JP2012530496A5 - - Google Patents
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- JP2012530496A5 JP2012530496A5 JP2012516307A JP2012516307A JP2012530496A5 JP 2012530496 A5 JP2012530496 A5 JP 2012530496A5 JP 2012516307 A JP2012516307 A JP 2012516307A JP 2012516307 A JP2012516307 A JP 2012516307A JP 2012530496 A5 JP2012530496 A5 JP 2012530496A5
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- 108010045030 monoclonal antibodies Proteins 0.000 claims 17
- 102000005614 monoclonal antibodies Human genes 0.000 claims 17
- 230000000875 corresponding Effects 0.000 claims 9
- 230000035772 mutation Effects 0.000 claims 8
- 238000006467 substitution reaction Methods 0.000 claims 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 102000004965 antibodies Human genes 0.000 claims 5
- 108090001123 antibodies Proteins 0.000 claims 5
- 239000000611 antibody drug conjugate Substances 0.000 claims 5
- 108091008116 antibody drug conjugates Proteins 0.000 claims 5
- 102220250290 rs1554074673 Human genes 0.000 claims 4
- 108010005144 Bevacizumab Proteins 0.000 claims 3
- 102220398847 METTL15 H97E Human genes 0.000 claims 3
- 206010061289 Metastatic neoplasm Diseases 0.000 claims 3
- 108010062724 Ranibizumab Proteins 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000001394 metastastic Effects 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 102220344151 rs1287146448 Human genes 0.000 claims 3
- 102200058908 ANG K64Q Human genes 0.000 claims 2
- 206010021425 Immune system disease Diseases 0.000 claims 2
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims 2
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims 2
- 229920001850 Nucleic acid sequence Polymers 0.000 claims 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 claims 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 206010064930 Age-related macular degeneration Diseases 0.000 claims 1
- 206010004161 Basedow's disease Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 206010055114 Colon cancer metastatic Diseases 0.000 claims 1
- 102100014838 FCGRT Human genes 0.000 claims 1
- 101710003435 FCGRT Proteins 0.000 claims 1
- 208000003807 Graves Disease Diseases 0.000 claims 1
- 201000004779 Graves' disease Diseases 0.000 claims 1
- 102200092453 HEPH Y98F Human genes 0.000 claims 1
- 102200034855 LIMCH1 Y53F Human genes 0.000 claims 1
- 102220442983 MTR K64S Human genes 0.000 claims 1
- 208000002780 Macular Degeneration Diseases 0.000 claims 1
- 206010038038 Rectal cancer Diseases 0.000 claims 1
- 206010039073 Rheumatoid arthritis Diseases 0.000 claims 1
- 229960000070 antineoplastic Monoclonal antibodies Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000005259 measurement Methods 0.000 claims 1
