# US 11,440,962 B2 · Anti-CD3epsilon antibodies

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- Number: US 11,440,962 B2
- Document ID: US11440962B2
- Status: Granted
- Kind: B2
- Application number: 16/649,149
- Filed: 2018-09-20
- Published: 2020-09-24
- Granted: 2022-09-13
- Earliest claimed: 2017-09-21
- Assignees: Wuxi Biologics Ireland Limited
- Applicants: WuXi Biologics Ireland Limited
- Inventors: Jing Li; Qin Mei
- Web page: https://patentgrep.com/patent/US11440962B2

## CPC

- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61P 35/00: Antineoplastic agents
- G01N 33/74: involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/7051: T-cell receptor (TcR)-CD3 complex
- 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
- 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

The present disclosure provides isolated monoclonal anti-CD3epsilon antibodies or antigen-binding fragments thereof comprising one or more heavy chain CDR sequences selected from the group consisting of: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, and 47, and/or one or more kappa light chain CDR sequences selected from the group consisting of: SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46 and 48, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and the use thereof.

## Claims

### Claim 1

An isolated antibody or an antigen-binding fragment thereof, comprising:
a) heavy chain CDR sequences comprising SEQ ID NO: 7, SEQ ID NO: 9, and SEQ ID NO: 11; and kappa light chain CDR sequences comprising SEQ ID NO: 8, SEQ ID NO: 10, and SEQ ID NO: 12;
b) heavy chain CDR sequences comprising SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 5; and kappa light chain CDR sequences comprising SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 6;
c) heavy chain, CDR sequences comprising SEQ ID NO: 13, SEQ ID NO: 15, and SEQ ID NO: 17; and kappa light chain CDR sequences comprising SEQ ID NO: 14, SEQ ID NO: 16, and SEQ ID NO: 18;
d) heavy chain CDR sequences comprising SEQ ID NO: 19, SEQ ID NO: 21, and SEQ ID NO: 23; and kappa light chain CDR sequences comprising SEQ ID NO: 20, SEQ ID NO: 22, and SEQ ID NO: 24;
e) heavy chain CDR sequences comprising SEQ ID NO: 25, SEQ ID NO: 27, and SEQ ID NO: 29; and kappa light chain CDR sequences comprising SEQ ID NO: 26, SEQ ID NO: 28, and SEQ ID NO: 30;
f) heavy chain CDR sequences comprising SEQ ID NO: 31, SEQ ID NO: 33, and SEQ ID NO: 35; and kappa light chain CDR sequences comprising SEQ ID NO: 32, SEQ ID NO: 34, and SEQ ID NO: 36;
g) heavy chain CDR sequences comprising SEQ ID NO: 37, SEQ ID NO: 39, and SEQ ID NO: 41; and kappa light chain CDR sequences comprising SEQ ID NO: 38, SEQ ID NO: 40, and SEQ ID NO: 42; or
h) heavy chain CDR sequences comprising SEQ ID NO: 43, SEQ ID NO: 45, and SEQ ID NO: 47; and kappa light chain CDR sequences comprising SEQ ID NO: 44, SEQ ID NO: 46, and SEQ ID NO: 48.

### Claim 2 (depends on 1)

The antibody or an antigen-binding fragment thereof of claim 1, comprising:
a) a heavy chain variable region comprising SEQ ID NO: 117 and a kappa light chain variable region comprising SEQ ID NO: 119;
b) a heavy chain variable region comprising SEQ ID NO: 81 and a kappa light chain variable region comprising SEQ ID NO: 83;
c) a heavy chain variable region comprising SEQ ID NO: 85 and a kappa light chain variable region comprising SEQ ID NO: 87;
d) a heavy chain variable region comprising SEQ ID NO: 89 and a kappa light chain variable region comprising SEQ ID NO: 91;
e) a heavy chain variable region comprising SEQ ID NO: 93 and a kappa light chain variable region comprising SEQ ID NO: 95;
f) a heavy chain variable region comprising SEQ ID NO: 97 and a kappa light chain variable region comprising SEQ ID NO: 99;
g) a heavy chain variable region comprising SEQ ID NO: 101 and a kappa light chain variable region comprising SEQ ID NO: 103;
h) a heavy chain variable region comprising SEQ ID NO: 105 and a kappa light chain variable region comprising SEQ ID NO: 107;
i) a heavy chain variable region comprising SEQ ID NO: 109 and a kappa light chain variable region comprising SEQ ID NO: 111; or
j) a heavy chain variable region comprising SEQ ID NO: 113 and a kappa light chain variable region comprising SEQ ID NO: 115.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, further comprising an immunoglobulin constant region, optionally a constant region of IgG, optionally a constant region of human IgG1.

