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US 11,952,423 B2Granted
Bispecific antibody
AssigneesMie University, Daiichi Sankyo Company, Limited
InventorsHiroshi Shiku, Yasushi Akahori, Kento Tanaka, Ayaka Yatsu, Junya Ichikawa, Toshiaki Ohtsuka, Shiho Kozuma, Ryuji Hashimoto, Makiko Nakayama, Naoya Shinozaki, Kensuke Nakamura, Ichiro Watanabe, Shinji Furuzono
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Abstract
A novel antibody that can be used as an anti-tumor agent and an anti-tumor agent that comprises, as an active ingredient, a molecule containing such an antibody.
Claims28
An antibody that binds specifically to human HLA/NY-ESO or a binding fragment thereof comprising:
- (i) a heavy chain CDRH1 consisting of the amino acid sequence as shown in SEQ ID NO:
- 54,
- (ii) a heavy chain CDRH2 consisting of the amino acid sequence as shown in SEQ ID NO:
- 55,
- (iii) a heavy chain CDRH3 consisting of the amino acid sequence as shown in SEQ ID NO:
- 56,
- (iv) a light chain CDRL1 consisting of an amino acid sequence derived from the amino acid sequence as shown in SEQ ID NO:
- 57 in which amino acid 7 is W,
- (v) a light chain CDRL2 consisting of the amino acid sequence of DNN, and
- (vi) a light chain CDRL3 consisting of the amino acid sequence as shown in SEQ ID NO:
- 59.
8 more elements
A molecule which comprises;
- (I) a first polypeptide comprising an antibody or a binding fragment thereof that binds specifically to human HLA/NY-ESO, wherein the antibody or the binding fragment thereof that binds specifically to human HLA/NY-ESO is an scFv, an scFv that binds specifically to CD3, and an Fc region (i) in that order from the N terminus toward the C terminus;
- and a second polypeptide comprising an Fc region (ii), wherein the first polypeptide is associated with the second polypeptide in the Fc region (i) and the Fc region (ii);
- wherein the first polypeptide comprises an amino acid sequence consisting of amino acids 20 to 745 of the amino acid sequence as shown in SEQ ID NO:
- 96, an amino acid sequence consisting of amino acids 20 to 750 of SEQ ID NO:
- 156, or an amino acid sequence consisting of amino acids 20 to 750 of SEQ ID NO:
- 157;
- wherein the second polypeptide comprises an amino acid sequence of amino acids 20 to 246 of SEQ ID NO:
- 84;
- or
- (II) a first polypeptide comprising the antibody or the binding fragment thereof that binds specifically to human HLA/NY-ESO, wherein the antibody or the binding fragment thereof that binds specifically to human HLA/NY-ESO is an scFv, an scFv that binds specifically to CD3, and an Fc region (i) in that order from the N terminus toward the C terminus;
- and a second polypeptide comprising an Fc region (ii), wherein the first polypeptide is associated with the second polypeptide in the Fc region (i) and the Fc region (ii);
- wherein the first polypeptide comprises an amino acid sequence consisting of amino acids 20 to 745 of the amino acid sequence as shown in SEQ ID NO:
- 96, an amino acid sequence consisting of amino acids 20 to 750 of SEQ ID NO:
- 156, or an amino acid sequence consisting of amino acids 20 to 750 of SEQ ID NO:
- 157;
- wherein the second polypeptide comprises an amino acid sequence of amino acids 20 to 246 of SEQ ID NO:
- 84;
- wherein 1 or 2 amino acids are deleted from the carboxyl terminus of the amino acid sequence of at least one polypeptide comprised in the molecule.
15 more elements
A molecule which comprises:
- (I) a first polypeptide that comprises, from N terminus to C terminus, an scFv that binds specifically to human HLA/NY-ESO, a heavy chain variable region and constant region CH1 of an antibody or fragment thereof that binds specifically to CD3, and an immunoglobulin Fc region (i);
- a second polypeptide that comprises an immunoglobulin hinge region and an immunoglobulin Fc region (ii);
- and
- a third polypeptide that comprises an antibody light chain of the antibody or fragment thereof that binds specifically to CD3, the antibody light chain consisting of a variable region and a constant region;
- wherein the first polypeptide is associated with the second polypeptide in the Fc region (i) and in the Fc region (ii), and the first polypeptide is associated with the third polypeptide in the heavy chain variable region and the constant region CH1 of the antibody;
- wherein the first polypeptide comprises an amino acid sequence of amino acids 21 to 394 of SEQ ID NO:
- 160, an amino acid sequence of amino acids 20 to 724 of SEQ ID NO:
- 160, or an amino acid sequence of amino acids 20 to 719 of SEQ ID NO:
- 197;
- wherein the second polypeptide comprises an amino acid sequence of amino acids 20 to 246 of SEQ ID NO:
- 84;
- wherein the third polypeptide comprises an amino acid sequence of amino acids 21 to 127 of SEQ ID NO:
- 161 or amino acids 21 to 233 of SEQ ID NO:
- 161;
- or
- (II) a first polypeptide that comprises, from N terminus to C terminus, an scFv that binds specifically to human HLA/NY-ESO, a heavy chain variable region and constant region CH1 of an antibody or fragment thereof that binds specifically to CD3, and an immunoglobulin Fc region (i);
- a second polypeptide that comprises an immunoglobulin hinge region and an immunoglobulin Fc region (ii);
- and
- a third polypeptide that comprises an antibody light chain of the antibody or fragment thereof that binds specifically to CD3, the antibody light chain consisting of a variable region and a constant region;
- wherein the first polypeptide is associated with the second polypeptide in the Fc region (i) and in the Fc region (ii), and the first polypeptide is associated with the third polypeptide in the heavy chain variable region and the constant region CH1 of the antibody;
- wherein the first polypeptide comprises an amino acid sequence of amino acids 21 to 394 of SEQ ID NO:
- 160, an amino acid sequence of amino acids 20 to 724 of SEQ ID NO:
- 160, or an amino acid sequence of amino acids 20 to 719 of SEQ ID NO:
- 197;
- wherein the second polypeptide comprises an amino acid sequence of amino acids 20 to 246 of SEQ ID NO:
- 84;
- wherein the third polypeptide comprises an amino acid sequence of amino acids 21 to 127 of SEQ ID NO:
- 161 or amino acids 21 to 233 of SEQ ID NO:
- 161;
- wherein 1 or 2 amino acids are deleted from the carboxyl terminus of the amino acid sequence of at least one polypeptide comprised in the molecule.
27 more elements
Dependencies are inferred from the claim text.