HLA-restricted, peptide-specific antigen binding proteins

Patent metadata

Field	Value
Publication number	US-9453075-B2
Application number	US-201414299509-A
Country	US
Kind code	B2
Filing date	Jun 9, 2014
Priority date	Feb 11, 2011
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

Antigen binding proteins with TCR-like paratopes, that is, with an antigen binding region specific for an HLA-A2 restricted peptide are disclosed. The antigen binding proteins encompass antibodies in a variety of forms, including full-length antibodies, substantially intact antibodies, Fab fragments, F(ab′)2 fragments, and single chain Fv fragments. Fusion proteins, such as scFv fusions with immunoglobulin or T-cell receptor domains, incorporating the specificity of the antigen binding region for each peptide are also contemplated by the invention. Furthermore, immunoconjugates may include antibodies to which is linked a radioisotope, fluorescent or other detectable marker, cytotoxin, or other molecule are also encompassed by the invention. Among other things, immunoconjugates can be used for delivery of an agent to elicit a therapeutic effect or to facilitate an immune effector function.

First claim

The invention claimed is:

1. An antigen-binding protein comprising one of:
(A) an antigen binding region having the amino acid sequence of SEQ ID NO: 5;
(B) an antigen binding region comprising a V H and a V L respectively, with the amino acid sequences SEQ ID NOs: 24 and 25; or
(C) (i)
(a) a light chain (LC) complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO: 56;
(b) a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 58; and
(c) a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 65; and
(ii) (a) a heavy chain (HC) complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO: 39;
(b) a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 41; and
(c) a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 49.

2. The antigen-binding protein of claim 1 , wherein the antigen-binding protein is an antibody.

3. The antigen-binding protein of claim 2 , wherein the antibody is a full-length antibody, an intact antibody, a Fab fragment, a F(ab′) 2 fragment or a single chain variable fragment (scFv).

4. The antigen-binding protein of claim 1 , wherein the antigen-binding protein is a chimeric antigen receptor (CAR).

5. The antigen-binding protein of claim 1 , wherein the antigen-binding protein specifically binds to an epitope on an human leukocyte antigen (HLA)/peptide complex.

6. The isolated antigen-binding protein of claim 5 , wherein the peptide of the HLA/peptide complex has the amino acid sequence LLDFVRFMGV (SEQ ID NO:4).

7. The isolated antigen-binding protein of claim 1 , wherein the HLA of the HLA/peptide complex is HLA-A2.

8. A fusion protein comprising an antigen-binding protein of claim 1 .

9. A single-chain variable fragment (scFv) comprising the amino acid sequences set forth in SEQ ID NO: 5.

10. A scFv comprising a V H and a V L linked by an amino acid spacer, wherein the V H and V L respectively comprise the amino acid sequences set forth in SEQ ID NOS: 24 and 25.

11. An immunoconjugate comprising a first component which is an antigen-binding protein or fragment thereof of claim 1 .

12. The immunoconjugate of claim 11 , comprising a second component having a second amino acid sequence.

13. The immunoconjugate of claim 12 , further comprising a cytotoxin.

14. The immunoconjugate of claim 12 , wherein the second component is a binding protein or antibody having a binding specificity for a target that is different from the HLA-peptide complex.

15. A bispecific antibody comprising an antigen-binding protein of claim 1 .

16. A pharmaceutical composition comprising an antibody binding protein of claim 1 .

Assignees

• Cheung Nai-Kong
• Tassev Dimiter
• Hu Jian
• Memorial Sloan Kettering Cancer Center

Inventors

• Cheung Nai-Kong
• Tassev Dimiter
• Hu Jian

Classifications

• A61K40/4243

  Wilms tumor 1 [WT1] · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/15

  Natural-killer [NK] cells; Natural-killer T [NKT] cells · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K16/2833 Primary

  against MHC-molecules, e.g. HLA-molecules · CPC title