JPWO2021064137A5 - - Google Patents

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JPWO2021064137A5
JPWO2021064137A5 JP2022520371A JP2022520371A JPWO2021064137A5 JP WO2021064137 A5 JPWO2021064137 A5 JP WO2021064137A5 JP 2022520371 A JP2022520371 A JP 2022520371A JP 2022520371 A JP2022520371 A JP 2022520371A JP WO2021064137 A5 JPWO2021064137 A5 JP WO2021064137A5
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JP2022551081A (en
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Ｂ７Ｈ６に特異的に結合する第１の抗原結合単位とＣＤ３に特異的に結合する第２の抗原結合単位とを含むタンパク質であって、前記Ｂ７Ｈ６に特異的に結合する第１の抗原結合単位は、ｉ）～ｘｉｉｉ）：
ｉ）配列番号：６７（ＣＤＲ１）、配列番号：６８（ＣＤＲ２）及び配列番号：６９（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：７０（ＣＤＲ１）、配列番号：７１（ＣＤＲ２）及び配列番号：７２（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｉｉ）配列番号：７３（ＣＤＲ１）、配列番号：７４（ＣＤＲ２）及び配列番号：７５（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：７６（ＣＤＲ１）、配列番号：７７（ＣＤＲ２）及び配列番号：７８（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｉｉｉ）配列番号：７９（ＣＤＲ１）、配列番号：８０（ＣＤＲ２）及び配列番号：８１（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：８２（ＣＤＲ１）、配列番号：８３（ＣＤＲ２）及び配列番号：８４（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｉｖ）配列番号：８５（ＣＤＲ１）、配列番号：８６（ＣＤＲ２）及び配列番号：８７（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：８８（ＣＤＲ１）、配列番号：８９（ＣＤＲ２）及び配列番号：９０（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｖ）配列番号：９１（ＣＤＲ１）、配列番号：９２（ＣＤＲ２）及び配列番号：９３（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：９４（ＣＤＲ１）、配列番号：９５（ＣＤＲ２）及び配列番号：９６（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｖｉ）配列番号：９７（ＣＤＲ１）、配列番号：９８（ＣＤＲ２）及び配列番号：９９（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１００（ＣＤＲ１）、配列番号：１０１（ＣＤＲ２）及び配列番号：１０２（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｖｉｉ）配列番号：１０３（ＣＤＲ１）、配列番号：１０４（ＣＤＲ２）及び配列番号：１０５（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１０６（ＣＤＲ１）、配列番号：１０７（ＣＤＲ２）及び配列番号：１０８（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｖｉｉｉ）配列番号：１０９（ＣＤＲ１）、配列番号：１１０（ＣＤＲ２）及び配列番号：１１１（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１１２（ＣＤＲ１）、配列番号：１１３（ＣＤＲ２）及び配列番号：１１４（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｉｘ）配列番号：１１５（ＣＤＲ１）、配列番号：１１６（ＣＤＲ２）及び配列番号：１１７（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１１８（ＣＤＲ１）、配列番号：１１９（ＣＤＲ２）及び配列番号：１２０（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｘ）配列番号：１２１（ＣＤＲ１）、配列番号：１２２（ＣＤＲ２）及び配列番号：１２３（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１２４（ＣＤＲ１）、配列番号：１２５（ＣＤＲ２）及び配列番号：１２６（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｘｉ）配列番号：１２７（ＣＤＲ１）、配列番号：１２８（ＣＤＲ２）及び配列番号：１２９（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１３０（ＣＤＲ１）、配列番号：１３１（ＣＤＲ２）及び配列番号：１３２（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；
ｘｉｉ）配列番号：１３３（ＣＤＲ１）、配列番号：１３４（ＣＤＲ２）及び配列番号：１３５（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１３６（ＣＤＲ１）、配列番号：１３７（ＣＤＲ２）及び配列番号：１３８（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位；並びに
ｘｉｉｉ）配列番号：１３９（ＣＤＲ１）、配列番号：１４０（ＣＤＲ２）及び配列番号：１４１（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：１４２（ＣＤＲ１）、配列番号：１４３（ＣＤＲ２）及び配列番号：１４４（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲとを含む抗原結合単位
から選択され、
ＣＤ３に特異的に結合する第２の抗原結合単位は、配列番号：２５７（ＣＤＲ１）、配列番号：２５８（ＣＤＲ２）及び配列番号：２５９（ＣＤＲ３）のアミノ酸配列を含む軽鎖ＣＤＲと配列番号：２６０（ＣＤＲ１）、配列番号：２６１（ＣＤＲ２）及び配列番号：２６２（ＣＤＲ３）のアミノ酸配列を含む重鎖ＣＤＲを含む、
タンパク質。 A protein comprising a first antigen-binding unit that specifically binds to B7H6 and a second antigen-binding unit that specifically binds to CD3, wherein the first antigen-binding unit that specifically binds to B7H6 is , i ) to xiii) :
i ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:67 (CDR1), SEQ ID NO:68 (CDR2) and SEQ ID NO:69 (CDR3) and SEQ ID NO:70 (CDR1), SEQ ID NO:71 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 72 (CDR3);
ii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:73 (CDR1), SEQ ID NO:74 (CDR2) and SEQ ID NO:75 (CDR3) and SEQ ID NO:76 (CDR1), SEQ ID NO:77 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 78 (CDR3);
iii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:79 (CDR1), SEQ ID NO:80 (CDR2) and SEQ ID NO:81 (CDR3) and SEQ ID NO:82 (CDR1), SEQ ID NO:83 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO:84 (CDR3);
iv ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:85 (CDR1), SEQ ID NO:86 (CDR2) and SEQ ID NO:87 (CDR3) and SEQ ID NO:88 (CDR1), SEQ ID NO:89 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO:90 (CDR3);
v ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:91 (CDR1), SEQ ID NO:92 (CDR2) and SEQ ID NO:93 (CDR3) and SEQ ID NO:94 (CDR1), SEQ ID NO:95 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO:96 (CDR3);
vi ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:97 (CDR1), SEQ ID NO:98 (CDR2) and SEQ ID NO:99 (CDR3) and SEQ ID NO:100 (CDR1), SEQ ID NO:101 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 102 (CDR3);
vii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO: 103 (CDRl), SEQ ID NO: 104 (CDR2) and SEQ ID NO: 105 (CDR3) and SEQ ID NO: 106 (CDRl), SEQ ID NO: 107 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 108 (CDR3);
viii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:109 (CDR1), SEQ ID NO:110 (CDR2) and SEQ ID NO:111 (CDR3) and SEQ ID NO:112 (CDR1), SEQ ID NO:113 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 114 (CDR3);
ix ) light chain CDRs comprising the amino acid sequences of SEQ ID NO: 115 (CDR1), SEQ ID NO: 116 (CDR2) and SEQ ID NO: 117 (CDR3) and SEQ ID NO: 118 (CDR1), SEQ ID NO: 119 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 120 (CDR3);
x ) light chain CDRs comprising the amino acid sequences of SEQ ID NO: 121 (CDR1), SEQ ID NO: 122 (CDR2) and SEQ ID NO: 123 (CDR3) and SEQ ID NO: 124 (CDR1), SEQ ID NO: 125 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 126 (CDR3);
xi ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:127 (CDR1), SEQ ID NO:128 (CDR2) and SEQ ID NO:129 (CDR3) and SEQ ID NO:130 (CDR1), SEQ ID NO:131 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 132 (CDR3);
xii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:133 (CDR1), SEQ ID NO:134 (CDR2) and SEQ ID NO:135 (CDR3) and SEQ ID NO:136 (CDR1), SEQ ID NO:137 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 138 (CDR3); and
xiii ) light chain CDRs comprising the amino acid sequences of SEQ ID NO:139 (CDR1), SEQ ID NO:140 (CDR2) and SEQ ID NO:141 (CDR3) and SEQ ID NO:142 (CDR1), SEQ ID NO:143 (CDR2) and an antigen-binding unit comprising a heavy chain CDR comprising the amino acid sequence of SEQ ID NO: 144 (CDR3)
is selected from
A second antigen binding unit that specifically binds to CD3 comprises light chain CDRs comprising the amino acid sequences of SEQ ID NO:257 (CDR1), SEQ ID NO:258 (CDR2) and SEQ ID NO:259 (CDR3) and SEQ ID NO: 260 (CDR1), SEQ ID NO: 261 (CDR2) and SEQ ID NO: 262 (CDR3).
