JP2014511179A5 - - Google Patents
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- JP2014511179A5 JP2014511179A5 JP2013554656A JP2013554656A JP2014511179A5 JP 2014511179 A5 JP2014511179 A5 JP 2014511179A5 JP 2013554656 A JP2013554656 A JP 2013554656A JP 2013554656 A JP2013554656 A JP 2013554656A JP 2014511179 A5 JP2014511179 A5 JP 2014511179A5
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- 102000004965 antibodies Human genes 0.000 claims description 59
- 108090001123 antibodies Proteins 0.000 claims description 59
- 102100004042 PTK7 Human genes 0.000 claims description 8
- 101700007351 PTK7 Proteins 0.000 claims description 8
- 108010045030 monoclonal antibodies Proteins 0.000 claims description 3
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- 206010033128 Ovarian cancer Diseases 0.000 claims 6
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 6
- 201000011231 colorectal cancer Diseases 0.000 claims 6
- 201000005202 lung cancer Diseases 0.000 claims 6
- 201000002528 pancreatic cancer Diseases 0.000 claims 6
- 201000000849 skin cancer Diseases 0.000 claims 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 4
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- NFGXHKASABOEEW-UHFFFAOYSA-N (+)-methoprene Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
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- 108010061543 Neutralizing Antibodies Proteins 0.000 claims 1
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- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 229960000070 antineoplastic Monoclonal antibodies Drugs 0.000 description 1
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Description
実施例８
ＰＴＫ７モジュレーターの配列決定及びヒト化
８（ａ）配列決定：
[0302] 上述したことに基づいて、固定化したヒトＰＴＫ７へ結合するいくつかの例示の別個のモノクローナル抗体と、マウスＰＴＫ７と見かけ上高い親和性で交差反応する抗体を配列決定とさらなる分析のために選択した。図面６Ａ及び６Ｂ中の表形式に示すように、実施例７において作製した選択モノクローナル抗体からの軽鎖可変領域（図面６Ａ）及び重鎖可変領域（図面６Ｂ）の配列分析により、その多くが新規の相補性決定領域を有して、しばしば新規のＶＤＪ再配列を示すことが確認された。図面６Ａ及び６Ｂに示す相補性決定領域は、ＶＢＡＳＥ２分析に由来していることに留意されたい。
ＰＴＫ７モジュレーターの配列決定及びヒト化
８（ａ）配列決定：
[0302] 上述したことに基づいて、固定化したヒトＰＴＫ７へ結合するいくつかの例示の別個のモノクローナル抗体と、マウスＰＴＫ７と見かけ上高い親和性で交差反応する抗体を配列決定とさらなる分析のために選択した。図面６Ａ及び６Ｂ中の表形式に示すように、実施例７において作製した選択モノクローナル抗体からの軽鎖可変領域（図面６Ａ）及び重鎖可変領域（図面６Ｂ）の配列分析により、その多くが新規の相補性決定領域を有して、しばしば新規のＶＤＪ再配列を示すことが確認された。図面６Ａ及び６Ｂに示す相補性決定領域は、ＶＢＡＳＥ２分析に由来していることに留意されたい。
Claims (38)
- （ａ）配列番号６２として示される軽鎖可変領域及び配列番号６３として示される重鎖可変領域；又は
（ｂ）配列番号５０として示される軽鎖可変領域及び配列番号５１として示される重鎖可変領域
を含む抗体を含む、又は該抗体と競合する、ヒトＰＴＫ７に特異的に結合する単離された抗体。 - （ａ）又は（ｂ）を含む抗体の結合を少なくとも約４０％阻害する、請求項１に記載の抗体。
- 中和抗体、枯渇性抗体、及び／又は内在化抗体である、請求項１に記載の抗体。
