Anti-cd3 antibodies, anti-cd123 antibodies and bispecific antibodies specifically binding to cd3 and/or cd123

2:

• The method of claim 1, wherein:
• L1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 389:
• L2 comprises an amino acid sequence as set forth in SEQ ID NO:
• 389;
• and
• L3 and L4 are 0 amino acids in length.

3:

• The method of claim 1, wherein:
• VD1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 385:
• VD2 comprises an amino acid sequence as set forth in SEQ ID NO:
• 141;
• VD3 comprises an amino acid sequence as set forth in SEQ ID NO:
• 138;
• VD4 comprises an amino acid sequence as set forth in SEQ ID NO:
• 383;
• CL comprises an amino acid sequence as set forth in SEQ ID NO:
• 310;
• and
• CH1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 313.

4:

• The method of claim 1, wherein:
• (a) the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 388, or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 388, which comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 378, a CDR2-L comprising an amino acid sequence WAS, a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 379, a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 11;
• and
• (b) the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 390, or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 390, which comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 7, a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 8, a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 382.

7:

• A method of treating a disease or disorder in a subject in need thereof, comprising:
• administering to the subject a therapeutically effective amount of an antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein the first polypeptide chain comprises a structure represented by the formula [IV]:
• VD1-L1-VD2-L2-CL-L5-Fc2 [IV]
• and the second polypeptide chain comprises a structure represented by the formula [III]:
• VD3-L3-VD4-L4-CH1-Fc [III]
• wherein:
• VD1 is a light chain variable domain of a first immunoglobulin;
• VD2 is a light chain variable domain of a second immuoglobulin;
• VD3 is a heavy chain variable domain of the second immunoglobulin;
• VD4 is a heavy chain variable domain of the first immunoglobulin;
• CL is a light chain constant domain of an immunoglobulin;
• CH1 is a CH1 heavy chain constant domain of an immunoglobulin;
• Fc is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains of a first immunoglobulin;
• Fc2 is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains of a second immunoglobulin;
• and
• L1, L2, L3, L4, and L5 are amino acid linkers;
• wherein the first polypeptide chain of formula [IV] and the second polypeptide chain of formula [III] form a cross-over light chain-heavy chain pair;
• and
• wherein VD1 comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 378, a CDR2-L comprising an amino acid sequence of WAS, and a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 379;
• VD2 comprises a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 11;
• VD3 comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 7, and a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 8;
• and
• VD4 comprises a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 382.

8:

• The method of claim 7, wherein:
• L1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 389:
• L2 comprises an amino acid sequence as set forth in SEQ ID NO:
• 389;
• and
• L3, L4, and L5 are 0 amino acids in length.

9:

• The method of claim 7, wherein:
• Fc comprises an amino acid sequence as set forth in SEQ ID NO:
• 394;
• and
• Fc2 comprises an amino acid sequence as set forth in SEQ ID NO:
• 392.

10:

• The method of claim 7, wherein:
• VD1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 385:
• VD2 comprises an amino acid sequence as set forth in SEQ ID NO:
• 141;
• VD3 comprises an amino acid sequence as set forth in SEQ ID NO:
• 138;
• VD4 comprises an amino acid sequence as set forth in SEQ ID NO:
• 383;
• CL comprises an amino acid sequence as set forth in SEQ ID NO:
• 310;
• and
• CH1 comprises an amino acid sequence as set forth in SEQ ID NO:
• 313.

11:

• The method of claim 7, wherein:
• (a) the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 391, or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 391, which comprises a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 378, a CDR2-L comprising an amino acid sequence WAS, a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 379, a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 142, a CDR5-L comprising an amino acid sequence of KVS, and a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 11;
• and
• (b) the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 393, or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 393, which comprises a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 6, a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 7, a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 8, a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 381, a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 384, and a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 382.

12:

