Heterodimer molecule based on CH3 domain, and preparation method and use thereof

1. A heterodimer molecule, comprising a first polypeptide chain and a second polypeptide chain, wherein said first polypeptide chain comprises a first CH3 domain of an antibody heavy chain constant region, said second polypeptide chain comprises a second CH3 domain of an antibody heavy chain constant region, wherein said first CH3 domain and said second CH3 domain differ from a corresponding wild-type CH3 domain of a human antibody heavy chain constant region by amino acid mutations, wherein the amino acid mutations consist of substitution mutations selected from one of groups (1) to (4):

(1) in said first CH3 domain: T366+K409+K392, in said second CH3 domain: T366+L368+Y407+D399+F405;

(2) in said first CH3 domain: T366+K409, in said second CH3 domain: T366+L368+Y407+F405;

(3) in said first CH3 domain: T366+K409+Y349, in said second CH3 domain: T366+L368+Y407+F405+E357; and

(4) in said first CH3 domain: T366+K409+Y349+S354, in said second CH3 domain: T366+L368+Y407+F405+E357;

wherein in said first CH3 domain:

said amino acid mutation at T366 is T366W;

said amino acid mutation at K409 is K409A;

said amino acid mutation at K392 is K392D;

said amino acid mutation at Y349 is Y349D; and

said amino acid mutation at S354 is S354D;

and wherein in said second CH3 domain:

said amino acid mutation at T366 is T366S;

said amino acid mutation at L368 is L368A and said amino acid mutation at Y407 is Y407V; or said amino acid mutation at L368 is L368G and said amino acid mutation at Y407 is Y407A;

said amino acid mutation at D399 is D399S;

said amino acid mutation at F405 is F405K; and

said amino acid mutation at E357 is E357A;

wherein said amino acid is numbered according to the EU index of the KABAT numbering of the antibody Fc region; and

wherein said wild-type CH3 domain of the human antibody heavy chain constant region is a CH3 domain of a human IgG1 heavy chain constant region.

2. The heterodimer molecule according to claim 1 , wherein said first CH3 domain and said second CH3 domain comprise one group of amino acid mutations selected from the following groups:

1) said first CH3 domain: T366W+K409A+K392D, said second CH3 domain: T366S+L368A+Y407V+D399S+F405K;

2) said first CH3 domain: T366W+K409A, said second CH3 domain: T366S+L368G+Y407A+F405K;

3) said first CH3 domain: T366W+K409A+Y349D, said second CH3 domain: T366S+L368A+Y407V+F405K+E357A;

4) said first CH3 domain: T366W+K409A+Y349D+S354D, said second CH3 domain: T366S+L368A+Y407V+F405K+E357A.

3. The heterodimer molecule according to claim 1 , wherein said first polypeptide chain and said second polypeptide chain further comprise a CH2 domain of an antibody heavy chain constant region, respectively.

4. The heterodimer molecule according to claim 1 , wherein said first polypeptide chain and said second polypeptide chain further comprise a hinge region of an antibody heavy chain constant region or a part thereof, respectively.

5. The heterodimer molecule according to claim 1 , wherein said first polypeptide chain and/or said second polypeptide chain further comprise a molecule binding region, and said molecule binding region comprises an antigen binding region.

6. The heterodimer molecule according to claim 5 , wherein said antigen binding region comprises an antibody variable region.

7. The heterodimer molecule according to claim 1 , wherein said heterodimer molecule is a bispecific antibody, a bispecific fusion protein or an antibody-fusion protein chimera.

8. A composition, comprising the heterodimer molecule according to claim 1 , and optionally a pharmaceutically acceptable carrier or excipient.