JP2023036899A - 抗体媒介性受容体シグナル伝達を増強するための組成物及び方法 - Google Patents
抗体媒介性受容体シグナル伝達を増強するための組成物及び方法 Download PDFInfo
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Abstract
Description
本発明は、概して、機能が増強された治療用抗体に関する。具体的には、本発明は、Fc領域の変異体を含むポリペプチド、及びそれを含む抗体に関する。より詳細には本発明は、ポリペプチドのFc領域における1つ以上のアミノ酸置換の結果として、エフェクター機能が変化したFc領域含有ポリペプチドに関する。
モノクローナル抗体は大きな潜在的治療能力を有し、今日の医療ポートフォリオにおいて重要な役割を果たしている。この10年間で、製薬業界における大きな流れは、がん、喘息、関節炎、及び多発性硬化症などの多くの病気の治療のための治療薬としてモノクローナル抗体(mAb)を開発することであった。
野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、残基位置228、234、235、345、409、430、440またはそれらの組み合わせにおけるアミノ酸置換を含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、前記操作されたポリペプチド。
[本発明1002]
KabatのEUインデックスによる残基位置228のアミノ酸が、プロリン(P)またはセリン(S)によって置換されている、本発明1001のポリペプチド。
[本発明1003]
KabatのEUインデックスによる残基位置234のアミノ酸が、アラニン(A)によって置換されている、本発明1001のポリペプチド。
[本発明1004]
KabatのEUインデックスによる残基位置235のアミノ酸が、アラニン(A)によって置換されている、本発明1001のポリペプチド。
[本発明1005]
KabatのEUインデックスによる残基位置345のグルタミン酸(E)が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)によって置換されている、本発明1001のポリペプチド。
[本発明1006]
KabatのEUインデックスによる残基位置409のアミノ酸が、リジン(K)またはアルギニン(R)によって置換されている、本発明1001のポリペプチド。
[本発明1007]
KabatのEUインデックスによる残基位置430のグルタミン酸(E)が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)によって置換されている、本発明1001のポリペプチド。
[本発明1008]
KabatのEUインデックスによる残基位置440のセリン(S)が、トリプトファン(W)によって置換されている、本発明1001のポリペプチド。
[本発明1009]
前記アミノ酸置換が、L234A、L235A、E345K、及びE430Gを含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、本発明1001のポリペプチド。
[本発明1010]
前記アミノ酸置換が、S228P、E345K、R409K、及びE430Gを含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、本発明1001のポリペプチド。
[本発明1011]
野生型IgG Fc領域を含むポリペプチドと比較して1つ以上のヒトFc受容体に対して低い親和性を示す、本発明1001のポリペプチド。
[本発明1012]
野生型IgG Fc領域を含むポリペプチドと比較して受容体クラスタリングの増加をさらに示す、本発明1011のポリペプチド。
[本発明1013]
ヒトIgG1、IgG2、またはIgG4のFc領域を含む、本発明1001のポリペプチド。
[本発明1014]
抗体またはFc融合タンパク質である、本発明1001のポリペプチド。
[本発明1015]
前記抗体が、単一特異性抗体、二重特異性抗体、または多重特異性抗体である、本発明1014のポリペプチド。
[本発明1016]
薬物、毒素、放射性標識、またはそれらの組み合わせとコンジュゲートしている、本発明1001のポリペプチド。
[本発明1017]
BCMA、CAIX、CCR4、PD-L1、PD-L2、PD1、グルココルチコイド誘導腫瘍壊死因子受容体(GITR)、TIGIT、重症急性呼吸器症候群(SARS)、中東呼吸器症候群(MERS)、インフルエンザ、またはフラビウイルスに特異的な抗体である、本発明1001のポリペプチド。
[本発明1018]
グルココルチコイド誘導腫瘍壊死因子受容体(GITR)に特異的な抗体である、本発明1001のポリペプチド。
[本発明1019]
CCR4に特異的な抗体である、本発明1001のポリペプチド。
[本発明1020]
野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号4に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、X7、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
[本発明1021]
X1が、セリン(S)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1022]
X2が、アラニン(A)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1023]
X3が、アラニン(A)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1024]
X4が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1025]
X5が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1026]
X6が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1027]
X7が、トリプトファン(W)を含むアミノ酸置換である、本発明1020のポリペプチド。
[本発明1028]
野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号5に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
[本発明1029]
X1が、セリン(S)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1030]
X2が、アラニン(A)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1031]
X3が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1032]
X4が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1033]
X5が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1034]
X6が、トリプトファン(W)を含むアミノ酸置換である、本発明1028のポリペプチド。
[本発明1035]
野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号6に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、X7、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
[本発明1036]
X1が、KabatのEUインデックスによる残基位置228におけるアミノ酸の置換であり、かつプロリン(P)を含む、本発明1035のポリペプチド。
[本発明1037]
X2が、アラニン(A)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1038]
X3が、アラニン(A)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1039]
X4が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1040]
X5が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1041]
X6が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1042]
X7が、トリプトファン(W)を含むアミノ酸置換である、本発明1035のポリペプチド。
[本発明1043]
表1Bに開示された可変領域アミノ酸配列、及び表3B(配列番号18、19、21、22、24)、表4B(配列番号18、19、20、22、26)、表5B(配列番号18、19、22、29、及び30)、または表6B(配列番号36、37、38、40、及び42)に開示された変異型Fc領域アミノ酸配列を含む、組換えGITR抗体。
[本発明1044]
表1Bに開示された可変領域アミノ酸配列、及び表3B(配列番号18、19、21、24)、表4B(配列番号18、19、20、26)、表5B(配列番号18、19、29、及び30)、または表6B(配列番号36、37、38、及び42)に開示された変異型Fc領域アミノ酸配列を含む、組換えCCR4抗体。
[本発明1045]
本発明1043の組換えGITR抗体を対象に投与することを含む、前記対象における腫瘍の治療方法。
[本発明1046]
本発明1044の組換えCCR4抗体を対象に投与することを含む、血液由来がんの治療方法。
[本発明1047]
前記血液由来がんが、リンパ腫または白血病である、本発明1046の方法。
[本発明1048]
細胞と該細胞上のリガンドに結合する抗体とを接触させることを含む、細胞の細胞内シグナル伝達を増強する方法であって、前記抗体が、野生型ヒトIgG Fc領域のFc変異体を含み、前記Fc変異体が、E345、E430、及び/またはS440にアミノ酸置換を含み、前記残基が、KabatのEUインデックスにしたがって番号付けされる、前記方法。
[本発明1049]
前記置換が、E430G、E430S、E430F、E430T、E345K、E345Q、E345R、E345Y、S440W、またはそれらの組み合わせを含む、本発明1048の方法。
[本発明1050]
前記置換が、E345K及びE430Gである、本発明1049の方法。
[本発明1051]
細胞と該細胞上のリガンドに結合する抗体とを接触させることを含む、細胞の受容体クラスタリングを誘導する方法であって、前記抗体が、野生型ヒトIgG Fc領域のFc変異体を含み、前記Fc変異体が、E345、E430、及び/またはS440にアミノ酸置換を含み、前記残基が、KabatのEUインデックスにしたがって番号付けされる、前記方法。
[本発明1052]
前記置換が、E430G、E430S、E430F、E430T、E345K、E345Q、E345R、E345Y、S440W、またはそれらの組み合わせを含む、本発明1051の方法。
[本発明1053]
前記置換が、E345K及びE430Gである、本発明1052の方法。
[本発明1054]
腫瘍が、固形腫瘍または液性腫瘍である、本発明1045の方法。
本発明のその他の特徴及び利点は、下記の発明を実施するための形態及び特許請求の範囲により明らかとなり、かつそれらに包含されるであろう。
1つ以上の好ましい実施形態の詳細な説明が本明細書に提供される。しかしながら、本発明は様々な形態で具体化することができることを理解されたい。したがって、本明細書に開示された詳細は、限定として解釈されるべきではなく、むしろ特許請求の範囲の基礎として、及び任意の適切な方法で本発明を使用することを当業者に教示するための代表的な基礎として解釈される。
の核酸配列を含む。
