# US 12,180,277 B2 · LILRB4-binding antibody and methods of use thereof

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- Number: US 12,180,277 B2
- Document ID: US12180277B2
- Status: Granted
- Kind: B2
- Application number: 17/435,387
- Filed: 2020-03-02
- Published: 2022-05-12
- Granted: 2024-12-31
- Earliest claimed: 2019-03-01
- Assignees: Board of Regents, The University of Texas System
- Applicants: Board of Regents, The University of Texas System
- Inventors: Naveen Sharma; James P. Allison
- Web page: https://patentgrep.com/patent/US12180277B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- G01N 33/575: for cancer
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided herein are LILRB4-binding antibodies and methods of treating cancer by administering the LILRB4-binding antibodies alone or in combination with other therapies. Recombinant polypeptides comprising the CDRs of LILRB4-binding antibodies are also provided.

## Claims

### Claim 1

An isolated monoclonal antibody, wherein the antibody specifically binds to LILRB4 and comprises:
(I)
(a) a first VH CDR of SEQ ID NO: 1
(GFMFSSYW);
(b) a second VH CDR of SEQ ID NO: 2
(INKDVTTT);
(c) a third VH CDR of SEQ ID NO: 3
(VRNHGSRYAYFDV);
(d) a first VL CDR of SEQ ID NO: 4
(TQHRTFY);
(e) a second VL CDR of SEQ ID NO: 5
(VNSDGSQ);
and
(f) a third VL CDR of SEQ ID NO: 6
(GVNYESGKQYGYV).

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the antibody comprises a VH domain at least about 80% identical to the VH domain of SEQ ID NO: 10 and a VL domain at least about 80% identical to the VL domain of SEQ ID NO: 11.

### Claim 3 (depends on 2)

The antibody of claim 2, wherein the antibody comprises a VH domain identical to the VH domain of SEQ ID NO: 10 and a VL domain identical to the VL domain of SEQ ID NO: 11.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein the antibody is recombinant.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the antibody is an IgG, IgM, IgA or an antigen binding fragment thereof.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein the antibody is a Fab′, a F(ab′)2, a monovalent scFv, or a bivalent scFv.

### Claim 7 (depends on 1)

The antibody of claim 1, wherein the antibody is a humanized antibody or de-immunized antibody.

### Claim 8 (depends on 1)

The antibody of claim 1, wherein the antibody is conjugated to an imaging agent, a chemotherapeutic agent, a toxin or a radionuclide.

### Claim 9 (depends on 1)

A composition comprising an antibody of claim 1 in a pharmaceutically acceptable carrier.

### Claim 10 (depends on 1)

An isolated polynucleotide molecule comprising a nucleic acid sequence encoding an antibody of claim 1.

### Claim 11

A recombinant polypeptide comprising an antibody VH domain comprising CDRs 1-3 of the VH domain of SEQ ID NOs: 1, 2, and 3 and an antibody VL domain comprising CDRs 1-3 of the VL domain of SEQ ID NOs: 4, 5, and 6.

### Claim 12 (depends on 11)

An isolated polynucleotide molecule comprising a nucleic acid sequence encoding a polypeptide of claim 11.

### Claim 13 (depends on 12)

A host cell comprising one or more polynucleotide molecule(s) of claim 12.

### Claim 14 (depends on 13)

The host cell of claim 13, wherein the host cell is a mammalian cell, a yeast cell, a bacterial cell, a ciliate cell or an insect cell.

### Claim 15

A method for treating cancer in a subject comprising administering an effective amount of an antibody that specifically binds to LILRB4 and comprises:
(I)
(a) a first VH CDR of SEQ ID NO: 1
(GFMFSSYW);
(b) a second VH CDR of SEQ ID NO: 2
(INKDVTTT);
(c) a third VH CDR of SEQ ID NO: 3
(VRNHGSRYAYFDV);
(d) a first VL CDR of SEQ ID NO: 4
(TQHRTFY);
(e) a second VL CDR of SEQ ID NO: 5
(VNSDGSQ);
and
(f) a third VL CDR of SEQ ID NO: 6
(GVNYESGKQYGYV).

### Claim 16 (depends on 15)

The method of claim 15, wherein the cancer is leukemia, breast cancer, melanoma, prostate cancer, or pancreatic cancer.

### Claim 17 (depends on 15)

The method of claim 15, wherein the antibody is administered intravenously, intradermally, intratumorally, intramuscularly, intraperitoneally, subcutaneously, or locally.

### Claim 18 (depends on 15)

The method of claim 15, further comprising administering at least a second anticancer therapy to the subject.

### Claim 19 (depends on 18)

The method of claim 18, wherein the second anticancer therapy is a surgical therapy, chemotherapy, radiation therapy, cryotherapy, hormonal therapy, immunotherapy or cytokine therapy.

### Claim 20 (depends on 15)

The method of claim 15, wherein the treatment of cancer comprises treatment of a solid tumor.