JP2010520204A5 - - Google Patents
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- JP2010520204A5 JP2010520204A5 JP2009551740A JP2009551740A JP2010520204A5 JP 2010520204 A5 JP2010520204 A5 JP 2010520204A5 JP 2009551740 A JP2009551740 A JP 2009551740A JP 2009551740 A JP2009551740 A JP 2009551740A JP 2010520204 A5 JP2010520204 A5 JP 2010520204A5
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- 239000008194 pharmaceutical composition Substances 0.000 claims 26
- 108090001123 antibodies Proteins 0.000 claims 21
- 102000004965 antibodies Human genes 0.000 claims 21
- 230000004044 response Effects 0.000 claims 6
- 230000011664 signaling Effects 0.000 claims 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 5
- 102000009465 Growth Factor Receptors Human genes 0.000 claims 5
- 108010009202 Growth Factor Receptors Proteins 0.000 claims 5
- 102000038595 IGF Type 1 Receptor Human genes 0.000 claims 5
- 108010031794 IGF Type 1 Receptor Proteins 0.000 claims 5
- 239000003112 inhibitor Substances 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 102100013180 KDR Human genes 0.000 claims 3
- -1 bcr-abl Proteins 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 101710030888 KDR Proteins 0.000 claims 2
- 102100009279 KRAS Human genes 0.000 claims 2
- 101710033922 KRAS Proteins 0.000 claims 2
- 230000036091 Metabolic activity Effects 0.000 claims 2
- 108010061219 Panitumumab Proteins 0.000 claims 2
- 102000017256 epidermal growth factor-activated receptor activity proteins Human genes 0.000 claims 2
- 108040009258 epidermal growth factor-activated receptor activity proteins Proteins 0.000 claims 2
- 230000004634 feeding behavior Effects 0.000 claims 2
- 230000002503 metabolic Effects 0.000 claims 2
- 229960001972 panitumumab Drugs 0.000 claims 2
- 229940120638 Avastin Drugs 0.000 claims 1
- 102100013105 CDK1 Human genes 0.000 claims 1
- 101700051654 CDK1 Proteins 0.000 claims 1
- 108010022830 Cetuximab Proteins 0.000 claims 1
- 102100016662 ERBB2 Human genes 0.000 claims 1
- 101700025368 ERBB2 Proteins 0.000 claims 1
- 229940082789 Erbitux Drugs 0.000 claims 1
- 229960001433 Erlotinib Drugs 0.000 claims 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N Erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N Gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims 1
- 229940080856 Gleevec Drugs 0.000 claims 1
- 229940022353 Herceptin Drugs 0.000 claims 1
- 108010026702 IMC1C11 Proteins 0.000 claims 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N Imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 1
- 206010022437 Insomnia Diseases 0.000 claims 1
- 108010001127 Insulin Receptor Proteins 0.000 claims 1
- 102000003746 Insulin Receptor Human genes 0.000 claims 1
- 229940084651 Iressa Drugs 0.000 claims 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims 1
- 206010061289 Metastatic neoplasm Diseases 0.000 claims 1