Promegaのレポーターシステムを用いてADCCアッセイを実施した。純度>99%のGITR+細胞を有する細胞集団を得るために、CHO-GITR細胞のプールを選別した。細胞を15k細胞/ウェルでプレーティングし、様々な濃度の異なるaGITR抗体と共にインキュベートした。Promega ADCCバイオアッセイエフェクター細胞を5:1のE:T比で添加し、プレートを37℃、5%CO2で6時間インキュベートした。インキュベーション後、Bio-Gloルシフェラーゼアッセイ試薬を添加し、発光シグナルをBMG PolarStartマルチラベルプレートリーダーを用いて検出した。データは、予想通り、IgG1野生型モノマー及び六量体構築物のみが顕著なADCC活性を示したことを示している。六量体化が、野生型IgG1におけるADCCの大きさを低下させるようにみえることもまた興味深い。陰性対照IgGは、特異的ADCC活性を示さなかった。
本発明をその発明を実施するための形態と共に記載してきたが、前述の説明は例示を意図したものであり、本発明の範囲を限定するものではなく、これは添付の特許請求の範囲によって定義される。他の態様、利点、及び変更は、添付の特許請求の範囲内である。
SEQUENCE LISTING
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<120> COMPOSITIONS AND METHODS FOR AUGMENTING ANTIBODY MEDIATED
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Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
165 170 175
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
180 185 190
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
195 200 205
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu
210 215 220
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
225 230 235 240
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
245 250 255
Ser Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
260 265 270
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
275 280 285
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
290 295 300
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
305 310 315 320
Ser Leu Ser Pro Gly Lys
325
<210> 3
<211> 327
<212> PRT
<213> Homo sapiens
<400> 3
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 4
<211> 330
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<220>
<221> MOD_RES
<222> (228)..(228)
<223> Lys, Gln, Arg, or Tyr
<220>
<221> MOD_RES
<222> (313)..(313)
<223> Gly, Ser, Phe, or Thr
<400> 4
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Xaa Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Xaa Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Trp Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 5
<211> 326
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<220>
<221> MOD_RES
<222> (224)..(224)
<223> Lys, Gln, Arg, or Tyr
<220>
<221> MOD_RES
<222> (309)..(309)
<223> Gly, Ser, Phe, or Thr
<400> 5
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
100 105 110
Pro Ala Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
115 120 125
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
130 135 140
Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly
145 150 155 160
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn
165 170 175
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp
180 185 190
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro
195 200 205
Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Xaa
210 215 220
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn
225 230 235 240
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
245 250 255
Ser Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
260 265 270
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg
275 280 285
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
290 295 300
Ser Val Met His Xaa Ala Leu His Asn His Tyr Thr Gln Lys Trp Leu
305 310 315 320
Ser Leu Ser Pro Gly Lys
325
<210> 6
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<220>
<221> MOD_RES
<222> (225)..(225)
<223> Lys, Gln, Arg, or Tyr
<220>
<221> MOD_RES
<222> (310)..(310)
<223> Gly, Ser, Phe, or Thr
<400> 6
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Xaa Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Xaa Ala Leu His Asn His Tyr Thr Gln Lys Trp
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
<210> 7
<211> 355
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 7
caggtgcagc tggtgcagtc tgggggaggc ttggtacagc ctggggggtc cctgagactc 60
tcctgtgcag cctctggatt cacctttagc agccatgcca tgagctgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180
gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240
ctgcaaatga acagcctgag agccgaggac acggccgtat attactgtgc gaaaatcggt 300
acggcggatg cttttgatat ctggggccaa gggaccacgg tcaccgtctc ctcag 355
<210> 8
<211> 331
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 8
cagtctgccc tgactcagcc accctcagtg tctgggaccc ccggacagag ggtcaccatc 60
tcttgttctg gaggcgtccc caacatcgga agtaatcctg taaactggta cctccaccgc 120
ccaggaacgg cccccaaact cctcatctat aatagcaatc agtggccctc aggggtccct 180
gaccgatttt ctggctccag gtctggcacc tcagcctccc tggccatcag tgggctccag 240
tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgga tggtctggtt 300
ttcggcggag ggaccaagtt gaccgtccta g 331
<210> 9
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 9
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser His
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Ile Gly Thr Ala Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr
100 105 110
Thr Val Thr Val Ser Ser
115
<210> 10
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 10
Gln Ser Ala Leu Thr Gln Pro Pro Ser Val Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Gly Val Pro Asn Ile Gly Ser Asn
20 25 30
Pro Val Asn Trp Tyr Leu His Arg Pro Gly Thr Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Asn Ser Asn Gln Trp Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Arg Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln
65 70 75 80
Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu
85 90 95
Asp Gly Leu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105 110
<210> 11
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 11
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ala Ser Ala
