Bcma binding molecules and methods of use thereof
AssigneeKite Pharma, Inc.
InventorsJed WILTZIUS, Ruben ALVAREZ RODRIGUEZ
Life of this patent
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Abstract
The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.
Claims123
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to B-cell maturation antigen (BCMA), wherein the antigen binding molecule comprises:
- (a) a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising, consisting of, or consisting essentially of the amino acid sequence GX2X3X4X5X6X7SY (SEQ ID NO:
- 145), wherein:
- X2 is not present or G;
- X3 is not present or S;
- X4 is F, G, I, or Y;
- X5 is S or T;
- X6 is F or S;
- and
- X7 is S or T;
- and/or
- (b) a VH CDR2 comprising, consisting of, or consisting essentially of the amino acid sequence X1IX3X4X5X6X7X8X9X10YX12X13X14X15X16X17 (SEQ ID NO:
- 146), wherein:
- X1 is A, G, I, S, T, or V;
- X3 is I, N, or S;
- X4 is G, P, S, or Y;
- X5 is D, G, I, or S;
- X6 is F, G, or S;
- X7 is not present or G or S;
- X8 is N, S, or T;
- X9 is A, I, K, or T;
- X10 is N, S, or Y;
- X12 is A or N;
- X13 is D, P, or Q;
- X14 is K or S;
- X15 is F, L, or V;
- X16 is K or Q;
- and
- X17 is G or S;
- and/or
- (c) a VH CDR3 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17DX19 (SEQ ID NO:
- 147), wherein:
- X1 is A or V;
- X2 is K or R;
- X3 is not present or D, G, or T;
- X4 is not present or A, D, G, P, R, or S;
- X5 is not present or E, F, G, L, Q, or T;
- X6 is not present or E, M, Q, W, or Y;
- X7 is not present or A, E, L, or S;
- X8 is not present or G, P, S, or T;
- X9 is not present or G, P, or S;
- X10 is not present or I, L, P, or Y;
- X11 is not present or W;
- X12 is not present or H;
- X13 is not present or E or Y;
- X14 is not present or D, G, H, P, S, W, or Y;
- X15 is A, G, L, W, or Y;
- X16 is not present or A, G, I, P, or V;
- X17 is F, L, or M;
- and
- X19 is I, L, V, or Y;
- and/or
- (d) a light chain variable region (VL) CDR1 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2SQX5X6X7X8X9X10X11X12X13X14X15LX17 (SEQ ID NO:
- 148), wherein
- X1 is K or R;
- X2 is A or S;
- X5 is G or S;
- X6 is I, L, or V;
- X7 is L or S;
- X8 is not present or H or Y;
- X9 is not present or S;
- X10 is not present or N or S;
- X11 is not present or G or N;
- X12 is not present or N;
- X13 is not present or K or Y;
- X14 is N, R, or S;
- X15 is N, W, or Y;
- and
- X17 is A or D;
- (e) a VL CDR2 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2SX4X5X6X7 (SEQ ID NO:
- 149), wherein
- X1 is D, G, L, S, or W;
- X2 is A or G;
- X4 is N, S, or T;
- X5 is L or R;
- X6 is A, E, or Q;
- and
- X7 is S or T;
- and/or
- (f) a VL CDR3 comprising, consisting of, or consisting essentially of the amino acid sequence X1QX3X4X5X6PX8T (SEQ ID NO:
- 150), wherein
- X1 is M or Q;
- X3 isF, G, H, I, R, orY;
- X4 is A, F, H, I, L, or Y;
- X5 is A, G, H, S, T, V, or Y;
- X6 is F, L, T, W, or Y;
- and
- X8 is not present or F, L, P, or W.
An isolated polynucleotide encoding a chimeric antigen receptor (CAR) or T cell receptor (TCR) comprising an antigen binding molecule that specifically binds to B-cell maturation antigen (BCMA), wherein the antigen binding molecule comprises a VH CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 41-48.
