IP Library › Granted Patent US 10,633,445

Granted Patent B2

US 10,633,445 · App. 15/759,148 · Granted Apr 28, 2020

T-cell receptor (TCR)-binding antibodies and uses thereof

Inventors: Laurence J. N. Cooper (Houston, TX); Bipulendu Jena (Houston, TX)

Assignee: BOARD OF REGENTS THE UNIVERSITY OF TEXAS SYSTEM

C07K16/2809 A61K39/39558 C07K14/7051 C07K16/2833 C07K16/2896 C12N5/0636 C07K2317/34 C07K2317/56 C07K2317/565 C07K2317/622

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Quick Facts

Patent No.: US 10,633,445
App. No.: 15/759,148
Granted: Apr 28, 2020
Kind: B2

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Abstract

Antibodies and antigen binding fragments thereof are provided that bind to T-cell receptors (e.g., TCRα), essentially independent of T-cell epitope specificity. Methods for manipulation of T-cells and methods of treatment using such antibodies are likewise provided.

Claims (49)

1. An isolated antibody or antigen-binding fragment thereof that specifically binds to an epitope of T-cell receptor alpha (TCRα) polypeptide, wherein the antibody or antigen-binding fragment thereof comprises a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein

(a) HCDR1 has the amino acid sequence of SEQ ID NO: 2; or SEQ ID NO: 15;

(b) HCDR2 has the amino acid sequence of SEQ ID NO: 3; or SEQ ID NO: 16;

(d) LCDR1 has the amino acid sequence of SEQ ID NO: 4; or SEQ ID NO: 9;

(e) LCDR2 has the amino acid sequence of SEQ ID NO: 5; and

(f) LCDR3 has the amino acid sequence of SEQ ID NO: 6; or SEQ ID NO: 10.

2. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof is human or humanized.

3. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment thereof is a Fab, Fab′, F(ab′)2, scFv, or disulfide-linked Fv (sdFv).

4. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is an IgG, IgM or IgA antibody.

5. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof is membrane bound.

6. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof is conjugated to a reporter gene.

7. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 11, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 12.

8. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 11, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 14.

9. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 13, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 12.

10. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody antigen-binding fragment thereof comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 19, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 20.

11. An isolated polynucleotide comprising a sequence encoding the antibody or antigen binding fragment thereof according to claim 7 .

12. An isolated polynucleotide comprising a sequence encoding the antibody or antigen binding fragment thereof according to claim 8 .

13. An isolated polynucleotide comprising a sequence encoding the antibody or antigen binding fragment thereof according to claim 9 .

14. An isolated polynucleotide comprising a sequence encoding the antibody or antigen binding fragment thereof according to claim 10 .

15. A method for selecting a cell comprising a T-cell Receptor a chain (TCRα) comprising:

(i) contacting the cell with an antibody or antigen-binding fragment thereof that specifically binds to an epitope of T-cell receptor alpha (TCRα) polypeptide; wherein the antibody or antigen-binding fragment thereof comprises a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein

(a) HCDR1 has the amino acid sequence of SEQ ID NO: 2; or SEQ ID NO: 15;

(b) HCDR2 has the amino acid sequence of SEQ ID NO: 3; or SEQ ID NO: 16;

(d) LCDR1 has the amino acid sequence of SEQ ID NO: 4; or SEQ ID NO: 9;

(e) LCDR2 has the amino acid sequence of SEQ ID NO: 5; and

(f) LCDR3 has the amino acid sequence of SEQ ID NO: 6; or SEQ ID NO: 10; and

(ii) ii selecting a cell comprising the TCR α chain.

16. The method of claim 15 , wherein the antibody or antigen-binding fragment thereof is conjugated to a reporter gene.

17. A method for expanding and/or activating T-cells comprising contacting the T-cells with artificial antigen presenting cells (aAPCs) in the presence of an antibody or antigen binding fragment thereof that binds to an epitope of T-cell Receptor (TCR), alpha polypeptide, wherein the antibody or antigen-binding fragment thereof comprises a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein

(a) HCDR1 has the amino acid sequence of SEQ ID NO: 2; or SEQ ID NO: 15;

(b) HCDR2 has the amino acid sequence of SEQ ID NO: 3; or SEQ ID NO: 16;

(d) LCDR1 has the amino acid sequence of SEQ ID NO: 4; or SEQ ID NO: 9;

(e) LCDR2 has the amino acid sequence of SEQ ID NO: 5; and

(f) LCDR3 has the amino acid sequence of SEQ ID NO: 6; or SEQ ID NO: 10.

18. The method of claim 17 , wherein the antibody or antigen-binding fragment thereof further comprises a transmembrane domain.

19. A method of treating an autoimmune disease or a T cell leukemia in a subject in need of treatment, comprising administering an antibody or antigen-binding fragment thereof comprising a set of complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein

(a) HCDR1 has the amino acid sequence of SEQ ID NO: 2; or SEQ ID NO: 15;

(b) HCDR2 has the amino acid sequence of SEQ ID NO: 3; or SEQ ID NO: 16;

(d) LCDR1 has the amino acid sequence of SEQ ID NO: 4; or SEQ ID NO: 9;

(e) LCDR2 has the amino acid sequence of SEQ ID NO: 5; and

(f) LCDR3 has the amino acid sequence of SEQ ID NO: 6; or SEQ ID NO: 10.

20. An isolated host cell comprising one or more polynucleotide molecule(s) encoding an antibody or antigen-binding fragment thereof of claim 1 .

21. The antibody or antigen-binding fragment thereof according to claim 1 , wherein the epitope of T-cell receptor alpha (TCRα) polypeptide comprises GSTLRG (SEQ ID NO:1).

22. The method of claim 15 , wherein the epitope of T-cell receptor alpha (TCRα) polypeptide comprises GSTLRG (SEQ ID NO:1).

23. The method of claim 17 , wherein the epitope of T-cell receptor alpha (TCRα) polypeptide comprises GSTLRG (SEQ ID NO:1).

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2018

From: COOPER, LAURENCE J.N.; JENA, BIPULENDU

To: BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM

Reel/Frame 047487/0036 →

Continuity (2)

Provisional Application 62218990 · Sep 15, 2015

Related Publication 20180362648A1 · Dec 20, 2018