US 8,945,868 B2Granted

Methods and compositions for modification of a HLA locus

AssigneesSangamo BioSciences, Inc., Board of Regents, The University of Texas Systems

InventorsTrevor Collingwood, Laurence J. N. Cooper, Philip D. Gregory, Michael C. Holmes, Jeffrey C. Miller, Edward J. Rebar, Andreas Reik, Fyodor Urnov

Life of this patent

Estimating the term…

Abstract

Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

Claims9

Dependent claims

A protein comprising an engineered zinc finger DNA-binding domain, wherein the engineered zinc finger DNA-binding domain comprises four, five or six zinc finger DNA recognition regions designated and ordered F1 to F4, F1 to F5 or F1 to F6 from N-terminus to C-terminus and further wherein the engineered zinc finger DNA-binding domain comprises the zinc finger DNA recognition regions selected from the group consisting of:

(i) F1:
QSSHLTR (SEQ ID NO:1);
F2:
RSDHLTT (SEQ ID NO:2);
F3:
RSDTLSQ (SEQ ID NO:3);
F4:
RSADLSR (SEQ ID NO:4);
F5:
QSSDLSR (SEQ ID NO:5);
and
F6:
RSDALTQ (SEQ ID NO:6), wherein the protein binds to the target site set forth in SEQ ID NO:97 in an endogenous human leukocyte antigen (HLA) A2 gene;
(ii) F1:
QKTHLAK (SEQ ID NO:7);
F2:
RSDTLSN (SEQ ID NO:8);
F3:
RKDVRIT (SEQ ID NO:9);
F4:
RSDHLST (SEQ ID NO:10);
and
F5:
DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:98 in an endogenous HLA A2 gene;
(iii) F1:
QNAHRKT (SEQ ID NO:12);
F2:
RSDSLLR (SEQ ID NO:13);
F3:
RNDDRKK (SEQ ID NO:14);
F4:
RSDHLST (SEQ ID NO:10);
and
F5:
DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:99 in an endogenous HLA A2 gene;
(iv) F1:
DRSHLSR (SEQ ID NO:15);
F2:
RSDDLTR (SEQ ID NO:16);
F3:
DRSDLSR (SEQ ID NO:17);
and
F4:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:100 in an endogenous HLA A3 gene;
(v) F1:
DRSALSR (SEQ ID NO:19);
F2:
QSSDLRR (SEQ ID NO:20);
F3:
DRSALSR (SEQ ID NO:19);
F4:
DRSHLAR (SEQ ID NO:21);
F5:
RSDDLSK (SEQ ID NO:22);
and
F6:
DRSHLAR (SEQ ID NO:21), wherein the protein binds to the target site set forth in SEQ ID NO:101 in an endogenous HLA A3 gene;
(vi) F1:
SSELLNE (SEQ ID NO:23);
F2:
TSSHLSR (SEQ ID NO:24);
F3:
QSGDRNK (SEQ ID NO:25);
F4:
RSANLAR (SEQ ID NO:26);
and
F5:
RSDNLRE (SEQ ID NO:27), wherein the protein binds to the target site set forth in SEQ ID NO:102 in an endogenous HLA B gene;
(vii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
RSDDLTR (SEQ ID NO:16);
F3:
DQSTLRN (SEQ ID NO:29);
F4:
DRSNLSR (SEQ ID NO:30);
and
F5:
DAFTRTR (SEQ ID NO:31), wherein the protein binds to the target site set forth in SEQ ID NO:103 in an endogenous HLA B gene;
(viii) F1:
RSDNLSE (SEQ ID NO:32);
F2:
ASKTRKN (SEQ ID NO:33);
F3:
TSGNLTR (SEQ ID NO:34);
and
F4:
RSDALAR (SEQ ID NO:35), wherein the protein binds to the target site set forth in SEQ ID NO:104 in an endogenous HLA B gene;
(ix) F1:
DRSALSR (SEQ ID NO:19);
F2:
QSGNLAR (SEQ ID NO:36);
F3:
DRSALSR (SEQ ID NO:19);
F4:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:105 in an endogenous HLA B gene;
(x) F1:
RSDNLSE (SEQ ID NO:32);
F2:
ASKTRKN (SEQ ID NO:33);
F3:
QSGHLSR (SEQ ID NO:18);
F4:
TSGHLSR (SEQ ID NO:37);
and
F5:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:106 in an endogenous HLA B gene;
(xi) F1:
RSADLTR (SEQ ID NO:38);
