ANTI-CD3e ANTIBODIES AND USES THEREOF

1 . An antibody or antigen-binding fragment thereof that binds to CD3e (T-cell surface glycoprotein CD3 epsilon chain) comprising:

a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3, wherein the VH CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR1 amino acid sequence, the VH CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR2 amino acid sequence, and the VH CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VH CDR3 amino acid sequence; and

a light chain variable region (VL) comprising CDRs 1, 2, and 3, wherein the VL CDR1 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR1 amino acid sequence, the VL CDR2 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR2 amino acid sequence, and the VL CDR3 region comprises an amino acid sequence that is at least 80% identical to a selected VL CDR3 amino acid sequence,

wherein the selected VH CDRs 1, 2, and 3 amino acid sequences and the selected VL CDRs, 1, 2, and 3 amino acid sequences are one of the following:

(1) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs: 1, 2, 3, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs: 4, 5, 6, respectively;

(2) the selected VH CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs: 7, 8, 9, respectively, and the selected VL CDRs 1, 2, 3 amino acid sequences are set forth in SEQ ID NOs: 10, 11, 12, respectively.

2 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the VH comprises CDRs 1, 2, 3 with the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3 respectively, and the VL comprises CDRs 1, 2, 3 with the amino acid sequences set forth in SEQ ID NOs: 4, 5, and 6, respectively.

3 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the VH comprises CDRs 1, 2, 3 with the amino acid sequences set forth in SEQ ID NOs: 7, 8, and 9, respectively, and the VL comprises CDRs 1, 2, 3 with the amino acid sequences set forth in SEQ ID NOs: 10, 11, and 12, respectively.

4 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is a bispecific antibody.

5 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment specifically binds to human CD3e.

6 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is a humanized antibody or antigen-binding fragment thereof.

7 . The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment is a single-chain variable fragment (scFV).

8 . A nucleic acid comprising a polynucleotide encoding a polypeptide comprising:

(1) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25, 26, 27, or 36, binds to CD3e;

(2) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 4, 5, and 6, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 21, 22, 23, 24, or 35, binds to CD3e;

(3) an immunoglobulin heavy chain or a fragment thereof comprising a heavy chain variable region (VH) comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 7, 8, and 9, respectively, and wherein the VH, when paired with a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 32, 33, 34, or 38, binds to CD3e;

(4) an immunoglobulin light chain or a fragment thereof comprising a VL comprising CDRs 1, 2, and 3 comprising the amino acid sequences set forth in SEQ ID NOs: 10, 11, and 12, respectively, and wherein the VL, when paired with a VH comprising the amino acid sequence set forth in SEQ ID NO: 28, 29, 30, 31, or 37, binds to CD3e.

9 .- 18 . (canceled)

19 . A vector comprising one or more of the nucleic acids of claim 8 .

20 .- 21 . (canceled)

22 . A cell comprising the vector of claim 19 .

23 . The cell of claim 22 , wherein the cell is a CHO cell.

24 . A cell comprising one or more of the nucleic acids of claim 8 .

25 .- 26 . (canceled)

27 . A method of producing an antibody or an antigen-binding fragment thereof, the method comprising

(a) culturing the cell of claim 24 under conditions sufficient for the cell to produce the antibody or the antigen-binding fragment; and

(b) collecting the antibody or the antigen-binding fragment produced by the cell.

28 . An antibody or antigen-binding fragment thereof that binds to CD3e comprising a heavy chain variable region (VH) comprising an amino acid sequence that is at least 90% identical to a selected VH sequence, and a light chain variable region (VL) comprising an amino acid sequence that is at least 90% identical to a selected VL sequence, wherein the selected VH sequence and the selected VL sequence are one of the following:

(1) the selected VH sequence is SEQ ID NO: 21, 22, 23, 24, or 35, and the selected VL sequence is SEQ ID NO: 25, 26, 27, or 36;

(2) the selected VH sequence is SEQ ID NO: 28, 29, 30, 31, or 37, and the selected VL sequence is SEQ ID NO: 32, 33, 34, or 38.

29 .- 33 . (canceled)

34 . An antibody-drug conjugate comprising the antibody or antigen-binding fragment thereof of claim 1 covalently bound to a therapeutic agent.

35 . (canceled)

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

37 . (canceled)

38 . A method of decreasing immune response or treating an autoimmune disease in a subject, the method comprising

administering an effective amount of a composition comprising an antibody or antigen-binding fragment thereof of claim 1 to the subject.

39 . The method of claim 38 , wherein the subject has a graft-versus-host disease, type I diabetes, arthritis, Crohn's disease, or ulcerative colitis.

40 .- 43 . (canceled)

44 . A method of treating a subject having cancer, the method comprising administering a therapeutically effective amount of a composition comprising the antibody or antigen-binding fragment thereof of claim 1 to the subject.

45 . The method of claim 44 , wherein the antibody or antigen-binding fragment is a bispecific antibody, and the bispecific antibody also specifically binds to a tumor associated antigen.

46 .- 51 . (canceled)