US 12,071,482 B2
Compositions and methods related to engineered Fc constructs
Carlos J. Bosques, Cambridge, MA (US); James S. Huston, Cambridge, MA (US); Jonathan C. Lansing, Cambridge, MA (US); Leona E. Ling, Cambridge, MA (US); James Meador, III, Cambridge, MA (US); Daniel Ortiz, Cambridge, MA (US); and Laura Rutitzky, Cambridge, MA (US)
Assigned to Momenta Pharmaceuticals, Inc., Titusville, NJ (US)
Filed by MOMENTA PHARMACEUTICALS, INC., Titusville, NJ (US)
Filed on Aug. 20, 2021, as Appl. No. 17/407,814.
Application 17/407,814 is a continuation of application No. 16/363,846, filed on Mar. 25, 2019, granted, now 11,124,573.
Application 16/363,846 is a continuation of application No. 15/141,413, filed on Apr. 28, 2016, granted, now 10,239,944, issued on Mar. 26, 2019.
Application 15/141,413 is a continuation of application No. PCT/US2015/028926, filed on May 1, 2015.
Claims priority of provisional application 62/081,923, filed on Nov. 19, 2014.
Claims priority of provisional application 61/987,863, filed on May 2, 2014.
Prior Publication US 2022/0033499 A1, Feb. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); C07K 14/00 (2006.01); C07K 16/00 (2006.01); C07K 16/46 (2006.01)
CPC C07K 16/283 (2013.01) [C07K 14/00 (2013.01); C07K 16/00 (2013.01); C07K 16/46 (2013.01); C07K 2317/14 (2013.01); C07K 2317/33 (2013.01); C07K 2317/52 (2013.01); C07K 2317/526 (2013.01); C07K 2317/60 (2013.01); C07K 2319/30 (2013.01)] 13 Claims
 
1. A method for treating rheumatoid arthritis and immune thrombocytopenia comprising administering to a human subject in need thereof an Fc construct having three Fc domains and comprising:
a) a first polypeptide comprising a first Fc domain monomer and a second Fc domain monomer joined by a linker;
b) a second polypeptide comprising a third Fc domain monomer and a fourth Fc domain monomer joined by a linker;
c) a third polypeptide that comprises a fifth Fc domain monomer; and
d) a fourth polypeptide that comprises a sixth Fc domain monomer;
wherein the first and the third Fc domain monomers combine to form a first Fc domain, the second and the fifth Fc domain monomer combine to form a second Fc domain, and the fourth and the sixth Fc domain monomer combine to form a third Fc domain;
the first polypeptide comprises the same amino acid sequence as the second polypeptide, and the third polypeptide comprises the same amino acid sequence as the fourth polypeptide; and
each of the first, second, third, fourth, fifth, and sixth Fc domain monomers comprises a human IgG1 CH2 domain monomer and a human IgG1 CH3 domain monomer,
the CH3 domains of the first and third Fc domain monomers comprise substitutions in at least two positions are selected from the group consisting of K409D/D399K, K392D/D399K, E357K/K370E, D356K/K439D, K409E/D399K, K392E/D399K, E357K/K370D, and D356K/K439E (all positions by EU numbering system) that promote dimerization between the first Fc domain monomer and the third Fc domain monomer,
the CH3 domains of the second and fifth Fc domain monomers comprise amino acid substitutions to provide a complementary dimerization selectivity modules that promote dimerization between the second Fc domain monomer and the fifth Fc domain monomer where one of the complementary dimerization selectivity modules of the second and fifth Fc domain monomers comprises an engineered protuberance and the other of the complementary dimerization selectivity modules of the second and fifth Fc domain monomers comprises an engineered cavity where the engineered protuberance comprises at least one substitution selected from the group consisting of S354C, T366W, T366Y, T394W, T394F, and F405W and the engineered cavity comprises at least one substitution selected from the group consisting of Y349C, T366S, L368A, Y407V, Y407T, Y407A, F405A, and T394S (all positions by EU numbering system), and
the CH3 domains of the fourth and sixth Fc domain monomers comprise amino acid substitutions to provide a complementary dimerization selectivity modules that promote dimerization between the fourth Fc domain monomer and the sixth Fc domain monomer where one of the complementary dimerization selectivity modules of the fourth and sixth Fc domain monomers comprises an engineered protuberance and the other of the complementary dimerization selectivity modules of the fourth and sixth Fc domain monomers comprises an engineered cavity where the engineered protuberance comprises at least one substitution selected from the group consisting of S354C, T366W, T366Y, T394W, T394F, and F405W and the engineered cavity comprises at least one substitution selected from the group consisting of Y349C, T366S, L368A, Y407V, Y407T, Y407A, F405A, and T394S (all positions by EU numbering system).