US Patent No. 9,884,921

BISPECIFIC HETERODIMERIC DIABODIES AND USES THEREOF


Patent No. 9,884,921
Issue Date February 06, 2018
Title Bispecific Heterodimeric Diabodies And Uses Thereof
Inventorship Chad Michael May, Tarrytown, NY (US)
Adam Reid Root, Byfield, MA (US)
William A. Brady, San Diego, CA (US)
Lioudmila Gennadievna Tchistiakova, Stoneham, MA (US)
Lidia Mosyak, Newton, MA (US)
Laird Bloom, Needham, MA (US)
Paul A. Moore, North Bethesda, MD (US)
Leslie S. Johnson, Darnestown, MD (US)
Assignee Pfizer Inc., New York, NY (US)

Claim of US Patent No. 9,884,921

1. A bispecific heterodimeric diabody that specifically binds to an epitope of human P-cadherin and to an epitope of CD3 comprising
a first polypeptide chain and a second polypeptide chain, wherein:
a. the first polypeptide comprises, in the N-terminal to C-terminal direction:
i. a Domain 1, comprising a sub-Domain 1A and a sub-Domain 1B, and
ii. a first heterodimer-promoting domain; and
b. the second polypeptide chain comprises, in the N-terminal to C-terminal direction:
i. a Domain 2, comprising a sub-Domain 2B and a sub-Domain 2A and
ii. a second heterodimer-promoting domain, and
wherein sub-Domain 1A and sub-Domain 2A form a P-cadherin VL/VH binding domain comprising a variable heavy (VH) domain of
an anti-P-cadherin antibody (P-CAD VH) and a variable light (VL) domain of an anti-P-cadherin antibody (P-CAD VL), and sub-Domain
1B and sub-Domain 2B form a CD3 VL/VH binding domain comprising a VL domain of an anti-CD3 antibody (CD3 VL) and a VH binding
domain of an anti-CD3 antibody (CD3 VH); or

wherein sub-Domain 1A and sub-Domain 2A form a CD3 VL/VH binding domain comprising a CD3 VL and a CD3 VH, and sub-Domain 1B
and sub-Domain 2B form a P-cadherin VL/VH binding domain comprising a P-CAD VH and a P-CAD VL; and

wherein the first and second polypeptide chains comprise:
i. a P-CAD VL CDR1, a P-CAD VL CDR2, and a P-CAD VL CDR3 of a P-CAD VL comprising a sequence of SEQ ID NO: 1, 3, 5, 7, 9,
11, 13, 15, 17, 19, 21 or 23;

ii. a CD3 VH CDR1, a CD3 VH CDR2, and a CD3 VH CDR3 of a CD3 VH comprising a sequence of SEQ ID NO: 45 or 46;
iii. a CD3 VL CDR1, a CD3 VL CDR2, and a CD3 VL CDR3 of a CD3 VL comprising a sequence of SEQ ID NO: 47; and/or
iv. a P-CAD VH CDR1, a P-CAD VH CDR2, and a P-CAD VH CDR3 of a P-CAD VH comprising a sequence of SEQ ID NO: 2, 4, 6, 8, 10,
12, 14, 16, 18, 20, 22 or 24;

c. the sub-Domain 1A and the sub-Domain 1B are linked by a glycine-serine linker (Linker 1), and the sub-Domain 2B and the
sub-Domain 2A are linked by a glycine-serine linker (Linker 1);

d. the first heterodimer-promoting domain comprises a cysteine linker (Linker 2) on sub-Domain 1B and/or the second heterodimer-promoting
domain comprises a cysteine linker (Linker 2) on sub-Domain 2A; and

e. the first and second polypeptide chains are covalently bonded to one another by at least one disulfide bond.