Cd20 and cd22 targeting antigen-binding molecules for use in proliferative diseases

Patent metadata

Field	Value
Publication number	US-2024384006-A1
Application number	US-202218286941-A
Country	US
Kind code	A1
Filing date	May 6, 2022
Priority date	May 6, 2021
Publication date	Nov 21, 2024
Grant date	—

Abstract

The present invention provides CD20 and CD22 targeting antigen-binding molecules characterized by comprising a first and a second domain, binding to CD20 and CD22, respectively, a third domain binding to an extracellular epitope of the human and the Macaca CD3ε chain and optionally a fourth domain, which is a Fc modality. Moreover, the invention provides a polynucleotide, encoding the antigen-binding molecule, a vector comprising this polynucleotide, host cells, expressing the antigen-binding molecule and a pharmaceutical composition comprising the same.

First claim

1 . A CD20 and CD22 targeting antigen-binding molecule comprising at least three binding domains, wherein
(i) the first binding domain comprises a paratope which immuno-specifically binds to CD20, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from:
a) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63,
b) CDR H1-3 of SEQ ID NO: 71-73 and CDR L1-3 of SEQ ID NO: 74-76,
c) CDR H1-3 of SEQ ID NO: 84-86 and CDR L1-3 of SEQ ID NO: 87-89, and
d) CDR H1-3 of SEQ ID NO: 97 −99 and CDR L1-3 of SEQ ID NO: 100-102;
(ii) the second binding domain comprises a paratope which immuno-specifically binds to CD22, wherein the first binding domain comprises a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from
a) CDR H1-3 of SEQ ID NO: 138-140 and CDR L1-3 of SEQ ID NO: 141-143,
b) CDR H1-3 of SEQ ID NO: 151-153 and CDR L1-3 of SEQ ID NO: 154-156,
c) CDR H1-3 of SEQ ID NO: 164-166 and CDR L1-3 of SEQ ID NO: 167-169,
d) CDR H1-3 of SEQ ID NO: 177-179 and CDR L1-3 of SEQ ID NO: 180-182,
e) CDR H1-3 of SEQ ID NO: 190-192 and CDR L1-3 of SEQ ID NO: 193-195,
f) CDR H1-3 of SEQ ID NO: 203-205 and CDR L1-3 of SEQ ID NO: 206-208,
g) CDR H1-3 of SEQ ID NO: 125-127 and CDR L1-3 of SEQ ID NO: 128-130,
h) CDR H1-3 of SEQ ID NO: 216-218 and CDR L1-3 of SEQ ID NO: 219-221, and
i) CDR H1-3 of SEQ ID NO: 379-381 and CDR L1-3 of SEQ ID NO: 382-384; and
(iii) the third binding domain comprises a paratope which immune-specifically binds to an extracellular epitope of the human and/or the Macaca CD3ε chain,
wherein the first, second and third binding domain are arranged in an amino to carboxyl order, and wherein the first binding domain and the second binding domain are linked by a peptide linker having a length of 5 to 24, preferably 18 amino acids.

2 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the antigen-binding molecule comprises a fourth domain which comprises two polypeptide monomers, each comprising a hinge, a CH2 and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker
wherein said forth domain preferably comprises in an amino to carboxyl order:
hinge-CH2-CH3-linker-hinge-CH2-CH3

and/or wherein preferably each of said polypeptide monomers in the fourth domain has an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of: SEQ ID NO: 17-24, wherein preferably each of said polypeptide monomers has an amino acid sequence selected from SEQ ID NO: 17-24,
and/or wherein preferably the CH2 domain comprises an intra domain cysteine disulfide bridge,
and/or wherein the first, second, third and fourth binding domain are arranged in an amino to carboxyl order.

3 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the antigen-binding molecule is a single chain antigen-binding molecule, preferably a CD20 and CD22 targeting scFv antigen-binding molecule.

4 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the peptide linker between the first binding domain and the second binding domain is selected from having a length of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 23, or 24 amino acids, preferably 5, 6, 7, 8, 9, 10, 11 or 12 amino acids, more preferably 6 amino acids.

