JP2021516951A - Lag‐3に対する単一ドメイン抗体およびその使用 - Google Patents
Lag‐3に対する単一ドメイン抗体およびその使用 Download PDFInfo
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
Description
本願は、2018年3月30日に出願された国際特許出願第PCT/CN2018/081356号の優先権の恩恵を主張するものであり、その開示は参照により全体として組み込まれる。
[ASCIIテキストファイルの配列表の提出]
(1)SEQ ID NO:39のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:115のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:191のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(2)SEQ ID NO:40のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:116のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:192のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(3)SEQ ID NO:41のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:117のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:193のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(4)SEQ ID NO:42のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:118のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:194のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(5)SEQ ID NO:43のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:119のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:195のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(6)SEQ ID NO:44のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:120のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:196のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(7)SEQ ID NO:45のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:121のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:197のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(8)SEQ ID NO:46のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:122のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:198のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(9)SEQ ID NO:54のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:130のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;および、SEQ ID NO:206のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(10)SEQ ID NO:61のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:137のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:213のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(11)SEQ ID NO:70のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:146のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:222のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(12)SEQ ID NO:72のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:148のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:224のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;または、
(13)SEQ ID NO:73のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:149のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:225のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアントのいずれか1つを含む。
[I.定義]
表1.HVRの表示
[II.抗LAG‐3コンストラクト]
(I)抗LAG‐3単一ドメイン抗体
(1)アミノ酸位置1(例えば、QまたはE)、(2)アミノ酸位置5(例えば、AまたはV)、(3)アミノ酸位置11(例えば、SまたはL)、(4)アミノ酸位置14(例えば、AまたはP)、(5)アミノ酸位置44(例えば、EまたはG)、(6)アミノ酸位置45(例えば、RまたはL)、(7)アミノ酸位置71(例えば、KまたはR)、(8)アミノ酸位置74(例えば、AまたはS)、(9)アミノ酸位置86(例えば、RまたはK)、(10)アミノ酸位置87(例えば、AまたはP)、(11)アミノ酸位置92(例えば、MまたはV)、または(12)アミノ酸位置117(例えば、QまたはL)から成る群から選択される1または複数のアミノ酸置換を含む。ここで、アミノ酸位置はSEQ ID NO:295に基づく。
[単一ドメイン抗体]
[LAG‐3]
[抗体親和性]
[キメラまたはヒト化抗体]
[ヒト抗体]
[ライブラリ由来抗体]
[生物学的活性]
[(II)融合物コンストラクト]
[抗LAG‐3重鎖のみ抗体(HCAb)]
(LALA)変異を含む。いくつかの実施形態において、Fc断片は、エフェクターレスhIgG1 FcなどのエフェクターレスIgG1 Fcである。いくつかの実施形態において、Fc断片はヒトIgG4 Fc(S228P)である。いくつかの実施形態において、抗LAG‐3 HCAbは単量体である。いくつかの実施形態において、抗LAG‐3 HCAbは二量体である。いくつかの実施形態において、抗LAG‐3 HCAbは多重特異性かつ多価(二重特異性かつ2価など)であり、例えば、本明細書に記載の2つ以上の異なる抗LAG‐3 sdAbを含む。いくつかの実施形態において、抗LAG‐3 HCAbは、単一特異性かつ多価(例えば、2価)であり、例えば、同一の抗LAG‐3 sdAbのコピーを2つ以上含む。
[多価および/または多重特異性のコンストラクト]
[融合ポリペプチド]
[b)VHおよびVLを含む第2の抗原結合部分]
[c)例示的抗LAG‐3 MABP]
[ペプチドリンカー]
[III)抗体バリアント]
[a)置換、挿入、欠失およびバリアント]
表2.アミノ酸置換
[b)グリコシル化バリアント]
[c)Fc領域バリアント]
(すなわち、改善または低下のいずれか)をもたらす変更がFc領域に加えられる(例えば、米国特許第6,194,551号、WO 99/51642およびIdusogie et al. J.Immunol. 164: 4178−4184 (2000)に記載)。
[d)システイン改変された抗体バリアント]
[e)抗体誘導体]
[III.医薬組成物]
[IV. LAG‐3関連疾患を治療する方法]
[V.調製の方法]
[1.原核細胞における組換え産生物]
[a)ベクター構築]
[b)原核生物宿主細胞]
[c)タンパク質産生]
d)タンパク質精製
[2.真核細胞における組換え産生物]
[a)シグナル配列成分]
[b)複製起点]
[c)選択遺伝子成分]
[d)プロモーター成分]
[e)エンハンサー要素成分]
[f)転写終結因子]
[g)宿主細胞の選択および形質転換]
[h)宿主細胞の培養]
[i)タンパク質精製]
[3.ポリクローナル抗体]
[4.モノクローナル抗体]
[5.ヒト化抗体]
[6.ヒト抗体]
[VI.製品およびキット]
[例]
[例1:抗LAG‐3 sdAbの生成]
[免疫化]
[ライブラリ構築]
[選択およびハイスループットスクリーニング]
例2:非ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の調製およびin vitro評価
sdAb‐Fc融合タンパク質の産生
[表面プラズモン共鳴(SPR)による標的タンパク質結合および異種間反応試験]
表2.LAG‐3に対する非ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の親和性決定
[FACS分析によるCHO‐huLAG‐3細胞結合およびリガンド結合の阻害]
