US2021230311A1PendingUtilityA1
Cytotoxicity-inducing therapeutic agent
Assignee: CHUGAI PHARMACEUTICAL CO LTDPriority: Sep 26, 2014Filed: Apr 8, 2021Published: Jul 29, 2021
Est. expirySep 26, 2034(~8.2 yrs left)· nominal 20-yr term from priority
Inventors:Junichi NezuAtsushi NaritaTakahiro IshiguroMika SakuraiHirotake ShiraiwaNaoka HironiwaTomoyuki IgawaYumiko Kawai
C12N 15/09C12N 5/10C07K 16/46C07K 2317/565C07K 16/303C07K 2317/94A61P 35/00C07K 2317/24C07K 16/468C07K 2317/92C07K 2317/567C07K 2317/526A61K 2039/505C07K 16/2809A61K 39/395C07K 16/28C07K 2317/31C07K 2317/71C07K 2317/73A61P 37/04C07K 2317/524C07K 16/30A61P 43/00C07K 2317/34C12N 15/63A61K 39/3955C07K 2317/52
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Claims
Abstract
Novel multispecific 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.
Claims
exact text as granted — not AI-modified1 .- 29 . (canceled)
30 . 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 light 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.
31 . The multispecific antigen-binding molecule of claim 30 , wherein the cytotoxic activity is T-cell-dependent cytotoxic activity.
32 . The multispecific antigen-binding molecule of claim 30 , wherein the T-cell receptor complex-binding activity is T-cell receptor binding activity.
33 . The multispecific antigen-binding molecule of claim 30 , wherein the T-cell receptor complex-binding activity is CD3c chain binding activity.
34 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (1) comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having an amino acid sequence selected from the group consisting of:
(a1) SEQ ID NO:40; (a2) SEQ ID NO:197; (a3) SEQ ID NO:206; (a4) SEQ ID NO:211; and (a5) SEQ ID NO:215.
35 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (2) comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having an amino acid sequence selected from the group consisting of:
(b1) SEQ ID NO:52; (b2) SEQ ID NO:103; (b3) SEQ ID NO:122; (b4) SEQ ID NO:128; (b5) SEQ ID NO:129; (b6) SEQ ID NO:132; (b7) SEQ ID NO:142; (b8) SEQ ID NO:144; (b9) SEQ ID NO:164; (b10) SEQ ID NO:168; (b11) SEQ ID NO:421; (b12) SEQ ID NO:424; (b13) SEQ ID NO:426; (b14) SEQ ID NO:429; and (b15) SEQ ID NO:430.
36 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (1) and (2) comprises a combination of heavy chain CDR1, CDR2, and CDR3 selected from the group consisting of:
(c1) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:52; (c2) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:421; (c3) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:426; (c4) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:429; (c5) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:430; (c6) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:197; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:128; (c7) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:142; (c8) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:144; (c9) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:164; (c10) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:168; (c11) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:142; (c12) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:144; (c13) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:164; (c14) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:168; (c15) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; (c16) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:122; (c17) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:129; (c18) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an light chain having the amino acid sequence of SEQ ID NO:132; and (c19) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:424.
37 . The multispecific antigen-binding molecule of claim 34 , wherein the CDR1, CDR2, and CDR3 are based on Kabat numbering.
38 . The multispecific antigen-binding molecule of claim 30 , wherein antibody variable region of (1) comprises an heavy chain variable region amino acid sequence selected from the group consisting of:
(a1) SEQ ID NO:40; (a2) SEQ ID NO:197; (a3) SEQ ID NO:206; (a4) SEQ ID NO:211; and (a5) SEQ ID NO:215.
