# US 11,306,149 B2 · Anti-CD40 antibodies and uses thereof

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- Number: US 11,306,149 B2
- Document ID: US11306149B2
- Status: Granted
- Kind: B2
- Application number: 16/958,563
- Filed: 2018-12-27
- Published: 2020-10-29
- Granted: 2022-04-19
- Earliest claimed: 2017-12-27
- Assignees: Bristol-Myers Squibb Company; CytomX Therapeutics, Inc.
- Applicants: Bristol-Myers Squibb Company; CytomX Therapeutics, Inc.
- Inventors: Bryan C. Barnhart; Brigitte Devaux; Aaron P. Yamniuk; Shannon L. Okada; Brenda L. Stevens; James William West
- Web page: https://patentgrep.com/patent/US11306149B2

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/515: Complete light chain, i.e. VL + CL
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40 and comprise improved heavy and light chain variable regions that impart improved yield and reduced aggregation. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.

## Claims

### Claim 1

An isolated antibody, or antigen binding portion thereof, that specifically binds to human CD40 comprising:
a) a heavy chain variable region (VH) which comprises a CDR1, CDR2, and CDR3, wherein the CDR1 of the VH comprises the amino acid sequence GYNMN (SEQ ID NO: 55), the CDR2 of the VH comprises the amino acid sequence NIDPYYGNTNYNQKFKG (SEQ ID NO: 56), and the CDR3 of the VH comprises the amino acid sequence LGLQLYALDY (SEQ ID NO: 58); and
b) a light chain variable region (VL) which comprises a CDR1, CDR2, and CDR3, wherein the CDR1 of the VL comprises the amino acid sequence RASQSLVHSNANTYLH (SEQ ID NO: 63), the CDR2 of the VL comprises the amino acid sequence KLTNRFF (SEQ ID NO: 64), and the CDR3 of the VL comprises the amino acid sequence QQSIHVPWT (SEQ ID NO: 66).

### Claim 2 (depends on 1)

The isolated antibody, or antigen binding portion thereof, of claim 1, wherein:
a) the VH comprises the amino acid sequence selected from the group consisting of residues 1-119 of SEQ ID NOs: 9, 11, 52, and 54; and
b) the VL comprises the amino acid sequence of SEQ ID NO: 49.

### Claim 3 (depends on 2)

The isolated antibody, or antigen binding portion thereof, of claim 2, wherein:
a) the VH comprises the amino acid sequence of residues 1-119 of SEQ ID NO: 11; and
b) the VL comprises the amino acid sequence of SEQ ID NO: 49.

### Claim 4 (depends on 2)

The isolated antibody, or antigen binding portion thereof, of claim 2, wherein:
a) the VH comprises the amino acid sequence of SEQ ID NO: 54; and
b) the VL comprises the amino acid sequence of SEQ ID NO: 49.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 1; and
b) a carrier.

### Claim 6 (depends on 1)

The isolated antibody, or antigen binding portion thereof, of claim 1, which comprises a heavy chain constant region selected from an IgG1, an IgG2, an IgG3, an IgG4, or a variant thereof.

### Claim 7 (depends on 6)

The isolated antibody, or antigen binding portion thereof, of claim 6, wherein the heavy chain constant region is IgG1 and comprises the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 8 (depends on 2)

The isolated antibody, or antigen binding portion thereof, of claim 2, which comprises a heavy chain constant region selected from an IgG1, an IgG2, an IgG3, an IgG4, or a variant thereof.

### Claim 9 (depends on 8)

The isolated antibody, or antigen binding portion thereof, of claim 8, wherein the heavy chain constant region is IgG1 and comprises the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 10 (depends on 4)

The isolated antibody, or antigen binding portion thereof, of claim 4, which comprises a heavy chain constant region selected from an IgG1, an IgG2, an IgG3, an IgG4, or a variant thereof.

### Claim 11 (depends on 10)

The isolated antibody, or antigen binding portion thereof, of claim 10, wherein the heavy chain constant region is IgG1 and comprises the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 12 (depends on 2)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 2; and
b) a carrier.

### Claim 13 (depends on 4)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 4; and
b) a carrier.

### Claim 14 (depends on 7)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 7; and
b) a carrier.

### Claim 15 (depends on 9)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 9; and
b) a carrier.

### Claim 16 (depends on 11)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 11; and
b) a carrier.

### Claim 17 (depends on 1)

A bispecific molecule comprising the isolated antibody, or antigen binding portion thereof, of claim 1.

### Claim 18 (depends on 3)

The isolated antibody, or antigen binding portion thereof, of claim 3, which comprises a heavy chain constant region selected from an IgG1, an IgG2, an IgG3, an IgG4, or a variant thereof.

### Claim 19 (depends on 18)

The isolated antibody, or antigen binding portion thereof, of claim 18, wherein the heavy chain constant region is IgG1 and comprises the amino acid sequence set forth in SEQ ID NO: 44.

### Claim 20 (depends on 3)

A pharmaceutical composition comprising:
a) the isolated antibody, or antigen binding portion thereof, of claim 3; and
b) a carrier.