Novel anti-cd3epsilon antibodies

Patent metadata

Field	Value
Publication number	US-2020299384-A1
Application number	US-201816649149-A
Country	US
Kind code	A1
Filing date	Sep 20, 2018
Priority date	Sep 21, 2017
Publication date	Sep 24, 2020
Grant date	—

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.

First claim

1 - 3 . (canceled)

4 . 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 from 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.

5 - 7 . (canceled)

8 . The antibody or an antigen-binding fragment thereof of claim 4 , 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.

9 . The antibody or antigen-binding fragment thereof of claim 8 , further comprising one or more amino acid residue substitutions yet retains specific binding affinity to CD3epsilon, wherein the substitution is in one or more CDR sequences, and/or in one or more FR sequences, and/or in one or both variable region sequences.

10 - 11 . (canceled)

12 . The antibody or antigen-binding fragment thereof of claim 4 , further comprising an immunoglobulin constant region, optionally a constant region of IgG, optionally a constant region of human IgG1.

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

14 . The antibody or antigen-binding fragment thereof of claim 4 , 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.

15 . (canceled)

16 . The antibody or an antigen-binding fragment thereof of claim 14 , wherein the antibody or an antigen-binding fragment thereof is bispecific and has a first specificity for CD3epsilon, and a second specificity.

17 . The antibody or an antigen-binding fragment thereof of claim 16 , 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.

18 . (canceled)

19 . The antibody or antigen-binding fragment thereof claim 4 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.

20 . (canceled)

21 . The antibody or an antigen-binding fragment thereof of claim 4 , 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.

22 - 25 . (canceled)

26 . A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 4 , and a pharmaceutically acceptable carrier.

27 . An isolated polynucleotide encoding the antibody or an antigen-binding fragment thereof of claim 4 .

28 . (canceled)

29 . A vector comprising the isolated polynucleotide of claim 27 .

30 . A host cell comprising the vector of claim 29 .

31 . A method of expressing the antibody or antigen-binding fragment thereof of claim 4 , comprising culturing a host cell comprising a vector comprising an isolated polynucleotide encoding the antibody or antigen-binding fragment thereof of claim 4 under the condition at which the vector is expressed.

32 . 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 4 .

33 - 34 . (canceled)

35 . The method of claim 32 , wherein the antibody or antigen-binding fragment thereof is bispecific and the disease or condition is cancer.

36 . (canceled)

37 . 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 4 .

38 . (canceled)

39 . 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 16 , 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.

40 - 43 . (canceled)

44 . A kit comprising the antibody or antigen-binding fragment thereof of claim 4 , 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.

Assignees

• Wuxi Biologics Ireland Ltd

Inventors

• Li Jing
• Mei Qin

Classifications

• C07K2317/31

  multispecific · CPC title

• C07K16/2809 Primary

  against the T-cell receptor (TcR)-CD3 complex · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61K2039/505

  comprising antibodies · CPC title