Patent JP-2008515773-A (JP)
Title: 新規な抗ｉｇｆ−ｉｒ抗体及びその使用
IPC: C07K16/28
Filed: 2005-07-27
Abstract: 本発明は、ヒトインスリン様成長因子Ｉ受容体ＩＧＦ−ＩＲと特異的に結合することができ、且つ／又はそのＩＧＦ−ＩＲのチロシンキナーゼ活性を特異的に阻害することができる新規な抗体、特にマウスのモノクローナル抗体、キメラモノクローナル抗体及びヒト化モノクローナル抗体、並びにこれらの抗体をコードするアミノ酸配列及び核酸配列に関する。本発明はまた、ＩＧＦ−ＩＲを過剰発現する癌又はその受容体の過剰発現に関連した病状の予防的処置及び／又は治療的処置を目的とした薬剤としての、並びにＩＧＦ−ＩＲの過剰発現に関連した疾患の診断のための方法又はキットにおけるこれら抗体の使用を含む。本発明は最後に、このような抗体と、抗ＥＧＦＲ抗体、及び／又は抗ＶＥＧＦ抗体、及び／又は腫瘍進行もしくは転移に関与する他の成長因子に対する抗体、及び／又は化合物、及び／又は抗癌剤、又は毒素と共役した物質とを組み合わせて含む、製品及び／又は組成物、並びに特定の癌の予防及び／又は治療のためのその使用に関する。     【配列表】                          SEQUENCE LISTING     <110> PIERRE FABRE MEDICAMENT   <120> Novel anti-IGF-IR antibodies and uses thereof   <130> D22514   <140>  PCT/IB2005/002619 <141>  2005-07-27   <150> US 60/591 932 <151> 2004-07-29   <150> FR 04/08379 <151> 2004-07-29   <160> 26   <170> PatentIn version 3.1   <210> 1 <211> 16 <212> PRT <213> Mus musculus   <400> 1   Arg Ser Ser Gln Thr Ile Ile His Ser Asn Gly Asn Thr Tyr Leu Glu  1               5                   10                  15     <210> 2 <211> 7 <212> PRT <213> Mus musculus   <400> 2   Lys Val Ser Asn Arg Phe Ser  1               5      <210> 3 <211> 10 <212> PRT <213> Mus musculus   <400> 3   Phe Gln Gly Ser His Val Pro Tyr Thr Phe  1               5                   10     <210> 4 <211> 5 <212> PRT <213> Mus musculus   <400> 4   Asp Tyr Trp Met Asn  1               5      <210> 5 <211> 17 <212> PRT <213> Mus musculus   <400> 5   Leu Ile His Pro Ser Asp Ser Glu Thr Arg Leu Asp Gln Asn Phe Tyr  1               5                   10                  15   Asp     <210> 6 <211> 13 <212> PRT <213> Mus musculus   <400> 6   Ser Val Ile Tyr Tyr Gly Asn Tyr Arg Trp Tyr Phe Asp 1               5                   10     <210> 7 <211> 11 <212> PRT <213> Mus musculus   <400> 7   Lys Ala Ser Gln Asn Val Val Thr Asn Val Ala  1               5                   10     <210> 8 <211> 7 <212> PRT <213> Mus musculus   <400> 8   Ser Ala Ser Tyr Arg Tyr Ser  1               5      <210> 9 <211> 9 <212> PRT <213> Mus musculus   <400> 9   His Gln Tyr Asn Asn Phe Pro Leu Thr  1               5      <210> 10 <211> 5 <212> PRT <213> Mus musculus   <400> 10   Glu Tyr Gly Val Ser  1               5      <210> 11 <211> 16 <212> PRT <213> Mus musculus   <400> 11   Val Ile Trp Gly Gly Arg Asp Thr Tyr Tyr His Ser Pro Leu Lys Ser  1               5                   10                  15     <210> 12 <211> 6 <212> PRT <213> Mus musculus   <400> 12   His Glu Gly Met Asp Tyr  1               5      <210> 13 <211> 11 <212> PRT <213> Mus musculus   <400> 13   Ile Thr Ser Thr Asp Ile Asp Asp Asp Met Asn  1               5                   10     <210> 14 <211> 7 <212> PRT <213> Mus musculus   <400> 14   Glu Gly Asn Thr Leu Arg Pro  1               5      <210> 15 <211> 9 <212> PRT <213> Mus musculus   <400> 15   Leu Gln Ser Asp Lys Met Pro Leu Thr  1               5      <210> 16 <211> 5 <212> PRT <213> Mus musculus   <400> 16   Asn Tyr Ala Met Ser  1               5      <210> 17 <211> 16 <212> PRT <213> Mus musculus   <400> 17   Ser Ile Gly Ser Ala Gly Tyr Ile His Tyr Pro Asp Ser Val Lys Gly  1               5                   10                  15     <210> 18 <211> 9 <212> PRT <213> Mus musculus   <400> 18   Glu Gly Gly Leu Val Trp Phe Ala Tyr  1               5      <210> 19 <211> 112 <212> PRT <213> Mus musculus   <400> 19   Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly  1               5                   10                  15   Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Thr Ile Ile His Ser              20                  25                  30   Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser          35                  40                  45   Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro      50                  55                  60   Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile  65                  70                  75                  80   Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly                  85                  90                  95   Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys              100                 105                 110      <210> 20 <211> 123 <212> PRT <213> Mus musculus   <400> 20   Gln Ala Gln Leu Gln Gln Pro Gly Ala Val Leu Val Arg Pro Gly Ala  1               5                   10                  15   Ser Val Lys Leu Ser Cys Lys Ala Ser Ser Tyr Ser Phe Thr Asp Tyr              20                  25                  30   Trp Met Asn Trp Val Lys Arg Arg Pro Gly Gln Gly Leu Gln Trp Ile          35                  40                  45   Gly Leu Ile His Pro Ser Asp Ser Glu Thr Arg Leu Asp Gln Asn Phe      50                  55                  60   Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Phe Ser Ser Thr Ala Tyr  65                  70                  75                  80   Met Gln Leu Asn Ser Pro Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys                  85                  90                  95   Thr Arg Ser Val Ile Tyr