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US009993566B2MULT MAIMULOQOTI TAITE (12 ) United States Patent ( 10 ) Patent No. : US 9 , 993 ,566 B2 Liu et al. (45 ) Date of Patent : * Jun. 12 , 2018 ( 54 ) SEZ6 MODULATORS AND METHODS OF ( 56 ) References Cited USE U . S . PATENT DOCUMENTS @(71 ) Applicant : AbbVie Stemcentrx LLC , North 5 , 112 , 946 A 5 / 1992 Maione Chicago , IL (US ) 5 ,336 ,603 A 8 / 1994 Capon et al. 5 , 349 ,053 A 9 / 1994 Landolfi @(72 ) Inventors : David Liu , South San Francisco , CA 5 , 359 ,046 A 10 / 1994 Capon et al. (US ) ; Deepti Rokkam , Sunnyvale , CA 5 , 447 , 851 A 9 / 1995 Beutler et al. (US ) ; Sheila Bheddah , San Francisco , 5 , 530 , 101 A 6 / 1996 Queen et al. 5 ,622 , 929 A 4 / 1997 Willner et al . CA (US ) ; Javier Lopez -Molina , New 5 ,693 , 762 A 12 / 1997 Queen et al . York , NY (US ) ; Laura Saunders, San 6 ,180 , 370 B1 1 / 2001 Queen et al . 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No. : 14 /915 , 563 8 , 163, 736 B2 . 4 /2012 Gauzy et al . 8 ,788 ,213 B2 7 / 2014 Bright ( 22 ) PCT Filed : Aug . 27, 2014 8 , 889 ,833 B2 11/ 2014 Yue et al. 9 ,676 ,850 B2 * 6 /2017 Saunders . C07K 16 / 28 ( 86 ) PCT No. : PCT/ US2014 / 053014 2003 /0211991 Al 11 /2003 Su $ 371 ( c ) ( 1 ), (Continued ) ( 2 ) Date : Feb . 29 , 2016 FOREIGN PATENT DOCUMENTS ( 87 ) PCT Pub . No . : W02015 / 031541 CN 1343774 A 4 / 2002 EP 0367166 5 / 1990 PCT Pub . Date : Mar. 5 , 2015 (Continued ) (65 ) Prior Publication Data US 2016 / 0287720 A1 Oct . 6 , 2016 OTHER PUBLICATIONS Gorlov et al. Seizure 6 - like (SEZÓL ) gene and risk for lung cancer . Related U . S . Application Data Cancer Research 67 ( 17 ) : 8406 -8411 , Sep . 1 , 2007. * ( 60 ) Provisional application No . 61 / 871, 289 , filed on Aug . Gussow et al . (Methods in Enzymology . 1991 ; 203 : 99 - 121) . * George et al . (Circulation . 1998 ; 97 : 900 - 906 ) . * 28 , 2013 NM _ 001098635 — Homo sapiens seizure related 6 homolog (51 ) Int . Ci. (SEZ6 ) , transcript variant 2 , mRNA . NM _ 021286 — Mus musculus seizure related gene 6 (Sezo ) , tran CO7K 16 / 00 ( 2006 .01 ) script variant 1 , mRNA . A61K 4748 ( 2006 . 01) NM _ 178860 — Homo sapiens seizure related 6 homolog (SEZO ) , CO7K 16 / 28 ( 2006 .01 ) transcript variant 1 , mRNA . GOIN 33 / 574 ( 2006 .01 ) NP _ 001092105 — seizure protein 6 homolog isoform 2 precursor CO7K 16 / 18 ( 2006 .01 ) [Homo sapiens ] . A61K 47 /68 ( 2017 . 01 ) NP _ 001099224 — seizure protein 6 homolog precursor [Rattus A61K 39 / 00 ( 2006 . 01 ) norvegicus ] . ( 52 ) U . S . CI. (Continued ) CPC . .. A61K 47 /48384 ( 2013 .01 ) ; A61K 47/ 6803 ( 2017 .08 ) ; A61K 47 /6843 ( 2017 .08 ); A61K 47 /6849 ( 2017 . 08 ) ; CO7K 16 / 18 ( 2013 .01 ) ; Primary Examiner — Brad Duffy CO7K 16 / 28 ( 2013 .01 ) ; GOIN 33 / 57407 (74 ) Attorney , Agent, or Firm — Womble Bond Dickinson (2013 .01 ) ; GOIN 33 /57423 ( 2013 .01 ) ; A61K (US ) LLP 2039 / 505 ( 2013 .01 ) ; CO7K 2317 /20 ( 2013 .01 ) ; CO7K 2317 / 24 ( 2013 .01 ) ; CO7K 2317 / 33 (57 ) ABSTRACT ( 2013 .01 ) ; CO7K 2317 / 34 ( 2013 .01 ) ; CO7K 2317 / 565 (2013 . 01 ) ; COZK 2317 /73 ( 2013 .01 ) ; Novel modulators , including antibodies and derivatives CO7K 2317 /77 (2013 .01 ) thereof , and methods of using such modulators to treat (58 ) Field of Classification Search proliferative disorders are provided . None See application file for complete search history . 41 Claims, 72 Drawing Sheets US 9 ,993 ,566 B2 Page 2 ( 56 ) References Cited Bork et al ., “ The CUB domain . 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  • Investigating the Nedd4-Mediated