protein. 前記Ｂ７Ｈ６に特異的に結合する第１の抗原結合単位が、ｉ）～ｘｉｉｉ）：
ｉ）配列番号：１６７のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１６８のアミノ酸配列を含む重鎖可変ドメイン；
ｉｉ）配列番号：１６９のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１７０のアミノ酸配列を含む重鎖可変ドメイン；
ｉｉｉ）配列番号：１７１のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１７２のアミノ酸配列を含む重鎖可変ドメイン；
ｉｖ）配列番号：１７３のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１７４のアミノ酸配列を含む重鎖可変ドメイン；
ｖ）配列番号：１７５のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１７６のアミノ酸配列を含む重鎖可変ドメイン；
ｖｉ）配列番号：１７７のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１７８のアミノ酸配列を含む重鎖可変ドメイン；
ｖｉｉ）配列番号：１７９のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１８０のアミノ酸配列を含む重鎖可変ドメイン；
ｖｉｉｉ）配列番号：１８１のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１８２のアミノ酸配列を含む重鎖可変ドメイン；
ｉｘ）配列番号：１８３のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１８４のアミノ酸配列を含む重鎖可変ドメイン；
ｘ）配列番号：１８５のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１８６のアミノ酸配列を含む重鎖可変ドメイン；
ｘｉ）配列番号：１８７のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１８８のアミノ酸配列を含む重鎖可変ドメイン；
ｘｉｉ）配列番号：１８９のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１９０のアミノ酸配列を含む重鎖可変ドメイン；並びに
ｘｉｉｉ）配列番号：１９１のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：１９２のアミノ酸配列を含む重鎖可変ドメイン；
からなる群より選択される、請求項１に記載のタンパク質。 The first antigen-binding unit that specifically binds to B7H6 comprises: i) -xiii ) :
i ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:167 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:168;
ii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:169 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:170;
iii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:171 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:172;
iv ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:173 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:174;
v ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:175 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:176;
vi ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:177 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:178;
vii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:179 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:180;
viii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:181 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:182;
ix ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:183 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:184;
x ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:185 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:186;
xi ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:187 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:188;
xii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:189 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:190;
