# US 11,433,141 B2 · Anti-B7-H4 antibody

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- Number: US 11,433,141 B2
- Document ID: US11433141B2
- Status: Granted
- Kind: B2
- Application number: 16/320,587
- Filed: 2017-07-25
- Published: 2019-11-14
- Granted: 2022-09-06
- Earliest claimed: 2016-07-26
- Assignees: Shizuoka Prefecture
- Applicants: Shizuoka Prefecture
- Inventors: Yasuto Akiyama; Akira Iizuka
- Web page: https://patentgrep.com/patent/US11433141B2

## CPC

- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 35/00: Antineoplastic agents
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/31: multispecific
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

An object is to produce a new anti-B7-H4 antibody having high specificity and affinity and provide a composition for treating cancer making use thereof. A monoclonal antibody that specifically binds to an extracellular domain protein of a human B7-H4 protein is newly produced and an “anti-B7-H4 antibody-effector cell complex” in which the monoclonal antibody and an effector cell are bound in order to enhance the antibody-dependent cellular cytotoxicity of the monoclonal antibody or a bispecific antibody comprising an antigen recognition region of the monoclonal antibody and an effector cell antigen recognition region is further produced and used as a composition for treating cancer.

## Claims

### Claim 1

An antibody that specifically binds to an extracellular domain of a human B7-H4 protein comprising amino acid residues Leu25 to Ser259 of SEQ ID NO: 33, and comprises the following:
(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6.

### Claim 2 (depends on 1)

The antibody according to claim 1, wherein the antibody is a monoclonal antibody.

### Claim 3 (depends on 2)

A hybridoma that produces the antibody according to claim 2.

### Claim 4 (depends on 1)

An antibody conjugate-effector cell complex in which an effector cell is bound to an antibody conjugate, wherein the antibody conjugate comprises a first antibody consisting of the antibody according to claim 1 conjugated to a second antibody that recognizes the effector cell antigen.

### Claim 5 (depends on 4)

The antibody conjugate-effector cell complex according to claim 4, wherein the first antibody is conjugated to the second antibody via a third antibody that recognizes both the first antibody and the second antibody.

### Claim 6 (depends on 4)

The antibody conjugate-effector cell complex according to claim 4, wherein the effector cell is an effector cell taken from a cancer patient to be treated.

### Claim 7

A bispecific antibody comprising any one of following regions (a) to (c) that specifically bind to an extracellular domain of a human B7-H4 protein composed of a region from Leu25 to Ser259 of SEQ ID NO: 33, and a heavy chain variable region and a light chain variable region that specifically bind to an effector cell antigen:
(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6;
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of positions 4 to 104 of SEQ ID NO: 6; and
(c) a heavy chain variable region comprising the amino acid sequence of positions 3 to 111 of SEQ ID NO: 4 and a light chain variable region comprising the amino acid sequence of positions 4 to 104 of SEQ ID NO: 6.

### Claim 8 (depends on 7)

The bispecific antibody according to claim 7, wherein the effector cell antigen is a CD3 antigen.

### Claim 9 (depends on 7)

The bispecific antibody according to claim 7, wherein the bispecific antibody is a single chain antibody or a Fab-scFv fusion.

### Claim 10 (depends on 7)

The bispecific antibody according to claim 7, comprising:
(a′) the amino acid sequence of SEQ ID NO: 32;
(b′) the amino acid sequence of SEQ ID NO: 37; or
(c′) the amino acid sequence of SEQ ID NO: 39 and the amino acid sequence of SEQ ID NO: 41.

### Claim 11 (depends on 1)

A nucleic acid comprising a sequence encoding the antibody according to claim 1.

### Claim 12 (depends on 11)

The nucleic acid according to claim 11, comprising the following:
(A) the nucleic acid sequence of SEQ ID NO: 3 and the nucleic acid sequence of SEQ ID NO: 5.

### Claim 13 (depends on 11)

A vector comprising the nucleic acid according to claim 11.

### Claim 14 (depends on 13)

A transformant obtained by introducing the vector according to claim 13 into a host cell.

### Claim 15 (depends on 7)

A bispecific antibody-effector cell complex in which the bispecific antibody according to claim 7 and an effector cell are bound.

### Claim 16 (depends on 7)

A nucleic acid comprising a sequence encoding the bispecific antibody according to claim 7.

### Claim 17 (depends on 16)

The nucleic acid according to claim 16, comprising any one of following sequences (A) to (C):
(A) the nucleic acid sequence of SEQ ID NO: 3 and the nucleic acid sequence of SEQ ID NO:5;
(B) the nucleic acid sequence of positions 448 to 780 of SEQ ID NO: 36 and the nucleic acid sequence of positions 76 to 378 of SEQ ID NO: 36; or
(C) the nucleic acid sequence of positions 64 to 390 of SEQ ID NO: 38 and the nucleic acid sequence of positions 76 to 378 of SEQ ID NO: 40.

### Claim 18 (depends on 16)

The nucleic acid according to claim 16, comprising
(A′) the nucleic acid sequence of SEQ ID NO: 31;
(B′) the nucleic acid sequence of SEQ ID NO: 36; or
(C′) the nucleic acid sequence of SEQ ID NO: 38 and the nucleic acid sequence of SEQ ID NO: 40.

### Claim 19 (depends on 16)

A vector comprising the nucleic acid according to claim 16.

### Claim 20 (depends on 19)

A transformant obtained by introducing the vector according to claim 19 into a host cell.