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( 12 ) United States Patent US010202605B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 ,202 , 605 B2 Kang et al. (45 ) Date of Patent: * Feb . 12, 2019 (54 ) METHODS OF IDENTIFYING AND (56 ) References Cited TREATING POOR - PROGNOSIS CANCERS U . S . 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Application Data (Continued ) (63 ) Continuation of application No . 15 /004 ,706 , filed on FOREIGN PATENT DOCUMENTS Jan . 22 , 2016 , now Pat. No. 9 , 932 , 587 , which is a continuation of application No . 14 /619 , 977 , filed on WOwo WO 1997 / 30731 8 / 1997 Feb . 11 , 2015 , now abandoned , which is a WO 1999 /02685 1 / 1999 continuation of application No. 12 /215 ,998 , filed on (Continued ) Jun . 30 , 2008 , now abandoned . OTHER PUBLICATIONS (60 ) Provisional application No . 60 / 937 ,789 , filed on Jun . Santiago et al, PNAS , 2008 , vol . 105 , pp . 5809 -5814 . * 28 , 2007 . Takahagi et al , Molecular Reproduction and Development, 2005 , vol. 71, pp . 331 - 338 . * (51 ) Int . Cl. Amano , et al. “ Dosage - Dependent over - Expression of Genes in the C07H 21/ 02 ( 2006 . 01 ) Trisomic Region of TSLCJE Mouse Model for Down Syndrome. ” Hum Mol Genet , 13 ( 13 ) : 1333 - 1340 ( 2004 ) . CO7H 21/ 04 ( 2006 .01 ) Anderson and Young , “ Quantitative Filter Hybridization . ” In Nucleic A61K 31/ 70 ( 2006 .01 ) Acid Hybridisation : A Practical Approach (Hames , et a 1 , Eds . ) , pp . C12N 15 / 113 ( 2010 .01 ) 73 - 111, IRL Press , Oxford Washington , DC ( 1985 ) . A61K 31 /00 ( 2006 .01 ) Ballestrero , et al . “ Tumor Necrosis Factor - Related Apoptosis A61K 31 /7105 ( 2006 .01 ) Inducing Ligand Cooperates with Anticancer Drugs to Overcome C120 1 / 6886 ( 2018 .01 ) Chemoresistance in Antiapoptotic Bcl - 2 Family Members Express A61K 31 / 337 ( 2006 .01 ) ing Jurkat Cells. " Clin Cancer Res, 10 ( 4 ) : 1463 - 1470 ( 2004 ) . A61K 31 / 704 ( 2006 . 01 ) (Continued ) A61K 45 /06 ( 2006 . 01 ) Primary Examiner — Sean McGarry A61K 31/ 713 ( 2006 .01 ) ( 74 ) Attorney , Agent, or Firm — Medlen & Carroll, LLP C12N 5 / 00 ( 2006 . 01 ) (52 ) U . S . CI. (57 ) ABSTRACT CPC . .. .. .. C12N 15 / 1135 ( 2013 .01 ) ; A61K 31/ 00 The present invention relates generally to methods for ( 2013 .01 ) ; A61K 31/ 337 ( 2013 . 01 ) ; A61K identifying cancer patients with a poor prognosis , and to 31 / 704 ( 2013 .01 ) ; A6IK 31/ 713 ( 2013 .01 ) ; therapeutic modalities for improving prognosis by combat A61K 31 /7105 ( 2013 .01 ) ; A61K 45 / 06 ing metastasis and abrogating chemoresistance in cancer (2013 . 01 ) ; C120 1 /6886 ( 2013 .01 ) ; C12N cells . Embodiments of the present invention provide an 2310 / 11 (2013 .01 ) ; CI2N 2310 / 14 ( 2013 .01 ) ; objective means of prognostication regarding the long - term C12N 2320 /30 ( 2013 .01 ) ; C12N 2320 / 31 outcome of an incident of cancer, breast cancer in particular . (2013 . 01 ) ; C12Q 2600 / 118 ( 2013 .01 ) ; C12Q Therapeutic modalities include immunotherapy and anti 2600/ 156 (2013 .01 ) sense therapy . Prognosis is determined by measuring the ( 58 ) Field of Classification Search number of copies of the metadherin gene in the patient' s None cells . See application file for complete search history . 15 Claims, 15 Drawing Sheets US 10 ,202 ,605 B2 Page 2 (56 ) References Cited Brown and Ruoslahti , “ Metadherin , a Cell Surface Protein in Breast Tumors That Mediates Lung Metastasis . ” Cancer Cell , 5 ( 4 ) : 365 U . S . PATENT DOCUMENTS 374 (2004 ) . 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