39 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (2) comprises an heavy chain variable region amino acid sequence selected from the group consisting of:
(b1) SEQ ID NO:52; (b2) SEQ ID NO:103; (b3) SEQ ID NO:122; (b4) SEQ ID NO:128; (b5) SEQ ID NO:129; (b6) SEQ ID NO:132; (b7) SEQ ID NO:142; (b8) SEQ ID NO:144; (b9) SEQ ID NO:164; (b10) SEQ ID NO:168; (b11) SEQ ID NO:421; (b12) SEQ ID NO:424; (b13) SEQ ID NO:426; (b14) SEQ ID NO:429; and (b15) SEQ ID NO:430.
40 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (1) and (2) comprises a combination selected from the group consisting of:
(c1) an antibody variable region of (1) that comprises an heavy chain variable region amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises an heavy chain variable region amino acid sequence of SEQ ID NO:52; (c2) an antibody variable region of (1) that comprises an heavy chain variable region amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises an heavy chain variable region amino acid sequence of SEQ ID NO:421; (c3) an antibody variable region of (1) that comprises the heavy chain variable region an heavy chain variable region amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises an heavy chain variable region amino acid sequence of SEQ ID NO:426; (c4) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:429; (c5) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:40; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:430; (c6) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:197; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:128; (c7) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:142; (c8) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:144; (c9) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:164; (c10) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:206; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:168; (c11) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:142; (c12) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:144; (c13) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:164; (c14) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:211; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:168; (c15) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:103; (c16) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:122; (c17) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:129; (c18) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:132; and (c19) an antibody variable region of (1) that comprises an heavy chain amino acid sequence of SEQ ID NO:215; and an antibody variable region of (2) that comprises an heavy chain amino acid sequence of SEQ ID NO:424.
41 . The multispecific antigen-binding molecule of claim 30 , wherein the common light chain comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having an amino acid sequence selected from the group consisting of:
(d1) SEQ ID NO:53; (d2) SEQ ID NO:223; (d3) SEQ ID NO:299; (d4) SEQ ID NO:301; (d5) SEQ ID NO:302; (d6) SEQ ID NO:304; (d7) SEQ ID NO:306; (d8) SEQ ID NO:307; (d9) SEQ ID NO:309; (d10) SEQ ID NO:310; and (d11) SEQ ID NO:319.
42 . The multispecific antigen-binding molecule of claim 30 , wherein the common light chain comprises an amino acid sequence selected from the group consisting of:
(d1) SEQ ID NO:53; (d2) SEQ ID NO:223; (d3) SEQ ID NO:299; (d4) SEQ ID NO:301; (d5) SEQ ID NO:302; (d6) SEQ ID NO:304; (d7) SEQ ID NO:306; (d8) SEQ ID NO:307; (d9) SEQ ID NO:309; (d10) SEQ ID NO:310; and (d11) SEQ ID NO:319.
43 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (1) and (2) comprises a combination of heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 selected from the group consisting of:
(e1) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:128; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53; (e2) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:197; the CDR1, CDR2, and CDR3 antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:128; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:299; (e3) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:128; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:310; (e4) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:128; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of; (e5) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:142; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e6) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:144; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e7) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:164; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e9) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:142; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e10) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:142; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:299; (e11) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:144; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e12) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:164; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e13) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:168; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:223; (e14) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53; (e15) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:299; (e16) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:301; (e17) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:302; (e18) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:304; (e19) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:306; (e20) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:307; (e21) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:103; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:309; (e22) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:122; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53; (e23) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:129; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53; (e24) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:132; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53; and (e25) an antibody variable region of (1) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the CDR1, CDR2, and CDR3 sequences of an heavy chain variable region having the amino acid sequence of SEQ ID NO:424; and a common light chain that comprises the CDR1, CDR2, and CDR3 sequences of an light chain variable region having the amino acid sequence of SEQ ID NO:53.
