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US 11,400,157 B2Granted
Multiple antigen binding molecular fusion, pharmaceutical composition, method for identifying linear epitope, and method for preparing multiple antigen binding molecular fusion
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsTomoyuki Igawa, Naoka Hironiwa, Hiroki Kawauchi
Life of this patent
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Abstract
A multiple antigen-binding molecule fusion molecule containing a multiple antigen-binding molecule (α) having an immune cell antigen-binding region and a cancer antigen-binding region, a cancer tissue-specific protease-cleavable linker (β), and a masking molecule (γ) containing a polypeptide having the amino acid sequence QDGNE (SEQ ID NO: 15), in which the multiple antigen-binding molecule (α) and the masking molecule (γ) are linked via the cancer tissue-specific protease-cleavable linker (β).
Claims12
A multiple antigen-binding molecule fusion molecule comprising:
- a multiple antigen-binding molecule (α) which comprises
- an immune cell antigen-binding region which recognizes an antigen that comprises a polypeptide consisting of the amino acid sequence QDGNE (SEQ ID NO:
- 15) and wherein the immune cell antigen-binding region recognizes at least one type of immune cell antigen other than the antigen that comprises a polypeptide consisting of the amino acid sequence QDGNE (SEQ ID NO:
- 15), and a cancer antigen-binding region which recognizes a cancer antigen;
- a cancer tissue-specific protease-cleavable linker (β) which comprises a polypeptide consisting of a target sequence of a cancer tissue-specific protease;
- and
- a masking molecule (γ) which comprises a polypeptide consisting of the amino acid sequence QDGNE (SEQ ID NO:
- 15);
- wherein the multiple antigen-binding molecule (α) is an antibody or an antibody fragment comprising at least two Fv regions, and the cancer antigen-binding region and the immune cell antigen-binding region are formed by different Fv regions;
- wherein the cancer tissue-specific protease-cleavable linker (β) is fused to a heavy chain N-terminus or a light chain N-terminus of the Fv region that forms the immune cell antigen-binding region;
- wherein the multiple antigen-binding molecule (α) and the masking molecule (γ) are linked via the cancer tissue-specific protease-cleavable linker (β);
- and
- wherein the cancer tissue-specific protease-cleavable linker (β) and the masking molecule (γ) form a linear fusion polypeptide, and
- wherein the number of amino acids in the fusion polypeptide is 11 or more to 65 or less when the cancer tissue-specific protease-cleavable linker (β) is fused to the heavy chain N-terminus of the Fv region that forms the immune cell antigen-binding region;
- and
- the number of amino acids in the fusion polypeptide is 16 or more to 65 or less when the cancer tissue-specific protease-cleavable linker (β) is fused to the light chain N terminus of the Fv region that forms the immune cell antigen-binding region.
13 more elements
Dependencies are inferred from the claim text.