Heterodimeric fusion protein
AssigneeNantong Yichen Biopharma. Co. Ltd.
InventorsFeng WANG, Huayang ZHENG, Yuhan ZHANG
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Abstract
Disclosed are a heterodimeric fusion protein and its preparation and application The heavy chain and the light chain of the first antigen binding domain Fab are fused to N-terminus of two Fc chains, respectively, and on this basis, the second antigen binding domain scfv, Fab2, Fv, nanobody or a biologically active peptide is fused to N-terminus of Fab or C-terminus of the Fc. The heterodimeric fusion protein obtained has the following characteristics: each domain in fusion proteins maintained its antigen binding capacity, functional conformation and pharmaceutical properties; at least one antigen binding domain can bind to antigen monovalently; the heterodimeric fusion proteins have a prolonged half-life due to the Fc fragment.
Claims47
A heterodimeric fusion protein, comprising:
- a) a first polypeptide chain, comprising a Fab heavy chain and a first Fc chain, wherein the Fab heavy chain is fused to N-terminal of the first Fc chain directly or via a linker;
- b) a second polypeptide chain, comprising a Fab light chain and a second Fc chain, wherein the Fab light chain is fused to N-terminal of the second Fc chain directly or via a linker;
- wherein, the Fab heavy chain of the first polypeptide chain and the Fab light chain of the second polypeptide chain form a first antigen binding domain;
- and the first and second Fc chain form an Fc dimerization domain;
- wherein, the constant domains CH1 and CL of Fab can be interchanged in two chains.
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A heterodimeric fusion protein, comprising:
- a) a first polypeptide chain, comprising:
- Fc, (L1)n, CH1, L2, and VH from N-terminal to C-terminal sequentially;
- b) a second polypeptide chain, comprising:
- Fc, (L3)n, CL, L4, and VL from N-terminal to C-terminal sequentially;
- or
- a) a first polypeptide chain, comprising:
- Fc, (L1)n, CL, L2, and VH from N-terminal to C-terminal sequentially;
- b) a second polypeptide chain, comprising:
- Fc, (L3)n, CH1, L4, and VL from N-terminal to C-terminal sequentially,
- wherein, n is 0 or 1;
- L1, L2, L3 and L4 are linkers;
- VH and VL form a first antigen binding domain.
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A host cell, comprising:
- an expression vector, comprising a polynucleotide encoding the first polypeptide chain, and
- an expression vector, comprising a polynucleotide encoding the second polypeptide chain;
- the first polypeptide chain comprising a Fab heavy chain and a first Fc chain, wherein the Fab heavy chain is fused to N-terminal of the first Fc chain directly or via a linker;
- the second polypeptide chain comprising a Fab light chain and a second Fc chain, wherein the Fab light chain is fused to N-terminal of the second Fc chain directly or via a linker;
- wherein, the Fab heavy chain of the first polypeptide chain and the Fab light chain of the second polypeptide chain form a first antigen binding domain;
- and the first and the second Fc chain form an Fc dimerization domain.
Dependencies are inferred from the claim text.