	US 11,787,862 B2
	Bispecific trivalent antibodies binding to Claudin6 or Claudin18.2 and CD3 for treatment of Claudin expressing cancer diseases
Ugur Sahin, Mainz (DE); Christiane Stadler, Bensheim (DE); Leyla Fischer, Gau-Odernheim (DE); Arne Jendretzki, Mainz-Kostheim (DE); Özlem Türeci, Mainz (DE); Fabrice Le Gall, Mainz (DE); and Maria Kreuzberg, Aachen (DE)
Assigned to BioNTech SE, Mainz (DE); and ASTELLAS PHARMA INC., Tokyo (JP)
Appl. No. 16/335,373
Filed by BIONTECH AG, Mainz (DE); and Astellas Pharma Inc., Tokyo (JP)
PCT Filed Sep. 20, 2017, PCT No. PCT/EP2017/073773 § 371(c)(1), (2) Date Mar. 21, 2019, PCT Pub. No. WO2018/054973, PCT Pub. Date Mar. 29, 2018.
Claims priority of application No. PCT/EP2016/072688 (WO), filed on Sep. 23, 2016.
Prior Publication US 2019/0309067 A1, Oct. 10, 2019
Int. Cl. C07K 16/28 (2006.01); C12N 15/86 (2006.01); A61P 35/00 (2006.01); A61K 39/00 (2006.01)

CPC C07K 16/2809 (2013.01) [A61P 35/00 (2018.01); C07K 16/28 (2013.01); C12N 15/86 (2013.01); A61K 2039/505 (2013.01); A61K 2039/53 (2013.01); C07K 2317/31 (2013.01); C07K 2317/35 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)]

32 Claims

1. A nucleic acid encoding a binding agent comprising at least three binding domains, wherein a first binding domain binds to a T cell-specific antigen and a second binding domain and a third binding domain bind to a claudin, wherein the binding agent comprises

(a) a first polypeptide comprising a VH domain with a specificity for the T cell-specific antigen (VH(T)), a VH domain with a specificity for the claudin (VH(CLDN)) and a VL domain with a specificity for the claudin (VL(CLDN)); and

(b) a second polypeptide comprising a VL domain with a specificity for the T cell-specific antigen (VL(T)), a VH domain with a specificity for the claudin (VH(CLDN)) and a VL domain with a specificity for the claudin (VL(CLDN)); and

wherein

each VH(CLDN) comprises:

a HCDR1 having the amino acid sequence set forth in SEQ ID NO: 44,

a HCDR2 having the amino acid sequence set forth in SEQ ID NO: 45, and

a HCDR3 having the amino acid sequence set forth in SEQ ID NO: 46; and

each VL(CLDN) comprises:

a LCDR1 having the amino acid sequence set forth in SEQ ID NO: 50,

a LCDR2 having the amino acid sequence set forth in SEQ ID NO: 51, and

a LCDR3 having the amino acid sequence set forth in SEQ ID NO: 52; and

wherein each VH(CLDN) comprises the amino acid sequence set forth in SEQ ID NO: 8 and each VL(CLDN) comprises the amino acid sequence set forth in SEQ ID NO: 9 or a variant thereof, wherein said variant comprises no more than two amino acid substitutions relative to SEQ ID NO: 9.