20 25 30
Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asn Pro Gly Asn Val Asn Thr Lys Tyr Asn Glu Lys Phe
50 55 60
Lys Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Arg Pro Leu Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 12
<211> 112
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 12
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Ile Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Met Ser Ser Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 13
<211> 285
<212> DNA
<213> Homo sapiens
<400> 13
accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 60
gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 120
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 180
tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 240
tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaa 285
<210> 14
<211> 48
<212> DNA
<213> Homo sapiens
<400> 14
gcagagccca aatcttgtga caaaactcac acatgcccac cgtgccca 48
<210> 15
<211> 330
<212> DNA
<213> Homo sapiens
<400> 15
gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 60
ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 120
cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 180
ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 240
caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 300
cccatcgaga aaaccatctc caaagccaaa 330
<210> 16
<211> 324
<212> DNA
<213> Homo sapiens
<400> 16
gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 60
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 120
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 180
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 240
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 300
ctctccctgt ctccgggtaa atga 324
<210> 17
<211> 321
<212> DNA
<213> Homo sapiens
<400> 17
ggtcagccca aggctgcccc ctcggtcact ctgttcccgc cctcctctga ggagcttcaa 60
gccaacaagg ccacactggt gtgtctcata agtgacttct acccgggagc cgtgacagtg 120
gcctggaagg cagatggcag ccccgtcaag gcgggagtgg agaccaccac accctccaaa 180
caaagcaaca acaagtacgc ggccagcagc tatctgagcc tgacgcctga gcagtggaag 240
tcccacagaa gctacagctg ccaggtcacg catgaaggga gcaccgtgga gaagacagtg 300
gcccctacag aatgttcatg a 321
<210> 18
<211> 97
<212> PRT
<213> Homo sapiens
<400> 18
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys
<210> 19
<211> 16
<212> PRT
<213> Homo sapiens
<400> 19
Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
<210> 20
<211> 110
<212> PRT
<213> Homo sapiens
<400> 20
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
100 105 110
<210> 21
<211> 107
<212> PRT
<213> Homo sapiens
<400> 21
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
1 5 10 15
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
100 105
<210> 22
<211> 106
<212> PRT
<213> Homo sapiens
<400> 22
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
1 5 10 15
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
20 25 30
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro
35 40 45
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
50 55 60
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
65 70 75 80
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
85 90 95
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
100 105
<210> 23
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 23
gcacctgaag ccgccggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 60
ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 120
cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 180
ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 240
caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 300
cccatcgaga aaaccatctc caaagccaaa 330
<210> 24
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 24
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
100 105 110
<210> 25
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 25
gggcagcccc gaaagccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 60
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 120
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 180
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 240
aacgtcttct catgctccgt gatgcatgga gctctgcaca accactacac gcagaagagc 300
ctctccctgt ctccgggtaa atga 324
<210> 26
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 26
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
1 5 10 15
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
100 105
<210> 27
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 27
gcacctgaag ccgccggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 60
ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 120
cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 180
ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 240
caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 300
cccatcgaga aaaccatctc caaagccaaa 330
<210> 28
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 28
gggcagcccc gaaagccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 60
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 120
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 180
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 240
aacgtcttct catgctccgt gatgcatgga gctctgcaca accactacac gcagaagagc 300
ctctccctgt ctccgggtaa atga 324
<210> 29
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 29
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
100 105 110
<210> 30
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 30
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