    Investigating the Nedd4-Mediated

    INVESTIGATING THE NEDD4-MEDIATED UBIQUITINATION OF PMEPA1, AND ITS POTENTIAL ROLE IN THE REGULATION OF THE ANDROGEN RECEPTOR AS PART OF THE STEROID RESPONSE PATHWAY IN PROSTATIC CANCER HELEN MARGARET MARKS School of Biological & Chemical Sciences, Queen Mary, University of London THESIS SUBMITTED TO THE UNIVERSITY OF LONDON FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Page 1 of 229 Declaration DECLARATION BY CANDIDATE I declare that the work presented in this thesis is my own and that the thesis presented is the one upon which I expect to be examined. Any quotation or paraphrase from the published or unpublished work of another person has been duly acknowledged in the work which I present for examination. Signed (Candidate) .................................................. Date: .................. Page 2 of 229 Abstract ABSTRACT Ubiquitination is an extremely important post-translational modification, regulating a wide variety of cellular processes including proteasomal degradation, subcellular targeting, endocytosis and DNA repair. The HECT class of E3 ligases catalyse the final step of ubiquitin conjugation to the substrate; the Nedd4 family make up 9 members of this class in humans, and are implicated in pathologies ranging from congenital ion channel misregulation to cancer, via the TGF-ß signalling pathway. The Nedd4-like proteins contain WW substrate recognition domains, which recognise and bind proline–rich PY motifs. This work focuses on the interaction between Nedd4 and PMEPA1, a membrane protein showing altered expression in prostate cancer and a known Nedd4 substrate. PMEPA1 is recognised as important in several cancers, although its detailed function is not yet known; it is upregulated in prostate cancer and has been postulated to decrease cellular androgen receptor (AR) via a negative feedback loop involving Nedd4 in a ubiquitin-proteasome dependent process.
  • Molecular Network Pathways and Functional Analysis of Tumor

    Molecular Network Pathways and Functional Analysis of Tumor

    Cancer Gene Therapy (2012) 19, 38–48 r 2012 Nature America, Inc. All rights reserved 0929-1903/12 www.nature.com/cgt ORIGINAL ARTICLE Molecular network pathways and functional analysis of tumor signatures associated with development of resistance to viral gene therapy T-J Song1,2,*, D Haddad1,3,*, P Adusumilli1, T Kim1, B Stiles1, M Hezel1, ND Socci1,4,MGo¨nen5 and Y Fong1 1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 2Department of Surgery, New York College of Medicine, Korea University, Seoul, South Korea; 3Institute for Biochemistry and Virchow Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg, Germany; 4Department of Bioinformatics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA and 5Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Replication-competent attenuated herpes simplex viruses have proven effective in killing many cancer cell lines. However, determinants of resistance to oncolytic therapy are mostly unknown. We developed viral therapy-resistant cells and examined changes in gene-expression pattern compared with therapy-sensitive parental cells. Colon cancer cell line HT29 and hepatoma cell line PLC5 were exposed to increasing concentrations of virus G207. Therapy-resistant cells were isolated and grown in vitro. Tumorigenicity was confirmed by ability of cell lines to form tumors in mice. Human Genome U133A complementary DNA microarray chips were used to determine gene-expression patterns, which were analyzed in the context of molecular network interactions, pathways and gene ontology. In parental cell lines, 90–100% of cells were killed by day 7 at 1.0 multiplicity of infection.
  • TMEPAI Genome Editing in Triple Negative Breast Cancer Cells

    TMEPAI Genome Editing in Triple Negative Breast Cancer Cells

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Tsukuba Repository TMEPAI genome editing in triple negative breast cancer cells 著者 Wardhani Bantari W.K., Puteri Meidi U., Watanabe Yukihide, Louisa Melva, Setiabudy Rianto, Kato Mitsuyasu journal or Medical journal of Indonesia publication title volume 26 number 1 page range 14-18 year 2017-05 権利 Copyright @ 2017 Authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0 /), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are properly cited. URL http://hdl.handle.net/2241/00146612 doi: 10.13181/mji.v26i1.1871 Creative Commons : 表示 - 非営利 http://creativecommons.org/licenses/by-nc/3.0/deed.ja 14 Med J Indones, Vol. 26, No. 1 March 2017 Basic Medical Research TMEPAI genome editing in triple negative breast cancer cells Bantari W.K. Wardhani,1 Meidi U. Puteri,2 Yukihide Watanabe,3 Melva Louisa,4 Rianto Setiabudy,4 Mitsuyasu Kato3 1 Doctoral Program in Biomedicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia 2 Medical Sciences Master Program, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan 3 Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan 4 Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia ABSTRAK ABSTRACT Latar belakang: Clustered regularly interspaced short Background: Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) merupakan teknik untuk mengedit genom dengan efektif.