5 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the peptide linker between the first binding domain and the second binding domain is selected from the group consisting of S(G 4 S) n , (G 4 S) n , G 4n , and G 5n , wherein n equals 1, 2, 3 or 4, preferably n equals 1 or 2, more preferably SG 4 S.

6 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein
the first binding domain and the second binding domain each comprise a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from: a) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 138-140 and CDR L1-3 of SEQ ID NO: 141-143 of the second binding domain; b) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 151-153 and CDR L1-3 of SEQ ID NO: 154-156 of the second binding domain; c) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 164-166 and CDR L1-3 of SEQ ID NO: 167-169 of the second binding domain; d) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 177-179 and CDR L1-3 of SEQ ID NO: 180-182 of the second binding domain, e) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 190-192 and CDR L1-3 of SEQ ID NO: 193-195 of the second binding domain; f) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 203-205 and CDR L1-3 of SEQ ID NO: 206-208 of the second binding domain; g) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 125-127 and CDR L1-3 of SEQ ID NO: 128-130 of the second binding domain, h) CDR H1-3 of SEQ ID NO: 58-60 and CDR L1-3 of SEQ ID NO: 61-63 of the first binding domain and CDR H1-3 of SEQ ID NO: 216-218 and CDR L1-3 of SEQ ID NO: 219-221 of the second binding domain; i) CDR H1-3 of SEQ ID NO: 71-73 and CDR L1-3 of SEQ ID NO: 74-76 of the first binding domain and CDR H1-3 of SEQ ID NO: 379-381 and CDR L1-3 of SEQ ID NO: 382-384 of the second binding domain, j) CDR H1-3 of SEQ ID NO: 71-73 and CDR L1-3 of SEQ ID NO: 74-76 of the first binding domain and CDR H1-3 of SEQ ID NO: 203-205 and CDR L1-3 of SEQ ID NO: 206-208 of the second binding domain; k) CDR H1-3 of SEQ ID NO: 84-86 and CDR L1-3 of SEQ ID NO: 87-89 of the first binding domain and CDR H1-3 of SEQ ID NO: 164-166 and CDR L1-3 of SEQ ID NO: 167-169 of the second binding domain, l) CDR H1-3 of SEQ ID NO: 97 −99 and CDR L1-3 of SEQ ID NO: 100-102 of the first binding domain and CDR H1-3 of SEQ ID NO: 177-179 and CDR L1-3 of SEQ ID NO: 180-182 of the second binding domain; m) CDR H1-3 of SEQ ID NO: 97 −99 and CDR L1-3 of SEQ ID NO: 100-102 of the first binding domain and CDR H1-3 of SEQ ID NO: 190-192 and CDR L1-3 of SEQ ID NO: 193-195 of the second binding domain.

7 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the first binding domains is capable of binding to CD20 and the second binding domain is capable of binding to CD22 simultaneously, preferably wherein CD20 and CD22 are on the same target cell,

8 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the third binding domain comprise a VH region comprising CDR-H1, CDR-H2 and CDR-H3 and a VL region comprising CDR-L1, CDR-L2 and CDR-L3 selected from:
a) CDR H1-3 of SEQ ID NO: 392-394 and CDR L1-3 of SEQ ID NO: 395-397; and b) CDR H1-3 of SEQ ID NO: 401-403 and CDR L1-3 of SEQ ID NO: 404-406.

9 . The CD20 and CD22 targeting antigen-binding molecule of claim 1 , wherein the antigen-binding molecule comprises in an amino to carboxyl order:
(a) the first domain; (b) a peptide linker preferably having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-4 and 9-12, preferably 11; (c) the second domain, (d) a peptide linker preferably having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-3; and (e) the third domain,

Assignees

• Amgen Res Munich Gmbh

Inventors

• Panzer Marc
• Honer Jonas
• Deisting Wibke
• Raum Tobias
• Gaedtke Lars
• Rau Doris
• Winkel Lisa

Classifications

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/53

  Hinge · CPC title