1 5 10 15
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
100 105
<210> 31
<211> 294
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 31
gctagcacca agggcccatc cgtcttcccc ctggcgccct gctccaggag cacctccgag 60
agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 120
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 180
ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacgaagacc 240
tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agtt 294
<210> 32
<211> 36
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 32
gagtccaaat atggtccccc atgcccacca tgccca 36
<210> 33
<211> 330
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 33
gcacctgagt tcctgggggg accatcagtc ttcctgttcc ccccaaaacc caaggacact 60
ctcatgatct cccggacccc tgaggtcacg tgcgtggtgg tggacgtgag ccaggaagac 120
cccgaggtcc agttcaactg gtacgtggat ggcgtggagg tgcataatgc caagacaaag 180
ccgcgggagg agcagttcaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 240
caggactggc tgaacggcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccgtcc 300
tccatcgaga aaaccatctc caaagccaaa 330
<210> 34
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 34
gggcagcccc gagagccaca ggtgtacacc ctgcccccat ccccggagga gatgaccaag 60
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 120
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 180
gacggctcct tcttcctcta cagcaagcta accgtggaca agagcaggtg gcaggagggg 240
aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagagc 300
ctctccctgt ctctgggtaa atga 324
<210> 35
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 35
ggtcagccca aggctgcccc ctcggtcact ctgttcccgc cctcctctga ggagcttcaa 60
gccaacaagg ccacactggt gtgtctcata agtgacttct acccgggagc cgtgacagtg 120
gcctggaagg cagatggcag ccccgtcaag gcgggagtgg agaccaccac accctccaaa 180
caaagcaaca acaagtacgc ggccagcagc tatctgagcc tgacgcctga gcagtggaag 240
tcccacagaa gctacagctg ccaggtcacg catgaaggga gcaccgtgga gaagacagtg 300
gcccctacag aatgttcatg a 321
<210> 36
<211> 98
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 36
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val
<210> 37
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 37
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro
1 5 10
<210> 38
<211> 110
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 38
Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys
100 105 110
<210> 39
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 39
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Pro Glu
1 5 10 15
Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
100 105
<210> 40
<211> 106
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 40
Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser
1 5 10 15
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
20 25 30
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro
35 40 45
Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn
50 55 60
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
65 70 75 80
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
85 90 95
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
100 105
<210> 41
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 41
gggcagcccc gaaagccaca ggtgtacacc ctgcccccat ccccggagga gatgaccaag 60
aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag 120
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 180
gacggctcct tcttcctcta cagcaagcta accgtggaca agagcaggtg gcaggagggg 240
aatgtcttct catgctccgt gatgcatgga gctctgcaca accactacac acagaagagc 300
ctctccctgt ctctgggtaa atga 324
<210> 42
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 42
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Pro Glu
1 5 10 15
Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
100 105
<210> 43
<211> 324
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<400> 43
cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct 60
ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag 120
tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac 180
agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag 240
aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag 300
agcttcaaca ggggagagtg ttga 324
<210> 44
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 44
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
1 5 10 15
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
20 25 30
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
35 40 45
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
65 70 75 80
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
85 90 95
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 45
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 45
Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser
20 25
<210> 46
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 46
Gly Phe Thr Phe Ser Ser His Ala
1 5
<210> 47
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 47
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
1 5 10 15
Ala
<210> 48
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 48
Ile Ser Gly Ser Gly Gly Ser Thr
1 5
<210> 49
<211> 38
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 49
Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
1 5 10 15
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys
35
<210> 50
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 50
Ala Lys Ile Gly Thr Ala Asp Ala Phe Asp Ile
1 5 10
<210> 51
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 51