F2:
QSGDLTR (SEQ ID NO:28);
F3:
QSGNLAR (SEQ ID NO:36);
and
F4:
QSGDLTR (SEQ ID NO:28), wherein the protein binds to the target site set forth in SEQ ID NO:107 in an endogenous HLA B gene;
(xii) F1:
QSGHLSR (SEQ ID NO:18);
F2:
RSDHLST (SEQ ID NO:10);
F3:
QSADRTK (SEQ ID NO:39);
F4:
TSGSLSR (SEQ ID NO:40);
and
F5:
QSADRTK (SEQ ID NO:39), wherein the protein binds to the target site set forth in SEQ ID NO:108 in an endogenous HLA C gene;
(xiii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
RSDHLST (SEQ ID NO:10);
F3:
QSADRTK (SEQ ID NO:39);
F4:
RSDNLSA (SEQ ID NO:41);
and
F5:
RSDNRTT (SEQ ID NO:42), wherein the protein binds to the target site set forth in SEQ ID NO:109 in an endogenous HLA C gene;
(xiv) F1:
QRSNLVR (SEQ ID NO:43);
F2:
DRSALAR (SEQ ID NO:44);
F3:
QSSDLRR (SEQ ID NO:20);
F4:
RSDDLTR (SEQ ID NO:16);
and
F5:
RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:110 in an endogenous HLA C gene;
(xv) F1:
RSDDLTR (SEQ ID NO:16);
F2:
DRSDLSR (SEQ ID NO:17);
F3:
QSGHLSR (SEQ ID NO:18);
F4:
RSDHLSA (SEQ ID NO:45);
and
F5:
ESRYLMV (SEQ ID NO:46), wherein the protein binds to the target site set forth in SEQ ID NO:111 in an endogenous HLA C gene;
(xvi) F1:
RSDHLST (SEQ ID NO:10);
F2:
DNANRTK (SEQ ID NO:47);
F3:
QSGDLTR (SEQ ID NO:28);
F4:
RSDALST (SEQ ID NO:48);
and
F5:
ASSNRKT (SEQ ID NO:49), wherein the protein binds to the target site set forth in SEQ ID NO:112 in an endogenous DBP2 gene;
(xvii) F1:
TSGNLTR (SEQ ID NO:34);
F2:
DRSDLSR (SEQ ID NO:17);
F3:
RSDNLSE (SEQ ID NO:32);
F4:
RSANLTR (SEQ ID NO:50);
and
F5:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:113 in an endogenous DBP2 gene;
(xviii) F1:
RSDNLSE (SEQ ID NO:32);
F2:
TSGSLTR (SEQ ID NO:51);
F3:
TSGHLSR (SEQ ID NO:37);
F4:
RSDNLSQ (SEQ ID NO:52);
and
F5:
ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:114 in an endogenous DRA gene;
(xix) F1:
RSDNLSR (SEQ ID NO:54);
F2:
DNNARIN (SEQ ID NO:55);
F3:
RSDSLSV (SEQ ID NO:56);
F4:
QNQHRIN (SEQ ID NO:57);
and
F5:
RSDHLSR (SEQ ID NO:58), wherein the protein binds to the target site set forth in SEQ ID NO:115 in an endogenous DRA gene;
(xx) F1:
DSSDRKK (SEQ ID NO:59);
F2:
DRSHLTR (SEQ ID NO:60);
F3:
RSDALAR (SEQ ID NO:35);
F4:
QSSDLSR (SEQ ID NO:5);
and
F5:
RSDNLTT (SEQ ID NO:61), wherein the protein binds to the target site set forth in SEQ ID NO:116 in an endogenous transporter associated with antigen processing 1 (TAP1) gene;
(xxi) F1:
RSANLAR (SEQ ID NO:26);
F2:
QSGHLSR (SEQ ID NO:18);
F3:
TSGNLTR (SEQ ID NO:34);
F4:
QSGALVI (SEQ ID NO:62);
F5:
RSDHLSE (SEQ ID NO:63);
and
F6:
RKHDRTK (SEQ ID NO:64), wherein the protein binds to the target site set forth in SEQ ID NO:117 in an endogenous TAP1 gene;
(xxii) F1:
QSSDLSR (SEQ ID NO:5);
F2:
QSGDLTR (SEQ ID NO:28);
F3:
QSSHLTR (SEQ ID NO:1):
F4:
RSDDRKT (SEQ ID NO:65);
F5:
TSGNLTR (SEQ ID NO:34);
and
F6:
RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:118 in an endogenous transporter associated with antigen processing 2(TAP2) gene;
(xxiii) F1:
RSDNLST (SEQ ID NO:66);
F2:
RSDALAR (SEQ ID NO:35);
F3:
RSDVLSA (SEQ ID NO:67);
F4:
DRSNRIK (SEQ ID NO:68);
F5:
RREDLIT (SEQ ID NO:69);
and
F6:
TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:119 in an endogenous TAP2 gene;
(xxiv) F1:
RSDNLSE (SEQ ID NO:32);