xiii ) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:191 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:192;
2. The protein of claim 1, selected from the group consisting of: 前記ＣＤ３に特異的に結合する第２の抗原結合単位が、
配列番号：２９３のアミノ酸配列を含む軽鎖可変ドメイン及び配列番号：２９４のアミノ酸配列を含む重鎖可変ドメイン
を含む、請求項１又は２に記載のタンパク質。 A second antigen-binding unit that specifically binds to the CD3 ,
a light chain variable domain comprising the amino acid sequence of SEQ ID NO:293 and a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:294
3. The protein of claim 1 or 2 , comprising : ｉ）前記Ｂ７Ｈ６に特異的に結合する第１の抗原結合単位が、そのＮ末端からＣ末端へ、第１の軽鎖可変ドメインと、第１の軽鎖定常ドメインと、第１のペプチドリンカーと、第１の重鎖可変ドメインと、第１の重鎖定常ＣＨ１ドメインとを含み；及び
ｉｉ）前記ＣＤ３に特異的に結合する第２の抗原結合単位が、そのＮ末端からＣ末端へ、第２の軽鎖可変ドメインと、第２の軽鎖定常ドメインと、第２のペプチドリンカーと、第２の重鎖可変ドメインと、第２の重鎖定常ＣＨ１ドメインとを含む；
請求項１～３のいずれか一項に記載のタンパク質。 i) said first antigen-binding unit that specifically binds to B7H6 comprises, from its N-terminus to C-terminus, a first light chain variable domain, a first light chain constant domain and a first peptide linker , a first heavy chain variable domain, and a first heavy chain constant CH1 domain; and ii) a second antigen-binding unit that specifically binds to said CD3 comprises, from its N-terminus to its C-terminus, a second comprising two light chain variable domains, a second light chain constant domain, a second peptide linker, a second heavy chain variable domain and a second heavy chain constant CH1 domain;
The protein according to any one of claims 1-3 . 前記Ｂ７Ｈ６に対して特異的な第１の抗原結合単位が、配列番号：２０４、配列番号：２０５、配列番号：２０６、配列番号：２０７、配列番号：２０８、配列番号：２０９、配列番号：２１０、配列番号：２１１、配列番号：２１２、配列番号：２１３、配列番号：２１４、配列番号：２１５及び配列番号：２１６からなる群より選択されるアミノ酸配列を含み、前記ＣＤ３に対して特異的な第２の抗原結合単位が、配列番号：３０５のアミノ酸配列を含む、請求項４に記載のタンパク質。 the first antigen-binding unit specific for B7H6 is SEQ ID NO: 204 , SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210 , SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215 and SEQ ID NO: 216, wherein the CD3-specific 5. The protein of Claim 4, wherein the second antigen-binding unit comprises the amino acid sequence of SEQ ID NO:305. 第１及び第２のＦｃドメインをさらに含み、前記第１のＦｃドメインは前記第１の抗原結合単位に、好ましくは前記第１の抗原結合単位のＣ末端に共有結合されており、前記第２のＦｃドメインは前記第２の抗原結合単位に、好ましくは前記第２の抗原結合単位のＣ末端に共有結合されている、請求項４又は５に記載のタンパク質。 further comprising first and second Fc domains, wherein said first Fc domain is covalently linked to said first antigen-binding unit, preferably to the C-terminus of said first antigen-binding unit; 6. A protein according to claim 4 or 5 , wherein the Fc domain of is covalently linked to said second antigen binding unit, preferably to the C-terminus of said second antigen binding unit. ｉ）前記第１のＦｃドメインが位置３６６にチロシン（Ｙ）［Ｔ３６６Ｙ］を含み、前記第２のＦｃドメインが位置４０７にトレオニン（Ｔ）［Ｙ４０７Ｔ］を含み、又は
ｉｉ）前記第１のＦｃドメインが位置３６６にトリプトファン（Ｗ）［Ｔ３６６Ｗ］を含み、前記第２のＦｃドメインが位置３６６にセリン（Ｓ）［Ｔ３６６Ｓ］、位置３６８にアラニン（Ａ）［Ｌ３６８Ａ］及び位置４０７にバリン（Ｖ）［Ｙ４０７Ｖ］を含み、又は
