US 12,331,134 B2
Trispecific antibodies specific for HER2 and a blood brain barrier receptor and methods of use
Christian Klein, Bonstetten (CH); Julia Krueger, Munich (DE); Ekkehard Moessner, Kreuzlingen (CH); and Jens Niewoehner, Munich (DE)
Assigned to Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed by Hoffmann-La Roche Inc., Little Falls, NJ (US)
Filed on Jun. 10, 2022, as Appl. No. 17/837,633.
Application 17/837,633 is a continuation of application No. 15/845,970, filed on Dec. 18, 2017, abandoned.
Application 15/845,970 is a continuation of application No. PCT/EP2016/064124, filed on Jun. 20, 2016.
Claims priority of application No. 15173640 (EP), filed on Jun. 24, 2015.
Prior Publication US 2023/0212312 A1, Jul. 6, 2023
Int. Cl. C07K 16/32 (2006.01); C07K 16/18 (2006.01); C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/32 (2013.01) [C07K 16/18 (2013.01); C07K 16/2881 (2013.01); A61K 2039/505 (2013.01); A61K 2039/507 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/34 (2013.01); C07K 2317/41 (2013.01); C07K 2317/51 (2013.01); C07K 2317/515 (2013.01); C07K 2317/60 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/732 (2013.01); C07K 2317/734 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 19 Claims
 
1. A trispecific antibody specifically binding to HER2 and a blood-brain barrier receptor (BBB-R), comprising a first monovalent antigen binding site specific for extracellular domain II of HER2 and a second monovalent antigen binding site specific for extracellular domain IV of HER2, and a third monovalent antigen binding site specific for a BBB-R, wherein the trispecific antibody comprises a first Fab molecule that specifically binds to extracellular domain II of HER2 and a second Fab molecule that specifically binds to extracellular domain IV of HER2; wherein the sequence of the variable light chain of the first Fab molecule is identical to the sequence of the variable light chain of the second Fab molecule; and wherein the trispecific antibody comprises:
(a) a first heavy chain comprising a heavy chain CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 55, SEQ ID NO: 58 and SEQ ID NO: 14; a heavy chain CDR 2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 77; SEQ ID NO: 15 and SEQ ID NO: 60; and a heavy chain CDR 3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 56 or SEQ ID NO: 59 and SEQ ID NO: 16; and
(b) a second heavy chain comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 20, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 29 and a heavy chain CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 30 and SEQ ID NO: 79; and
(c) a first and a second light chain, wherein the variable light chains of the first and second light chain comprise a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 89, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:90 and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 19, and
wherein the third antigen binding site specific for the BBB-R is a scFv or a scFab.