Prostate Cancer Prognostics Using Biomarkers Prostatakrebsprognostik Mittels Biomarkern Prognostic Du Cancer De La Prostate Au Moyen De Biomarqueurs
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(19) TZZ Z_T (11) EP 2 885 640 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 33/574 (2006.01) C12Q 1/68 (2018.01) 18.07.2018 Bulletin 2018/29 C40B 30/04 (2006.01) (21) Application number: 13829137.2 (86) International application number: PCT/US2013/055429 (22) Date of filing: 16.08.2013 (87) International publication number: WO 2014/028884 (20.02.2014 Gazette 2014/08) (54) PROSTATE CANCER PROGNOSTICS USING BIOMARKERS PROSTATAKREBSPROGNOSTIK MITTELS BIOMARKERN PROGNOSTIC DU CANCER DE LA PROSTATE AU MOYEN DE BIOMARQUEURS (84) Designated Contracting States: • GHADESSI, Mercedeh AL AT BE BG CH CY CZ DE DK EE ES FI FR GB New Westminster, British Columbia V3M 6E2 (CA) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • JENKINS, Robert, B. PL PT RO RS SE SI SK SM TR Rochester, Minnesota 55902 (US) • VERGARA CORREA, Ismael A. (30) Priority: 16.08.2012 US 201261684066 P Bundoora, Victoria 3083 (AU) 13.02.2013 US 201361764365 P 14.03.2013 US 201361783124 P (74) Representative: Cornish, Kristina Victoria Joy et al Kilburn & Strode LLP (43) Date of publication of application: Lacon London 24.06.2015 Bulletin 2015/26 84 Theobalds Road London WC1X 8NL (GB) (73) Proprietors: • Genomedx Biosciences, Inc. (56) References cited: Vancouver BC V6B 2W9 (CA) WO-A1-2009/143603 WO-A1-2013/090620 • MAYO FOUNDATION FOR MEDICAL WO-A2-2006/091776 WO-A2-2006/110264 EDUCATION AND RESEARCH WO-A2-2007/056049 US-A1- 2006 134 663 Rochester, MN 55905 (US) US-A1- 2007 037 165 US-A1- 2007 065 827 US-A1- 2011 136 683 US-A1- 2011 294 123 (72) Inventors: US-B1- 7 914 988 • BUERKI, Christine Vancouver, British Columbia V5Y 1X3 (CA) Remarks: • CRISAN, Anamaria The complete document including Reference Tables Vancouver, British Columbia V6J 1L5 (CA) and the Sequence Listing can be downloaded from • DAVICIONI, Elai the EPO website La Jolla, CA 92037 (US) • ERHO, Nicholas, George Vancouver, British Columbia V6B 6H4 (CA) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 885 640 B1 Printed by Jouve, 75001 PARIS (FR) EP 2 885 640 B1 Description BACKGROUND OF THE INVENTION 5 [0001] Cancer is the uncontrolled growth of abnormal cells anywhere in a body. The abnormal cells are termed cancer cells, malignant cells, or tumor cells. Many cancers and the abnormal cells that compose the cancer tissue are further identified by the name of the tissue that the abnormal cells originated from (for example, breast cancer, lung cancer, colon cancer, prostate cancer, pancreatic cancer, thyroid cancer). Cancer is not confined to humans; animals and other living organisms can get cancer. Cancer cells can proliferate uncontrollably and form a mass of cancer cells. Cancer 10 cells can break away from this original mass of cells, travel through the blood and lymph systems, and lodge in other organs where they can again repeat the uncontrolled growth cycle. This process of cancer cells leaving an area and growing in another body area is often termed metastatic spread or metastatic disease. For example, if breast cancer cells spread to a bone (or anywhere else), it can mean that the individual has metastatic breast cancer. [0002] Standard clinical parameters such as tumor size, grade, lymph node involvement and tumor-node-metastasis 15 (TNM) staging (American Joint Committee on Cancer http://www.cancerstaging.org) may correlate with outcome and serve to stratify patients with respect to (neo)adjuvant chemotherapy, immunotherapy, antibody therapy and/or radio- therapy regimens. Incorporation of molecular markers in clinical practice may define tumor subtypes that are more likely to respond to targeted therapy. However, stage-matched tumors grouped by histological or molecular subtypes may respond differently to the same treatment regimen. Additional key genetic and epigenetic alterations may exist with 20 important etiological contributions. A more detailed understanding of the molecular mechanisms and regulatory pathways at work in cancer cells and the tumor microenvironment (TME) could dramatically improve the design of novel anti-tumor drugs and inform the selection of optimal therapeutic strategies. The development and implementation of diagnostic, prognostic and therapeutic biomarkers to characterize the biology of each tumor may assist clinicians in making important decisions with regard to individual patient care and treatment. Thus, disclosed herein are methods, compositions and 25 systems for the analysis of coding and non-coding targets for the diagnosis, prognosis and monitoring of a cancer. [0003] This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention. 