US 11,718,680 B2
Combination therapy of anti-CD20/anti-CD3 bispecific antibodies and 4-1BB (CD137) agonists
Marina Bacac, Schlieren (CH); Claudia Ferrara Koller, Schlieren (CH); Christian Klein, Schlieren (CH); Mario Perro, Schlieren (CH); Johannes Sam, Schlieren (CH); Pablo Umaña, Schlieren (CH); and Wei Xu, Schlieren (CH)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Mar. 16, 2020, as Appl. No. 16/820,504.
Application 16/820,504 is a continuation of application No. 16/446,478, filed on Jun. 19, 2019, abandoned.
Application 16/446,478 is a continuation of application No. PCT/EP2017/083222, filed on Dec. 18, 2017.
Claims priority of application No. 16205493 (EP), filed on Dec. 20, 2016.
Prior Publication US 2020/0325238 A1, Oct. 15, 2020
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C07K 16/46 (2006.01); A61K 39/00 (2006.01); A61K 9/00 (2006.01)
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.