• A method of treating a disease or disorder in a subject in need thereof, comprising:
• administering to the subject a therapeutically effective amount of an antibody-like binding protein that binds specifically to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide has a structure represented by the formula [I]:
• VD1-L1-VD2-L2-CL [I]
• and a second polypeptide has a structure represented by the formula [II]:
• VD3-L3-VD4-L4-CH1 [II]
• wherein:
• VD1 is a light chain variable domain of a first immunoglobulin;
• VD2 is a light chain variable domain of a second immuoglobulin;
• VD3 is a heavy chain variable domain of the second immunoglobulin;
• VD4 is a heavy chain variable domain of the first immunoglobulin;
• CL is a light chain constant domain of an immunoglobulin;
• CH1 is a CH1 heavy chain constant domain of an immunoglobulin;
• L1, L2, L3, and L4 are amino acid linkers;
• and
• wherein the first polypeptide and the second polypeptide form a cross-over light chain-heavy chain pair;
• and
• wherein VD1 consists of the amino acid sequence as set forth in SEQ ID NO:
• 385, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 385, which comprises a CDR1-L of sequence SEQ ID NO:
• 378, a CDR2-L of sequence WAS, and a CDR3-L of sequence SEQ ID NO:
• 379:
• VD2 consists of the amino acid sequence as set forth in SEQ ID NO:
• 141, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 141, which comprises a CDR1-L of sequence SEQ ID NO:
• 142, a CDR2-L of sequence KVS, and a CDR3-L of sequence SEQ ID NO:
• 11;
• VD3 consists of the amino acid sequence as set forth in SEQ ID NO:
• 138, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 138, which comprises a CDR1-H of sequence SEQ ID NO:
• 6, a CDR2-H of sequence SEQ ID NO:
• 7, and a CDR3-H of sequence SEQ ID NO:
• 8;
• and
• VD4 consists of the amino acid sequence as set forth in SEQ ID NO:
• 383, or an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 383, which comprises a CDR1-H of sequence SEQ ID NO:
• 381, a CDR2-H of sequence SEQ ID NO:
• 384, and a CDR3-H of sequence SEQ ID NO:
• 382.

13:

• The method of claim 12, wherein:
• (a) the first polypeptide consists of the amino acid sequence as set forth in SEQ ID NO:
• 388, which comprises VD1 of amino acid sequence SEQ ID NO:
• 385, L1 of amino acid sequence SEQ ID NO:
• 389, VD2 of amino acid sequence SEQ ID NO:
• 141, L2 of amino acid sequence SEQ ID NO:
• 389, and CL of amino acid sequence SEQ ID NO:
• 310:
• or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 388, wherein the three CDRs of amino acid sequences SEQ ID NO:
• 378, WAS, and SEQ ID NO:
• 379 of VD1, and the three CDRs of amino acid sequences SEQ ID NO:
• 142, KVS, and SEQ ID NO:
• 11 of VD2 are unaltered;
• and
• (b) the second polypeptide consists of the amino acid sequence as set forth in SEQ ID NO:
• 390, which comprises VD3 of amino acid sequence SEQ ID NO:
• 138, L3 is 0 amino acids, VD4 of amino acid sequence SEQ ID NO:
• 383, L4 is 0 amino acids, and CH1 of amino acid sequence SEQ ID NO:
• 313, or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 390, wherein the three CDRs of amino acid sequences SEQ ID NO:
• 381, SEQ ID NO:
• 384, and SEQ ID NO:
• 382 of VD4, and the three CDRs of amino acid sequences SEQ ID NO:
• 6, SEQ ID NO:
• 7, and SEQ ID NO:
• 8 of VD3 are unaltered.

14:

• The method of claim 12, wherein the polypeptide of formula [II] further comprises a Fc domain and has a structure represented by formula [III]:
• VD3-L3-VD4-L4-CH1-Fc [III]
• wherein the polypeptide of formula [I] further comprises a Fc domain (Fc2) and has a structure represented by formula [IV]:
• VD1-L1-VD2-L2-CL-L5-Fc2 [IV]
• wherein:
• Fc is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains of an immunoglobulin,
• Fc2 is the immunoglobulin hinge region and CH2, CH3 immunoglobulin heavy chain constant domains of an immunoglobulin, and
• L5 is an amino acid linker;
• and
• wherein:
• (a) the polypeptide according to formula [IV] consists of the amino acid sequence as set forth in SEQ ID NO:
• 391, which comprises VD1 of amino acid sequence SEQ ID NO:
• 385, L1 of amino acid sequence SEQ ID NO:
• 389, VD1 of amino acid sequence SEQ ID NO:
• 141, L2 of amino acid sequence SEQ ID NO:
• 389, CL of amino acid sequence SEQ ID NO:
• 310, L5 which is 0 amino acids, and Fc2 of amino acid sequence SEQ ID NO:
• 392;
• or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 391, wherein the three CDRs of amino acid sequences SEQ ID NO:
• 378, WAS, and SEQ ID NO:
• 379 of VD1, and the three CDRs of amino acid sequences SEQ ID NO:
• 142, KVS, and SEQ ID NO:
• 11 of VD2 are unaltered;
• and
• (b) the polypeptide according to formula [III] consists of the amino acid sequence as set forth in SEQ ID NO:
• 393, which comprises VD3 of amino acid sequence SEQ ID NO:
• 138, L3 is 0 amino acids, VD4 of amino acid sequence SEQ ID NO:
• 383, L4 is 0 amino acids, CH1 of amino acid sequence SEQ ID NO:
• 313, and Fc of amino acid sequence SEQ ID NO:
• 394:
• or
• an amino acid sequence that is at least 85% identical to the amino acid sequence as set forth in SEQ ID NO:
• 393, wherein the three CDRs of amino acid sequences SEQ ID NO:
• 381, SEQ ID NO:
• 384, and SEQ ID NO:
• 382 of VD4, and the three CDRs of amino acid sequences SEQ ID NO:
• 6, SEQ ID NO:
• 7, and SEQ ID NO:
• 8 of VD3 are unaltered;
• and
• wherein the polypeptide of formula [IV] and the polypeptide of formula [III] form a cross-over light chain-heavy chain pair.

