 6. Claims Nos.: because they are dependent claims and are not drafted in accordance with the second and third sentences of Rule 6.4(a). Box No. Ill 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: (See extra sheet.) 1. As all required addtional search fees were timely paid by the applicant, this international search report covers all searchable claims. I IAs all searchable claims could be searched without effort justifying an additional fee, this Authority did not invite payment of any additional fee. I IAs 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. I INo required additional search fees were timely paid by the applicant. Consequently, this international search report restricted to the invention first mentioned in the claims; it is covered by claims Nos.: Remark on Protest The additional search fees were accompanied by the applicant's protest and, where applicable, the payment of a protest fee. I IThe additional search fees were accompanied by the applicant's protest but the applicable protest fee was not paid within the time limit specified in the invitation. No protest accompanied the payment of additional search fees. Form PCT/ISA/210 (continuation of first sheet (2)) (July 2009)

5 Information on patent family members PCT/US2012/ Patent document Publication Patent family Publication cited in search report date member(s) date WO A AU A CA Al EP A WO A US Al AU Al CA Al EP A EP A US B wo A wo A W A AU Al WO A US Al CN A CN B EP Al EP A J P A WO Al US Al CN A EP A EP A EP A EP Al EP Al EP Al J P A J P A US Al us B wo A wo A W Al us Al us B W Al AR Al AU Al AU A CA Al CN A CO A EP Al EP A EP A Form PCT/ISA/210 (patent family annex) (July 2009)

6 (Continuation of Box No. Ill) This ISA found multiple inventions in this international application as follows: Group 1, claims 1-5, 11, 14, and 15 (all partial) and claim 6, drawn to a composition or a method related to a cancer having a homozygous deletion in enolase 1 (EN01) and an of EN02. Group 2, claims 1-5, 11, 14, and 15 (all partial) and claim 7, drawn to a composition or a method related to a cancer having a homozygous deletion in hexose-6-phosphate dehydrogenase (H6PD) and an of glucose-6-dehydrogenase (G6PD). Group 3, claims 1-5, 11, 14, and 15 (all partial), drawn to a composition or a method related to a cancer having a homozygous deletion in kinesin family member I B (KIFIB) and an of KIF1A or KIF1C. Group 4, claims 1-5, 11, 14, and 15 (all partial) and claim 8, drawn to a composition or a method related to a cancer having a homozygous deletion in Nicotinamide nucleotide adenylyl transferase 1 (NMNAT1) and an of NMNAT2 or NMNAT3. Group 5, claims 1-5, 11, 14, and 15 (all partial), drawn to a composition or a method related to a cancer having a homozygous deletion in ubiquitination factor E4B (UBE4B) and an of UBE4A. Group 6, claims 1-5, 11, 14, and 15 (all partial) and claim 9, drawn to composition or a method related to a cancer having a homozygous deletion in aconitase 1 (ACOl) and an of AC02 or AC03. Group 7, claims 1-5, 11, 14, and 15 (all partial), drawn to a composition or a method related to a cancer having a homozygous deletion in kelch-like 9 (KLHL9) and an of KLHL13. Group 8, claims 1-5, 11, 14, and 15 (all partial) and claim 10, a composition or a method related to a cancer having a homozygous deletion in pantothenate kinase 1 (PANKl) and an of PANK3. Group 9, claims 1-5, 11, 14, and 15 (all partial), drawn to a composition or a method related to a cancer having a homozygous deletion in kinase family member 20B (KIF20B) and an of KIF20A. Group 10, claims and 43-61, drawn to a composition or a method related to a cancer comprising a heterozygous mutation that inactivates one copy of ENOl gene and an of glycolysis. Group 11, claims and 73-76, drawn to a composition or a method related to a cancer comprising a heterozygous mutation that inactivates one copy of ARS gene and an of an ARS. Form PCT/ISA/210 (extra sheet) (July 2009)

7 Information on patent family members PCT/US2012/ Patent document Publication Patent family Publication cited in search report date member(s) date EP A EP A EP A EP A EP A EP A EP A EP A EP A EP A EP A IL D IL D IL D IL D IL D IL D IL D IL D IL D IL D J P A J P A R A MX A NZ A NZ A RU A SG Al Tff A ZA A US Al AT T DE Dl Form PCT/ISA/210 (patent family annex) (July 2009)