F2:
KRCNLRC (SEQ ID NO:71);
F3:
DRSDLSR (SEQ ID NO:17);
F4:
QTTHRNR (SEQ ID NO:72);
F5:
DRSDLSR (SEQ ID NO:17), and
F6:
QSSTRAR (SEQ ID NO:73), wherein the protein binds to the target site set forth in SEQ ID NO:120 in an endogenous tapasin gene;
(xxv) F1:
QSSDLR (SEQ ID NO:5);
F2:
RSDNLTR (SEQ ID NO:74);
F3:
QSSHLTR (SEQ ID NO:1);
F4:
QSSDLTR (SEQ ID NO:75);
F5:
RSDNLAR (SEQ ID NO:76);
and
F6:
QKVNLMS (SEQ ID NO:77), wherein the protein binds to the target site set forth in SEQ ID NO:121 in an endogenous tapasin gene;
(xxvi) F1:
TSGNLTR (SEQ ID NO:34);
F2:
LSQDLNR (SEQ ID NO:78);
F3:
RSDSLSA (SEQ ID NO:79);
F4:
DRSHLAR (SEQ ID NO:21);
F5:
RSDHLST (SEQ ID NO:10);
and
F6:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:122 in an endogenous tapasin gene;
(xxvii) F1:
RSDDLTR (SEQ ID NO:16);
F2:
SSSNLTK (SEQ ID NO:80);
F3:
TSGSLSR (SEQ ID NO:40);
F4:
QSGDLTR (SEQ ID NO:28);
F5:
RSDHLSE (SEQ ID NO:63);
and
F6:
RNRDRIT (SEQ ID NO:81), wherein the protein binds to the target site set forth in SEQ ID NO:123 in an endogenous tapasin gene;
(xxviii) F1:
RSDDLTR (SEQ ID NO:16);
F2:
RSDHLSE (SEQ ID NO:63);
F3:
NSRNRKT (SEQ ID NO:82);
F4:
RSDNLSQ (SEQ ID NO:52);
and
F5:
ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:124 in an endogenous class 2 transactivator (CTIIA) gene;
(xxvix) F1:
RSDDLSR (SEQ ID NO:83);
F2:
RNDDRKK (SEQ ID NO:14);
F3:
DRSDLSR (SEQ ID NO:17);
F4:
RSDHLSE (SEQ ID NO:63);
and
F5:
ARSTRTN (SEQ ID NO:84), wherein the protein binds to the target site set forth in SEQ ID NO:125 in an endogenous CTIIIA gene;
(xxx) F1:
TSGNLTR (SEQ ID NO:34);
F2:
QSGNLAR (SEQ ID NO:36);
F3:
RSDHLTQ (SEQ ID NO:85);
F4:
ASMALNE (SEQ ID NO:86);
and
F5:
TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:126 in an endogenous regulatory factor X protein 5 (RXF5) gene;
(xxxi) F1:
RSDVLSE (SEQ ID NO:87);
F2:
RNQHRKT (SEQ ID NO:88);
F3:
RSDHLST (SEQ ID NO:10);
F4:
QSSDLRR (SEQ ID NO:20);
F5:
RSDNLST (SEQ ID NO:66);
and
F6:
RSADRKN (SEQ ID NO:89), wherein the protein binds to the target site set forth in SEQ ID NO:127 in an endogenous RXF5 gene;
(xxxii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
QWGTRYR (SEQ ID NO:90);
F3:
ERGTLAR (SEQ ID NO:91);
F4:
RSDNLRE (SEQ ID NO:27);
F5:
QSGDLTR (SEQ ID NO:28);
and
F6:
TSGSLTR (SEQ ID NO:51), wherein the protein binds to the target site set forth in SEQ ID NO:128 in an endogenous T-cell receptor alpha (TRAC) gene;
(xxxiii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
WRSSLAS (SEQ ID NO:92);
F3:
QSGDLTR (SEQ ID NO:28);
F4:
HKWVLRQ (SEQ ID NO:93);
and
F5:
DRSNLTR (SEQ ID NO:94), wherein the protein binds to the target site set forth in SEQ ID NO:129 in an endogenous TRAC gene;
(xxxiv)F1:
RSDVLSA (SEQ ID NO:67);
F2:
DRSNRIK (SEQ ID NO:68);
F3:
RSDVLSE (SEQ ID NO:87);
F4:
QSGNLAR (SEQ ID NO:36);
and
F5:
QSGSLTR (SEQ ID NO:95), wherein the protein binds to the target site set forth in SEQ ID NO:130 in an endogenous T-cell receptor beta (TRBC) gene;
and
(xxxv) F1:
RSDHLST (SEQ ID NO:10);
F2:
RSDNLTR (SEQ ID NO:74);
F3:
DRSNLSR (SEQ ID NO:30);
F4:
TSSNRKT (SEQ ID NO:96);
F5:
RSANLAR (SEQ ID NO:26);
and
F6:
RNDDRKK (SEQ ID NO:14), wherein the protein binds to the target site set forth in SEQ ID NO:131 in an endogenous TRBC gene.

