Therapeutic antibodies

A bispecific canine antigen-binding molecule comprising a first antigen binding domain or antigen binding portion thereof that specifically binds canine CD3, and a second antigen binding domain that specifically binds canine CD20, wherein:

• (a) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first heavy chain variable region (VH) comprising VH complementarity determining region (CDR)1, VH CDR2, and VH CDR3 and (ii) a first light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 67;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 68;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 69;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (b) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 87;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 88;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 89;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (c) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 157;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 158;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 159 the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (d) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 167;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 168;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 169;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (e) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 177;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 178;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 179;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (f) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 187;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 188;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 189;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (g) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 327;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 328;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 329;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 480;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 481;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 482;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 480;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 481;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 482;
• (h) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 337;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 338;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 339;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 490;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 491;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 492;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 490;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 491;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 492;
• (i) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 357;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 358;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 359;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 460;
• and the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 461;
• the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 462;
• (j) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 347;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 348;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 349;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 350;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 351;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 352;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 350;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 351;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 352;
• or
• (k) the first antigen binding domain or antigen-binding portion thereof comprises (i) a first VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a first VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 107;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 108;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 109;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 110;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 111;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 112;
• and
• the second antigen binding domain or antigen-binding portion thereof comprises (i) a second VH comprising VH CDR1, VH CDR2, and VH CDR3 and (ii) a second VL comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 527;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 528;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 529;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 110;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 111;
• and the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 112.

A canine antibody or antigen-binding portion thereof that binds canine CD3, wherein the antibody or antigen-binding portion comprises (i) a heavy chain variable region (VH) comprising VH complementarity determining region (CDR)1, VH CDR2, and VH CDR3;

• and (ii) a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
• (a) the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 47;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 48;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 49;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 50;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 51;
• the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 52;
• (b) the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 87;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 88;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 89;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 90;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 91;
• the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 92;
• (c) the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 127;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 128;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 129;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 130;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 131;
• the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 132;
• or
• (d) the VH CDR1 comprises the amino acid sequence SEQ ID NO:
• 167;
• the VH CDR2 comprises the amino acid sequence SEQ ID NO:
• 168;
• the VH CDR3 comprises the amino acid sequence SEQ ID NO:
• 169;
• the VL CDR1 comprises the amino acid sequence SEQ ID NO:
• 170;
• the VL CDR2 comprises the amino acid sequence SEQ ID NO:
• 171;
• the VL CDR3 comprises the amino acid sequence SEQ ID NO:
• 172.