# US 12,503,517 B2 · Antibodies binding CD40 and uses thereof

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- Number: US 12,503,517 B2
- Document ID: US12503517B2
- Status: Granted
- Kind: B2
- Application number: 17/906,898
- Filed: 2021-03-30
- Published: 2023-11-16
- Granted: 2025-12-23
- Earliest claimed: 2020-03-30
- Assignees: Biosion Inc.
- Applicants: Biosion Inc.
- Inventors: Mark Zhiqing Ma; Jinyu Liu; Zhengping Zhang; Hongjiang Xu
- Web page: https://patentgrep.com/patent/US12503517B2

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61K 39/001129: {Molecules with a "CD" designation not provided for elsewhere}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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

## Abstract

Provided is an isolated monoclonal antibody or an antigen-binding portion thereof that specifically binds human CD40. A nucleic acid molecule encoding the antibody or antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or the antigen-binding portion thereof are also provided. An immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody or antigen-binding portion thereof, as well as a treatment method using the same are further provided.

## Claims

### Claim 1

An isolated monoclonal antibody or an antigen-binding portion thereof, capable of binding to CD40, comprising (i) a heavy chain variable region comprising a VH CDR1 region, a VH CDR2 region and a VH CDR3 region, and (ii) a light chain variable region comprising a VL CDR1 region, a VL CDR2 region and a VL CDR3 region, wherein the VH CDR1 region, the VH CDR2 region, the VH CDR3 region, the VL CDR1 region, the VL CDR2 region and the VL CDR3 region comprise amino acid sequences set forth in (1) SEQ ID NOs: 1, 4, 7, 10, 13 and 16, respectively; (2) SEQ ID NOs: 2, 5, 8, 11, 14 and 17, respectively; or (3) SEQ ID NOs: 3, 6, 9, 12, 15 and 18, respectively.

### Claim 2 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NOs: 19, 20, 21 or 22, wherein 49th amino acid residue in SEQ ID NO: 20 is A or S.

### Claim 3 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, wherein the light chain variable region comprises an amino acid sequence having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to SEQ ID NO: 23, 24, 25 or 26, wherein 49th and 87th amino acid residues in SEQ ID NO: 24 are K and F respectively, or Y and Y respectively.

### Claim 4 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, wherein the heavy chain variable region and the light chain variable region comprise amino acid sequences having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to (1) SEQ ID NOs: 19 and 23, respectively; (2) SEQ ID NOs: 20 and 24, respectively, wherein 49th amino acid residue in SEQ ID NO: 20 is A, wherein 49th and 87th amino acid residues in SEQ ID NO: 24 are K and F respectively; (3) SEQ ID NOs: 20 and 24, respectively, wherein 49th amino acid residue in SEQ ID NO: 20 is S, wherein 49th and 87th amino acid residues in SEQ ID NO: 24 are K and F respectively; (4) SEQ ID NOs: 20 and 24, respectively, wherein 49th amino acid residue in SEQ ID NO: 20 is A, wherein 49th and 87th amino acid residues in SEQ ID NO: 24 are Y and Y respectively; (5) SEQ ID NOs: 20 and 24, respectively, wherein 49th amino acid residue in SEQ ID NO: 20 is S, wherein 49th and 87th amino acid residues in SEQ ID NO: 24 are Y and Y respectively; (6) SEQ ID NOs: 21 and 25, respectively; or (7) SEQ ID NOs: 22 and 26, respectively.

### Claim 5 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, comprising a heavy chain constant region having an amino acid sequence of SEQ ID NOs: 27 or 28, linked to the heavy chain variable region, and a light chain constant region having an amino acid sequence of SEQ ID NO: 29, linked to the light chain variable region.

### Claim 6 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, which is able to (a) bind human CD40; (b) bind monkey CD40; (c) block CD40-CD40L interaction; and/or (d) activate CD40 signaling.

### Claim 7 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, which is a mouse, chimeric or humanized antibody or antigen-binding portion thereof.

### Claim 8 (depends on 1)

The isolated monoclonal antibody or the antigen-binding portion thereof of claim 1, which is an IgG1, IgG2 or IgG4 isotype.

### Claim 9 (depends on 1)

A nucleotide encoding the isolated monoclonal antibody or the antigen-binding portion thereof of claim 1.

### Claim 10 (depends on 9)

An expression vector containing the nucleotide of claim 9.

### Claim 11 (depends on 10)

A host cell containing the expression vector of claim 10.

### Claim 12 (depends on 9)

A host cell containing the nucleotide of claim 9.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising the antibody or the antigen-binding portion thereof of claim 1, and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 13)

The pharmaceutical composition of claim 13, further comprising an anti-tumor agent and/or a cytokine.

### Claim 15 (depends on 13)

A method for treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 13.

### Claim 16 (depends on 15)

The method of claim 15, wherein the cancer is a solid or non-solid tumor.

### Claim 17 (depends on 16)

The method of claim 16, wherein the cancer is selected from the group consisting of B cell lymphoma, chronic lymphocytic leukemia, multiple myeloma, melanoma, colon adenocarcinoma, pancreas cancer, colon cancer, gastric intestine cancer, prostate cancer, bladder cancer, kidney cancer, ovary cancer, cervix cancer, breast cancer, lung cancer, and nasopharynx cancer.

### Claim 18 (depends on 13)

A method for treating an infectious disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 13.

### Claim 19 (depends on 13)

A method for treating an autoimmune disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 13.