44 . The multispecific antigen-binding molecule of claim 30 , wherein the antibody variable region of (1) and (2) comprises a combination of heavy chain variable region and light chain variable region sequences selected from the group consisting of:
(f1) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:128; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:53; (f2) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:128; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:299; (f3) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:128; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:310; (f4) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:197; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:128; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:319; (f5) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:142; and a common light chain variable region and that comprises the amino acid sequence of SEQ ID NO:223; (f6) an H antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:144; and a common light chain variable region the amino acid sequence of SEQ ID NO:223; (f7) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:206; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:164; and a common light chain variable region and that comprises the amino acid sequence of SEQ ID NO:223; (f9) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:142; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:223; (f10) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:142; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:299; (f11) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:144; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:223; (f12) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:164; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:223; (f13) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:211; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:168; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:223; (f14) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:53; (f15) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:299; (f16) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:301; (f17) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:302; (f18) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:304; (f19) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:306; (f20) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:307; (f21) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:103; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:309; (f22) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:122; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:53; (f23) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:129; and a common light chain variable region and that comprises the amino acid sequence of SEQ ID NO:53; (f24) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:132; and a common light chain variable region and that comprises the amino acid sequence of SEQ ID NO:53; and (f25) an antibody variable region of (1) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:215; an antibody variable region of (2) that comprises the heavy chain variable region amino acid sequence of SEQ ID NO:424; and a common light chain variable region that comprises the amino acid sequence of SEQ ID NO:53.
45 . The multispecific antigen-binding molecule of claim 30 , wherein the Fc region of (3) comprises a mutation in an amino acid sequence selected from the group consisting of SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, and SEQ ID NO:26.
46 . The multispecific antigen-binding molecule of claim 45 , wherein the Fc region of (3) comprises a mutation in at least one amino acid residue position selected from the following positions specified by EU numbering:
position 220, position 226, position 229, position 231, position 232, position 233, position 234, position 235, position 236, position 237, position 238, position 239, position 240, position 264, position 265, position 266, position 267, position 269, position 270, position 295, position 296, position 297, position 298, position 299, position 300, position 325, position 327, position 328, position 329, position 330, position 331, and position 332.
47 . The multispecific antigen-binding molecule of claim 45 , wherein the Fc region of (3) comprises a mutation in at least one amino acid residue selected from the following amino acid residue positions specified by EU numbering:
Arg at amino acid position 234, Ala or Arg at amino acid position 235, Lys at amino acid position 239, and Ala at amino acid position 297.
48 . The multispecific antigen-binding molecule of claim 45 , wherein the Fc region of (3) further comprises an amino acid mutation that promotes formation of a heterodimeric Fc region.
49 . The multispecific antigen-binding molecule of claim 48 , wherein the heterodimeric Fc region comprises a combination selected from the group consisting of:
(g1) a first Fc that comprises the amino acid sequence of SEQ ID NO:57, and a second Fc that comprises the amino acid sequence of SEQ ID NO:58; and (g2) a first Fc that comprises the amino acid sequence of SEQ ID NO:60 or 62, and a second Fc that comprises the amino acid sequence of SEQ ID NO:61.
50 . The multispecific antigen-binding molecule of claim 30 , which is a bispecific antibody.
51 . A bispecific antibody comprising a first and a second antibody variable domain selected from the group consisting of:
(h1) a first antibody variable domain having glypican 3-binding activity that comprises an antibody heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region having the amino acid sequence of SEQ ID NO:215 and a constant region having the amino acid sequence of SEQ ID NO:61n; a second antibody variable domain having T-cell receptor complex-binding activity that comprises an heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region 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 heavy chain variable region 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 heavy chain variable region 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 light chain variable region having the amino acid sequence of SEQ ID NO:223.
52 . A nucleic acid that encodes 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 light 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.
53 . A method for producing a multispecific antigen-binding molecule that comprises culturing a cell comprising the nucleic acid of claim 52 and purifying the multispecific antigen-binding molecule.
54 . A vector comprising the nucleic acid of claim 52 .
55 . A cell comprising the nucleic acid of claim 52 .
56 . A cell comprising the vector of claim 54 .Join the waitlist — get patent alerts
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