Methods and compositions for modulating PD1

• US 9,402,879 B2
• Filed: 09/27/2013
• Issued: 08/02/2016
• Est. Priority Date: 09/27/2007
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Biosciences, Inc.
• Inventors: Holmes, Michael C, Gregory, Philip D., Mendel, Matthew C., Meng, Xiangdong, Paschon, David, Reik, Andreas, Urnov, Fyodor
• Primary Examiner(s): DUNSTON, JENNIFER ANN
• Application Number:
  US14/039,828
• Publication Number:
  US 20140030240A1
• Time in Patent Office: 1,040 Days
• Field of Search: None
• US Class Current: 1/1
• 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 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:

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.