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 52
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 52
Gln Ser Ala Leu Thr Gln Pro Pro Ser Val Ser Gly Thr Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Gly
20 25
<210> 53
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 53
Val Pro Asn Ile Gly Ser Asn Pro
1 5
<210> 54
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 54
Val Asn Trp Tyr Leu His Arg Pro Gly Thr Ala Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 55
<211> 36
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 55
Gln Trp Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Arg Ser Gly
1 5 10 15
Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala
20 25 30
Asp Tyr Tyr Cys
35
<210> 56
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 56
Ala Ala Trp Asp Asp Ser Leu Asp Gly Leu Val
1 5 10
<210> 57
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 57
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
1 5 10
<210> 58
<211> 25
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 58
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser
20 25
<210> 59
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 59
Gly Tyr Thr Phe Ala Ser Ala Trp
1 5
<210> 60
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 60
Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly
1 5 10 15
Trp
<210> 61
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 61
Ile Asn Pro Gly Asn Val Asn Thr
1 5
<210> 62
<211> 40
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 62
Lys Tyr Asn Glu Lys Phe Lys Gly Arg Ala Thr Leu Thr Val Asp Thr
1 5 10 15
Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys Ala Arg
35 40
<210> 63
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 63
Ser Thr Tyr Tyr Arg Pro Leu Asp Tyr
1 5
<210> 64
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 64
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 65
<211> 26
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 65
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser
20 25
<210> 66
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 66
Gln Ser Ile Leu Tyr Ser Ser Asn Gln Lys Asn Tyr
1 5 10
<210> 67
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 67
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile
1 5 10 15
Tyr
<210> 68
<211> 6
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 68
Trp Ala Ser Thr Arg Glu
1 5
<210> 69
<211> 33
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 69
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
1 5 10 15
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
20 25 30
Cys
<210> 70
<211> 8
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 70
His Gln Tyr Met Ser Ser Tyr Thr
1 5
<210> 71
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
peptide
<400> 71
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
1 5 10
<210> 72
<211> 1005
<212> DNA
<213> Homo sapiens
<220>
<221> CDS
<222> (1)..(993)
<400> 72
cta gct agc acc aag ggc cca tcg gtc ttc ccc ctg gca ccc tcc tcc 48
Leu Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
1 5 10 15
aag agc acc tct ggg ggc aca gcg gcc ctg ggc tgc ctg gtc aag gac 96
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
20 25 30
tac ttc ccc gaa ccg gtg acg gtg tcg tgg aac tca ggc gcc ctg acc 144
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
35 40 45
agc ggc gtg cac acc ttc ccg gct gtc cta cag tcc tca gga ctc tac 192
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
50 55 60
tcc ctc agc agc gtg gtg acc gtg ccc tcc agc agc ttg ggc acc cag 240
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
65 70 75 80
acc tac atc tgc aac gtg aat cac aag ccc agc aac acc aag gtg gac 288
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
85 90 95
aag aaa gca gag ccc aaa tct tgt gac aaa act cac aca tgc cca ccg 336
Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
100 105 110
tgc cca gca cct gaa ctc ctg ggg gga ccg tca gtc ttc ctc ttc ccc 384
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro
115 120 125
cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca 432
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
130 135 140
tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac 480
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
145 150 155 160
tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg 528
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
165 170 175
gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc 576
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
180 185 190
ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc 624
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
195 200 205
aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa 672
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
210 215 220
ggg cag ccc cga aag cca cag gtg tac acc ctg ccc cca tcc cgg gat 720
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
225 230 235 240
gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc 768
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
245 250 255
tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag 816
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
260 265 270
aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc 864
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
275 280 285
ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg 912
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
290 295 300