Tyr Gly Asn Tyr Arg Trp Tyr Phe Asp Val              100                 105                 110    Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser          115                 120      <210> 21 <211> 107 <212> PRT <213> Mus musculus   <400> 21   Asp Ile Val Met Thr Gln Ser Gln Lys Phe Met Ser Thr Ser Val Gly  1               5                   10                  15   Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn Val Val Thr Asn              20                  25                  30   Val Ala Trp Tyr Gln His Lys Pro Gly His Ser Pro Lys Pro Leu Ile          35                  40                  45   Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp Arg Phe Thr Gly      50                  55                  60   Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Asn Val Gln Ser  65                  70                  75                  80   Glu Asp Leu Ala Glu Tyr Phe Cys His Gln Tyr Asn Asn Phe Pro Leu                  85                  90                  95   Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys              100                 105      <210> 22 <211> 114 <212> PRT <213> Mus musculus   <400> 22   Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln  1               5                   10                  15   Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Glu Tyr              20                  25                  30   Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu          35                  40                  45   Gly Val Ile Trp Gly Gly Arg Asp Thr Tyr Tyr His Ser Pro Leu Lys      50                  55                  60   Ser Arg Leu Ser Ile Thr Lys Asp Asn Ser Lys Ser Gln Val Phe Leu  65                  70                  75                  80   Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala                  85                  90                  95   Lys His Glu Gly Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val              100                 105                 110    Ser Ser        <210> 23 <211> 114 <212> PRT <213> Mus musculus   <400> 23   Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln  1               5                   10                  15   Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser Leu Asn Glu Tyr              20                  25                  30   Gly Val Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu          35                  40                  45   Gly Val Ile Trp Gly Gly Gly Asp Thr Tyr Tyr His Ser Pro Leu Lys      50                  55                  60   Ser Arg Leu Ser Ile Thr Lys Asp Asn Ser Lys Ser Gln Val Phe Leu  65                  70                  75                  80   Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Met Tyr Tyr Cys Ala                  85                  90                  95   Lys His Glu Gly Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val              100                 105                 110    Ser Ser        <210> 24 <211> 107 <212> PRT <213> Mus musculus   <400> 24   Glu Thr Thr Val Thr Gln Ser Pro Ala Ser Leu Ser Val Ala Thr Gly  1               5                   10                  15   Glu Lys Val Thr Ile Arg Cys Ile Thr Ser Thr Asp Ile Asp Asp Asp              20                  25                  30   Met Asn Trp Tyr Gln Gln Lys Pro Gly Glu Pro Pro Lys Leu Leu Ile          35                  40                  45   Ser Glu Gly Asn Thr Leu Arg Pro Gly Val Pro Ser Arg Phe Ser Ser      50                  55                  60   Ser Gly Tyr Gly Thr Asp Phe Val Leu Thr Ile Glu Asn Thr Leu Ser  65                  70                  75                  80   Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gln Ser Asp Lys Met Pro Leu                  85                  90                  95   Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys              100                 105      <210> 25 <211> 117 <212> PRT <213> Mus musculus   <400> 25   Glu Val Asn Leu Val Glu Ser Gly Gly Ile Leu Val Lys Pro Gly Gly  1               5                   10                  15   Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr              20                  25                  30   Ala Met Ser Trp Val Arg Gln Thr Pro Glu Lys Arg Leu Glu Trp Val          35                  40                  45   Ala Ser Ile Gly Ser Ala Gly Tyr Ile His Tyr Pro Asp Ser Val Lys      50                  55                  60   Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Ile Leu Tyr Leu  65                  70                  75                  80   Gln Met Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala                  85                  90                  95   Arg Glu Gly Gly Leu Val Trp Phe Ala Tyr Trp Gly Gln Gly Thr Leu              100                 105                 110    Val Thr Val Ser Ala          115    <210> 26 <211> 16 <212> PRT <213> Mus musculus   <400> 26   Val Ile Trp Gly Gly Gly Asp Thr Tyr Tyr His Ser Pro Leu Lys Ser  1               5                   10                  15