15:

• A method of treating a disease or disorder in a subject in need thereof, comprising:
• administering to the subject a therapeutically effective amount of an antibody-like binding protein comprising two polypeptide chains that form two antigen-binding sites, wherein:
• a first polypeptide chain comprises:
• a CDR1-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 378;
• a CDR2-L comprising an amino acid sequence WAS:
• a CDR3-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 379;
• a CDR4-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 142:
• a CDR5-L comprising an amino acid sequence of KVS;
• and
• a CDR6-L comprising an amino acid sequence as set forth in SEQ ID NO:
• 11:
• and
• wherein a second polypeptide chain comprises:
• a CDR1-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 6:
• a CDR2-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 7;
• a CDR3-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 8;
• a CDR4-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 381;
• a CDR5-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 384;
• and
• a CDR6-H comprising an amino acid sequence as set forth in SEQ ID NO:
• 382.

28:

• A method of treating a disease or disorder in a subject in need thereof, comprising:
• administering to the subject a therapeutically effective amount of an antibody-like binding protein that specifically binds to CD3ε and CD123 comprising two polypeptide chains that form two antigen-binding sites,
• wherein a first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 388 and a second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 390 or the first polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 391 and the second polypeptide chain comprises an amino acid sequence as set forth in SEQ ID NO:
• 393.

29:

• An isolated antibody that binds to the extracellular domain of human CD3ε protein comprising:
• a) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence GFX1X2X3X4AW (SEQ ID NO:
• 331), wherein X1 is T or S, X2 is F or V, X3 is S or T and X4 is N, K, L, or Y, or any combination thereof;
• a CDR2-H comprising amino acid sequence IKX1X2X3NX4YX5T (SEQ ID NO:
• 332), wherein X1 is A or D, X2 is K or R, X3 is S or A, X4 is N or S, and X5 is A or E, or any combination thereof;
• and a CDR3-H comprising amino acid sequence TWRHYYSSHTMDA (SEQ ID NO:
• 69), or RALTYYGYKRDAMDG (SEQ ID NO:
• 129), or RX1X2X3YX4X5X6X7X8X9X10X11DX12 (SEQ ID NO:
• 333), wherein X1 is Y, G, or A, X2 is V, T, or L, X3 is H, N, Y, or Q, X4 is G, R, or A, X5 is F or V or no amino acid, X6 is R or no amino acid, X7 is F, S, or I or no amino acid, X8 is F, L, N, M, Y, S, A, or G, X9 is Y, A, K, S, N, T, F, or L, X10 is A, P, G, or T, X11 is M, L, F, or S, and X12 is A, V, or Y, or any combination thereof;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence QX1LX2HX3NGX4TY (SEQ ID NO:
• 334) wherein X1 is R or S, X2 is V or E, X3 is N, D, or T, and X4 is N or Y, or any combination thereof;
• and a CDR2-L comprising amino acid sequence KVS;
• and a CDR3-L comprising an amino acid sequence GQGX1X2YPFT (SEQ ID NO:
• 335) wherein X1 is T, A or S and X2 is H, E or Q, or any combination thereof;
• or
• b) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 30 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 30 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 31 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 31 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 32 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 32 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 34 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 34 by one amino acid substitution;
• a CDR2-L comprising amino acid sequence RDD or an amino acid sequence differing from the amino acid sequence RDD by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 35 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 35 by one amino acid substitution;
• or
• c) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 50 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 50 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 51 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 51 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 52 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 52 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 54 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 54 by one amino acid substitution;
• a CDR2-L comprising amino acid sequence NAN or an amino acid sequence differing from the amino acid sequence NAN by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 55 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 55 by one amino acid substitution;
• or
• d) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 90 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 90 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 91 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 91 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 32 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 32 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 93 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 93 by one amino acid substitution;
• a CDR2-L comprising amino acid sequence GAS or an amino acid sequence differing from the amino acid sequence GAS by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 94 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 94 by one amino acid substitution;
• or
• e) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 96 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 96 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 97 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 97 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 98 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 98 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 100 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 100 by one amino acid substitution, a CDR2-L comprising amino acid sequence NTN or an amino acid sequence differing from the amino acid sequence NTN by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 101 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 101 by one amino acid substitution;
• or
• f) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 103 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 103 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 104 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 104 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 105 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 105 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• by one amino acid substitution;
• a CDR2-L comprising amino acid sequence KVS or an amino acid sequence differing from the amino acid sequence KVS by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 11 by one amino acid substitution;
• or
• g) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 116 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 116 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 117 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 117 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 118 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 118 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 100 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 100 by one amino acid substitution;
• a CDR2-L comprising amino acid sequence VTN or an amino acid sequence differing from the amino acid sequence VTN by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 120 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 120 by one amino acid substitution;
• or
• h) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 122 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 122 by one amino acid substitution;
• a CDR2-H comprising amino acid sequence SEQ ID NO:
• 123 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 123 by one or more amino acid substitutions;
• and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 124 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 124 by one amino acid substitution;
• and
• a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 126 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 126 by one amino acid substitution;
• a CDR2-L comprising amino acid sequence RDD or an amino acid sequence differing from the amino acid sequence RDD by one amino acid substitution;
• and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 127 or an amino acid sequence differing from the amino acid sequence SEQ ID NO:
• 127 by one amino acid substitution.