aac gtc ttc tca tgc tcc gtg atg cat gga gct ctg cac aac cac tac 960
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
305 310 315 320
acg cag aag agc ctc tcc ctg tct ccg ggt aaa tgaggatccg cg 1005
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 73
<211> 331
<212> PRT
<213> Homo sapiens
<400> 73
Leu Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
1 5 10 15
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
20 25 30
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
35 40 45
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
50 55 60
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
65 70 75 80
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
85 90 95
Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
100 105 110
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro
115 120 125
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
130 135 140
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
145 150 155 160
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
165 170 175
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
180 185 190
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
195 200 205
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
210 215 220
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
225 230 235 240
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
245 250 255
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
260 265 270
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
275 280 285
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
290 295 300
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
305 310 315 320
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 74
<211> 1005
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<220>
<221> CDS
<222> (1)..(993)
<400> 74
cta gct agc acc aag ggc cca tcg gtc ttc ccc ctg gca ccc tcc tcc 48
Leu Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
1 5 10 15
aag agc acc tct ggg ggc aca gcg gcc ctg ggc tgc ctg gtc aag gac 96
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
20 25 30
tac ttc ccc gaa ccg gtg acg gtg tcg tgg aac tca ggc gcc ctg acc 144
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
35 40 45
agc ggc gtg cac acc ttc ccg gct gtc cta cag tcc tca gga ctc tac 192
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
50 55 60
tcc ctc agc agc gtg gtg acc gtg ccc tcc agc agc ttg ggc acc cag 240
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
65 70 75 80
acc tac atc tgc aac gtg aat cac aag ccc agc aac acc aag gtg gac 288
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
85 90 95
aag aaa gca gag ccc aaa tct tgt gac aaa act cac aca tgc cca ccg 336
Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
100 105 110
tgc cca gca cct gaa gcc gcc ggg gga ccg tca gtc ttc ctc ttc ccc 384
Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro
115 120 125
cca aaa ccc aag gac acc ctc atg atc tcc cgg acc cct gag gtc aca 432
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
130 135 140
tgc gtg gtg gtg gac gtg agc cac gaa gac cct gag gtc aag ttc aac 480
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
145 150 155 160
tgg tac gtg gac ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg 528
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
165 170 175
gag gag cag tac aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc 576
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
180 185 190
ctg cac cag gac tgg ctg aat ggc aag gag tac aag tgc aag gtc tcc 624
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
195 200 205
aac aaa gcc ctc cca gcc ccc atc gag aaa acc atc tcc aaa gcc aaa 672
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
210 215 220
ggg cag ccc cga aag cca cag gtg tac acc ctg ccc cca tcc cgg gat 720
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
225 230 235 240
gag ctg acc aag aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc 768
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
245 250 255
tat ccc agc gac atc gcc gtg gag tgg gag agc aat ggg cag ccg gag 816
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
260 265 270
aac aac tac aag acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc 864
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
275 280 285
ttc ctc tac agc aag ctc acc gtg gac aag agc agg tgg cag cag ggg 912
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
290 295 300
aac gtc ttc tca tgc tcc gtg atg cat gga gct ctg cac aac cac tac 960
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
305 310 315 320
acg cag aag agc ctc tcc ctg tct ccg ggt aaa tgaggatccg cg 1005
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 75
<211> 331
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 75
Leu Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
1 5 10 15
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
20 25 30
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
35 40 45
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
50 55 60
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
65 70 75 80
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
85 90 95
Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
100 105 110
Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro
115 120 125
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
130 135 140
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
145 150 155 160
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