表3 LAG‐3に対する非ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の結合およびリガンド結合のブロッキングのデータ
[抗LAG‐3 sdAbのヒト化]
[ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の産生]
表4.ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の発現
表5.ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質の親和性決定
表6.ヒト化抗LAG‐3 sdAb‐Fc融合タンパク質のためのLAG‐3ブロックレポータアッセイ
PD‐1×LAG‐3 BABPの構築
表7.例示的なPD‐1×LAG‐3コンストラクト
[PD‐1×LAG‐3 BABPの親和性決定]
表9.PD‐1×LAG‐3 BABPの結合およびブロッキングのデータ
表10.PD‐1×LAG‐3 BABPのin vitro機能アッセイ
[配列表]
表11.抗LAG‐3 sdAb SEQ ID NO
SEQ ID NO: 268 (AS20592 sdAb核酸配列)GAGGTGCAACTGGTGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGGATACATCATCAGTAGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTGATAGTGATGGTGGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAACGCCAAGAACACTCTGTATCTGCAAATGGACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGATTTTTGTTGGGTAGATGAGGATCGCCACCTCTATGAGTATAACTCCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 269 (AS20594 sdAb核酸配列)CAGGTGCAGCTGGCGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGGATACACCATCAGTAGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTGATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAACGCCAAGAACACTCTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGATTTTTGTTGGGTGGACGACTTCTATGAGTATAACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 270 (AS20601 sdAb核酸配列)GAGGTGCAACTGGCGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGGATACACCTACGGTGGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAACTATTAATAGTGATGGTAGCACAAACTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAACGCCAAGAACACTCTGTATCTGCAAATGAACAGCCTGAGCCCTGAGGACACTGCCATGTACTACTGCGCGGTGGATCTCGCCCCATGTTGGGTAGCTGGTCCCATCGAGGCCGCTGACTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 271 (AS20846 sdAb核酸配列)CAGGTGCACCTGATGGAGTCTGGGGGAGGCTCGGTGCAGGTTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGGATACACCGTCAGTAGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTGATAGTGATGGTAGCGTAAGTTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAACGCCAAGAACACTCTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTTCTGTGCGGCAGATCTTTGCTGGGTGGACCAGGACCAGGGAGAATATAACACCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 272 (AS20916 sdAb核酸配列)GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTGCAGGCAGGGGGGTCTCTGAGACTCTCCTGTACAGCCTCTGGATTGACTTTTGATGATTATGCCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCTCATGTATTAGCTGGAGTGGTGGTAGCACATACTATACCGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTACTGTGCGGCAGATTTGTTCTGTCCCCCACCTGATGATACTACGGGTTGGGGTATGGACCCTCCCGAGCATAACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 273 (AS21317 sdAb核酸配列)CAGGTTCAGCTGGTGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTTTCCTGTGCAGCCTCTGGATACACCTTGAGTAGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTGATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAACGCCAAGAACACTCTGTTTCTGCAAATGAACGGCCTGAAACCTGAGGACACTGCGGTGTACTACTGTGCTCCACTATGCTGGGTTGATTACCCATTGCCGTCGGGCCCATACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA
SEQ ID NO: 274 (AS20410 sdAbアミノ酸配列;CDRを鉤括弧で示す)QVQLAESGGGSVHAGGSLRLSCVVS「EYTFSSDSMG」WFRQAPGKEREGVA「AIDSDGSTSYAGSVKG」RFTISKDNAENTLYLQMNSLKPEDTAMYYCAT「SPLWLLSRLDPADFEY」WGQGTQVTVSS
SEQ ID NO: 275 (AS20592 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGSVQAGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISKDNAKNTLYLQMDSLKPEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTQVTVSS
SEQ ID NO: 276 (AS20594 sdAbアミノ酸配列;CDRを鉤括弧で示す)QVQLAESGGGSVQAGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTQVTVSS
SEQ ID NO: 277 (AS20601 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLAESGGGSVQAGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKEREGVA「TINSDGSTNYADSVKG」RFTISKDNAKNTLYLQMNSLSPEDTAMYYCAV「DLAPCWVAGPIEAADFGY」WGQGTQVTVSS
SEQ ID NO: 278 (AS20846 sdAbアミノ酸配列;CDRを鉤括弧で示す)QVHLMESGGGSVQVGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTQVTVSS
SEQ ID NO: 279 (AS20916 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQAGGSLRLSCTAS「GLTFDDYAMG」WFRQAPGKEREGVS「CISWSGGSTYYTDSVKG」RFTISRDNAKNTLYLQMNSLKPEDTAMYYCAA「DLFCPPPDDTTGWGMDPPEHNY」WGQGTQVTVSS
SEQ ID NO: 280 (AS21317 sdAbアミノ酸配列;CDRを鉤括弧で示す)QVQLVESGGGSVQAGGSLRLSCAAS「GYTLSSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNAKNTLFLQMNGLKPEDTAVYYCAP「LCWVDYPLPSGPY」WGQGTQVTVSS
SEQ ID NO: 281 (AS20592M6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGSVQAGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSSGGTSYADSVKG」RFTISKDNAKNTLYLQMDSLKPEDTAMYYCAA「DFCWVDEDRHLYEYQS」WGQGTQVTVSS