397 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/188,417Filed 21 Jul 2011 · us provisional application
Priority: 21 Jul 2010
Published: US 2012/0060230 A18 Mar 2012
Granted: 3 Feb 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07K 14/70539
Immunoglobulin superfamily: mHC-molecules, e.g. HLA-molecules
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/31
Characterised by the recombinant expression of specific molecules in the cells of the immune system: chimeric antigen receptors [CAR]
A61K 40/4211
Immunoglobulin superfamily: cd19 or b4

Family

Application61/400,009Us provisional application · filed 21 Jul 2010
Application61/404,685Us provisional application · filed 6 Oct 2010
US 2012/0060230 A1Pre-grant publication · published 8 Mar 2012
US 8,945,868 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.

(i) F1:
QSSHLTR (SEQ ID NO:1);
F2:
RSDHLTT (SEQ ID NO:2);
F3:
RSDTLSQ (SEQ ID NO:3);
F4:
RSADLSR (SEQ ID NO:4);
F5:
QSSDLSR (SEQ ID NO:5);
and
F6:
RSDALTQ (SEQ ID NO:6), wherein the protein binds to the target site set forth in SEQ ID NO:97 in an endogenous human leukocyte antigen (HLA) A2 gene;
(ii) F1:
QKTHLAK (SEQ ID NO:7);
F2:
RSDTLSN (SEQ ID NO:8);
F3:
RKDVRIT (SEQ ID NO:9);
F4:
RSDHLST (SEQ ID NO:10);
and
F5:
DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:98 in an endogenous HLA A2 gene;
(iii) F1:
QNAHRKT (SEQ ID NO:12);
F2:
RSDSLLR (SEQ ID NO:13);
F3:
RNDDRKK (SEQ ID NO:14);
F4:
RSDHLST (SEQ ID NO:10);
and
F5:
DSSARKK (SEQ ID NO:11), wherein the protein binds to the target site set forth in SEQ ID NO:99 in an endogenous HLA A2 gene;
(iv) F1:
DRSHLSR (SEQ ID NO:15);
F2:
RSDDLTR (SEQ ID NO:16);
F3:
DRSDLSR (SEQ ID NO:17);
and
F4:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:100 in an endogenous HLA A3 gene;
(v) F1:
DRSALSR (SEQ ID NO:19);
F2:
QSSDLRR (SEQ ID NO:20);
F3:
DRSALSR (SEQ ID NO:19);
F4:
DRSHLAR (SEQ ID NO:21);
F5:
RSDDLSK (SEQ ID NO:22);
and
F6:
DRSHLAR (SEQ ID NO:21), wherein the protein binds to the target site set forth in SEQ ID NO:101 in an endogenous HLA A3 gene;
(vi) F1:
SSELLNE (SEQ ID NO:23);
F2:
TSSHLSR (SEQ ID NO:24);
F3:
QSGDRNK (SEQ ID NO:25);
F4:
RSANLAR (SEQ ID NO:26);
and
F5:
RSDNLRE (SEQ ID NO:27), wherein the protein binds to the target site set forth in SEQ ID NO:102 in an endogenous HLA B gene;
(vii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
RSDDLTR (SEQ ID NO:16);
F3:
DQSTLRN (SEQ ID NO:29);
F4:
DRSNLSR (SEQ ID NO:30);
and
F5:
DAFTRTR (SEQ ID NO:31), wherein the protein binds to the target site set forth in SEQ ID NO:103 in an endogenous HLA B gene;
(viii) F1:
RSDNLSE (SEQ ID NO:32);
F2:
ASKTRKN (SEQ ID NO:33);
F3:
TSGNLTR (SEQ ID NO:34);
and
F4:
RSDALAR (SEQ ID NO:35), wherein the protein binds to the target site set forth in SEQ ID NO:104 in an endogenous HLA B gene;
(ix) F1:
DRSALSR (SEQ ID NO:19);
F2:
QSGNLAR (SEQ ID NO:36);
F3:
DRSALSR (SEQ ID NO:19);
F4:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:105 in an endogenous HLA B gene;
(x) F1:
RSDNLSE (SEQ ID NO:32);
F2:
ASKTRKN (SEQ ID NO:33);
F3:
QSGHLSR (SEQ ID NO:18);
F4:
TSGHLSR (SEQ ID NO:37);
and
F5:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:106 in an endogenous HLA B gene;
(xi) F1:
RSADLTR (SEQ ID NO:38);
F2:
QSGDLTR (SEQ ID NO:28);
F3:
QSGNLAR (SEQ ID NO:36);
and
F4:
QSGDLTR (SEQ ID NO:28), wherein the protein binds to the target site set forth in SEQ ID NO:107 in an endogenous HLA B gene;
(xii) F1:
QSGHLSR (SEQ ID NO:18);
F2:
RSDHLST (SEQ ID NO:10);
F3:
QSADRTK (SEQ ID NO:39);
F4:
TSGSLSR (SEQ ID NO:40);
and
F5:
QSADRTK (SEQ ID NO:39), wherein the protein binds to the target site set forth in SEQ ID NO:108 in an endogenous HLA C gene;
(xiii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
RSDHLST (SEQ ID NO:10);
F3:
QSADRTK (SEQ ID NO:39);
F4:
RSDNLSA (SEQ ID NO:41);
and
F5:
RSDNRTT (SEQ ID NO:42), wherein the protein binds to the target site set forth in SEQ ID NO:109 in an endogenous HLA C gene;
(xiv) F1:
QRSNLVR (SEQ ID NO:43);
F2:
DRSALAR (SEQ ID NO:44);
F3:
QSSDLRR (SEQ ID NO:20);
F4:
RSDDLTR (SEQ ID NO:16);
and
F5:
RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:110 in an endogenous HLA C gene;
(xv) F1:
RSDDLTR (SEQ ID NO:16);
F2:
DRSDLSR (SEQ ID NO:17);
F3:
QSGHLSR (SEQ ID NO:18);
F4:
RSDHLSA (SEQ ID NO:45);
and
F5:
ESRYLMV (SEQ ID NO:46), wherein the protein binds to the target site set forth in SEQ ID NO:111 in an endogenous HLA C gene;
(xvi) F1:
RSDHLST (SEQ ID NO:10);
F2:
DNANRTK (SEQ ID NO:47);
F3:
QSGDLTR (SEQ ID NO:28);
F4:
RSDALST (SEQ ID NO:48);
and
F5:
ASSNRKT (SEQ ID NO:49), wherein the protein binds to the target site set forth in SEQ ID NO:112 in an endogenous DBP2 gene;
(xvii) F1:
TSGNLTR (SEQ ID NO:34);
F2:
DRSDLSR (SEQ ID NO:17);
F3:
RSDNLSE (SEQ ID NO:32);
F4:
RSANLTR (SEQ ID NO:50);
and
F5:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:113 in an endogenous DBP2 gene;
(xviii) F1:
RSDNLSE (SEQ ID NO:32);
F2:
TSGSLTR (SEQ ID NO:51);
F3:
TSGHLSR (SEQ ID NO:37);
F4:
RSDNLSQ (SEQ ID NO:52);
and
F5:
ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:114 in an endogenous DRA gene;
(xix) F1:
RSDNLSR (SEQ ID NO:54);
F2:
DNNARIN (SEQ ID NO:55);
F3:
RSDSLSV (SEQ ID NO:56);
F4:
QNQHRIN (SEQ ID NO:57);
and