ｉｉｉ）前記第２のＦｃドメインが位置３６６にチロシン（Ｙ）［Ｔ３６６Ｙ］を含み、前記第１のＦｃドメインが位置４０７にトレオニン（Ｔ）［Ｙ４０７Ｔ］を含み、又は
ｉｖ）前記第２のＦｃドメインが位置３６６にトリプトファン（Ｗ）［Ｔ３６６Ｗ］を含み、前記第１のＦｃドメインが位置３６６にセリン（Ｓ）［Ｔ３６６Ｓ］、位置３６８にアラニン（Ａ）［Ｌ３６８Ａ］及び位置４０７にバリン（Ｖ）［Ｙ４０７Ｖ］を含み、
好ましくは、前記第１又は前記第２のＦｃドメインが、さらに、位置４３５にアルギニン［Ｈ４３５Ｒ］及び位置４３６にフェニルアラニン［Ｙ４３６Ｆ］を含む、
請求項６に記載のタンパク質。 i) said first Fc domain comprises a tyrosine (Y) [T366Y] at position 366 and said second Fc domain comprises a threonine (T) [Y407T] at position 407, or ii) said first Fc domain contains a tryptophan (W) [T366W] at position 366, said second Fc domain contains a serine (S) at position 366 [T366S], an alanine (A) at position 368 [L368A] and a valine (V ) [Y407V], or iii) said second Fc domain comprises a tyrosine (Y) at position 366 [T366Y] and said first Fc domain comprises a threonine (T) at position 407 [Y407T]; or iv) said second Fc domain comprises a tryptophan (W) at position 366 [T366W] and said first Fc domain contains a serine (S) at position 366 [T366S] and an alanine (A) at position 368 [L368A ] and a valine (V) at position 407 [Y407V],
Preferably, said first or said second Fc domain further comprises an arginine [H435R] at position 435 and a phenylalanine [Y436F] at position 436,
A protein according to claim 6 . 前記第１及び／又は前記第２のＦｃドメインが、位置２３４にアラニン［Ｌ２３４Ａ］及び位置２３５にアラニン［Ｌ２３５Ａ］を含み、好ましくは前記第１のＦｃドメインが配列番号：２４２のアミノ酸配列を含み、前記第２のＦｃドメインが配列番号：２４３のアミノ酸配列を含む、請求項６又は７に記載のタンパク質。 said first and/or said second Fc domain comprises an alanine [L234A] at position 234 and an alanine [L235A] at position 235, preferably said first Fc domain comprises the amino acid sequence of SEQ ID NO: 242 8. The protein of claim 6 or 7 , wherein said second Fc domain comprises the amino acid sequence of SEQ ID NO:243. 配列番号：２２８、配列番号：２２９、配列番号：２３０、配列番号：２３１、配列番号：２３２、配列番号：２３３、配列番号：２３４、配列番号：２３５、配列番号：２３６、配列番号：２３７、配列番号：２３８、配列番号：２３９及び配列番号：２４０からなる群より選択されるアミノ酸配列を含む、Ｂ７Ｈ６に特異的に結合する第１のポリペプチド鎖と、配列番号：３１１のアミノ酸配列を含む、ＣＤ３に特異的に結合する第２のポリペプチド鎖とを含む、請求項４～８のいずれか一項に記載のタンパク質。 SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, a first polypeptide chain that specifically binds to B7H6 comprising an amino acid sequence selected from the group consisting of SEQ ID NO:238, SEQ ID NO:239 and SEQ ID NO:240; and the amino acid sequence of SEQ ID NO:311 , and a second polypeptide chain that specifically binds to CD3. 前記第１及び前記第２のポリペプチド鎖が、ジスルフィド結合を介して連結され、二重特異性の、二価の及びヘテロ二量体のタンパク質を形成している、請求項９に記載のタンパク質。 10. The protein of claim 9 , wherein said first and said second polypeptide chains are linked via disulfide bonds to form a bispecific, bivalent and heterodimeric protein. . 請求項１～５のいずれか一項に記載のタンパク質の前記第１の抗原結合単位及び／又は前記第２の抗原結合単位をコードし、場合により、第１及び／又は第２のＦｃドメインをさらにコードする単離された核酸分子。 encoding said first antigen-binding unit and/or said second antigen-binding unit of a protein according to any one of claims 1 to 5 , optionally comprising a first and/or second Fc domain An isolated nucleic acid molecule that further encodes. 