SEQ ID NO: 282 (AS20592VH4 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVS「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 283 (AS20592VH5 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 284 (AS20592VH6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 285 (AS20592VH7 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGREGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 286 (AS20592VH8 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 287 (AS20592VH9 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 288 (AS20592VH10 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 289 (AS20592VH10M1 sdAbアミノ酸配列;CDRを鉤括弧で示す) EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSSGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 290 (AS20594VH5 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 291 (AS20594VH6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 292 (AS20594VH7 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGREGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 293 (AS20594VH8 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 294 (AS20594VH9 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 295 (AS20594VH10 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 296 (AS20594VH10M1 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSSGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 297 (AS20846VH4 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVS「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 298 (AS20846VH5 sdAbアミノ酸配列;CDRを鉤括弧で示す) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVS「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 299 (AS20846VH6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 300 (AS20846VH7 sdAbアミノ酸配列;CDRを鉤括弧で示す) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 301 (AS20846VH8 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 302 (AS20846VH9 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 303 (AS20846VH10 sdAbアミノ酸配列;CDRを鉤括弧で示す) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 304 (AS20846VH12 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 305 (AS20846VH12M1 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSSGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 306 (AS20601VH4 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 307 (AS20601VH4.M6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TIASEGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 308 (AS20601VH4.M7 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TIASSGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 309 (AS20601VH11 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TINSDGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 310 (AS20601VH11.M6 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TIASEGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 311 (AS20601VH11.M7 sdAbアミノ酸配列;CDRを鉤括弧で示す)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TIASSGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 312 (AS20410 HCAb二量体形アミノ酸配列)QVQLAESGGGSVHAGGSLRLSCVVS「EYTFSSDSMG」WFRQAPGKEREGVA「AIDSDGSTSYAGSVKG」RFTISKDNAENTLYLQMNSLKPEDTAMYYCAT「SPLWLLSRLDPADFEY」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 313 (AS20592 HCAb二量体形アミノ酸配列)EVQLVESGGGSVQAGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISKDNAKNTLYLQMDSLKPEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 314 (AS20594 HCAb二量体形アミノ酸配列)QVQLAESGGGSVQAGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 315 (AS20601 HCAb二量体形アミノ酸配列)EVQLAESGGGSVQAGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKEREGVA「TINSDGSTNYADSVKG」RFTISKDNAKNTLYLQMNSLSPEDTAMYYCAV「DLAPCWVAGPIEAADFGY」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 316 (AS20846 HCAb二量体形アミノ酸配列)QVHLMESGGGSVQVGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 317 (AS20916 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQAGGSLRLSCTAS「GLTFDDYAMG」WFRQAPGKEREGVS「CISWSGGSTYYTDSVKG」RFTISRDNAKNTLYLQMNSLKPEDTAMYYCAA「DLFCPPPDDTTGWGMDPPEHNY」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 318 (AS21317 HCAb二量体形アミノ酸配列)QVQLVESGGGSVQAGGSLRLSCAAS「GYTLSSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNAKNTLFLQMNGLKPEDTAVYYCAP「LCWVDYPLPSGPY」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 319 (AS20592M6 HCAb二量体形アミノ酸配列)EVQLVESGGGSVQAGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSSGGTSYADSVKG」RFTISKDNAKNTLYLQMDSLKPEDTAMYYCAA「DFCWVDEDRHLYEYQS」WGQGTQVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 320 (AS20592VH4 