F5:
RSDHLSR (SEQ ID NO:58), wherein the protein binds to the target site set forth in SEQ ID NO:115 in an endogenous DRA gene;
(xx) F1:
DSSDRKK (SEQ ID NO:59);
F2:
DRSHLTR (SEQ ID NO:60);
F3:
RSDALAR (SEQ ID NO:35);
F4:
QSSDLSR (SEQ ID NO:5);
and
F5:
RSDNLTT (SEQ ID NO:61), wherein the protein binds to the target site set forth in SEQ ID NO:116 in an endogenous transporter associated with antigen processing 1 (TAP1) gene;
(xxi) F1:
RSANLAR (SEQ ID NO:26);
F2:
QSGHLSR (SEQ ID NO:18);
F3:
TSGNLTR (SEQ ID NO:34);
F4:
QSGALVI (SEQ ID NO:62);
F5:
RSDHLSE (SEQ ID NO:63);
and
F6:
RKHDRTK (SEQ ID NO:64), wherein the protein binds to the target site set forth in SEQ ID NO:117 in an endogenous TAP1 gene;
(xxii) F1:
QSSDLSR (SEQ ID NO:5);
F2:
QSGDLTR (SEQ ID NO:28);
F3:
QSSHLTR (SEQ ID NO:1):
F4:
RSDDRKT (SEQ ID NO:65);
F5:
TSGNLTR (SEQ ID NO:34);
and
F6:
RSDDLTR (SEQ ID NO:16), wherein the protein binds to the target site set forth in SEQ ID NO:118 in an endogenous transporter associated with antigen processing 2(TAP2) gene;
(xxiii) F1:
RSDNLST (SEQ ID NO:66);
F2:
RSDALAR (SEQ ID NO:35);
F3:
RSDVLSA (SEQ ID NO:67);
F4:
DRSNRIK (SEQ ID NO:68);
F5:
RREDLIT (SEQ ID NO:69);
and
F6:
TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:119 in an endogenous TAP2 gene;
(xxiv) F1:
RSDNLSE (SEQ ID NO:32);
F2:
KRCNLRC (SEQ ID NO:71);
F3:
DRSDLSR (SEQ ID NO:17);
F4:
QTTHRNR (SEQ ID NO:72);
F5:
DRSDLSR (SEQ ID NO:17), and
F6:
QSSTRAR (SEQ ID NO:73), wherein the protein binds to the target site set forth in SEQ ID NO:120 in an endogenous tapasin gene;
(xxv) F1:
QSSDLR (SEQ ID NO:5);
F2:
RSDNLTR (SEQ ID NO:74);
F3:
QSSHLTR (SEQ ID NO:1);
F4:
QSSDLTR (SEQ ID NO:75);
F5:
RSDNLAR (SEQ ID NO:76);
and
F6:
QKVNLMS (SEQ ID NO:77), wherein the protein binds to the target site set forth in SEQ ID NO:121 in an endogenous tapasin gene;
(xxvi) F1:
TSGNLTR (SEQ ID NO:34);
F2:
LSQDLNR (SEQ ID NO:78);
F3:
RSDSLSA (SEQ ID NO:79);
F4:
DRSHLAR (SEQ ID NO:21);
F5:
RSDHLST (SEQ ID NO:10);
and
F6:
QSGHLSR (SEQ ID NO:18), wherein the protein binds to the target site set forth in SEQ ID NO:122 in an endogenous tapasin gene;
(xxvii) F1:
RSDDLTR (SEQ ID NO:16);
F2:
SSSNLTK (SEQ ID NO:80);
F3:
TSGSLSR (SEQ ID NO:40);
F4:
QSGDLTR (SEQ ID NO:28);
F5:
RSDHLSE (SEQ ID NO:63);
and
F6:
RNRDRIT (SEQ ID NO:81), wherein the protein binds to the target site set forth in SEQ ID NO:123 in an endogenous tapasin gene;
(xxviii) F1:
RSDDLTR (SEQ ID NO:16);
F2:
RSDHLSE (SEQ ID NO:63);
F3:
NSRNRKT (SEQ ID NO:82);
F4:
RSDNLSQ (SEQ ID NO:52);
and
F5:
