(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 2012/167278 Al 6 December 2012 (06.12.2012) P O P C T (51) International Patent Classification: [RU/GB]; 6 Kilwarlin Crescent, Hillsborough, Northern G01N 33/50 (2006.01) C12Q 1/68 (2006.01) Ireland BT26 6QF (GB). KENNEDY, Richard [GB/GB]; 15 Edgcumbe Gardens, Belfast, Northern Ireland BT4 2EG (21) International Application Number: (GB). DAVISON, Timothy [US/US]; 301 Washington PCT/US20 12/040805 Street, Apt. 2109, Conshohocken, PA 19428 (US). (22) International Filing Date: WINTER, Andreas [DE/DE]; Wallensteinstrasse 19, 4 June 2012 (04.06.2012) 86368 Gersthofen (DE). MCCAVIGAN, Andrena [IE/IE]; 25 Pier Rampart, Derryadd, Lurgan, County (25) Filing Language: English Armagh, BT66 6QH (IE). (26) Publication Language: English (74) Agent: NLX, F., Brent; Johnson, Marcou & Isaacs, LLC, (30) Priority Data: 317a. E. Liberty Street, Savannah, GA 31401 (US). 61/492,488 2 June 201 1 (02.06.201 1) US (81) Designated States (unless otherwise indicated, for every (71) Applicant (for all designated States except US): ALMAC kind of national protection available): AE, AG, AL, AM, DIAGNOSTICS LIMITED [IE/GB]; Almac House, 20 AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, Seagoe Industrial Estate, Craigavon, Northern Ireland CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, BT63 5QD (GB). DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (72) Inventors; and KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (75) Inventors/Applicants (for US only): HARKIN, Dennis, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, Paul [IE/GB]; 195 Ballygowan Road, Dromore Co. Down, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, Northern Ireland BT25 IRQ (GB). MCDYER, Fionnuala SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, [IE/GB]; Apt. 50 South Studios, Tates Avenue, Belfast, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Northern Ireland BT9 7BS (GB). WILSON, Claire [GB/GB]; The Coach House, Wimpstone, Strat- (84) Designated States (unless otherwise indicated, for every ford-upon-avon, Warwickshire CV37 8NS (GB). O'BRI¬ kind of regional protection available): ARIPO (BW, GH, EN, Eamonn, J. [GB/GB]; 1 Abercorn Drive, Hillsbor GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, ough, Co. Down, Northern Ireland BT26 6LB (GB). UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, MICHIE, Caroline [GB/GB]; 1 Kingsburgh Rd, Edin TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, burgh EH12 6EG (GB). GOURLEY, Charlie [GB/GB]; EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 46 Tarmachan Road, Dumfermline KY1 1 8LA (GB). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, HILL, Lauren, A. [GB/GB]; 24 Brustin Lee, Ballygally, ML, MR, NE, SN, TD, TG). Larne, Northern Ireland BT40 2QA (GB). KEATING, Katherine, E. [IE/GB]; 44 Waterfoot Road, Magherafelt, Published: Northern Ireland BT45 6LQ (GB). O'DONNELL, Jude — with international search report (Art. 21(3)) [IE/GB]; 8 Camaghy Road South, Galbally, Dungannon, Northern Ireland BT70 2NL (GB). BYLESJO, Max — before the expiration of the time limit for amending the [SE/GB]; 9 Locksley Lane, 110 Upper Lisburn Road, Bel claims and to be republished in the event of receipt of fast, Northern Ireland BT10 0BB (GB). DEHARO, Steve amendments (Rule 48.2(h)) [FR/GB]; Apartment 2, 3 The Manor, Blacks Road, Belfast — with sequence listing part of description (Rule 5.2(a)) Northern Ireland BT10 OTJ (GB). PROUTSKI, Vitali 00 (54) Title: MOLECULAR DIAGNOSTIC TEST FOR CANCER (57) Abstract: Methods and compositions are provided for the identification of a molecular diagnostic test for cancer. The test iden - tifies cancer subtypes that are responsive to anti-angiogenesis therapeutics and enables classification of a patient within this subtype. The present invention can be used to determine whether patients with cancer are clinically responsive or non- responsive to a thera - o peutic regimen prior to administration of any anti-angiogenic agent. This test may be used in different cancer types and with different drugs that directly or indirectly affect angiogenesis or angiogenesis signalling. In addition, the present invention may be used as a prognostic indicator for certain cancer types. In particular, the present invention is directed to the use of certain combinations of pre - o dictive markers, wherein the expression of the predictive markers correlates with responsiveness or non-responsiveness to a thera peutic regimen. MOLECULAR DIAGNOSTIC TEST FOR CANCER CROSS-REFERENCE TO RELATED APPLICATIONS [0001] The present invention claims the priority benefit of U.S. Provisional Patent Application 61/492,488 filed June 2, 201 1, which is incorporated herein by reference. FIELD OF THE INVENTION [0002] The present invention relates to a molecular diagnostic test useful for diagnosing cancers from different anatomical sites that includes the use of a common subtype related to angiogenesis. The