IP Library Granted Patent US 11,440,962
Granted Patent B2
US 11,440,962 · App. 16/649,149 · Granted Sep 13, 2022

Anti-CD3epsilon antibodies

Inventors: Jing Li (Shanghai, CN); Qin Mei (Shanghai, CN)
Assignee: WUXI BIOLOGICS IRELAND LIMITED
C07K16/2809A61K47/6803C07K2317/24C07K2317/31C07K2317/33C07K2317/565C07K2317/567C07K2317/77C07K2317/92
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Quick Facts
Patent No.
US 11,440,962
App. No.
16/649,149
Granted
Sep 13, 2022
Kind
B2
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 (37)

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.

2. 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.

3. 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.

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

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

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

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

12. A vector comprising the isolated polynucleotide of claim 11 .

13. A host cell comprising the vector of claim 12 .

14. 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.

15. 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 .

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

17. 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 .

18. 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.

19. 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.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2020
From: LI, JING; MEI, QIN
To: WUXI BIOLOGICS (SHANGHAI) CO., LTD.
Reel/Frame 052860/0617 →
Priority Claims (1)
WO PCT/CN2017/102622 · Sep 21, 2017 · international
Continuity (1)
Related Publication 20200299384A1 · Sep 24, 2020