# US 9,040,669 B2 · HLA-restricted, peptide-specific antigen binding proteins

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- Number: US 9,040,669 B2
- Document ID: US9040669B2
- Status: Granted
- Kind: B2
- Application number: 13/984,646
- Filed: 2012-02-13
- Published: 2014-01-23
- Granted: 2015-05-26
- Earliest claimed: 2011-02-11
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Nai-Kong Cheung; Dimiter Tassev; Jian Hu
- Inventors: Nai-Kong Cheung; Dimiter Tassev; Jian Hu
- Web page: https://patentgrep.com/patent/US9040669B2

## CPC

- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4243: {Wilms tumor 1 [WT1]}
- C07K 16/085: Orthoherpesviridae (F), e.g. pseudorabies virus or Epstein-Barr virus
- C07K 16/18: against material from animals or humans
- A61K 2039/505: {comprising antibodies}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 2317/31: multispecific
- C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- C07K 2319/03: containing a transmembrane segment
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Antigen binding proteins with T cell receptor-like paratopes, that is, with an antigen binding region specific for an human leukocyte antigen-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.

## Claims

### Claim 1

An isolated antigen-binding protein comprising one of:
(A) an antigen binding region having the amino acid sequence of SEQ ID NO: 2;
(B) an antigen binding region comprising a VH and a VL respectively, with the amino acid sequences SEQ ID NO: 22 and SEQ ID NO: 23; 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: 57; and
(c) a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 64; and
(ii) (a) a heavy chain (HC) complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO: 38;
(b) a HC CDR2 comprising the amino acid sequence of SEQ ID NO: 40; and
(c) a HC CDR3 comprising the amino acid sequence of SEQ ID NO: 48.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 2)

The isolated 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).

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

The isolated antigen-binding protein of claim 1, wherein the peptide of the HLA/peptide complex has the amino acid sequence RMFPNAPYL (SEQ ID NO:1).

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

An immunoconjugate comprising an antigen-binding protein of claim 1 or antigen-binding fragment thereof.

### Claim 10 (depends on 9)

The immunoconjugate of claim 9, comprising a second component having a second amino acid sequence.

### Claim 11 (depends on 9)

The immunoconjugate according to claim 9, further comprising a cytotoxin.

### Claim 12 (depends on 10)

The immunoconjugate of claim 10, 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.

### Claim 13 (depends on 1)

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

### Claim 14 (depends on 1)

A pharmaceutical composition comprising the antigen binding protein of claim 1.

### Claim 15

An isolated single-chain variable fragment (scFv) comprising the amino acid sequence set forth in SEQ ID NO: 2.

### Claim 16

An isolated scFv comprising a VH and a VL linked by an amino acid spacer, wherein the VH and VL respectively comprise the amino acid sequences set forth in SEQ ID NO: 22 and SEQ ID NO: 23.