Methods and compositions for modulating PD1

• US 10,046,028 B2
• Filed: 04/20/2016
• Issued: 08/14/2018
• Est. Priority Date: 09/27/2007
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Gregory, Philip D., Holmes, Michael C., Mendel, Matthew C., Meng, Xiangdong, Paschon, David, Reik, Andreas, Urnov, Fyodor
• Primary Examiner(s): Dunston, Jennifer
• Application Number:
  US15/133,862
• Publication Number:
  US 20160220634A1
• Time in Patent Office: 846 Days
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/46433 Antigens related to auto-immune diseases; Preparations to induce self-tolerance
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 2319/71 containing domain for transcriptional activaation, e.g. VP16
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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

Claims

1. A method of activating PD1 expression in a human subject having an autoimmune disease or disorder, the method comprising

activating 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 transcriptional activation domain to the cell, wherein the zinc finger protein comprises comprising 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) F1;

QSGHLSR (SEQ ID NO;

     1), F2;

RSDSLSV (SEQ ID NO;

     2), F3;

HNDSRKN (SEQ ID NO;

     3), F4;

RSDDLTR (SEQ ID NO;

     4), and F5;

RSDHLTQ (SEQ ID NO;

     5);

(ii) F1;

RSAALSR (SEQ ID NO;

     6), F2;

RSDDLTR (SEQ ID NO;

     4), F3;

RSDHLTT (SEQ ID NO;

     7), F4;

DRSALSR (SEQ ID NO;

     8), and F5;

DRSALAR (SEQ ID NO;

     9);

(iii) F1;

RSAALAR (SEQ ID NO;

     10), F2;

RSDDLSK (SEQ ID NO;

     11), F3;

RNDHRKN (SEQ ID NO;

     12), F4;

DRSALSR (SEQ ID NO;

     8), and F5;

DRSALAR (SEQ ID NO;

     9);

(iv) F1;

RSDHLSE (SEQ ID NO;

     13), F2;

TSSDRTK (SEQ ID NO;

     14), F3;

RSDHLSE (SEQ ID NO;

     13), and F4;

QSASRKN (SEQ ID NO;

     15);

(v) F1;

RSDVLSE (SEQ ID NO;

     16), F2;

RSANLTR (SEQ ID NO;

     17), F3;

RSDHLSQ (SEQ ID NO;

     18), F4;

TSSNRKT (SEQ ID NO;

     19), F5;

DRSNLSR (SEQ ID NO;

     20), and F6;

RSDALAR (SEQ ID NO;

     21);

or

(vi) F1;

DDWNLSQ (SEQ ID NO;

     22), F2;

RSANLTR (SEQ ID NO;

     17), F3;

RSDHLSQ (SEQ ID NO;

     18), F4;

TSSNRKT (SEQ ID NO;

     19), F5;

DRSNLSR (SEQ ID NO;

     20), and F6;

RSDALAR (SEQ ID NO;

     21);

(vii) F1;

RSSALSR (SEQ ID NO;

     23), F2;

RPLALKH (SEQ ID NO;

     24), F3;

RNDHRKN (SEQ ID NO;

     12), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(viii) F1;

QSGHLSR (SEQ ID NO;

     1), F2;

RSDSLSV (SEQ ID NO;

     2), F3;

HNDSRKN (SEQ ID NO;

     3), F4;

RANSLLR (SEQ ID NO;

     26), and F5;

RSDHLTQ (SEQ ID NO;

     5);

(ix) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RNNNLRT (SEQ ID NO;

     29), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(x) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

TNWHLRT (SEQ ID NO;

     30), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xi) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RTPHLTL (SEQ ID NO;

     31), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xii) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RSAQLAT (SEQ ID NO;

     32), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xiii) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RCTHLYL (SEQ ID NO;

     33), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xiv) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RPTQRYS (SEQ ID NO;

     34), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xiv) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RANHREC (SEQ ID NO;

     35), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xvi) F1;

RKFARPS (SEQ ID NO;

     36), F2;

RNFSRSD (SEQ ID NO;

     37), F3;

HPHHRMC (SEQ ID NO;

     38), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xvii) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RMGRLST (SEQ ID NO;

     39), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xviii) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RHSRLTT (SEQ ID NO;

     40), F4;

TRPVLMR (SEQ ID NO;

     41), and F5;

DRSALAR (SEQ ID NO;

     9);

(xix) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RANHRVC (SEQ ID NO;

     42), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xx) F1;

RPSTLHR (SEQ ID NO;

     27), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RSTHLLG (SEQ ID NO;

     43), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxi) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28) F3;

RSCGLWS (SEQ ID NO;

     44), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxii) F1;

CNAALTR (SEQ ID NO;

     46), F2;

RSDELTR (SEQ ID NO;

     28), F3;

REEHRAT (SEQ ID NO;

     47), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxiii) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RHHHLAA (SEQ ID NO;

     48), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxiv) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RPMHLTN (SEQ ID NO;

     49), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxv) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RSPHLYH (SEQ ID NO;

     50), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxvi) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RCEALHH (SEQ ID NO;

     51), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSAQAR (SEQ ID NO;

     52);

(xxvii) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RCEALHH (SEQ ID NO;

     51), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9);

(xxviii) F1;

RNAALTR (SEQ ID NO;

     45), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RLPALLS (SEQ ID NO;

     53), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9); and

(xxix) F1;

HNAALTR (SEQ ID NO;

     54), F2;

RSDELTR (SEQ ID NO;

     28), F3;

RTYNRTQ (SEQ ID NO;

     55), F4;

TRPVLKR (SEQ ID NO;

     25), and F5;

DRSALAR (SEQ ID NO;

     9) and

administering the T cell to the human subject.

2. The method of claim 1, wherein the autoimmune disease is Hashimoto'"'"'s thyroiditis, Systemic lupus erythematosus, Sjogren'"'"'s syndrome, Graves'"'"' disease, Scleroderma, Rheumatoid arthritis, Multiple sclerosis, Myasthenia gravis and/or Diabetes.

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