ASNDRKK (SEQ ID NO:53), wherein the protein binds to the target site set forth in SEQ ID NO:124 in an endogenous class 2 transactivator (CTIIA) gene;
(xxvix) F1:
RSDDLSR (SEQ ID NO:83);
F2:
RNDDRKK (SEQ ID NO:14);
F3:
DRSDLSR (SEQ ID NO:17);
F4:
RSDHLSE (SEQ ID NO:63);
and
F5:
ARSTRTN (SEQ ID NO:84), wherein the protein binds to the target site set forth in SEQ ID NO:125 in an endogenous CTIIIA gene;
(xxx) F1:
TSGNLTR (SEQ ID NO:34);
F2:
QSGNLAR (SEQ ID NO:36);
F3:
RSDHLTQ (SEQ ID NO:85);
F4:
ASMALNE (SEQ ID NO:86);
and
F5:
TSSNLSR (SEQ ID NO:70), wherein the protein binds to the target site set forth in SEQ ID NO:126 in an endogenous regulatory factor X protein 5 (RXF5) gene;
(xxxi) F1:
RSDVLSE (SEQ ID NO:87);
F2:
RNQHRKT (SEQ ID NO:88);
F3:
RSDHLST (SEQ ID NO:10);
F4:
QSSDLRR (SEQ ID NO:20);
F5:
RSDNLST (SEQ ID NO:66);
and
F6:
RSADRKN (SEQ ID NO:89), wherein the protein binds to the target site set forth in SEQ ID NO:127 in an endogenous RXF5 gene;
(xxxii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
QWGTRYR (SEQ ID NO:90);
F3:
ERGTLAR (SEQ ID NO:91);
F4:
RSDNLRE (SEQ ID NO:27);
F5:
QSGDLTR (SEQ ID NO:28);
and
F6:
TSGSLTR (SEQ ID NO:51), wherein the protein binds to the target site set forth in SEQ ID NO:128 in an endogenous T-cell receptor alpha (TRAC) gene;
(xxxiii) F1:
QSGDLTR (SEQ ID NO:28);
F2:
WRSSLAS (SEQ ID NO:92);
F3:
QSGDLTR (SEQ ID NO:28);
F4:
HKWVLRQ (SEQ ID NO:93);
and
F5:
DRSNLTR (SEQ ID NO:94), wherein the protein binds to the target site set forth in SEQ ID NO:129 in an endogenous TRAC gene;
(xxxiv)F1:
RSDVLSA (SEQ ID NO:67);
F2:
DRSNRIK (SEQ ID NO:68);
F3:
RSDVLSE (SEQ ID NO:87);
F4:
QSGNLAR (SEQ ID NO:36);
and
F5:
QSGSLTR (SEQ ID NO:95), wherein the protein binds to the target site set forth in SEQ ID NO:130 in an endogenous T-cell receptor beta (TRBC) gene;
and
(xxxv) F1:
RSDHLST (SEQ ID NO:10);
F2:
RSDNLTR (SEQ ID NO:74);
F3:
DRSNLSR (SEQ ID NO:30);
F4:
TSSNRKT (SEQ ID NO:96);
F5:
RSANLAR (SEQ ID NO:26);
and
F6:
RNDDRKK (SEQ ID NO:14), wherein the protein binds to the target site set forth in SEQ ID NO:131 in an endogenous TRBC gene.

397 more elements

Facts

Application

13/188,417Filed 21 Jul 2011 · us provisional application

Priority

21 Jul 2010

Published

US 2012/0060230 A18 Mar 2012

Granted

3 Feb 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification25 codes

C07K 14/70539
Immunoglobulin superfamily: mHC-molecules, e.g. HLA-molecules
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/31
Characterised by the recombinant expression of specific molecules in the cells of the immune system: chimeric antigen receptors [CAR]
A61K 40/4211
Immunoglobulin superfamily: cd19 or b4