請求項９に記載の前記第１及び／又は前記第２のポリペプチド鎖をコードする単離された核酸分子。 10. An isolated nucleic acid molecule encoding said first and/or said second polypeptide chain according to claim 9 . 請求項１１又は１２に記載の前記核酸分子を含む発現ベクター。 13. An expression vector comprising the nucleic acid molecule of claim 11 or 12 . 請求項１３に記載の前記発現ベクターで形質導入された宿主細胞。 14. A host cell transduced with the expression vector of claim 13 . 請求項１～１０のいずれか一項に記載のタンパク質を製造する方法であって、
ｉ）請求項１～１０のいずれか一項に記載のタンパク質の発現を可能にする条件下で、請求項１４に記載の前記宿主細胞を培養することと；
ｉｉ）前記タンパク質を回収することと；場合により、
ｉｉｉ）前記タンパク質をさらに精製及び／又は修飾及び／又は製剤化することと；
を含む、方法。 A method for producing the protein according to any one of claims 1 to 10 ,
i) culturing said host cell according to claim 14 under conditions permitting the expression of the protein according to any one of claims 1-10 ;
ii) recovering said protein;
iii) further purifying and/or modifying and/or formulating said protein;
A method, including 医薬において使用するための、請求項１～１０のいずれか一項に記載のタンパク質。 A protein according to any one of claims 1 to 10 for use in medicine. 請求項１～１０のいずれか一項に記載のタンパク質と、薬学的に許容し得る担体とを含む医薬組成物。 A pharmaceutical composition comprising the protein according to any one of claims 1 to 10 and a pharmaceutically acceptable carrier. 癌を処置する方法において使用するための、請求項１～１０のいずれか一項に記載のタンパク質。 A protein according to any one of claims 1 to 10 for use in a method of treating cancer. 前記癌がＢ７Ｈ６発現腫瘍であり、好ましくは、前記癌が（転移性）結腸直腸癌（（ｍ）ＣＲＣ）、非小細胞肺癌（ＮＳＣＬＣ）又は頭頸部扁平上皮癌腫（ＨＮＳＣＣ）である、請求項１８に記載の使用のためのタンパク質。 4. Claim wherein said cancer is a B7H6-expressing tumor, preferably said cancer is (metastatic) colorectal cancer ((m)CRC), non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC). 18. A protein for use according to 18. 前記タンパク質が、細胞傷害性若しくは細胞分裂阻害性化学療法剤、血管新生を阻害する治療活性化合物、シグナル伝達経路阻害剤（例えば、ＥＧＦＲ阻害剤）、免疫調節剤、免疫チェックポイント阻害剤、有糸分裂チェックポイント阻害剤又はホルモン療法剤と組み合わせて使用される、請求項１８若しくは１９に記載の使用のためのタンパク質。 The protein is a cytotoxic or cytostatic chemotherapeutic agent, a therapeutically active compound that inhibits angiogenesis, a signal transduction pathway inhibitor (e.g., EGFR inhibitor), an immunomodulatory agent, an immune checkpoint inhibitor, mitosis 20. Protein for use according to claim 18 or 19 in combination with a mitotic checkpoint inhibitor or a hormone therapy agent. 前記タンパク質が、免疫チェックポイント阻害剤、好ましくは抗ＰＤ－１抗体又は抗ＰＤ－Ｌ１抗体と組み合わせて使用される、請求項２０に記載の使用のためのタンパク質。 Protein for use according to claim 20 , wherein said protein is used in combination with an immune checkpoint inhibitor, preferably an anti-PD-1 antibody or an anti-PD-L1 antibody. 前記抗ＰＤ－１抗体が、ＰＤ１－１、ＰＤ１－２、ＰＤ１－３、ＰＤ１－４及びＰＤ１－５からなる群より選択される、請求項２１に記載の使用のためのタンパク質。 Protein for use according to claim 21 , wherein said anti-PD-1 antibody is selected from the group consisting of PD1-1, PD1-2, PD1-3, PD1-4 and PD1-5.
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