- アイソフォームａ、アイソフォームｂ、アイソフォームｃ、及びアイソフォームｄからなる群より選択されるＰＴＫ７アイソフォームに特異的に結合する、請求項１に記載の抗体。
- モノクローナル抗体、キメラ抗体、ＣＤＲ移植抗体、ヒト化抗体、若しくは組換えヒト抗体、又はそれらの断片である、請求項１に記載の抗体。
- 配列番号６３として示される重鎖可変領域の３つのＣＤＲ、及び配列番号６２として示される軽鎖可変領域の３つのＣＤＲを含む、請求項１に記載の抗体。
- （ａ）ＶＨＣＤＲ１について配列番号６３の残基３１〜３５、ＶＨＣＤＲ２について配列番号６３の残基５０〜６５、及びＶＨＣＤＲ３について配列番号６３の残基９５〜１０２として示される３つのＣＤＲを含む重鎖可変領域；及び／又は
（ｂ）ＶＬＣＤＲ１について配列番号６２の残基２４〜３４、ＶＬＣＤＲ２について配列番号６２の残基５０〜５６、及びＶＬＣＤＲ３について配列番号６２の残基８９〜９７として示される３つのＣＤＲを含む軽鎖可変領域
を含み、ＣＤＲ番号付けがカバット（Kabat）に従う、請求項６に記載の抗体。 - 配列番号５１として示される重鎖可変領域の３つのＣＤＲ、及び配列番号５０として示される軽鎖可変領域の３つのＣＤＲを含む、請求項１に記載の抗体。
- （ａ）ＶＨＣＤＲ１について配列番号５１の残基３１〜３５、ＶＨＣＤＲ２について配列番号５１の残基５０〜６５、及びＶＨＣＤＲ３について配列番号５１の残基９５〜１０２として示される３つのＣＤＲを含む重鎖可変領域；及び／又は
（ｂ）ＶＬＣＤＲ１について配列番号５０の残基２４〜３４、ＶＬＣＤＲ２について配列番号５０の残基５０〜５６、及びＶＬＣＤＲ３について配列番号５０の残基８９〜９７として示される３つのＣＤＲを含む軽鎖可変領域
を含み、ＣＤＲ番号付けがカバット（Kabat）に従う、請求項８に記載の抗体。 - 配列番号６３と少なくとも６０％同一であるアミノ酸配列を有する重鎖可変領域、及び配列番号６２と少なくとも６０％同一であるアミノ酸配列を有する軽鎖可変領域を含む、請求項１に記載の抗体。
- 配列番号６３として示される重鎖可変領域、及び配列番号６２として示される軽鎖可変領域を含む、請求項１０に記載の抗体。
- 配列番号６５と少なくとも６０％同一であるアミノ酸配列を有する重鎖可変領域、及び配列番号６４と少なくとも６０％同一であるアミノ酸配列を有する軽鎖可変領域を含む、請求項１に記載の抗体。
- 配列番号６５として示される重鎖可変領域、及び配列番号６４として示される軽鎖可変領域を含む、請求項１２に記載の抗体。
- キメラ抗体、ＣＤＲ移植抗体、ヒト化抗体、若しくは組換えヒト抗体、又はそれらの断片を含む抗体コンジュゲートであって、ヒトＰＴＫ７に特異的に結合し、抗体が細胞傷害剤とコンジュゲートする、連結する、又は他の方法で会合する、前記抗体コンジュゲート。
- 抗体が、請求項１〜１３のいずれか１項に記載の抗体である、請求項１４に記載の抗体コンジュゲート。
- 請求項１〜１３のいずれか１項に記載の重鎖可変領域及び／又は軽鎖可変領域をコードする、核酸。
- 配列番号４９、配列番号５１、配列番号６３、又は配列番号６５として示される重鎖可変領域、及び／又は配列番号４８、配列番号５０、配列番号６２、又は配列番号６４として示される軽鎖可変領域をコードする、核酸。
- 請求項１６に記載の核酸を含む、ベクター。
- 請求項１６に記載の核酸を含む、宿主細胞。
- 請求項１８に記載のベクターを含む、宿主細胞。
- 請求項１〜１３のいずれか１項に記載の抗体を含む、医薬組成物。
- 請求項１４に記載の抗体コンジュゲートを含む、医薬組成物。
- 被検者における癌の検出用、診断用、又はモニタリング用である、請求項２１に記載の医薬組成物。
- 癌が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌である、請求項２３に記載の医薬組成物。
- 被検者における癌の治療用である、請求項２２に記載の医薬組成物。
- 抗体が、請求項１〜１３のいずれか１項に記載の抗体である、請求項２５に記載の医薬組成物。
- 癌が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌である、請求項２５に記載の医薬組成物。
- 腫瘍始原細胞の頻度を被検者において低下させるための、請求項２２に記載の医薬組成物。
- 抗体が、請求項１〜１３のいずれか１項に記載の抗体である、請求項２８に記載の医薬組成物。
- 被検者が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌に罹患している、請求項２８に記載の医薬組成物。
- 被検者における癌の検出用、診断用、又はモニタリング用の薬剤を製造するための、請求項１〜１３のいずれか１項に記載の抗体の使用。
- 癌が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌である、請求項３１に記載の使用。
- 被検者における癌の治療用の薬剤を製造するための、キメラ抗体、ＣＤＲ移植抗体、ヒト化抗体、若しくは組換えヒト抗体、又はそれらの断片を含む治療有効量の抗体コンジュゲートの使用であって、抗体コンジュゲートがヒトＰＴＫ７に特異的に結合し、抗体が細胞傷害剤とコンジュゲートする、連結する、又は他の方法で会合する、前記使用。
- 抗体が、請求項１〜１３のいずれか１項に記載の抗体である、請求項３３に記載の使用。
- 癌が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌である、請求項３３に記載の使用。
- 腫瘍始原細胞の頻度を被検者において低下させるための薬剤を製造するための、キメラ抗体、ＣＤＲ移植抗体、ヒト化抗体、若しくは組換えヒト抗体、又はそれらの断片を含む抗体コンジュゲートの使用であって、抗体コンジュゲートがヒトＰＴＫ７に特異的に結合し、抗体が細胞傷害剤とコンジュゲートする、連結する、又は他の方法で会合する、前記使用。