- OUSFTKFNBAZUKL-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 OUSFTKFNBAZUKL-UHFFFAOYSA-N 0.000 claims 1
- 102100016979 PRKCB Human genes 0.000 claims 1
- 101710038830 PRKCB Proteins 0.000 claims 1
- 108091000081 Phosphotransferases Proteins 0.000 claims 1
- 102000001253 Protein Kinases Human genes 0.000 claims 1
- 101700007719 RAF1 Proteins 0.000 claims 1
- WINHZLLDWRZWRT-ATVHPVEESA-N Sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 1
- 229940120982 Tarceva Drugs 0.000 claims 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims 1
- 108091007928 VEGF receptors Proteins 0.000 claims 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N Vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 claims 1
- 101700069422 ZHX2 Proteins 0.000 claims 1
- 230000003213 activating Effects 0.000 claims 1
- 229960005395 cetuximab Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 235000021271 drinking Nutrition 0.000 claims 1
- 230000035622 drinking Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 229960005167 everolimus Drugs 0.000 claims 1
- 229960002584 gefitinib Drugs 0.000 claims 1
- 229960002411 imatinib Drugs 0.000 claims 1
- 101710030209 lin-45 Proteins 0.000 claims 1
- 230000001394 metastastic Effects 0.000 claims 1
- 230000029058 respiratory gaseous exchange Effects 0.000 claims 1
- 102220243160 rs121917743 Human genes 0.000 claims 1
- 102220288537 rs762053276 Human genes 0.000 claims 1
- 230000000152 swallowing Effects 0.000 claims 1
- 229960000235 temsirolimus Drugs 0.000 claims 1
Claims (21)
- IGF−1Rシグナル伝達阻害剤を含むヒト被験体において結腸直腸腫瘍を治療するための薬学的組成物であって、
ここにおいて、ヒト被験体が、EGFR、HER−2、bcr−abl、VEGFR、Kit、raf、mTOR、CDK1/2、VEGFR2、PKCβ、Mek、およびKDRからなる群から選択される増殖因子受容体チロシンキナーゼをターゲットとする剤でも治療され、そして、
上記薬学的組成物を投与された被験体が、以下の応答:
a. RECIST基準による安定な疾患、
b. RECIST基準による部分応答、
c. RECIST基準による完全応答、
d. PETによってアッセイされるような、前記腫瘍における代謝活性の減少、
e. PETによってアッセイされるような、前記腫瘍における代謝活性の排除、および
f. 前記腫瘍に関連する症状の改善
の少なくとも1つを示す、
結腸直腸腫瘍を治療するための薬学的組成物。 - 増殖因子受容体チロシンキナーゼがEGFRである、請求項1に記載の薬学的組成物。
- 前記被験体が、前記薬学的組成物の投与の6ヶ月以内に、前記応答を示す、請求項1又は2に記載の薬学的組成物。
- 前記被験体が、前記薬学的組成物の投与の60日以内に、前記応答を示す、請求項1ないし3のいずれか1項に記載の薬学的組成物。
- 前記症状が、
i)不規則であるか、努力を伴うか、または困難な呼吸;
ii)疼痛;
iii)睡眠困難;並びに
iv)摂食、飲用、または嚥下の困難
からなるグループから選択される症状である、請求項1ないし4のいずれか1項に記載の薬学的組成物。 - 少なくとも1用量で前記被験体に投与される、請求項1ないし5のいずれか1項に記載の薬学的組成物。
- 少なくとも前記応答が達成されるまで、断続的用量で前記被験体に投与される、請求項1ないし6のいずれか1項に記載の薬学的組成物。
- IGF−1Rシグナル伝達の前記阻害剤が:
a. IGF−1受容体に特異的に結合する抗体、
b. IGF−1受容体に特異的に結合する抗体断片、及び
c. IGF−1受容体に特異的に結合する抗体誘導体、
からなる群より選択される、請求項1ないし7のいずれか1項に記載の薬学的組成物。 - 前記抗体が:L1H1(配列番号2、配列番号106)、L2H2(配列番号4、配列番号108)、L3H3(配列番号6、配列番号110)、L4H4(配列番号8、配列番号112)、L5H5(配列番号10、配列番号114)、L6H6(配列番号12、配列番号116)、L7H7(配列番号14、配列番号118)、L8H8(配列番号16、配列番号120)、L9H9(配列番号18、配列番号122)、L10H10(配列番号20、配列番号124)、L11H11(配列番号22、配列番号126)、L12H12(配列番号24、配列番号128)、L13H13(配列番号26、配列番号130)、L14H14(配列番号28、配列番号132)、L15H15(配列番号30、配列番号134)、L16H16(配列番号32、配列番号136)、L17H17(配列番号34、配列番号138)、L18H18(配列番号36、配列番号140)、L19H19(配列番号38、配列番号142)、L20H20(配列番号40、配列番号144