CPC C07K 16/2887 (2013.01) [A61K 39/001112 (2018.08); A61K 39/001117 (2018.08); A61K 39/001129 (2018.08); A61P 35/00 (2018.01); C07K 14/70532 (2013.01); C07K 14/70575 (2013.01); C07K 16/2809 (2013.01); C07K 16/2818 (2013.01); C07K 16/2827 (2013.01); C07K 16/2878 (2013.01); C07K 16/468 (2013.01); A61K 9/0019 (2013.01); A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); C07K 2317/31 (2013.01); C07K 2317/52 (2013.01); C07K 2317/565 (2013.01); C07K 2317/71 (2013.01); C07K 2319/00 (2013.01)] | 32 Claims |
1. A method for treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject, wherein the method comprises administering to the subject an effective amount of an anti-CD20/anti-CD3 bispecific antibody and a 4-1BB agonist, wherein the anti-CD20/anti-CD3 bispecific antibody comprises: (a) a first antigen binding domain comprising a heavy chain variable region (VHCD3) comprising CDR-H1 sequence of SEQ ID NO:56, CDR-H2 sequency of SEQ ID NO:57, and CDR-H3 sequence of SEQ ID NO:58; and a light chain variable region (VLCD3) comprising CDR-L1 sequence of SEQ ID NO:59, CDR-L2 sequence of SEQ ID NO:60, and CDR-L3 sequence of SEQ ID NO:61; and (b) a second antigen binding domain comprising a heavy chain variable region (VHCD20) comprising CDR-H1 sequence of SEQ ID NO:64, CDR-H2 sequence of SEQ ID NO:65, and CDR-H3 sequence of SEQ ID NO:66; and a light chain variable region (VLCD20) comprising CDR-L1 sequence of SEQ ID NO:67, CDR-L2 sequence of SEQ ID NO:68, and CDR-L3 sequence of SEQ ID NO:69; and wherein the 4-1BB agonist comprises: (c) three ectodomains of 4-1BBL that independently comprise an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO: 6, SEQ ID NO:7, and SEQ ID NO:8; and (d) a CD19 heavy chain variable region (VHCD19) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 15, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 16, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17; and a CD19 light chain variable region (VLCD19) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 18, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 19, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:20; or a CD19 heavy chain variable region (VHCD19) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:9, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 11; and a CD19 light chain variable region (VLCD19) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 12, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 13, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:14.
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