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVS「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 321 (AS20592VH5 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 322 (AS20592VH6 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 323 (AS20592VH7 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGREGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 324 (AS20592VH8 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 325 (AS20592VH9 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 326 (AS20592VH10 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 327 (AS20592VH10M1 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSSGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 328 (AS20594VH5 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 329 (AS20594VH6 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 330 (AS20594VH7 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGREGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 331 (AS20594VH8 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 332 (AS20594VH9 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 333 (AS20594VH10 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 334 (AS20594VH10M1 HCAb二量体形アミノ酸配列) EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSSGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 335 (AS20846VH4 HCAb二量体形アミノ酸配列) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVS「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 336 (AS20846VH5 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVS「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 337 (AS20846VH6 HCAb二量体形アミノ酸配列) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 338 (AS20846VH7 HCAb二量体形アミノ酸配列) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGLEGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 339 (AS20846VH8 HCAb二量体形アミノ酸配列) EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 340 (AS20846VH9 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 341 (AS20846VH10 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 342 (AS20846VH12 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 343 (AS20846VH12M1 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSSGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 344 (AS20601VH4 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 345 (AS20601VH4.M6 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TIASEGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 346 (AS20601VH4.M7 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TIASSGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 347 (AS20601VH11 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TINSDGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 348 (AS20601VH11.M6 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TIASEGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 349 (AS20601VH11.M7 HCAb二量体形アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGREGVS「TIASSGSTNYADSVKG」RFTISRDNAKNTLYLQMNSLRPEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 350 (Human LAG−3 完全長アミノ酸配列)VPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAGVTWQHQPDSGPPAAAPGHPLAPGPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPLQPRVQLDERGRQRGDFSLWLRPARRADAGEYRAAVHLRDRALSCRLRLRLGQASMTASPPGSLRASDWVILNCSFSRPDRPASVHWFRNRGQGRVPVRESPHHHLAESFLFLPQVSPMDSGPWGCILTYRDGFNVSIMYNLTVLGLEPPTPLTVYAGAGSRVGLPCRLPAGVGTRSFLTAKWTPPGGGPDLLVTGDNGDFTLRLEDVSQAQAGTYTCHIHLQEQQLNATVTLAIITVTPKSFGSPGSLGKLLCEVTPVSGQERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERLLGAAVYFTELSSPGAQRSGRAPGALPAGHLLLFLILGVLSLLLLVTGAFGFHLWRRQWRPRRFSALEQGIHPPQAQSKIEELEQEPEPEPEPEPEPEPEPEPEQL
SEQ ID NO: 351 (Human LAG−3 細胞外ドメインアミノ酸配列)VPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAGVTWQHQPDSGPPAAAPGHPLAPGPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPLQPRVQLDERGRQRGDFSLWLRPARRADAGEYRAAVHLRDRALSCRLRLRLGQASMTASPPGSLRASDWVILNCSFSRPDRPASVHWFRNRGQGRVPVRESPHHHLAESFLFLPQVSPMDSGPWGCILTYRDGFNVSIMYNLTVLGLEPPTPLTVYAGAGSRVGLPCRLPAGVGTRSFLTAKWTPPGGGPDLLVTGDNGDFTLRLEDVSQAQAGTYTCHIHLQEQQLNATVTLAIITVTPKSFGSPGSLGKLLCEVTPVSGQERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERLLGAAVYFTELSSPGAQRSGRAPGALPAGHL
SEQ ID NO: 352 (ヒトIgG1ヒンジアミノ酸配列)EPKSSDKTHTCPPCP
SEQ ID NO: 353 (Mutated ヒトIgG1ヒンジアミノ酸配列)EPKSSDKTHTSPPSP
