IP Library Granted Patent US 9,402,879
Granted Patent B2
US 9,402,879 · App. 14/039,828 · Granted Aug 2, 2016

Methods and compositions for modulating PD1

Inventors: Philip D. Gregory (Richmond, CA); Michael C Holmes (Richmond, CA); Matthew C. Mendel (Richmond, CA); Xiangdong Meng (Richmond, CA); David Paschon (Richmond, CA); Andreas Reik (Richmond, CA); Fyodor Urnov (Richmond, CA)
Assignee: Sangamo BioSciences, Inc.
A61K38/1709A61K35/17C12N9/22C07K2319/71
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Quick Facts
Patent No.
US 9,402,879
App. No.
14/039,828
Granted
Aug 2, 2016
Kind
B2
Abstract

Disclosed herein are methods and compositions for modulating expression of a PD1 gene.

Claims (362)

1. A method of repressing PD1 expression in a human T-cell cell of a subject having a disease or disorder characterized by aberrant expression or regulation of a PD1 gene, the method comprising

repressing expression of the PD1 gene in an isolated T-cell by administering a polynucleotide encoding a fusion protein comprising a zinc finger protein and a functional domain to the cell, wherein the zinc finger protein comprises four, five or six zinc finger recognition regions ordered from F1 to F4, F1 to F5 or F1 to F6, from N-terminus to C-terminus, and wherein the recognition regions comprise the following amino acid sequences:

(i) 

(SEQ ID NO: 1)

F1: QSGHLSR,

(SEQ ID NO: 2)

F2: RSDSLSV,

(SEQ ID NO: 3)

F3: HNDSRKN,

(SEQ ID NO: 4)

F4: RSDDLTR,

and

(SEQ ID NO: 5)

F5: RSDHLTQ;

(ii)

(SEQ ID NO: 6)

F1: RSAALSR,

(SEQ ID NO: 4)

F2: RSDDLTR,

(SEQ ID NO: 7)

F3: RSDHLTT,

(SEQ ID NO: 8)

F4: DRSALSR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(iii)

(SEQ ID NO: 10)

F1: RSAALAR,

(SEQ ID NO: 11)

F2: RSDDLSK,

(SEQ ID NO: 12)

F3: RNDHRKN,

(SEQ ID NO: 8)

F4: DRSALSR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(iv)

(SEQ ID NO: 13)

F1: RSDHLSE,

(SEQ ID NO: 14)

F2: TSSDRTK,

(SEQ ID NO: 13)

F3: RSDHLSE,

and

(SEQ ID NO: 15)

F4: QSASRKN;

(v)

(SEQ ID NO: 16)

F1: RSDVLSE,

(SEQ ID NO: 17)

F2: RSANLTR,

(SEQ ID NO: 18)

F3: RSDHLSQ,

(SEQ ID NO: 19)

F4: TSSNRKT,

(SEQ ID NO: 20)

F5: DRSNLSR,

and

(SEQ ID NO: 21)

F6: RSDALAR;

or

(vi)

(SEQ ID NO: 22)

F1: DDWNLSQ,

(SEQ ID NO: 17)

F2: RSANLTR,

(SEQ ID NO: 18)

F3: RSDHLSQ,

(SEQ ID NO: 19)

F4: TSSNRKT,

(SEQ ID NO: 20)

F5: DRSNLSR,

and

(SEQ ID NO: 21)

F6: RSDALAR;

(vii)

(SEQ ID NO: 23)

F1: RSSALSR,

(SEQ ID NO: 24)

F2: RPLALKH,

(SEQ ID NO: 12)

F3: RNDHRKN,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(viii)

(SEQ ID NO: 1)

F1: QSGHLSR,

(SEQ ID NO: 2)

F2: RSDSLSV,

(SEQ ID NO: 3)

F3: HNDSRKN,

(SEQ ID NO: 26)

F4: RANSLLR,

and 

(SEQ ID NO: 5)

F5: RSDHLTQ;

(ix) 

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 29)

F3: RNNNLRT,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(x)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR, 

(SEQ ID NO: 30)

F3: TNWHLRT,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xi)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 31)

F3: RTPHLTL,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xii)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 32)

F3: RSAQLAT,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xiii)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 33)

F3: RCTHLYL,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xiv)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 34)

F3: RPTQRYS,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xiv)

(SEQ ID NO: 27)

F1: RPSTLHR, 

(SEQ ID NO: 28)

F2: RSDELTR, 

(SEQ ID NO: 35)

F3: RANHREC,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xvi)

(SEQ ID NO: 36)

F1: RKFARPS,

(SEQ ID NO: 37)

F2: RNFSRSD,

(SEQ ID NO: 38)

F3: HPHHRMC,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xvii)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 39)

F3: RMGRLST,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xviii)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 40)

F3: RHSRLTT,

(SEQ ID NO: 41)

F4: TRPVLMR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xix)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 42)

F3: RANHRVC,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xx)

(SEQ ID NO: 27)

F1: RPSTLHR,

(SEQ ID NO: 28)

F2: RSDELTR, 

(SEQ ID NO: 43)

F3: RSTHLLG, 

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xxi) 

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR

(SEQ ID NO: 44)

F3: RSCGLWS

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xxii)

(SEQ ID NO: 46)

F1: CNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 47)

F3: REEHRAT,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xxiii)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 48)

F3: RHHHLAA,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xxiv)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 49)

F3: RPMHLTN,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

(xxv)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 50)

F3: RSPHLYH,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xxvi)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 51)

F3: RCEALHH,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 52)

F5: DRSAQAR;

(xxvii)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 51)

F3: RCEALHH,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

(xxviii)

(SEQ ID NO: 45)

F1: RNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 53)

F3: RLPALLS,

(SEQ ID NO: 25)

F4: TRPVLKR,

and 

(SEQ ID NO: 9)

F5: DRSALAR;

or

(xxix)

(SEQ ID NO: 54)

F1: HNAALTR,

(SEQ ID NO: 28)

F2: RSDELTR,

(SEQ ID NO: 55)

F3: RTYNRTQ,

(SEQ ID NO: 25)

F4: TRPVLKR,

and

(SEQ ID NO: 9)

F5: DRSALAR;

and

administering the cell to the subject.

2. The method of claim 1 , wherein the fusion protein comprises a transcriptional repression domain.

3. The method of claim 1 , wherein the fusion protein comprises a cleavage domain.

4. The method of claim 1 , wherein the disease or disorder is a cancer or a viral infection.

5. The method of claim 4 , further comprising administering an anti-viral or anti-cancer therapy to the subject.

6. The method of claim 5 , wherein the anti-viral or anti-cancer therapy are administered prior to, concurrently or sequentially with the cell.

7. The method of claim 1 , wherein the cell is a CD4+ T-cell.

Assignments (1)
CHANGE OF NAME Recorded May 17, 2018
From: SANGAMO BIOSCIENCES, INC.
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 046186/0719 →
Continuity (5)
Continuation 12927557 · Nov 17, 2010
Continuation In Part 12284887 · Sep 25, 2008
Provisional Application 60995566 · Sep 27, 2007
Provisional Application 61281432 · Nov 17, 2009
Related Publication 20140030240A1 · Jan 30, 2014