Antibodies targeting steap-1 and cd3 and uses thereof
AssigneeJanux Therapeutics, Inc.
InventorsDavid CAMPBELL, Thomas R. DIRAIMONDO, John LAUDENSLAGER
Life of this patent
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Abstract
Disclosed herein are polypeptides or polypeptide complexes comprising an antibody or antigen binding fragment thereof that binds to six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) and a second antibody or antigen binding fragment thereof that binds to CD3.
Claims147
A polypeptide or polypeptide complex comprising an antibody or antigen binding fragment thereof that binds to six-transmembrane epithelial antigen of the prostate-1 (STEAP-1), wherein the antibody or antigen binding fragment thereof comprises an immunoglobulin light chain and an immunoglobulin heavy chain and comprises at least one amino acid mutation wherein the at least one amino acid mutation is selected from a position corresponding to V24, Y27, W35, G45, T58, L64, S66, T74, E99, and M111 of SEQ ID NO:
- 225 and Q3, S9, S12, A13, V15, D17, V19, T22, Q35, K48, A49, S66, P86, F89, T91, and Q106 of SEQ ID NO:
- 226, and wherein the polypeptide or polypeptide complex comprises a second antibody or antigen binding thereof that binds to CD3.
A polypeptide or polypeptide complex comprising an antibody or antigen binding fragment thereof that binds to six-transmembrane epithelial antigen of the prostate-1 (STEAP-1), wherein the antibody or antigen binding fragment thereof comprises an immunoglobulin light chain and an immunoglobulin heavy chain wherein the immunoglobulin heavy chain and the immunoglobulin light chain comprise a set of six CDR sequences selected from the group consisting of:
- CDR1-H:
- SEQ ID NO:
- 4, CDR2-H:
- SEQ ID NO:
- 10, CDR3-H:
- SEQ ID NO:
- 16,
- CDR1-L:
- SEQ ID NO:
- 22, CDR2-L:
- SEQ ID NO:
- 28, CDR3-L:
- SEQ ID NO:
- 34;
- CDR1-H:
- SEQ ID NO:
- 5, CDR2-H:
- SEQ ID NO:
- 11, CDR3-H:
- SEQ ID NO:
- 17,
- CDR1-L:
- SEQ ID NO:
- 23, CDR2-L:
- SEQ ID NO:
- 29, CDR3-L:
- SEQ ID NO:
- 35;
- CDR1-H:
- SEQ ID NO:
- 6, CDR2-H:
- SEQ ID NO:
- 12, CDR3-H:
- SEQ ID NO:
- 18,
- CDR1-L:
- SEQ ID NO:
- 24, CDR2-L:
- SEQ ID NO:
- 30, CDR3-L:
- SEQ ID NO:
- 36;
- CDR1-H:
- SEQ ID NO:
- 7, CDR2-H:
- SEQ ID NO:
- 13, CDR3-H:
- SEQ ID NO:
- 19,
- CDR1-L:
- SEQ ID NO:
- 25, CDR2-L:
- SEQ ID NO:
- 31, CDR3-L:
- SEQ ID NO:
- 37;
- and
- CDR1-H:
- SEQ ID NO:
- 8, CDR2-H:
- SEQ ID NO:
- 14, CDR3-H:
- SEQ ID NO:
- 20,
- CDR1-L:
- SEQ ID NO:
- 26, CDR2-L:
- SEQ ID NO:
- 32, CDR3-L:
- SEQ ID NO:
- 38;
- and wherein the polypeptide or polypeptide complex comprises a second antibody or antigen binding fragment thereof that binds to CD3.
A polypeptide or polypeptide complex comprising an antibody or antigen binding fragment thereof that binds to six-transmembrane epithelial antigen of the prostate-1 (STEAP-1), wherein the antibody or antigen binding fragment thereof comprises an immunoglobulin light chain and an immunoglobulin heavy chain wherein the immunoglobulin heavy chain and the immunoglobulin light chain comprise a set of six CDR sequences according to
- CDR1-H:
- SEQ ID NO:
- 3, CDR2-H:
- SEQ ID NO:
- 9, CDR3-H:
- SEQ ID NO:
- 15,
- CDR1-L:
- SEQ ID NO:
- 21, CDR2-L:
- SEQ ID NO:
- 27, CDR3-L:
- SEQ ID NO:
- 33;
- and wherein the polypeptide or polypeptide complex further comprises a second antibody or antigen binding fragment thereof that binds to CD3 wherein the second antibody or antigen binding fragment thereof that binds to CD3 comprises an immunoglobulin light chain comprising complementarity determining regions (CDRs):
- CDR1-L, CDR2-L, and CDR3-L, and an immunoglobulin heavy chain comprising CDRs:
- CDR1-H, CDR2-H, and CDR3-H,
- wherein CDR1-L comprises the amino acid sequence of SEQ ID NO:
- 80 or SEQ ID NO:
- 83;
- wherein CDR2-L comprises the amino acid sequence of GTK;
- wherein CDR3-L comprises the amino acid sequence of Z1-Z2-W-Z3-Z4-Z5-Z6-W-Z7-Z8 or SEQ ID NO:
- 82;
- wherein Z1 is V, G, P, L, I, M, S, T, or A;
- Z2 is L, G, P, V, I, M, S, T, or A;
- Z3 is Y, F, W, V, L, I, G, or A;
- Z4 is S, G, T, M, N, Q, H, or A;
- Z5 is N, Q, S, T, D, E, H, K, R, or A;
- Z6 is R, S, T, Q, D, E, H, K, N, or A;
- Z7 is V, G, P, L, I, M, S, T, or A;
- and
- Z8 is F, Y, W, V, L, I, G, or A;
- wherein CDR1-H comprises the amino acid sequence of SEQ ID NO:
- 61 or SEQ ID NO:
- 64;
- wherein CDR2-H comprises the amino acid sequence of SEQ ID NO:
- 62;
- wherein CDR3-H comprises the amino acid sequence of Z9-Z10-Z11-Z12-N-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Y-Z20-A-Z21 or SEQ ID NO:
- 63;
- and
- wherein Z9 is V, G, P, L, I, M, S, T, or A;
- Z10 is R, S, T, Q, D, E, H, K, N, or A;
- Z11 is H, R, K, G, T, S, N, Q, or A;
- Z12 is G, P, V, L, I, M, S, T, or A;
- Z13 is F, Y, W, V, L, I, G, or A;
- Z14 is G, P, V, L, I, M, S, T, or A;
- Z15 is N, Q, S, T, D, E, H, K, R, or A;
- Z16 is S, G, T, M, N, Q, H, or A;
- Z17 is Y, F, W, V, L, I, G, or A;
- Z18 is I, G, P, V, L, M, S, T, or A;
- Z19 is S, G, T, M, N, Q, H, or A;
- Z20 is W, F, Y, V, L, I, G, or A;
- and
- Z21 is Y, F, W, V, L, I, G, or A.
Dependencies are inferred from the claim text.