Methods related to engineered Fc constructs

Patent metadata

Field	Value
Publication number	US-12391759-B2
Application number	US-201716081829-A
Country	US
Kind code	B2
Filing date	Mar 2, 2017
Priority date	Mar 2, 2016
Publication date	Aug 19, 2025
Grant date	Aug 19, 2025

Abstract

The present invention relates to methods of using biologically active Fc domain-containing therapeutic constructs (Fc constructs) to induce immune cell activation of the immune response in a subject, and for example, to treat diseases such as cancers and infections in a subject. Such Fc constructs may include 5 or more Fc domains.

First claim

What is claimed is:

1. A method of inducing immune cell activation in a subject, the method comprising administering to the subject a composition comprising an Fc construct comprising:
a) a first polypeptide having the formula A-L1-B-L2-C; wherein
i) A comprises a first Fc domain monomer;
ii) L1 is a linker;
iii) B comprises a second Fc domain monomer;
iv) L2 is a linker; and
v) C comprises a third Fc domain monomer;

b) a second polypeptide having the formula A′-L1′-B′-L2′-C′; wherein
i) A′ comprises a fourth Fc domain monomer;
ii) L1′ is a linker;
iii) B′ comprises a fifth Fc domain monomer;
iv) L2′ is a linker; and
v) C′ comprises a sixth Fc domain monomer;

c) a third polypeptide that comprises a seventh Fc domain monomer;
d) a fourth polypeptide that comprises an eighth Fc domain monomer;
e) a fifth polypeptide that comprises a ninth Fc domain monomer; and
f) a sixth polypeptide that comprises a tenth Fc domain monomer;
wherein A and the seventh Fc domain monomer combine to form a first Fc domain, B and B′ combine to form a second Fc domain, C and the eighth Fc domain monomer combine to form a third Fc domain, A′ and the ninth Fc domain monomer combine to form a fourth Fc domain, and C′ and the tenth Fc domain monomer combine to form a fifth Fc domain;
wherein each of the first and seventh Fc domain monomers comprises a complementary dimerization selectivity module that promote dimerization between the first Fc domain monomer and the seventh Fc domain monomer,
each of the second and fifth Fc domain monomers comprises a complementary dimerization selectivity module that promote dimerization between the second Fc domain monomer and the fifth Fc domain monomer,
each of the third and eighth Fc domain monomers comprises a complementary dimerization selectivity module that promote dimerization between the third Fc domain monomer and the eighth Fc domain monomer;
each of the fourth and ninth Fc domain monomers comprises a complementary dimerization selectivity module that promote dimerization between the fourth Fc domain monomer and the ninth Fc domain monomer; and
each of the sixth and tenth Fc domain monomers comprises a complementary dimerization selectivity module that promote dimerization between the sixth Fc domain monomer and the tenth Fc domain monomer; and
g) each of the first and second polypeptides comprise the sequence:

(SEQ ID NO: 47)

DKTHTCPPCPAPELLGGPSVFLEPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPCRDKLTKNQVSLWCLVK

GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG

NVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGGGGGGGGGGGGGGGGDKT

HTCPPCPAPELLGGPSVFLEPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSDLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGKGGGGGGGGGGGGGGGGGGGGDKTHTC

PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN

WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK

ALPAPIEKTISKAKGQPREPQVYTLPPCRDKLTKNQVSLWCLVKGEYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

VMHEALHNHYTQKSLSLSPG;

and each of the third, fourth, fifth, and sixth polypeptides comprise the sequence:

(SEQ ID NO: 42)

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK

CKVSNKALPAPIEKTISKAKGQPREPQVCTLPPSRDELTKNQVSLSCAVD

GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG

NVFSCSVMHEALHNHYTQKSLSLSPG.

2. A method of inducing immune cell activation in a subject, the method comprising administering to the subject a composition comprising an Fc construct comprising:
a) a first polypeptide having the formula A-L1-B-L2-C; wherein
i) A comprises a first Fc domain monomer;
ii) L1 is a linker;
iii) B comprises a second Fc domain monomer;
iv) L2 is a linker; and
v) C comprises a third Fc domain monomer;

b) a second polypeptide having the formula A′-L1′-B′-L2′-C′; wherein
i) A′ comprises a fourth Fc domain monomer;
ii) L1′ is a linker;
iii) B′ comprises a fifth Fc domain monomer;
iv) L2′ is a linker; and
v) C′ comprises a sixth Fc domain monomer;

c) a third polypeptide that comprises a seventh Fc domain monomer;
d) a fourth polypeptide that comprises an eighth Fc domain monomer;
e) a fifth polypeptide that comprises a ninth Fc domain monomer; and
f) a sixth polypeptide that comprises a tenth Fc domain monomer;
wherein C and C′ combine to form a first Fc domain, B and the seventh Fc domain monomer combine to form a second Fc domain, A and the eighth Fc domain monomer combine to form a third Fc domain, B′ and the ninth Fc domain monomer combine to form a fourth Fc domain, and A′ and the tenth Fc domain monomer combine to form a fifth Fc domain;
wherein each of the third and sixth Fc domain monomers comprises complementary dimerization selectivity modules that promote dimerization between the third Fc domain monomer and the sixth Fc domain monomer,
each of the second and seventh Fc domain monomers comprises complementary dimerization selectivity modules that promote dimerization between the second Fc domain monomer and the seventh Fc domain monomer,
each of the first and eighth Fc domain monomers comprises complementary dimerization selectivity modules that promote dimerization between the first Fc domain monomer and the eighth Fc domain monomer;
each of the fifth and ninth Fc

Assignees

• Momenta Pharmaceuticals Inc

Inventors

• Bosques Carlos J
• Huston James S
• Lansing Jonathan C
• Ling Leona E
• Meador Iii James
• Ortiz Daniel
• Rutitzky Laura
• Schultes Birgit C

Classifications

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/35

  Valency · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K16/283 Primary

  against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851) · CPC title