- 229960000060 monoclonal antibodies Drugs 0.000 claims 1
- 201000001275 rectum cancer Diseases 0.000 claims 1
- 230000000306 recurrent Effects 0.000 claims 1
Claims (17)
- モノクローナル抗体又はその結合フラグメントであって、
（ａ）ヒトＶＥＧＦに特異的に結合し；
（ｂ）ヒトＶＥＧＦへの結合に関して、
ｉ．配列番号１のＶＨ配列及び配列番号２のＶＬ配列、又は
ｉｉ．配列番号９のＶＨ配列及び配列番号１０のＶＬ配列
を含む抗体と競合し；
（ｃ）配列番号３又は配列番号１１（ＣＤＲ−Ｈ１）、配列番号４（ＣＤＲ−Ｈ２）、配列番号５又は配列番号１２（ＣＤＲ−Ｈ３）、配列番号６（ＣＤＲ−Ｌ１）、配列番号７（ＣＤＲ−Ｌ２）、及び配列番号８（ＣＤＲ−Ｌ３）と比較して合計１０個までのアミノ酸置換を有する６個のＣＤＲを含み；
（ｄ）以下：
ｉ）ＣＤＲ−Ｈ２におけるＫ６４Ｓ；
ｉｉ）ＣＤＲ−Ｈ２におけるＫ６４Ｑ；
ｉｉｉ）ＣＤＲ−Ｈ２におけるＹ５３Ｆ及びＫ６４Ｑ；
ｉｖ）ＣＤＲ−Ｈ３におけるＨ９７Ｅ及びＹ９８Ｆ；
ｖ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｄと、ＣＤＲ−Ｈ３におけるＹ９９Ｄと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；
ｖｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｐと、ＣＤＲ−Ｈ３におけるＹ９９Ｄと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；
ｖｉｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｐと、ＣＤＲ−Ｈ３におけるＹ９９Ｅ；
ｖｉｉｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｅと、ＣＤＲ−Ｈ３におけるＹ９９Ｅ；
ｉｘ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｄと、ＣＤＲ−Ｈ３におけるＹ９９Ｅ；
ｘ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｅと、ＣＤＲ−Ｈ３におけるＹ９９Ｄと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；
ｘｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＹ９９Ｄと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；
ｘｉｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｐと、ＣＤＲ−Ｈ３におけるＹ９９Ｄ；
ｘｉｉｉ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｄと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；
ｘｉｖ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ；及び
ｘｖ）ＣＤＲ−Ｈ１におけるＮ３１Ｆと、ＣＤＲ−Ｈ３におけるＨ９７Ｐと、ＣＤＲ−Ｈ３におけるＳ１００ａＧ
から選択される少なくとも１つのアミノ酸置換又はアミノ酸置換の組合せを有し；並びに
（ｅ）場合により、下記に示す表６、表７、表８、表９、表１０、表１１、表１２−１〜表１２−９、或いは表１３〜表１６の１以上から選択される１種以上の他の突然変異もしくは突然変異の組合せを有する
- ｉ）からｘｖ）から選択される置換組合せ以外に、重鎖ＣＤＲが抗体ベバシズマブの重鎖ＣＤＲ配列又は抗体ラニビズマブの重鎖ＣＤＲ配列に比較して他の突然変異を含まない、請求項１に記載のモノクローナル抗体又はその結合フラグメント。
- ａ）６個のＣＤＲが抗体ベバシズマブ又は抗体ラニビズマブのＣＤＲ配列に比較して合計９カ所まで、８カ所まで、７カ所まで、６カ所まで、５カ所まで又は４カ所までのアミノ酸置換を有する；及び／又は
ｂ）任意の個別のＣＤＲが抗体ベバシズマブ又は抗体ラニビズマブの対応するＣＤＲ配列に比較して２カ所以下の又は３カ所以下のアミノ酸置換を有する、
請求項１又は２に記載のモノクローナル抗体又はその結合フラグメント。 - 夫々ヒトもしくはヒト化抗体、又はヒトもしくはヒト化抗体の抗ＶＥＧＦ結合フラグメントである、請求項１〜３のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。
- ＩｇＧ、例えばＩｇＧ１又はＩｇＧ２である、請求項１〜４のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。
- ａ）ＡＤＣＣ活性を増加する１種以上の突然変異をＦｃ領域に含む；
ｂ）フコシル化されていない；及び／又は
ｃ）ＦｃγＲとの結合性を増加する又はＦｃＲｎとの結合性を増加するのいずれかである１種以上の突然変異をＦｃ領域に含む、
請求項１〜５のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。 - ＡＤＣＣ活性を低下させる１種以上の突然変異をＦｃ領域に含む、請求項１〜５のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。
- （ａ）前記１種以上の突然変異以外に、配列番号１に対応するＶＨ配列及び配列番号２に対応するＶＬ配列を有する；
（ｂ）前記１種以上の突然変異以外に、配列番号９に対応する重鎖配列及び配列番号１０に対応する軽鎖配列を有する；
（ｃ）配列番号１に対応するＶＨ配列及び配列番号２に対応するＶＬ配列をもつ抗体の親和性の１．５から５０倍の、又は２から３０倍の親和性を有する；又は
（ｄ）配列番号９に対応する重鎖配列及び配列番号１０に対応する軽鎖配列をもつ抗体の親和性の１．５から５０倍の、又は２から３０倍の親和性を有し；
場合により、親和性がバイオセンサーにより分析されるＫＤの測定である、