### Claim 4 (depends on 1)

The antibody or an antigen-binding fragment thereof of claim 1, which is a humanized antibody.

### Claim 5 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, which is a camelized single domain antibody, a diabody, a scFv, an scFv dimer, a BsFv, a dsFv, a (dsFv)2, a dsFv-dsFv′, an Fv fragment, a Fab, a Fab′, a F(ab′)2, a bispecific antibody, a ds diabody, a nanobody, a domain antibody, or a bivalent domain antibody.

### Claim 6 (depends on 5)

The antibody or an antigen-binding fragment thereof of claim 5, wherein the antibody or an antigen-binding fragment thereof is bispecific and has a first specificity for CD3epsilon, and a second specificity.

### Claim 7 (depends on 6)

The antibody or an antigen-binding fragment thereof of claim 6, wherein the second specificity is for a second antigen different from CD3epsilon wherein presence of the second antigen in proximity to a CD3epsilon-expressing T cells is desirable for the second antigen to be recognized by immune system.

### Claim 8 (depends on 1)

The antibody or antigen-binding fragment thereof claim 1 linked to one or more conjugates, wherein the conjugate comprises a chemotherapeutic agent, a toxin, a radioactive isotope, a lanthanide, a luminescent label, a fluorescent label, or an enzyme-substrate label.

### Claim 9 (depends on 1)

The antibody or an antigen-binding fragment thereof of claim 1, capable of specifically binding to CD3epsilon, and optionally wherein the CD3epsilon are derived from mouse, rat, monkey or human, and optionally wherein the CD3epsilon is a recombinant CD3epsilon or a CD3epsilon expressed on a cell surface.

### Claim 10 (depends on 1)

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

### Claim 11 (depends on 1)

An isolated polynucleotide encoding the antibody or an antigen-binding fragment thereof of claim 1.

### Claim 12 (depends on 11)

A vector comprising the isolated polynucleotide of claim 11.

### Claim 13 (depends on 12)

A host cell comprising the vector of claim 12.

### Claim 14 (depends on 1)

A method of expressing the antibody or antigen-binding fragment thereof of claim 1, comprising culturing a host cell comprising a vector comprising an isolated polynucleotide encoding the antibody or antigen-binding fragment thereof of claim 1 under the condition at which the vector is expressed.

### Claim 15 (depends on 1)

A method of treating a CD3 related disease or condition, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of claim 1.

### Claim 16 (depends on 15)

The method of claim 15, wherein the antibody or antigen-binding fragment thereof is bispecific and the disease or condition is cancer.

### Claim 17 (depends on 1)

A method of activating CD3epsilon-expressing T cells in vivo or in vitro, comprising contacting the CD3epsilon-expressing T cells with the antibody or antigen-binding fragment thereof of claim 1.

### Claim 18 (depends on 6)

A method of promoting in vivo or in vitro processing of a second antigen by CD3epsilon —expressing T cell, comprising contacting the CD3epsilon-expressing T cells with the bispecific antibody or antigen-binding fragment thereof of claim 6, wherein the bispecific antibody or antigen-binding fragment is capable of specifically binding to both the CD3epsilon-expressing T cells and a second antigen thereby bringing both in close proximity.

### Claim 19 (depends on 1)

A kit comprising the antibody or antigen-binding fragment thereof of claim 1, useful in detecting CD3epsilon, optionally recombinant CD3epsilon, CD3epsilon expressed on cell surface, or CD3epsilon-expressing cells, or useful in diagnosing a CD3 related disease or condition in a subject.