Compositions and methods related to engineered Fc constructs

An Fc construct comprising:

• a). a first polypeptide having the formula A-L-B;
• wherein
• i). A comprises a first Fc domain monomer;
• ii). L is a linker;
• and
• iii). B comprises a second Fc domain monomer;
• b). a second polypeptide having the formula A′-L′-B′;
• wherein
• i). A′ comprises a third Fc domain monomer;
• ii). L′ is a linker;
• and
• iii). B′ comprises a fourth Fc domain monomer;
• c). a third polypeptide that comprises a fifth Fc domain monomer;
• and
• d). a fourth polypeptide that comprises a sixth Fc domain monomer;
• wherein A and A′ combine to form a first Fc domain, B and the fifth Fc domain monomer combine to form a second Fc domain, and B′ 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;
• the second Fc domain monomer comprises a different amino acid sequence than the fifth Fc domain monomer, and the fourth Fc domain monomer comprises a different amino acid sequence than the sixth Fc domain monomer, 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, wherein each CH3 domain monomer has no more than 10 single amino acid substitutions to promote complementary dimerization of Fc domain monomers.