165 170 175
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
180 185 190
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
195 200 205
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
210 215 220
Gly Gln Pro Arg Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
225 230 235 240
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
245 250 255
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
260 265 270
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
275 280 285
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
290 295 300
Asn Val Phe Ser Cys Ser Val Met His Gly Ala Leu His Asn His Tyr
305 310 315 320
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
325 330
<210> 76
<211> 984
<212> DNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polynucleotide
<220>
<221> CDS
<222> (1)..(981)
<400> 76
gct agc acc aag ggc cca tcc gtc ttc ccc ctg gcg ccc tgc tcc agg 48
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
agc acc tcc gag agc aca gcc gcc ctg ggc tgc ctg gtc aag gac tac 96
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
ttc ccc gaa ccg gtg acg gtg tcg tgg aac tca ggc gcc ctg acc agc 144
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
ggc gtg cac acc ttc ccg gct gtc cta cag tcc tca gga ctc tac tcc 192
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
ctc agc agc gtg gtg acc gtg ccc tcc agc agc ttg ggc acg aag acc 240
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
tac acc tgc aac gta gat cac aag ccc agc aac acc aag gtg gac aag 288
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
aga gtt gag tcc aaa tat ggt ccc cca tgc cca cca tgc cca gca cct 336
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
gag ttc ctg ggg gga cca tca gtc ttc ctg ttc ccc cca aaa ccc aag 384
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
gac act ctc atg atc tcc cgg acc cct gag gtc acg tgc gtg gtg gtg 432
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
gac gtg agc cag gaa gac ccc gag gtc cag ttc aac tgg tac gtg gat 480
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
ggc gtg gag gtg cat aat gcc aag aca aag ccg cgg gag gag cag ttc 528
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
aac agc acg tac cgt gtg gtc agc gtc ctc acc gtc ctg cac cag gac 576
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
tgg ctg aac ggc aag gag tac aag tgc aag gtc tcc aac aaa ggc ctc 624
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
ccg tcc tcc atc gag aaa acc atc tcc aaa gcc aaa ggg cag ccc cga 672
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
aag cca cag gtg tac acc ctg ccc cca tcc ccg gag gag atg acc aag 720
Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Pro Glu Glu Met Thr Lys
225 230 235 240
aac cag gtc agc ctg acc tgc ctg gtc aaa ggc ttc tac ccc agc gac 768
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
atc gcc gtg gag tgg gag agc aat ggg cag ccg gag aac aac tac aag 816
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
acc acg cct ccc gtg ctg gac tcc gac ggc tcc ttc ttc ctc tac agc 864
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
aag cta acc gtg gac aag agc agg tgg cag gag ggg aat gtc ttc tca 912
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
tgc tcc gtg atg cat gga gct ctg cac aac cac tac aca cag aag agc 960
Cys Ser Val Met His Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
ctc tcc ctg tct ctg ggt aaa tga 984
Leu Ser Leu Ser Leu Gly Lys
325
<210> 77
<211> 327
<212> PRT
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
polypeptide
<400> 77
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Lys Pro Gln Val Tyr Thr Leu Pro Pro Ser Pro Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Gly Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys
325
Claims (54)
- 野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、残基位置228、234、235、345、409、430、440またはそれらの組み合わせにおけるアミノ酸置換を含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、前記操作されたポリペプチド。
- KabatのEUインデックスによる残基位置228のアミノ酸が、プロリン(P)またはセリン(S)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置234のアミノ酸が、アラニン(A)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置235のアミノ酸が、アラニン(A)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置345のグルタミン酸(E)が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置409のアミノ酸が、リジン(K)またはアルギニン(R)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置430のグルタミン酸(E)が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)によって置換されている、請求項1に記載のポリペプチド。
- KabatのEUインデックスによる残基位置440のセリン(S)が、トリプトファン(W)によって置換されている、請求項1に記載のポリペプチド。
- 前記アミノ酸置換が、L234A、L235A、E345K、及びE430Gを含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、請求項1に記載のポリペプチド。
- 前記アミノ酸置換が、S228P、E345K、R409K、及びE430Gを含み、前記アミノ酸残基が、KabatのEUインデックスにしたがって番号付けされる、請求項1に記載のポリペプチド。
- 野生型IgG Fc領域を含むポリペプチドと比較して1つ以上のヒトFc受容体に対して低い親和性を示す、請求項1に記載のポリペプチド。
- 野生型IgG Fc領域を含むポリペプチドと比較して受容体クラスタリングの増加をさらに示す、請求項11に記載のポリペプチド。
- ヒトIgG1、IgG2、またはIgG4のFc領域を含む、請求項1に記載のポリペプチド。
- 抗体またはFc融合タンパク質である、請求項1に記載のポリペプチド。
- 前記抗体が、単一特異性抗体、二重特異性抗体、または多重特異性抗体である、請求項14に記載のポリペプチド。
- 薬物、毒素、放射性標識、またはそれらの組み合わせとコンジュゲートしている、請求項1に記載のポリペプチド。
- BCMA、CAIX、CCR4、PD-L1、PD-L2、PD1、グルココルチコイド誘導腫瘍壊死因子受容体(GITR)、TIGIT、重症急性呼吸器症候群(SARS)、中東呼吸器症候群(MERS)、インフルエンザ、またはフラビウイルスに特異的な抗体である、請求項1に記載のポリペプチド。
- グルココルチコイド誘導腫瘍壊死因子受容体(GITR)に特異的な抗体である、請求項1に記載のポリペプチド。
- CCR4に特異的な抗体である、請求項1に記載のポリペプチド。
- 野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号4に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、X7、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