30:

• The isolated antibody according to claim 29, comprising:
• a) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 6, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 7, and a CDR3-H of amino acid sequence SEQ ID NO:
• 8;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10 or SEQ ID NO:
• 142, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• b) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 14, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 15;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 17 or SEQ ID NO:
• 184, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• c) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 19, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 20;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 22, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• d) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 24, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 19, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 25;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 27;
• a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 28;
• or
• e) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 30, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 31, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 32:
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 34, a CDR2-L comprising amino acid sequence ROD, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 35;
• or
• f) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 38;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 28;
• or
• g) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 41;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 17, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• h) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 44;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• i) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 47;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• j) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 50, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 51, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 52;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 54, a CDR2-L comprising amino acid sequence NAN, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 55;
• or
• k) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 57, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 58;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 28;
• or
• l) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 61;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• m) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 64, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 65, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 47:
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 67, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 28;
• or
• n) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 69;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 71;
• or
• o) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 84;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 17, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• p) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 75, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 76, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 77;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• q) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 80, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 76, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 81;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• r) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 84;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• s) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 47:
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 88;
• or
• t) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 90, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 91, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 32;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 93, a CDR2-L comprising amino acid sequence GAS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 94;
• or
• u) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 96, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 97, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 98;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 100, a CDR2-L comprising amino acid sequence NTN, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 101;
• or
• v) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 103, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 104, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 105;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• w) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 80, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 19, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 108;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• x) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 37, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 111;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 113, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 114;
• or
• y) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 116, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 117, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 118;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 100, a CDR2-L comprising amino acid sequence VTN, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 120;
• or
• z) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 122, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 123, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 124;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 126, a CDR2-L comprising amino acid sequence ROD, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 127;
• or
• aa) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 13, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 19, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 129;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 10, a CDR2-L comprising amino acid sequence KVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 11;
• or
• bb) a heavy chain variable domain comprising a CDR1-H comprising amino acid sequence SEQ ID NO:
• 103, a CDR2-H comprising amino acid sequence SEQ ID NO:
• 104, and a CDR3-H comprising amino acid sequence SEQ ID NO:
• 105;
• and a light chain variable domain comprising a CDR1-L comprising amino acid sequence SEQ ID NO:
• 133, a CDR2-L comprising amino acid sequence LVS, and a CDR3-L comprising amino acid sequence SEQ ID NO:
• 134.

31:

• An antibody-like binding protein that binds specifically to human CD3ε comprising two polypeptide chains that form two antigen-binding sites, wherein a first polypeptide has a stricture represented by the formula [I]:
• VD-L1-VD1-L2-CL [I]
• and a second polypeptide has a structure represented by the formula [II]:
• VD3-L3-VD4-L4-CH1 [II]
• wherein:
• VD1 is a heavy or light chain variable domain of a first immunoglobulin;
• VD2 is a heavy or light chain variable domain of a second immuoglobulin;
• VD3 is a heavy or light chain variable domain of the second immunoglobulin;
• VD4 is a heavy or light chain variable domain of the first immunoglobulin;
• CL is a light chain constant domain of an immunoglobulin;
• CH1 is a CH1 heavy chain constant domain of an immunoglobulin;
• L1, L2, L3, and L4 are amino acid linkers;
• wherein the first polypeptide and the second polypeptide form a cross-over light chain-heavy chain pair;
• and
• wherein VD1 and VD4, or VD2 and VD3 comprise a heavy chain variable domain and a light chain variable domain of an antibody according to claim 29.