	US 12,391,759 B2
	Methods related to engineered Fc constructs
Carlos J. Bosques, Arlington, MA (US); James S. Huston, Watertown, MA (US); Jonathan C. Lansing, Reading, MA (US); Leona E. Ling, Winchester, MA (US); James Meador, III, Framingham, MA (US); Daniel Ortiz, Stoneham, MA (US); Laura Rutitzky, Somerville, MA (US); and Birgit C. Schultes, Arlington, MA (US)
Assigned to MOMENTA PHARMACEUTICALS, INC., Titusville, NJ (US)
Appl. No. 16/081,829
Filed by Momenta Pharmaceuticals, Inc., Cambridge, MA (US)
PCT Filed Mar. 2, 2017, PCT No. PCT/US2017/020519 § 371(c)(1), (2) Date Aug. 31, 2018, PCT Pub. No. WO2017/151971, PCT Pub. Date Sep. 8, 2017.
Claims priority of provisional application 62/443,451, filed on Jan. 6, 2017.
Claims priority of provisional application 62/443,495, filed on Jan. 6, 2017.
Claims priority of provisional application 62/302,419, filed on Mar. 2, 2016.
Prior Publication US 2022/0153833 A1, May 19, 2022
Int. Cl. C07K 16/28 (2006.01)

CPC C07K 16/283 (2013.01) [C07K 2317/35 (2013.01); C07K 2317/52 (2013.01)]

3 Claims

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.