METHODS AND COMPOSITIONS FOR ENGINEERING IMMUNITY

• US 20170196992A1
• Filed: 11/21/2016
• Published: 07/13/2017
• Est. Priority Date: 11/23/2015
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Biosciences, Inc. (Sangamo Therapeutics, Inc.)
• Inventors: Holmes, Michael C., Riley, Brigit E.
• Granted Patent: US 10,639,383 B2
• Time in Patent Office: Days
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 48/0058 Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector

Abstract

Nucleases and methods of using these nucleases for expressing an antibody from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.

Claims

1. A method of expressing, in a cell, an antibody that binds to a protein selected from the group of a cancer antigen, a cellular receptor, a cytokine, a growth factor, a growth factor receptor, a kinase inhibitor, an integrin, α

-synuclein, an amyloid protein, and a complement protein, the method comprising,

integrating a transgene encoding the antibody into a safe-harbor locus of the cell such that the cell produces the antibody.

2. The method of claim 1, wherein the safe harbor locus is an albumin gene.

3. The method of claim 1, wherein expression of the transgene is driven by an endogenous promoter.

4. The method of claim 1, wherein the transgene is a fusion protein comprising amino acids encoded by the transgene and by the endogenous safe-harbor locus into which the transgene is integrated.

5. The method of claim 1, wherein the cell is selected from the group consisting of a liver cell, a muscle cell and a stem cell.

6. The method of claim 5, wherein the stem cell is a hematopoietic stem cell or induced pluripotent stem cell.

7. The method of claim 1, wherein the antibody comprises a single chain fragment variable (ScFv), an intrabody or a diabody.

8. The method of claim 1, wherein the antibody is expressed in a cell of the subject and further wherein the antibody treats and/or prevents a cancer, an autoimmune disease, a neurological disorder, pain and/or osteoarthritis.

9. The method of claim 8, wherein the antibody is expressed in the liver, serum and/or brain of the subject.

10. The method of claim 1, wherein the transgene is delivered to the cell using a viral vector.

12. A genetically modified cell produced by the method of claim 1.

13. The method of claim 1, wherein the transgene is integrated into a cell in a live subject.

14. The method of claim 1, wherein the transgene is integrated into an isolated cell and further comprising the step of administering the isolated cell to a live subject.

15. The method of claim 13, wherein the antibody treats and/or prevents a cancer, an autoimmune disease, a neurological disorder, pain and/or osteoarthritis in the subject.

16. The method of claim 14, wherein the antibody treats and/or prevents a cancer, an autoimmune disease, a neurological disorder, pain and/or osteoarthritis in the subject.

11. The method of claim 11, wherein the viral vector is an AAV vector.