US 12,391,757 B2
Bispecific antibodies specific for PD1 and TIM3
Laura Codarri-Deak, Schlieren (CH); Georg Fertig, Penzberg (DE); Jens Fischer, Penzberg (DE); Christian Klein, Schlieren (CH); Viktor Levitski, Schlieren (CH); Valeria Lifke, Penzberg (DE); Mario Perro, Schlieren (CH); Joerg Thomas Regula, Penzberg (DE); Tilman Schlothauer, Basel (DE); Stefan Seeber, Penzberg (DE); Pablo Umana, Penzberg (CH); Ildiko Wuensche, Penzberg (DE); and Adrian Zwick, Penzberg (DE)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Sep. 3, 2021, as Appl. No. 17/446,943.
Application 16/367,017 is a division of application No. 15/280,372, filed on Sep. 29, 2016, granted, now 10,287,352, issued on May 14, 2019.
Application 17/446,943 is a continuation of application No. 16/367,017, filed on Mar. 27, 2019, granted, now 11,130,810.
Claims priority of application No. 15188036 (EP), filed on Oct. 2, 2015; and application No. 15188065 (EP), filed on Oct. 2, 2015.
Prior Publication US 2022/0259314 A1, Aug. 18, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2818 (2013.01) [C07K 16/2803 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/41 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/52 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/66 (2013.01); C07K 2317/71 (2013.01); C07K 2317/76 (2013.01); C07K 2317/77 (2013.01); C07K 2317/92 (2013.01)] 20 Claims
 
1. A method of producing a bispecific antibody, the method comprising the steps of a) transforming a host cell with vectors comprising polynucleotides encoding said bispecific antibody, b) culturing the host cell under conditions suitable for the expression of the bispecific antibody and c) recovering the bispecific antibody from the culture, wherein the bispecific antibody comprises a first antigen-binding site that specifically binds to PD1 and a second antigen-binding site that specifically binds to TIM3, wherein
said first antigen-binding site specifically binding to PD1 comprises
a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:37, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:38 and (iii) HVR-H3 comprising an amino acid sequence of SEQ ID NO:39; and
a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:40; (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:41, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:42; and
said second antigen-binding site specifically binding to TIM3 comprises
(a) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:1, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:2, and (iii) HVR-H3 comprising an amino acid sequence of SEQ ID NO:3; and
a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:11 or SEQ ID NO:12, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:5, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; or
(b) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 17, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:18, and (iii) HVR-H3 comprising an amino acid sequence of SEQ ID NO:19; and
a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:20, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:21, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:22; or
(c) a VH domain comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 29, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:30, and (iii) HVR-H3 comprising an amino acid sequence of SEQ ID NO:31; and
a VL domain comprising (i) HVR-L1 comprising the amino acid sequence of SEQ ID NO:32, (ii) HVR-L2 comprising the amino acid sequence of SEQ ID NO:33, and (iii) HVR-L3 comprising the amino acid sequence of SEQ ID NO:34.