- X1が、セリン(S)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X2が、アラニン(A)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X3が、アラニン(A)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X4が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X5が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X6が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- X7が、トリプトファン(W)を含むアミノ酸置換である、請求項20に記載のポリペプチド。
- 野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号5に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
- X1が、セリン(S)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- X2が、アラニン(A)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- X3が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- X4が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- X5が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- X6が、トリプトファン(W)を含むアミノ酸置換である、請求項28に記載のポリペプチド。
- 野生型ヒトIgG Fc領域のFc変異体を含む操作されたポリペプチドであって、前記Fc変異体が、配列番号6に対して少なくとも90%の同一性を含むアミノ酸配列を含み、アミノ酸置換が、X1、X2、X3、X4、X5、X6、X7、またはそれらの組み合わせにおいて起こる、前記操作されたポリペプチド。
- X1が、KabatのEUインデックスによる残基位置228におけるアミノ酸の置換であり、かつプロリン(P)を含む、請求項35に記載のポリペプチド。
- X2が、アラニン(A)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- X3が、アラニン(A)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- X4が、リジン(K)、グルタミン(Q)、アルギニン(R)、またはチロシン(Y)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- X5が、リジン(K)またはアルギニン(R)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- X6が、グリシン(G)、セリン(S)、フェニルアラニン(F)、またはトレオニン(T)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- X7が、トリプトファン(W)を含むアミノ酸置換である、請求項35に記載のポリペプチド。
- 表1Bに開示された可変領域アミノ酸配列、及び表3B(配列番号18、19、21、22、24)、表4B(配列番号18、19、20、22、26)、表5B(配列番号18、19、22、29、及び30)、または表6B(配列番号36、37、38、40、及び42)に開示された変異型Fc領域アミノ酸配列を含む、組換えGITR抗体。
- 表1Bに開示された可変領域アミノ酸配列、及び表3B(配列番号18、19、21、24)、表4B(配列番号18、19、20、26)、表5B(配列番号18、19、29、及び30)、または表6B(配列番号36、37、38、及び42)に開示された変異型Fc領域アミノ酸配列を含む、組換えCCR4抗体。
- 請求項43に記載の組換えGITR抗体を対象に投与することを含む、前記対象における腫瘍の治療方法。
- 請求項44に記載の組換えCCR4抗体を対象に投与することを含む、血液由来がんの治療方法。
- 前記血液由来がんが、リンパ腫または白血病である、請求項46に記載の方法。
- 細胞と該細胞上のリガンドに結合する抗体とを接触させることを含む、細胞の細胞内シグナル伝達を増強する方法であって、前記抗体が、野生型ヒトIgG Fc領域のFc変異体を含み、前記Fc変異体が、E345、E430、及び/またはS440にアミノ酸置換を含み、前記残基が、KabatのEUインデックスにしたがって番号付けされる、前記方法。
- 前記置換が、E430G、E430S、E430F、E430T、E345K、E345Q、E345R、E345Y、S440W、またはそれらの組み合わせを含む、請求項48に記載の方法。
- 前記置換が、E345K及びE430Gである、請求項49に記載の方法。
- 細胞と該細胞上のリガンドに結合する抗体とを接触させることを含む、細胞の受容体クラスタリングを誘導する方法であって、前記抗体が、野生型ヒトIgG Fc領域のFc変異体を含み、前記Fc変異体が、E345、E430、及び/またはS440にアミノ酸置換を含み、前記残基が、KabatのEUインデックスにしたがって番号付けされる、前記方法。
- 前記置換が、E430G、E430S、E430F、E430T、E345K、E345Q、E345R、E345Y、S440W、またはそれらの組み合わせを含む、請求項51に記載の方法。
- 前記置換が、E345K及びE430Gである、請求項52に記載の方法。
- 腫瘍が、固形腫瘍または液性腫瘍である、請求項45に記載の方法。
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SG11202100252SA (en) | 2018-07-19 | 2021-02-25 | Regeneron Pharma | BISPECIFIC ANTI-BCMA x ANTI-CD3 ANTIBODIES AND USES THEREOF |
TW202140553A (zh) | 2020-01-13 | 2021-11-01 | 美商威特拉公司 | C5ar1抗體分子及其用途 |
TW202246331A (zh) | 2021-01-13 | 2022-12-01 | 美商威特拉公司 | 人源化補體5a受體1抗體及其使用方法 |
WO2022241182A1 (en) * | 2021-05-13 | 2022-11-17 | Arizona Board Of Regents On Behalf Of Arizona State University | A plant produced anti-egfr mabs with specific glycosylation to improve the efficacy against cancer |
CN115873126A (zh) * | 2021-11-26 | 2023-03-31 | 深圳科兴药业有限公司 | 人生长激素融合蛋白及其制备和用途 |
WO2024039670A1 (en) | 2022-08-15 | 2024-02-22 | Dana-Farber Cancer Institute, Inc. | Antibodies against cldn4 and methods of use thereof |
WO2024039672A2 (en) | 2022-08-15 | 2024-02-22 | Dana-Farber Cancer Institute, Inc. | Antibodies against msln and methods of use thereof |
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US5912224A (en) * | 1996-02-22 | 1999-06-15 | The General Hospital Corporation | Methods and compositions for enhancing cellular response to TGF-β ligands |
AU2003217912A1 (en) * | 2002-03-01 | 2003-09-16 | Xencor | Antibody optimization |
AU2015200990B2 (en) * | 2009-03-20 | 2016-07-21 | Laboratoire Français Du Fractionnement Et Des Biotechnologies | Optimized Fc variants |
EP2869845B1 (en) * | 2012-07-06 | 2019-08-28 | Genmab B.V. | Dimeric protein with triple mutations |
AU2013372331A1 (en) * | 2013-01-10 | 2015-07-23 | Genmab B.V. | Human IgG1 Fc region variants and uses thereof |
EP2953972B1 (en) * | 2013-02-05 | 2020-07-08 | EngMab Sàrl | Method for the selection of antibodies against bcma |
SI3189081T1 (sl) * | 2014-09-05 | 2020-07-31 | Janssen Pharmaceutica Nv | Sredstva, ki se vežejo na CD123 in njihove uporabe |
LT3215528T (lt) * | 2014-11-06 | 2019-10-25 | Hoffmann La Roche | Fc srities variantai su modifikuota fcrn jungtimi ir naudojimo būdai |
JP2018510339A (ja) * | 2015-03-05 | 2018-04-12 | ユーシービー バイオファルマ エスピーアールエル | 重合体Fcタンパク質及びその機能的特徴を改変するためのスクリーニング方法 |
MX2017012805A (es) * | 2015-04-07 | 2018-04-11 | Genentech Inc | Complejo de unión a antígenos con actividad agonista y métodos de uso. |
JP7269167B2 (ja) * | 2016-10-14 | 2023-05-08 | デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド | モジュラー四価二重特異性抗体プラットフォーム |
CN110461868A (zh) * | 2016-11-01 | 2019-11-15 | 根马布私人有限公司 | 多肽变体及其用途 |
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CN110520158A (zh) | 2019-11-29 |
US20220213206A1 (en) | 2022-07-07 |
JP7231549B2 (ja) | 2023-03-01 |
WO2018145075A1 (en) | 2018-08-09 |
EP3576793A4 (en) | 2021-03-31 |
JP2020505054A (ja) | 2020-02-20 |
CA3049689A1 (en) | 2018-08-09 |
AU2018215673A1 (en) | 2019-07-25 |
EP3576793A1 (en) | 2019-12-11 |
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