- 抗体が、請求項１〜１３のいずれか１項に記載の抗体である、請求項３６に記載の使用。
- 被検者が、乳癌、卵巣癌、結直腸癌、膵臓癌、肺癌、又は皮膚癌に罹患している、請求項３６に記載の使用。
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161444614P | 2011-02-18 | 2011-02-18 | |
| US61/444,614 | 2011-02-18 | ||
| PCT/US2011/050451 WO2012031280A2 (en) | 2010-09-03 | 2011-09-02 | Identification and enrichment of cell subpopulations |
| USPCT/US2011/050451 | 2011-09-02 | ||
| PCT/US2012/025726 WO2012112943A1 (en) | 2011-02-18 | 2012-02-17 | Novel modulators and methods of use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017223676A Division JP2018104409A (ja) | 2011-02-18 | 2017-11-21 | 新規モジュレーターと使用の方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014511179A JP2014511179A (ja) | 2014-05-15 |
| JP2014511179A5 true JP2014511179A5 (ja) | 2015-08-20 |
| JP6296796B2 JP6296796B2 (ja) | 2018-03-28 |
Family
ID=46672972
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013554656A Active JP6296796B2 (ja) | 2011-02-18 | 2012-02-17 | 新規モジュレーターと使用の方法 |
| JP2017223676A Pending JP2018104409A (ja) | 2011-02-18 | 2017-11-21 | 新規モジュレーターと使用の方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017223676A Pending JP2018104409A (ja) | 2011-02-18 | 2017-11-21 | 新規モジュレーターと使用の方法 |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US9409995B2 (ja) |
| EP (2) | EP2675827B1 (ja) |
| JP (2) | JP6296796B2 (ja) |
| KR (1) | KR102022734B1 (ja) |
| CN (2) | CN107056945A (ja) |
| AR (1) | AR085281A1 (ja) |
| AU (3) | AU2012219313C1 (ja) |
| BR (1) | BR112013021134B1 (ja) |
| CA (1) | CA2827637C (ja) |
| CO (1) | CO6791571A2 (ja) |
| CY (1) | CY1123551T1 (ja) |
| DK (1) | DK2675827T3 (ja) |
| ES (1) | ES2829206T3 (ja) |
| HR (1) | HRP20201399T1 (ja) |
| HU (1) | HUE050657T2 (ja) |
| IL (3) | IL228018A (ja) |
| LT (1) | LT2675827T (ja) |
| MX (1) | MX356434B (ja) |
| MY (1) | MY173880A (ja) |
| PE (2) | PE20181076A1 (ja) |
| PH (1) | PH12018500452A1 (ja) |
| PL (1) | PL2675827T3 (ja) |
| PT (1) | PT2675827T (ja) |
| RS (1) | RS60841B1 (ja) |
| RU (2) | RU2627176C2 (ja) |
| SA (1) | SA112330278B1 (ja) |
| SG (2) | SG10201603926SA (ja) |
| SI (1) | SI2675827T1 (ja) |
| TW (2) | TWI624476B (ja) |
| WO (1) | WO2012112943A1 (ja) |
| ZA (1) | ZA201306958B (ja) |
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- 2018-11-14 IL IL263020A patent/IL263020A/en unknown
-
2019
- 2019-02-22 AU AU2019201258A patent/AU2019201258A1/en not_active Abandoned
-
2020
- 2020-09-02 HR HRP20201399TT patent/HRP20201399T1/hr unknown
- 2020-11-05 CY CY20201101046T patent/CY1123551T1/el unknown
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