An isolated polynucleotide encoding an antibody or an antigen binding molecule thereof that specifically binds to BCMA, wherein the antibody or the antigen binding molecule thereof comprises:
- (a) a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising, consisting of, or consisting essentially of the amino acid sequence GX2X3X4X5X6X7SY (SEQ ID NO:
- 145), wherein:
- X2 is not present or G;
- X3 is not present or S;
- X4 is F, G, I, or Y;
- X5 is S or T;
- X6 is F or S;
- and
- X7 is S or T;
- (b) a VH CDR2 comprising, consisting of, or consisting essentially of the amino acid sequence X1IX3X4X5X6X7X8X9X10YX12X13X14X15X16X17 (SEQ ID NO:
- 146), wherein:
- X1 is A, G, I, S, T, or V;
- X3 is I, N, or S;
- X4 is G, P, S, or Y;
- X5 is D, G, I, or S;
- X6 is F, G, or S;
- X7 is not present or G or S;
- X8 is N, S, or T;
- X9 is A, I, K, or T;
- X10 is N, S, or Y;
- X12 is A or N;
- X13 is D, P, or Q;
- X14 is K or S;
- X15 is F, L, or V;
- X16 is K or Q;
- and
- X17 is G or S;
- (c) a VH CDR3 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16X17DX19 (SEQ ID NO:
- 147), wherein:
- X1 is A or V;
- X2 is K or R;
- X3 is not present or D, G, or T;
- X4 is not present or A, D, G, P, R, or S;
- X5 is not present or E, F, G, L, Q, or T;
- X6 is not present or E, M, Q, W, or Y;
- X7 is not present or A, E, L, or S;
- X8 is not present or G, P, S, or T;
- X9 is not present or G, P, or S;
- X10 is not present or I, L, P, or Y,
- X11 is not present or W;
- X12 is not present or H;
- X13 is not present or E or Y;
- X14 is not present or D, G, H, P, S, W, or Y;
- X15 is A, G, L, W, or Y;
- X16 is not present or A, G, I, P, or V;
- X17 is F, L, or M;
- and
- X19 is I, L, V, or Y;
- (d) a light chain variable region (VL) CDR1 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2SQX5X6X7X8X9X10X11X12X13X14X15LX17 (SEQ ID NO:
- 148), wherein
- X1 is K or R;
- X2 is A or S;
- X5 is G or S;
- X6 is I, L, or V;
- X7 is L or S;
- X8 is not present or H or Y;
- X9 is not present or S;
- X10 is not present or N or S;
- X11 is not present or G or N;
- X12 is not present or N;
- X13 is not present or K or Y;
- X14 is N, R, or S;
- X15 is N, W, or Y;
- and
- X17 is A or D;
- (e) a VL CDR2 comprising, consisting of, or consisting essentially of the amino acid sequence X1X2SX4X5X6X7 (SEQ ID NO:
- 149), wherein
- X1 is D, G, L, S, or W;
- X2 is A or G;
- X4 is N, S, or T;
- X5 is L or R;
- X6 is A, E, or Q;
- and
- X7 is S or T;
- and/or
- (f) a VL CDR3 comprising, consisting of, or consisting essentially of the amino acid sequence X1QX3X4X5X6PX8T (SEQ ID NO:
- 150), wherein
- X1 is M or Q;
- X3 is F, G, H, I, R, or Y;
- X4 is A, F, H, I, L, or Y;
- X5 is A, G, H, S, T, V, or Y;
- X6 is F, L, T, W, or Y;
- and
- X8 is not present or F, L, P, or W.
An isolated polynucleotide encoding an antibody or an antigen binding molecule thereof that specifically binds to BCMA, wherein the antibody or the antigen binding molecule thereof comprises a VH CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 41-48.
A sequence comprising any of SEQ ID NO. 271 to SEQ ID NO. 410.
A vector comprising at least one sequence set forth in SEQ ID NO. 271 to SEQ ID NO. 410.
An immune cell comprising a sequence set forth in any of SEQ ID NO. 271 to SEQ ID NO. 410.
Dependencies are inferred from the claim text.