SEQ ID NO: 354 (BMS−986016 重鎖アミノ酸配列)QVQLQQWGAGLLKPSETLSLTCAVY「GGSFSDYYWN」WIRQPPGKGLEWIG「EINHRGSTNSNPSLKS」RVTLSLDTSKNQFSLKLRSVTAADTAVYYCAF「GYSDYEYNWFDP」WGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 355 (BMS−986016 軽鎖アミノ酸配列)EIVLTQSPATLSLSPGERATLSC「RASQSISSYLA」WYQQKPGQAPRLLIY「DASNRAT」GIPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QQRSNWPLT」FGQGTNLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 356 (ペムブロリズマブ重鎖アミノ酸配列)QVQLVQSGVEVKKPGASVKVSCKAS「GYTFTNYYMY」WVRQAPGQGLEWMG「GINPSNGGTNFNEKFKN」RVTLTTDSSTTTAYMELKSLQFDDTAVYYCAR「RDYRFDMGFDY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 357 (ペムブロリズマブ軽鎖アミノ酸配列)EIVLTQSPATLSLSPGERATLSC「RASKGVSTSGYSYLH」WYQQKPGQAPRLLIY「LASYLES」GVPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QHSRDLPLT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 358 (BLP‐21 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEPKSSDKTHTSPPSPQVQLVQSGVEVKKPGASVKVSCKAS「GYTFTNYYMY」WVRQAPGQGLEWMG「GINPSNGGTNFNEKFKN」RVTLTTDSSTTTAYMELKSLQFDDTAVYYCAR「RDYRFDMGFDY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 359 (BLP‐21 軽鎖アミノ酸配列)EIVLTQSPATLSLSPGERATLSC「RASKGVSTSGYSYLH」WYQQKPGQAPRLLIY「LASYLES」GVPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QHSRDLPLT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 360 (BLP‐22 重鎖アミノ酸配列)QVQLVQSGVEVKKPGASVKVSCKAS「GYTFTNYYMY」WVRQAPGQGLEWMG「GINPSNGGTNFNEKFKN」RVTLTTDSSTTTAYMELKSLQFDDTAVYYCAR「RDYRFDMGFDY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 361 (BLP‐22 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEPKSSDKTHTSPPSPEIVLTQSPATLSLSPGERATLSC「RASKGVSTSGYSYLH」WYQQKPGQAPRLLIY「LASYLES」GVPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QHSRDLPLT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 362 (BLP‐23 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEPKSSDKTHTSPPSPQVQLVQSGVEVKKPGASVKVSCKAS「GYTFTNYYMY」WVRQAPGQGLEWMG「GINPSNGGTNFNEKFKN」RVTLTTDSSTTTAYMELKSLQFDDTAVYYCAR「RDYRFDMGFDY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 363 (BLP‐23 軽鎖アミノ酸配列)EIVLTQSPATLSLSPGERATLSC「RASKGVSTSGYSYLH」WYQQKPGQAPRLLIY「LASYLES」GVPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QHSRDLPLT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 364 (BLP‐24 重鎖アミノ酸配列)QVQLVQSGVEVKKPGASVKVSCKAS「GYTFTNYYMY」WVRQAPGQGLEWMG「GINPSNGGTNFNEKFKN」RVTLTTDSSTTTAYMELKSLQFDDTAVYYCAR「RDYRFDMGFDY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 365 (BLP‐24 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEPKSSDKTHTSPPSPEIVLTQSPATLSLSPGERATLSC「RASKGVSTSGYSYLH」WYQQKPGQAPRLLIY「LASYLES」GVPARFSGSGSGTDFTLTISSLEPEDFAVYYC「QHSRDLPLT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 366 (Linker peptide (9GS) アミノ酸配列GGGGSGGGS
SEQ ID NO: 367 (リンカーペプチドアミノ酸配列)GGGGSGGGGSGGGGS
SEQ ID NO: 368 (リンカーペプチドアミノ酸配列、nは少なくとも1の整数)(G)n
SEQ ID NO: 369 (リンカーペプチドアミノ酸配列、nは少なくとも1の整数)(GS)n
SEQ ID NO: 370 (リンカーペプチドアミノ酸配列、nは少なくとも1の整数)(GSGGS)n
SEQ ID NO: 371 (リンカーペプチドアミノ酸配列、nは少なくとも1の整数)(GGGS)n
SEQ ID NO: 372 (リンカーペプチドアミノ酸配列、nは少なくとも1の整数)(GGGGS)n
SEQ ID NO: 373 (PD1−BM−min 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 374 (PD1−BM−min 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 375 (BLP‐1 重鎖アミノ酸配列)EVQLVESGGGSVQAGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKEREGVA「AIDSDGGTSYADSVKG」RFTISKDNAKNTLYLQMDSLKPEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTQVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 376 (BLP‐1 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 377 (BLP‐2 重鎖アミノ酸配列)QVQLAESGGGSVQAGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKEREGVA「AIDSDGSTSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYYCAA「DFCWVDDFYEYNY」WGQGTQVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 378 (BLP‐2 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 379 (BLP‐3 重鎖アミノ酸配列)EVQLAESGGGSVQAGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKEREGVA「TINSDGSTNYADSVKG」RFTISKDNAKNTLYLQMNSLSPEDTAMYYCAV「DLAPCWVAGPIEAADFGY」WGQGTQVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 380 (BLP‐3 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 381 (BLP‐4 重鎖アミノ酸配列)QVHLMESGGGSVQVGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKEREGVA「AIDSDGSVSYADSVKG」RFTISKDNAKNTLYLQMNSLKPEDTAMYFCAA「DLCWVDQDQGEYNT」WGQGTQVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 382 (BLP‐4 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 383 (BLP‐5 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 384 (BLP‐5 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 385 (BLP‐6 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 386 (BLP‐6 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 387 (BLP‐7 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 388 (BLP‐7 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSEPKSSDKTHTSPPSPDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 389 (BLP‐8 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 390 (BLP‐8 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSS
SEQ ID NO: 391 (BLP‐9 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 392 (BLP‐9 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 393 (BLP‐10 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 394 (BLP‐10 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 395 (BLP‐11 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 396 (BLP‐11 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSEPKSSDKTHTSPPSPDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 397 (BLP‐12 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 398 (BLP‐12 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSS
SEQ ID NO: 399 (BLP‐13 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 400 (BLP‐13 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 401 (BLP‐14 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 402 (BLP‐14 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 403 (BLP‐15 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 404 (BLP‐15 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEPKSSDKTHTSPPSPDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 405 (BLP‐16 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 406 (BLP‐16 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSS
SEQ ID NO: 407 (BLP‐17 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 408 (BLP‐17 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 409 (BLP‐18 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGKEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 410 (BLP‐18 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 411 (BLP‐19 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 412 (BLP‐19 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEPKSSDKTHTSPPSPDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 413 (BLP‐20 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 414 (BLP‐20 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECEPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSS
SEQ ID NO: 415 (BLP‐25 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 416 (BLP‐25 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 417 (BLP‐26 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 418 (BLP‐26 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 419 (BLP‐27 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 420 (BLP‐27 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 421 (BLP‐28 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 422 (BLP‐28 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 423 (BLP‐29 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 424 (BLP‐29 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 425 (BLP‐30 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 426 (BLP‐30 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 427 (BLP‐31 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 428 (BLP‐31 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 429 (BLP‐32 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 430 (BLP‐32 軽鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 431 (BLP‐33 重鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 432 (BLP‐33 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 433 (BLP‐34 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 434 (BLP‐34 軽鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYIISSYCMG」WFRQAPGKGLEGVA「AIDSDGGTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAMYYCAA「DFCWVDEDRHLYEYNS」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 435 (BLP‐35 重鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 436 (BLP‐35 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 437 (BLP‐36 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 438 (BLP‐36 軽鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTISSYCMG」WFRQAPGKGLEGVA「AIDSDGSTSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYYCAA「DFCWVDDFYEYNY」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 439 (BLP‐37 重鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 440 (BLP‐37 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 441 (BLP‐38 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 442 (BLP‐38 軽鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTVSSYCMG」WFRQAPGKGREGVS「AIDSDGSVSYADSVKG」RFTISKDNSKNTLYLQMNSLRAEDTAVYFCAA「DLCWVDQDQGEYNT」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 443 (BLP‐39 重鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSEVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 444 (BLP‐39 軽鎖アミノ酸配列)DIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
