THIRUTTUMTUMUTURUS009963747B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 , 963, 747 B2 Bryant et al. (45 ) Date of Patent: *May 8 , 2018 (54 ) METHODS FOR THE IDENTIFICATION , ( 56 ) References Cited ASSESSMENT, AND TREATMENT OF PATIENTS WITH CANCER THERAPY U . S . PATENT DOCUMENTS 8 , 278, 038 B2 10 / 2012 Bryant et al. ( 71 ) Applicant : Millennium Pharmaceuticals , Inc. , 8 , 889 ,354 B2 11 /2014 Bryant et al . Cambridge , MA (US ) 2004 /0156854 A1 8 /2004 Mulligan et al. (72 ) Inventors : Barbara M . Bryant, Cambridge, MA FOREIGN PATENT DOCUMENTS (US ) ; Andrew I. Damokosh , West Hartford , CT (US ) ; George J . Wo WO 2003 / 053215 7 / 2003 Mulligan , Lexington ,MA (US ) WO WO 04 /053066 A2 6 / 2004 WO WO 2006 / 133420 12 /2006 @( 73 ) Assignee : Millennium Pharmaceuticals , Inc ., Cambridge , MA (US ) OTHER PUBLICATIONS Adams, Julian , et al. , " Proteasome Inhibitors: A Novel Class of ( * ) Notice : Subject to any disclaimer, the term of this Potent and Effective Antitumor Agents , ” Cancer Research , vol. 59 patent is extended or adjusted under 35 ( Jun . 1 , 1999 ) pp . 2615 - 2622 . U . S . C . 154 (b ) by 0 days . days . Adams, Julian , “ Development of the Proteasome Inhibitor PS - 341, " The Oncologist , vol. 7 ( 2002 ) pp . 9 - 16 . This patent is subject to a terminal dis Lightcap , Eric S . , et al. , " Proteasome Inhibition Measurements : claimer . Clinical Application , ” Clinical Chemsitry , vol. 46 , No. 5 ( 2000 ) pp . 673 -683 . (21 ) Appl . 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Aug . 31 , 2012 , now Pat. No. 8 , 889, 354 , which is a Mulligan , George , et al. , “Gene expression profiling and correlation continuation of application No . 11 /449 , 195 , filed on with outcome in clinical trials of the proteasome inhibitor Jun . 8 , 2006 , now Pat. No. 8 ,278 ,038 . bortezomib ,” Blood , vol. 109 , No . 8 ( Apr. 15 , 2007 ) pp . 3177 - 3188 . Toczyski , David P ., et al. , “ The Epstein -Barr virus (EBV ) small RNA EBER1 binds and relocalizes ribosomal protein L22 in (60 ) Provisional application No. 60 /688 ,634 , filed on Jun . EBV -infected human B lymphocytes , ” Proceedings of the National 8 , 2005 . Academy of Science USA , vol . 91 ( Apr. 1994 ) pp . 3463 - 3467 . Maglott , Donna , et al. , “ Entrez Gene: gene -centered information at ( 51 ) Int . Cl. NCBI , ” Nucleic Acids Research , vol. 33 , Database issue ( 2005 ) pp . C120 1 /68 ( 2018 .01 ) D54 -D58 . GOIN 33 / 574 ( 2006 .01 ) (Continued ) G06F 19 / 20 ( 2011 .01 ) G06Q 50 / 22 ( 2018 .01 ) Primary Examiner — Sean E Aeder A61K 31 /69 ( 2006 .01 ) (74 ) Attorney , Agent, or Firm — Millennium G060 20 / 40 ( 2012 .01 ) Pharmaceuticals , Inc . G06F 19 /24 ( 2011. 01) U . S . CI. (57 ) ABSTRACT ??? . .. .. .. C12Q 1 /6886 (2013 .01 ) ; A61K 31/ 69 The present invention is directed to the identification of ( 2013 .01 ) ; GOIN 33 /57407 (2013 .01 ) ; GOIN predictive markers that can be used to determine whether 33 / 57415 (2013 .01 ) ; GOIN 33 / 57419 patients with cancer are clinically responsive or non - respon ( 2013 . 01 ) ; GOIN 33 /57423 ( 2013 .01 ) ; GOIN sive to a therapeutic regimen prior to treatment. In particular , 33 /57426 (2013 .01 ) ; GOIN 33 / 57434 the present invention is directed to the use of certain ( 2013 . 01 ) ; GOIN 33 / 57438 ( 2013 . 01 ) ; GOIN individual and /or combinations of predictive markers, 33 /57449 (2013 . 01 ) ; G06F 19 /20 ( 2013 .01 ) ; wherein the expression of the predictive markers correlates G06Q 20 /40 (2013 .01 ) ; G06Q 50 / 22 with responsiveness or non - responsiveness to a therapeutic ( 2013 . 01 ) ; C120 2600 / 106 ( 2013 . 01 ) ; C120 regimen . Thus , by examining the expression levels of indi 2600 / 136 ( 2013 .01 ) ; C12Q 2600 /158 vidual predictive markers and /or predictive markers com ( 2013 .01 ) ; GOIN 2800 / 44 (2013 .01 ) ; GOOF prising a marker set, it is possible to determine whether a 19 /24 (2013 .01 ) ; YO2A 90 /22 (2018 .01 ) ; YO2A therapeutic agent, or combination of agents , will be most 90 / 26 (2018 .01 ) likely to reduce the growth rate of tumors in a clinical (58 ) Field of Classification Search setting . 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