invention includes the derivation of a gene classification model from gene expression levels. One application is the stratification of response to, and selection of patients for cancer therapeutic drug classes and thus guide patient treatment selection. Another application is the stratification of cancer patients into those that respond and those that do not respond to anti-angiogenic therapeutics. The present invention provides a test that can guide therapy selection as well as selecting patient groups for enrichment strategies during clinical trial evaluation of novel therapeutics. The invention can be used as a prognostic indicator for certain cancers including ovarian cancer, breast cancer, and glioblastoma. The angiogenesis subtype can be identified from fresh/frozen (FF) or formalin fixed paraffin embedded FFPE patient samples. BACKGROUND [0003] The pharmaceutical industry continuously pursues new drug treatment options that are more effective, more specific or have fewer adverse side effects than currently administered drugs. Drug therapy alternatives are constantly being developed because genetic variability within the human population results in substantial differences in the effectiveness of many established drugs. Therefore, although a wide variety of drug therapy options are currently available, more therapies are always needed in the event that a patient fails to respond. [0004] Traditionally, the treatment paradigm used by physicians has been to prescribe a first-line drug therapy that results in the highest success rate possible for treating a disease. Alternative drug therapies are then prescribed if the first is ineffective. This paradigm is clearly not the best treatment method for certain diseases. For example, in diseases such as cancer, the first treatment is often the most important and offers the best opportunity for successful therapy, so there exists a heightened need to choose an initial drug that will be the most effective against that particular patient's disease. [0005] Ovarian cancer is the leading cause of death among all gynecological cancers in western countries. This high death rate is due to the diagnosis at an advanced stage in most patients. Epithelial ovarian cancer (EOC) constitutes 90% of ovarian malignancies and is classified into distinct histologic categories including serous, mucinous, endometrioid, clear cell, transitional, mixed, and undifferentiated subtypes. There is increasing evidence that these differed histologies arise from different aetiologies. There have been recent advances in the methodology used to classify epithelial ovarian cancer (McCluggage, W.G. "Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis," PATHOLOGY 201 1 Aug;43(5):420-32). One of the consequences of this is that many tumors that would previously been classified as endometrioid are now being classified as serous. [0006] The current standard treatment for ovarian cancer is debulking surgery and standard platinum taxane based cytotoxic chemotherapy. However, not all patients respond to this, and of those that do, approximately 70% will experience a recurrence. Specific targeted therapies for ovarian cancer based on histological or molecular classification have not yet reached the marketplace. Similarly for other types of cancer, there is still no accurate way of selecting appropriate cytotoxic chemotherapeutic agents. [0007] The advent of microarrays and molecular genomics has the potential for a significant impact on the diagnostic capability and prognostic classification of disease, which may aid in the prediction of the response of an individual patient to a defined therapeutic regimen. Microarrays provide for the analysis of large amounts of genetic information, thereby providing a genetic fingerprint of an individual. There is much enthusiasm that this technology will ultimately provide the necessary tools for custom-made drug treatment regimens. [0008] Currently, healthcare professionals have few mechanisms to help them identify cancer patients who will benefit from chemotherapeutic agents. Identification of the optimal first-line drug has been difficult because methods are not available for accurately predicting which drug treatment would be the most effective for a particular cancer's physiology. This deficiency results in relatively poor single agent response rates and increased cancer morbidity and death. Furthermore, patients often needlessly undergo ineffective, toxic drug therapy. [0009] Angiogenesis is a key component of neo-vascularisation of tumors and essential to tumorigenesis and metastatsis. As such, it is a key area for therapeutic intervention and has been correlated to poor prognosis and reduced survival. This has promoted the development of a number of agents that target angiogenesis related processes and pathways, including the market leader and first FDA-approved anti-angiogenic, bevacizumab (Avastin), produced by Genentech/Roche.