SEQ ID NO: 445 (BLP‐40 重鎖アミノ酸配列)EVQLVESGGGLVQPGGSLRLSCAAS「GFVFSRYDMA」WVRQAPGKGLEWVS「FISGGGSNTYYPDTVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCIS「PYYYAMEY」WGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
SEQ ID NO: 446 (BLP‐40 軽鎖アミノ酸配列)EPKSSDKTHTSPPSPEVQLVESGGGLVQPGGSLRLSCAAS「GYTYGGYCMG」WFRQAPGKGLEGVS「TINSDGSTNYADSVKG」RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAV「DLAPCWVAGPIEAADFGY」WGQGTLVTVSSDIQMTQSPSSVSASVGDRVTITC「KASQDVDTAVA」WYQQKPGKAPKLLIY「WASTRHT」GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC「QQYSTFPWT」FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Claims (44)
- LAG‐3を特異的に認識する単一ドメイン抗体(sdAb)を含む単離抗LAG‐3コンストラクトであって、前記sdAbは、SEQ ID NO:39〜76のいずれか1つのアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:115〜152のいずれか1つのアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:191〜228のいずれか1つのアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアントを含む、単離抗LAG‐3コンストラクト。
- 前記sdAbは、SEQ ID NO:39〜76のいずれか1つのアミノ酸配列を含むCDR1;SEQ ID NO:115〜152のいずれか1つのアミノ酸配列を含むCDR2;およびSEQ ID NO:191〜228のいずれか1つのアミノ酸配列を含むCDR3;または前記CDR1、前記CDR2、および前記CDR3の領域において最大約3個のアミノ酸置換を含むそれらのバリアントを含む、請求項1に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbは、
(1)SEQ ID NO:39のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:115のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:191のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(2)SEQ ID NO:40のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:116のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:192のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(3)SEQ ID NO:41のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:117のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:193のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(4)SEQ ID NO:42のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:118のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:194のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(5)SEQ ID NO:43のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:119のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:195のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(6)SEQ ID NO:44のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:120のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:196のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(7)SEQ ID NO:45のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:121のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:197のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(8)SEQ ID NO:46のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:122のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:198のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(9)SEQ ID NO:54のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:130のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;および、SEQ ID NO:206のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(10)SEQ ID NO:61のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:137のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:213のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(11)SEQ ID NO:70のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:146のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:222のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;
(12)SEQ ID NO:72のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:148のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:224のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント;または、
(13)SEQ ID NO:73のアミノ酸配列を含むCDR1、または、最大約3個のアミノ酸置換を含むそのバリアント;SEQ ID NO:149のアミノ酸配列を含むCDR2、または、最大約3個のアミノ酸置換を含むそのバリアント;およびSEQ ID NO:225のアミノ酸配列を含むCDR3、または、最大約3個のアミノ酸置換を含むそのバリアント
のいずれか1つを含む、請求項1または2に記載の単離抗LAG‐3コンストラクト。 - 前記sdAbは、
(1)SEQ ID NO:39のアミノ酸配列を含むCDR1;SEQ ID NO:115のアミノ酸配列を含むCDR2;およびSEQ ID NO:191のアミノ酸配列を含むCDR3;
(2)SEQ ID NO:40のアミノ酸配列を含むCDR1、SEQ ID NO:116のアミノ酸配列を含むCDR2;およびSEQ ID NO:192のアミノ酸配列を含むCDR3;
(3)SEQ ID NO:41のアミノ酸配列を含むCDR1;SEQ ID NO:117のアミノ酸配列を含むCDR2;およびSEQ ID NO:193のアミノ酸配列を含むCDR3;
(4)SEQ ID NO:42のアミノ酸配列を含むCDR1;SEQ ID NO:118のアミノ酸配列を含むCDR2;およびSEQ ID NO:194のアミノ酸配列を含むCDR3;
(5)SEQ ID NO:43のアミノ酸配列を含むCDR1;SEQ ID NO:119のアミノ酸配列を含むCDR2;およびSEQ ID NO:195のアミノ酸配列を含むCDR3;
(6)SEQ ID NO:44のアミノ酸配列を含むCDR1;SEQ ID NO:120のアミノ酸配列を含むCDR2;およびSEQ ID NO:196のアミノ酸配列を含むCDR3;
(7)SEQ ID NO:45のアミノ酸配列を含むCDR1;SEQ ID NO:121のアミノ酸配列を含むCDR2;およびSEQ ID NO:197のアミノ酸配列を含むCDR3;
(8)SEQ ID NO:46のアミノ酸配列を含むCDR1;SEQ ID NO:122のアミノ酸配列を含むCDR2;およびSEQ ID NO:198のアミノ酸配列を含むCDR3;
