Cytotoxicity-Inducing Therapeutic Agent
First Claim
Patent Images
1. A multispecific antigen-binding molecule that comprises:
- (1) a domain comprising an antibody variable region having glypican 3-binding activity,(2) a domain comprising an antibody variable region having T-cell receptor complex-binding activity, and(3) a domain comprising an Fc region with reduced binding activity towards an Fcγ
receptor,wherein the antibody variable region of (1) and the antibody variable region of (2) have a common L-chain amino acid sequence; and
wherein the multispecific antigen-binding molecule has a cytotoxic activity equivalent to or greater than the cytotoxic activity of a bispecific antibody having a glypican 3-binding domain comprising SEQ ID NOs;
47 and 48, and a T-cell receptor complex-binding domain comprising SEQ ID NOs;
49 and 50.
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Abstract
Novel multi specific antigen-binding molecules maintaining excellent cellular cytotoxicity and high stability, which comprise a domain that contains an antibody variable region having glypican 3-binding activity and a domain that contains an antibody variable region having T-cell receptor complex-binding activity, were discovered. Since the molecules of the present invention show a strong cytotoxicity against cells and tissues expressing glypican 3, it is possible to produce novel pharmaceutical compositions for treating or preventing various cancers.
46 Citations
29 Claims
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1. A multispecific antigen-binding molecule that comprises:
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(1) a domain comprising an antibody variable region having glypican 3-binding activity, (2) a domain comprising an antibody variable region having T-cell receptor complex-binding activity, and (3) a domain comprising an Fc region with reduced binding activity towards an Fcγ
receptor,wherein the antibody variable region of (1) and the antibody variable region of (2) have a common L-chain amino acid sequence; and
wherein the multispecific antigen-binding molecule has a cytotoxic activity equivalent to or greater than the cytotoxic activity of a bispecific antibody having a glypican 3-binding domain comprising SEQ ID NOs;
47 and 48, and a T-cell receptor complex-binding domain comprising SEQ ID NOs;
49 and 50. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A bispecific antibody comprising a first and a second antibody variable domain selected from the group consisting of:
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(h1) a first antibody variable domain H-chain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain H-chain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
424 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h2) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h3) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h4) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
301;(h5) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
302;(h6) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
304;(h7) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
306;(h8) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
307;(h9) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
309;(h10) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
122 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h11) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
129 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h12) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
132 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h13) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h14) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
310;(h15) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
319;(h16) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h17) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h18) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h19) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
144 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h20) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
144 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h21) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h22) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
164 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h23) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
168 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h24) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
164 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223; and(h25) a H-chainfirst antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61H-chain;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
168 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223.
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23. A nucleic acid that encodes a multispecific antigen-binding molecule that comprises:
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(1) a domain comprising an antibody variable region having glypican 3-binding activity, (2) a domain comprising an antibody variable region having T-cell receptor complex-binding activity, and (3) a domain comprising an Fc region with reduced binding activity towards an Fcγ
receptor,wherein the antibody variable region of (1) and the antibody variable region of (2) have a common L-chain amino acid sequence; and
wherein the multispecific antigen-binding molecule has a cytotoxic activity equivalent to or greater than the cytotoxic activity of a bispecific antibody having a glypican 3-binding domain comprising SEQ ID NOs;
47 and 48, and a T-cell receptor complex-binding domain comprising SEQ ID NOs;
49 and 50. - View Dependent Claims (24, 27, 28, 29)
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25. A nucleic acid that encodes a bispecific antibody comprising a first and a second antibody variable domain selected from the group consisting of:
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(h1) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
424 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h2) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h3) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h4) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
301;(h5) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
302;(h6) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
304;(h7) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
306;(h8) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
307;(h9) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
103 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
309;(h10) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
122 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h11) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
129 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h12) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
215 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
132 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h13) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h14) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
310;(h15) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
319;(h16) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
197 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
128 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
53;(h17) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
299;(h18) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h19) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
144 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h20) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
144 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h21) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
142 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h22) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
164 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h23) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
206 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
168 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223;(h24) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
164 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223; and(h25) a first antibody variable domain having glypican 3-binding activity that comprises an antibody H-chain having the amino acid sequence of SEQ ID NO;
211 and a constant region having the amino acid sequence of SEQ ID NO;
61;
a second antibody variable domain having T-cell receptor complex-binding activity that comprises an H-chain having the amino acid sequence of SEQ ID NO;
168 and a constant region having the amino acid sequence of SEQ ID NO;
60 or 62; and
a common antibody L-chain having the amino acid sequence of SEQ ID NO;
223. - View Dependent Claims (26)
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Specification