)、L21H21(配列番号42、配列番号146)、L22H22(配列番号44、配列番号148)、L23H23(配列番号46、配列番号150)、L24H24(配列番号48、配列番号152)、L25H25(配列番号50、配列番号154)、L26H26(配列番号52、配列番号156)、L27H27(配列番号54、配列番号158)、L28H28(配列番号56、配列番号160)、L29H29(配列番号58、配列番号162)、L30H30(配列番号60、配列番号164)、L31H31(配列番号62、配列番号166)、L32H32(配列番号64、配列番号168)、L33H33(配列番号66、配列番号170)、L34H34(配列番号68、配列番号172)、L35H35(配列番号70、配列番号174)、L36H36(配列番号72、配列番号176)、L37H37(配列番号74、配列番号178)、L38H38(配列番号76、配列番号180)、L39H39(配列番号78、配列番号182)、L40H40(配列番号80、配列番号184)、L41H41(配列番号82、配列番号186)、L42H42(配列番号84、配列番号188)、L43H43、(配列番号86、配列番号190)L44H44(配列番号88、配列番号192)、L45H45(配列番号90、配列番号194)、L46H46、(配列番号92、配列番号196)L47H47(配列番号94、配列番号198)、L48H48(配列番号96、配列番号200)、L49H49(配列番号98、配列番号202)、L50H50(配列番号100、配列番号204)、L51H51(配列番号102、配列番号206)及びL52H52(配列番号104、配列番号208)からなる組み合わせの群より選択される、軽鎖可変ドメインおよび重鎖可変ドメインの組み合わせを含む抗体;抗体IMC−A12、ヒト化抗体EM164、抗体huEM164 v1.0、抗体huEM164 v1.1、抗体huEM164 v1.2、抗体huEM164 v1.3、抗体CP−751,871、抗体7C10、ヒト化抗体7C10バージョン1、ヒト化抗体7C10バージョン2、並びに、ヒト化抗体7C10バージョン3、
からなる群より選択される、請求項8に記載の薬学的組成物。 - 前記抗体が、IGF−1受容体のL2ドメイン、FnIII 1ドメイン、FnIII 2ドメイン、あるいは、L1ドメイン及びFnIII 1ドメイン、に結合する、請求項8又は9のいずれか1項に記載の薬学的組成物。
- 前記抗体が、IGF−1Rへの結合に関して、抗体L16/H16(配列番号32/配列番号136)と競合する、請求項8ないし10のいずれか1項に記載の薬学的組成物。
- 前記抗体が、軽鎖L16(配列番号32)に少なくとも90%同一である軽鎖可変ドメインおよび重鎖H16(配列番号136)に少なくとも90%同一である重鎖可変ドメインを含む、請求項8ないし11のいずれか1項に記載の薬学的組成物。
- 前記抗体が、L16(配列番号32)の軽鎖可変ドメインおよびH16(配列番号136)の重鎖可変ドメインを含む、請求項8ないし12のいずれか1項に記載の薬学的組成物。
- 前記結腸直腸腫瘍が転移性腫瘍である、請求項1ないし13のいずれか1項に記載の薬学的組成物。
- IGF−1Rシグナル伝達の前記阻害剤が、インスリン受容体シグナル伝達を阻害するよりも少なくとも10倍多く、IGF−1受容体シグナル伝達を阻害する、請求項1ないし14のいずれか1項に記載の薬学的組成物。
- 前記増殖因子受容体チロシンキナーゼをターゲットとする剤が、パニツムマブ、セツキシマブ、HERCEPTINTM、GLEEVECTM、IRESSATM、ERBITUXTM、AVASTINTM、PTK787、SU11248、TARCEVATM、43−9006、CCI−779、RAD001、BMS−387032、IMC−1C11、LY333531、PD 184352、2C4およびGW2016からなる群から選択される、請求項1ないし15のいずれか1項に記載の薬学的組成物。
- 前記増殖因子受容体チロシンキナーゼをターゲットとする剤が、パニツムマブである請求項16に記載の薬学的組成物。
- 6ないし12mg/kgのIGF−1Rシグナル伝達阻害剤が、2週間間隔で投与される、請求項1ないし17のいずれか1項に記載の薬学的組成物。
- 6mg/kgの増殖因子受容体チロシンキナーゼをターゲットとする剤が、2週間間隔で投与される、請求項1ないし18のいずれか1項に記載の薬学的組成物。
- 結腸直腸腫瘍が野生型KRASアレルを有する、請求項1−19のいずれか1項に記載の薬学的組成物。
- 結腸直腸腫瘍が活性化突然変異KRASアレルを有する、請求項1−19のいずれか1項に記載の薬学的組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US90453807P | 2007-03-02 | 2007-03-02 | |
PCT/US2008/002710 WO2008108986A2 (en) | 2007-03-02 | 2008-02-29 | Methods and compositions for treating tumor diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2010520204A JP2010520204A (ja) | 2010-06-10 |
JP2010520204A5 true JP2010520204A5 (ja) | 2011-04-14 |
Family
ID=39683874
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009551740A Pending JP2010520204A (ja) | 2007-03-02 | 2008-02-29 | 腫瘍疾患を治療するための方法および組成物 |
Country Status (8)
Country | Link |
---|---|
US (2) | US20100166747A1 (ja) |
EP (1) | EP2129397B1 (ja) |
JP (1) | JP2010520204A (ja) |
AU (1) | AU2008223541B2 (ja) |
CA (1) | CA2679548C (ja) |
ES (1) | ES2707551T3 (ja) |
MX (1) | MX2009009379A (ja) |
WO (1) | WO2008108986A2 (ja) |
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