請求項１〜７のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。 - 例えば、少なくとも８５％、少なくとも９０％、少なくとも９５％又は少なくとも９８％の均一性まで精製されている、請求項１〜８のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント。
- 請求項１〜９のいずれか一項に記載のモノクローナル抗体又はその結合フラグメントを含む、抗体−薬剤コンジュゲート。
- 請求項１〜９のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント、或いは請求項１０に記載の抗体−薬剤コンジュゲートと、医薬的に許容可能な担体と、を含む医薬組成物。
- 請求項１〜８のいずれか一項に記載のモノクローナル抗体又はその結合フラグメントをコードするヌクレオチド配列を含む核酸。
- 請求項１２に記載の核酸を含むベクター。
- 請求項１３に記載のベクターで形質転換された原核宿主細胞もしくは真核宿主細胞、或いは請求項１２に記載のヌクレオチド配列を発現するように遺伝子組換えされた真核宿主細胞であって、
場合により、遺伝子組換えされた真核宿主細胞が哺乳動物宿主細胞である、宿主細胞。 - （ａ）請求項１４に記載の真核宿主細胞を培養すること；及び
（ｂ）モノクローナル抗体又はその結合フラグメントを回収すること
を含む、モノクローナル抗体又はその結合フラグメントの作製方法。 - 癌を治療するための医薬の製造における、請求項１〜９のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント、請求項１０に記載の抗体−薬剤コンジュゲート、又は請求項１１に記載の医薬組成物の使用であって、
場合により、癌が転移性結腸癌、転移性直腸癌、非扁平上皮型非小細胞肺癌又は転移性ＨＥＲ２陰性乳癌であり、さらに場合により癌が切除不能、局所進行、再発性又は転移性の非扁平上皮型非小細胞肺癌である、前記使用。 - 加齢黄斑変性又は免疫疾患を治療するための医薬の製造における、請求項１〜９のいずれか一項に記載のモノクローナル抗体又はその結合フラグメント、請求項１０に記載の抗体−薬剤コンジュゲート、又は請求項１１に記載の医薬組成物の使用であって、
場合により、免疫疾患が関節リウマチ又はグレーブス病である、前記使用。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21800509P | 2009-06-17 | 2009-06-17 | |
| US61/218,005 | 2009-06-17 | ||
| PCT/US2010/039029 WO2010148223A2 (en) | 2009-06-17 | 2010-06-17 | Anti-vegf antibodies and their uses |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012530496A JP2012530496A (ja) | 2012-12-06 |
| JP2012530496A5 true JP2012530496A5 (ja) | 2013-08-01 |
| JP5785941B2 JP5785941B2 (ja) | 2015-09-30 |
Family
ID=42543312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012516307A Expired - Fee Related JP5785941B2 (ja) | 2009-06-17 | 2010-06-17 | 抗ｖｅｇｆ抗体とその使用 |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US9079953B2 (ja) |
| EP (2) | EP2443150B1 (ja) |
| JP (1) | JP5785941B2 (ja) |
| KR (1) | KR20120034739A (ja) |
| CN (1) | CN102482349B (ja) |
| AU (1) | AU2010262836B2 (ja) |
| BR (1) | BRPI1012321A8 (ja) |
| CA (1) | CA2765755C (ja) |
| CL (1) | CL2011003182A1 (ja) |
| CO (1) | CO6480962A2 (ja) |
| CR (1) | CR20110653A (ja) |
| EC (1) | ECSP12011584A (ja) |
| ES (2) | ES2534355T3 (ja) |
| GT (1) | GT201100326A (ja) |
| HK (1) | HK1211961A1 (ja) |
| IL (2) | IL216835A0 (ja) |
| MX (2) | MX2011013781A (ja) |
| NZ (1) | NZ596837A (ja) |
| PE (1) | PE20120622A1 (ja) |
| RU (1) | RU2567639C2 (ja) |
| SG (2) | SG177265A1 (ja) |
| TW (1) | TWI510248B (ja) |
| UA (1) | UA104626C2 (ja) |
| WO (1) | WO2010148223A2 (ja) |
| ZA (1) | ZA201109098B (ja) |
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| EP3134115A4 (en) | 2014-04-25 | 2017-10-25 | The Trustees Of The University Of Pennsylvania | Methods and compositions for treating metastatic breast cancer and other cancers in the brain |
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