Cross-species-specific PSMAxCD3 bispecific single chain antibody

Patent metadata

Field	Value
Publication number	US-12281172-B2
Application number	US-202117221627-A
Country	US
Kind code	B2
Filing date	Apr 2, 2021
Priority date	Oct 1, 2008
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

The present invention relates to a bispecific single chain antibody molecule comprising a first binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 epsilon chain, wherein the epitope is part of an amino acid sequence comprised in the group consisting of SEQ ID NOs. 2, 4, 6, and 8, and a second binding domain capable of binding to prostate-specific membrane antigen (PSMA). The invention also provides nucleic acids encoding said bispecific single chain antibody molecule as well as vectors and host cells and a process for its production. The invention further relates to pharmaceutical compositions comprising said bispecific single chain antibody molecule and medical uses of said bispecific single chain antibody molecule.

First claim

The invention claimed is:

1. A bispecific single chain antibody molecule comprising a first binding domain that specifically binds to human CD3 epsilon (CD3ε) chain and a second binding domain that specifically binds to human prostate-specific membrane antigen (PSMA), wherein the first binding domain comprises a light chain variable (VL CD3ε) region comprising complementarity determining regions CDR-L1, CDR-L2, and CDR-L3 and a heavy chain variable (VH CD3ε) region comprising complementarity determining regions CDR-H1, CDR-H2, and CDR-H3, and wherein CDR-L1 has the sequence of SEQ ID NO: 171, CDR-L2 has the sequence of SEQ ID NO: 172, CDR-L3 has the sequence of SEQ ID NO: 173, CDR-H1 has the sequence of SEQ ID NO: 174, CDR-H2 has the sequence of SEQ ID NO: 175, and CDR-H3 has the sequence of SEQ ID NO: 176.

2. The bispecific single chain antibody molecule of claim 1 , wherein at least one of said first and second binding domains is humanized.

3. The bispecific single chain antibody molecule of claim 1 , wherein the VL CD3g region comprises the sequence of SEQ ID NO: 179 and the VH CD3ε region comprises the sequence of SEQ ID NO: 177.

4. The bispecific single chain antibody molecule of claim 1 , wherein the first binding domain comprises the amino acid sequence of SEQ ID NO: 185.

5. The bispecific single chain antibody molecule of claim 1 , wherein the second binding domain comprises a light chain variable (VL PSMA) region comprising complementarity determining regions CDR-L1, CDR-L2, and CDR-L3 and a heavy chain variable (VH PSMA) region comprising complementarity determining regions CDR-H1, CDR-H2, and CDR-H3, wherein:
a) CDR H1-3 comprises the sequences of SEQ ID NO: 394-396, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 389-391, respectively;
b) CDR H1-3 comprises the sequences of SEQ ID NO: 408-410, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 403-405, respectively;
c) CDR H1-3 comprises the sequences of SEQ ID NO: 422-424, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 417-419, respectively;
d) CDR H1-3 comprises the sequences of SEQ ID NO: 436-438, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 431-433, respectively;
e) CDR H1-3 comprises the sequences of SEQ ID NO: 445-447, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 450-452, respectively;
f) CDR H1-3 comprises the sequences of SEQ ID NO: 464-466, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 459-461, respectively;
g) CDR H1-3 comprises the sequences of SEQ ID NO: 478-480, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 473-475, respectively;
h) CDR H1-3 comprises the sequences of SEQ ID NO: 492-494, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 487-489, respectively;
i) CDR H1-3 comprises the sequences of SEQ ID NO: 506-508, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 501-503, respectively;
j) CDR H1-3 comprises the sequences of SEQ ID NO: 520-522, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 515-517, respectively;
k) CDR H1-3 comprises the sequences of SEQ ID NO: 534-536, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 529-531, respectively;
l) CDR H1-3 comprises the sequences of SEQ ID NO: 548-550, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 543-545, respectively;
m) CDR H1-3 comprises the sequences of SEQ ID NO: 562-564, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 557-559, respectively;
n) CDR H1-3 comprises the sequences of SEQ ID NO: 576-578, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 571-573, respectively;
o. CDR H1-3 comprises the sequences of SEQ ID NO: 590-592, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 585-587, respectively;
p) CDR H1-3 comprises the sequences of SEQ ID NO: 604-606, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 599-601, respectively;
q) CDR H1-3 comprises the sequences of SEQ ID NO: 618-620, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 613-615, respectively;
r) CDR H1-3 comprises the sequences of SEQ ID NO: 632-634, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 627-629, respectively;
s) CDR H1-3 comprises the sequences of SEQ ID NO: 646-648, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 641-643, respectively;
t) CDR H1-3 comprises the sequences of SEQ ID NO: 660-662, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 655-657, respectively;
u) CDR H1-3 comprises the sequences of SEQ ID NO: 674-676, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 669-671, respectively;
v) CDR H1-3 comprises the sequences of SEQ ID NO: 688-690, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 683-685, respectively;
w) CDR H1-3 comprises the sequences of SEQ ID NO: 702-704, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 697-699, respectively;
x) CDR H1-3 comprises the sequences of SEQ ID NO: 716-718, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 711-713, respectively;
y) CDR H1-3 comprises the sequences of SEQ ID NO: 729-731, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 724-726, respectively;
z) CDR H1-3 comprises the sequences of SEQ ID NO: 788-790, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 793-795, respectively;
aa) CDR H1-3 comprises the sequences of SEQ ID NO: 806-808, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 811-813, respectively;
ab) CDR H1-3 comprises the sequences of SEQ ID NO: 852-854, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 857-859, respectively;
ac) CDR H1-3 comprises the sequences of SEQ ID NO: 838-840, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 843-845, respectively;
ad) CDR H1-3 comprises the sequences of SEQ ID NO: 824-826, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 829-831, respectively;
ae) CDR H1-3 comprises the sequences of SEQ ID NO: 774-776, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 779-781, respectively;
af) CDR H1-3 comprises the sequences of SEQ ID NO: 688-690, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 683-685, respectively;
ag) CDR H1-3 comprises the sequences of SEQ ID NO: 870-872, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 875-877, respectively;
ah) CDR H1-3 comprises the sequences of SEQ ID NO: 888-890, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 893-895, respectively;
ai) CDR H1-3 comprises the sequences of SEQ ID NO: 924-926, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 929-931, respectively;
aj) CDR H1-3 comprises the sequences of SEQ ID NO: 1019-1021, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 1025-1027, respectively;
ak) CDR H1-3 comprises the sequences of SEQ ID NO: 1006-1008, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 1011-1013, respectively;
al) CDR H1-3 comprises the sequences of SEQ ID NO: 906-908, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 911-913, respectively;
am) CDR H1-3 comprises the sequences of SEQ ID NO: 992-994, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 997-999, respectively;
an) CDR H1-3 comprises the sequences of SEQ ID NO: 942-944, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 947-949, respectively;
ao) CDR H1-3 comprises the sequences of SEQ ID NO: 960-962, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 965-967, respectively; or
ap) CDR H1-3 comprises the sequences of SEQ ID NO:978-980, respectively and CDR L1-3 comprises the sequences of SEQ ID NO: 983-985, respectively.

Assignees

• Amgen Res Munich Gmbh

Inventors

• Kufer Peter
• Raum Tobias
• Kischel Roman
• LUTTERBÜSE Ralf
• Hoffmann Patrick
• Rau Doris
• Mangold Susanne
• Klinger Matthias
• Schaller Evelyne
• Hausmann Susanne
• Fluhr Petra
• Steiger Carola

Classifications

• C07K2317/34

  Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues · CPC title

• C07K2317/31

  multispecific · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title