30 SUMMARY OF THE INVENTION [0004] Disclosed herein in some embodiments is a method of prognosing prostate cancer in a subject, comprising (a) assaying an expression level in a sample from the subject for a plurality of targets, wherein the plurality of targets comprises more than one target selected from Tables 2, 4, 11 or 55; and (b) prognosing the cancer in a subject based 35 on the expression levels of the plurality of targets. In some embodiments, the plurality of targets comprises a coding target. In some embodiments, the coding target is a coding antisense sequence an exonic sequence. In some embod- iments, the plurality of targets comprises a non-coding target. In some embodiments, the non-coding target comprises an intronic sequence or partially overlaps an intronic sequence. In some embodiments, the non-coding target comprises an intronic sequence or partially overlaps an intronic sequence. In some embodiments, the non-coding target comprises 40 a sequence within the UTR or partially overlaps with a UTR sequence. In some embodiments, the non-coding target comprises an antisense sequence or partially overlaps with an antisense sequence. In some embodiments, the non- coding target comprises an intergenic sequence. In some embodiments, the target comprises a nucleic acid sequence. In some embodiments, the nucleic acid sequence is a DNA sequence. In some embodiments, the nucleic acid sequence is an RNA sequence. In some embodiments, the plurality of targets comprises at least 5 targets selected from Tables 45 2, 4, 11 or 55. In some embodiments, the plurality of targets comprises at least 10 targets selected from Tables 2, 4, 11 or 55. In some embodiments, the plurality of targets comprises at least 15 targets selected from Tables 2, 4, 11 or 55. In some embodiments, the plurality of targets comprises at least 20 targets selected from Tables 2, 4, 11 or 55. In some embodiments, the plurality of targets comprises at least 22 targets selected from Tables 2, 11 or 55. In some embodiments, the plurality of targets comprises at least 30 targets selected from Tables 2, 11 or 55. In some embodiments, the plurality 50 of targets comprises at least 35 targets selected from Tables 2, 11 or 55. In some embodiments, the plurality of targets comprises at least 40 targets selected from Tables 2, 11 or 55. In some embodiments, the plurality of targets comprises at least 5 targets selected from Tables 2, 4, 11 or 55. In some embodiments, the plurality of targets comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 targets selected from Tables 2, 4, 11 or 55. In some embodiments, 55 the plurality of targets is selected from SEQ ID NOs:1-43. In some embodiments, the plurality of targets is selected from SEQ ID NOs:1-22. In certain embodiments, the plurality of targets is selected from the group consisting of: PBX1, MYBPC1, LASP1, CAMK2N1, RABGAP1, UBE2C, PCAT-32, NF1B, TNFRSF19, PCDH7, ANO7, GLYATL1P4/PCAT- 80, C6orf10, IQGAP3, THBS2, EPPK1, NUSAP1, ZWILCH, S1P4, SENP7, ANLN, C10orf116, PPP6R3, PDS5B, TOP2A, 2 EP 2 885 640 B1 IL1RAP, CENPE, GALNT8, KCNQ1, C6orfl55, LUZP2, HEATR3, TMEM108, CFBXX bac-BPG116M5.17, ECHDC2, and ARNTL. In other embodiments the plurality of targets is selected from the group consisting of: PBX1, MYBPC1, LASP1, CAMK2N1, RABGAP1, UBE2C, PCAT-32, NF1B, TNFRSF19, PCDH7, ANO7, GLYATL1P4/PCAT-80, C6orf10, IQGAP3, THBS2, EPPK1, NUSAP1, ZWILCH, and S1P4. In some embodiments, prognosing the cancer includes de- 5 termining the malignancy of the cancer. In some embodiments, prognosing the cancer includes determining the stage of the cancer. In some embodiments, prognosing the cancer includes assessing the risk of cancer recurrence. In some embodiments, prognosing the cancer includes assessing the grade of the cancer. In some embodiments, the method further comprises sequencing the plurality of targets. In some embodiments, the method further comprises hybridizing the plurality of targets to a solid support. In some embodiments, the solid support is a bead or array. In some embodiments, 10 assaying the expression level of a plurality of targets may comprise the use of a probe set. In some embodiments, assaying the expression level may comprise the use of a classifier. The classifier may comprise a probe selection region (PSR). In some embodiments, the classifier may comprise the use of an algorithm.