(9)SEQ ID NO:54のアミノ酸配列を含むCDR1;SEQ ID NO:130のアミノ酸配列を含むCDR2;およびSEQ ID NO:206のアミノ酸配列を含むCDR3;
(10)SEQ ID NO:61のアミノ酸配列を含むCDR1;SEQ ID NO:137のアミノ酸配列を含むCDR2;およびSEQ ID NO:213のアミノ酸配列を含むCDR3;
(11)SEQ ID NO:70のアミノ酸配列を含むCDR1;SEQ ID NO:146のアミノ酸配列を含むCDR2;およびSEQ ID NO:222のアミノ酸配列を含むCDR3;
(12)SEQ ID NO:72のアミノ酸配列を含むCDR1;SEQ ID NO:148のアミノ酸配列を含むCDR2;およびSEQ ID NO:224のアミノ酸配列を含むCDR3;または
(13)SEQ ID NO:73のアミノ酸配列を含むCDR1;SEQ ID NO:149のアミノ酸配列を含むCDR2;およびSEQ ID NO:225のアミノ酸配列を含むCDR3
のいずれか1つを含む、請求項1から3のいずれか一項に記載の単離抗LAG‐3コンストラクト。 - 前記sdAbは、
(1)SEQ ID NO:1〜38のいずれか1つのアミノ酸配列を含むFR1;
(2)SEQ ID NO:77〜114のいずれか1つのアミノ酸配列を含むFR2;
(3)SEQ ID NO:153〜190のいずれか1つのアミノ酸配列を含むFR3;
(4)SEQ ID NO:229〜266のいずれか1つのアミノ酸配列を含むFR4
を含むVHHドメインを含む、請求項1から4のいずれか一項に記載の単離抗LAG‐3コンストラクト。 - 前記sdAbは、SEQ ID NO:274〜311のいずれか1つのアミノ酸配列を含むVHHドメイン、または、SEQ ID NO:274〜311のいずれか1つと少なくとも約80%の配列同一性を有するそのバリアントを含む、請求項1から5のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbは、SEQ ID NO:274〜311のいずれか1つのアミノ酸配列を含むVHHドメイン、または、前記VHHドメインにおいて最大約3個のアミノ酸置換を含むそのバリアントを含む、請求項6に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbと前記LAG‐3との間の結合のKDは約10−7M〜約10−12Mである、請求項1から7のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbと前記LAG‐3との間の結合のKDは約10−9M〜約10−11Mである、請求項8に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbは非ヒト哺乳動物由来のLAG‐3と交差反応する、請求項1から9のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- LAG‐3を特異的に認識する前記sdAbは、ラクダ型、キメラ型、ヒト型、部分ヒト化、または完全ヒト化である、請求項1から10のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記単離抗LAG‐3コンストラクトは、Fc断片に融合したLAG‐3を特異的に認識する前記sdAbを含む重鎖のみ抗体(HCAb)である、請求項1から11のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記HCAbは単量体または二量体である、請求項12に記載の単離抗LAG‐3コンストラクト。
- 前記Fc断片はヒトIgG1(hIgG1)Fc、エフェクターレスhIgG1 Fc、hIgG4 Fc、またはhIgG4 Fc(S228P)である、請求項12または13に記載の単離抗LAG‐3コンストラクト。
- 前記sdAbはペプチドリンカーを介して前記Fc断片に融合している、請求項12から14のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記ペプチドリンカーは、SEQ ID NO:352〜353および366〜372のいずれか1つのアミノ酸配列を含む、請求項15に記載の単離抗LAG‐3コンストラクト。
- 前記HCAbは、SEQ ID NO:312〜349のいずれか1つのアミノ酸配列を含む、請求項12から16のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- (a)LAG‐3を特異的に認識する前記sdAbを含む第1の抗原結合部分;および(b)第2のエピトープを特異的に認識する第2の抗原結合部分を含む、請求項1から11のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記第2の抗原結合部分は、完全長抗体、Fab、Fab'、(Fab')2、Fv、一本鎖Fv(scFv)、scFv‐scFv、ミニボディ、二重特異性抗体、または第2のsdAbを含む、請求項18に記載の単離抗LAG‐3コンストラクト。
- 前記単離抗LAG‐3コンストラクトは多重特異性である、請求項18または19に記載の単離抗LAG‐3コンストラクト。
- 前記第1の抗原結合部分および前記第2の抗原結合部分はペプチドリンカーを介して互いに融合している、請求項18から20のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記ペプチドリンカーは、SEQ ID NO:352〜353および366〜372のいずれか1つのアミノ酸配列を含む、請求項21に記載の単離抗LAG‐3コンストラクト。
- 前記第2の抗原結合部分は、2つの重鎖および2つの軽鎖から成る完全長抗体を含む、請求項18から22のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記完全長抗体のFc断片は、ヒトIgG1(hIgG1)Fc、エフェクターレスhIgG1 Fc、hIgG4 Fc、またはhIgG4 Fc(S228P)である、請求項23に記載の単離抗LAG‐3コンストラクト。
- LAG‐3を特異的に認識する前記sdAbのN末端は、前記完全長抗体の重鎖のC末端に融合している、請求項23または24に記載の単離抗LAG‐3コンストラクト。
- LAG‐3を特異的に認識する前記sdAbのC末端は、前記完全長抗体の重鎖のN末端に融合している、請求項23または24に記載の単離抗LAG‐3コンストラクト。
- LAG‐3を特異的に認識する前記sdAbのN末端は、前記完全長抗体の軽鎖のC末端に融合している、請求項23または24に記載の単離抗LAG‐3コンストラクト。
- LAG‐3を特異的に認識する前記sdAbのC末端は、前記完全長抗体の軽鎖のN末端に融合している、請求項23または24に記載の単離抗LAG‐3コンストラクト。
- 前記第2の抗原結合部分は、PD‐1、4‐1BB、PD‐L1、TIM‐3、TIGIT、CTLA‐4、VISTA、B7‐1、B7‐H3、CD47、OX40およびGITRから成る群から選択される免疫チェックポイント分子を特異的に認識する、請求項18から28のいずれか一項に記載の単離抗LAG‐3コンストラクト。
- 前記第2の抗原結合部分はPD‐1を特異的に認識する、請求項29に記載の単離抗LAG‐3コンストラクト。
- 前記第2の抗原結合部分は、
(i)SEQ ID NO:356のアミノ酸配列を含む重鎖のHC‐CDR1、HC‐CDR2およびHC‐CDR3、ならびに、SEQ ID NO:357のアミノ酸配列を含む軽鎖のLC‐CDR1、LC‐CDR2およびLC‐CDR3、または、
(ii)SEQ ID NO:373のアミノ酸配列を含む重鎖のHC‐CDR1、HC‐CDR2およびHC‐CDR3、ならびに、SEQ ID NO:374のアミノ酸配列を含む軽鎖のLC‐CDR1、LC‐CDR2およびLC‐CDR3
を含む、請求項30に記載の単離抗LAG‐3コンストラクト。 - 前記第2の抗原結合部分は、
(i)SEQ ID NO:356のアミノ酸配列を含む重鎖、および、SEQ ID NO:357のアミノ酸配列を含む軽鎖、または、
(ii)SEQ ID NO:373のアミノ酸配列を含む重鎖、および、SEQ ID NO:374のアミノ酸配列を含む軽鎖
を含む完全長抗体である、請求項30に記載の単離抗LAG‐3コンストラクト。 - LAG‐3を特異的に認識するsdAbを含む単離抗LAG‐3コンストラクトであって、前記sdAbは、SEQ ID NO:274〜311のいずれか1つのCDR1、CDR2およびCDR3を含む、単離抗LAG‐3コンストラクト。
- 請求項1から33のいずれか一項に記載の単離抗LAG‐3コンストラクトと競合してLAG‐3に特異的に結合する単離抗LAG‐3コンストラクト。
- 請求項1から34のいずれか一項に記載の単離抗LAG‐3コンストラクト、および、薬学的に許容される担体を備える医薬組成物。
- LAG‐3関連疾患を有する個体を治療する方法であって、請求項35に記載の医薬組成物の有効量を個体に投与する段階を含む方法。
- 前記LAG‐3関連疾患は癌である、請求項36に記載の方法。
- 前記癌は大腸癌である、請求項37に記載の方法。
- 前記個体はヒトである、請求項37または38に記載の方法。
- 請求項1から34のいずれか一項に記載の単離抗LAG‐3コンストラクトをコードする単離核酸。
- 請求項40に記載の単離核酸を含むベクター。
- 請求項40に記載の単離核酸、または、請求項41に記載のベクターを備える単離宿主細胞。
- 請求項1から34のいずれか一項に記載の単離抗LAG‐3コンストラクト、請求項35に記載の医薬組成物、請求項40に記載の単離核酸、請求項41に記載のベクター、または、請求項42に記載の単離宿主細胞を含むキット。
- 抗LAG‐3コンストラクトを産生する方法であって、(a)コードされた前記抗LAG‐3コンストラクトを発現するために効果的な条件下で請求項42に記載の単離宿主細胞を培養する段階と、(b)発現された前記抗LAG‐3コンストラクトを前記単離宿主細胞から取得する段階とを備える方法。
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