JP2016510002A5 - - Google Patents
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- JP2016510002A5 JP2016510002A5 JP2015559019A JP2015559019A JP2016510002A5 JP 2016510002 A5 JP2016510002 A5 JP 2016510002A5 JP 2015559019 A JP2015559019 A JP 2015559019A JP 2015559019 A JP2015559019 A JP 2015559019A JP 2016510002 A5 JP2016510002 A5 JP 2016510002A5
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- drug conjugate
- antibody drug
- pharmaceutical composition
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000611 antibody drug conjugate Substances 0.000 claims 31
- 108091008116 antibody drug conjugates Proteins 0.000 claims 31
- 108090001123 antibodies Proteins 0.000 claims 27
- 102000004965 antibodies Human genes 0.000 claims 27
- 239000008194 pharmaceutical composition Substances 0.000 claims 15
- 201000011510 cancer Diseases 0.000 claims 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims 7
- 229920002574 CR-39 Polymers 0.000 claims 6
- 208000000587 Small Cell Lung Carcinoma Diseases 0.000 claims 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 3
- 229940079593 drugs Drugs 0.000 claims 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 239000000562 conjugate Substances 0.000 claims 2
- 230000000955 neuroendocrine Effects 0.000 claims 2
- 229920002857 polybutadiene Polymers 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 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 1
- 102100013694 DLL3 Human genes 0.000 claims 1
- 101700003144 DLL3 Proteins 0.000 claims 1
- 108010016626 Dipeptides Proteins 0.000 claims 1
- 230000035693 Fab Effects 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 230000003302 anti-idiotype Effects 0.000 claims 1
- 108091006028 chimera Proteins 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 102000031144 human DLL3 protein Human genes 0.000 claims 1
- 108091005385 human DLL3 protein Proteins 0.000 claims 1
- 230000000977 initiatory Effects 0.000 claims 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims 1
- 108010045030 monoclonal antibodies Proteins 0.000 claims 1
- 102000005614 monoclonal antibodies Human genes 0.000 claims 1
- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical group C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
Claims (36)
- リンカーを介してピロロベンゾジアゼピン（ＰＢＤ）に共有結合的に連結された抗ＤＬＬ３抗体またはその免疫反応性フラグメントを含む抗体薬物コンジュゲートであって、ＰＢＤが以下：
- ＰＢＤがＰＢＤ５である、請求項１に記載の抗体薬物コンジュゲート。
- リンカーが切断可能なリンカーを含む、請求項１または２に記載の抗体薬物コンジュゲート。
- 切断可能なリンカーが、少なくとも２個のアミノ酸を含むぺプチジルリンカーを含む、請求項３に記載の抗体薬物コンジュゲート。
- ぺプチジルリンカーがバリン−アニリンジペプチドを含む、請求項４に記載の抗体薬物コンジュゲート。
- 下記構造：
- リンカーが更にマレイミド基を含む、請求項１から６のいずれか一項に記載の抗体薬物コンジュゲート。
- 抗ＤＬＬ３抗体が１個を超えるＰＢＤに共有結合的に連結している、請求項１から７のいずれか一項に記載の抗体薬物コンジュゲート。
- ＡＤＣが２個の薬物付加を有する、請求項１〜７のいずれか一項に記載の抗体薬物コンジュゲート。
- １〜８個のＰＢＤが抗ＤＬＬ３抗体に共有結合的に連結している、請求項１〜７のいずれか一項に記載の抗体薬物コンジュゲート。
- 抗体薬物コンジュゲートが、
および
- 抗体薬物コンジュゲートがＡＤＣ５である、請求項１１に記載の抗体薬物コンジュゲート。
- ＡＤＣがＡＤＣ５であり、Ａｂが１個を超えるＰＢＤに共有結合的に連結している、請求項１に記載の抗体薬物コンジュゲート。
- ＡＤＣがＡＤＣ５であり、ＡＤＣが２個の薬物負荷を有する、請求項１に記載の抗体薬物コンジュゲート。
- ＡＤＣがＡＤＣ５であり、１〜８個のＰＢＤが共有結合的に連結している、請求項１に記載の抗体薬物コンジュゲート。
- 抗ＤＬＬ３抗体が、モノクローナル抗体、キメラ抗体、ＣＤＲグラフティング抗体、ヒト化抗体、ヒト抗体、霊長類化抗体、多重特異性抗体、二重特異性抗体、一価抗体、多価抗体、抗イディオタイプ抗体、ダイアボディ、Ｆａｂフラグメント、Ｆ（ａｂ’）２フラグメント、ＦｖフラグメントおよびＳｃＦｖフラグメントから選択される抗ＤＬＬ３抗体；またはその免疫反応性フラグメントである、請求項１に記載の抗体薬物コンジュゲート。
- 抗ＤＬＬ３抗体が内在化抗体である、請求項１〜１６のいずれか一項に記載の抗体薬物コンジュゲート。
- 前記抗ＤＬＬ３抗体が、配列番号１または２に記載のアミノ酸配列を含むＤＬＬ３タンパク質のＤＳＬドメイン内のエピトープに特異的に結合する、請求項１〜１７のいずれか１項に記載のコンジュゲート。
- 前記抗ＤＬＬ３抗体が、アミノ酸Ｇ２０３、Ｒ２０５、およびＰ２０６を含むエピトープ（配列番号４）に結合する、請求項１８に記載のコンジュゲート。
- 前記抗ＤＬＬ３抗体が、配列番号１４９に記載のアミノ酸配列を含む軽鎖可変領域および配列番号１５１に記載のアミノ酸配列を含む重鎖可変領域を含む抗体を含む、またはヒトＤＬＬ３タンパク質に対する結合について該抗体と競合する、請求項１〜１９のいずれか一項に記載の抗体薬物コンジュゲート。
- 前記抗ＤＬＬ３抗体が、配列番号１４９に記載のアミノ酸配列を含む軽鎖可変領域の３つの相補性決定領域、および配列番号１５１に記載のアミノ酸配列を含む重鎖可変領域の３つの相補性決定領域を含む、請求項２０に記載の抗体薬物コンジュゲート。
- 抗ＤＬＬ３抗体が、ＣＤＲ−Ｌ１について配列番号１４９の残基２４〜３４、ＣＤＲ−Ｌ２について配列番号１４９の残基５０〜５６、ＣＤＲ−Ｌ３について配列番号１４９の残基８９〜９７、ＣＤＲ−Ｈ１について配列番号１５１の残基３１〜３５、ＣＤＲ−Ｈ２について配列番号１５１の残基５０〜６５、およびＣＤＲ−Ｈ３について配列番号１５１の残基９５〜１０２を含み、前記残基はＫａｂａｔの定義に従って番号付けされる、請求項２１に記載の抗体薬物コンジュゲート。
- 前記抗ＤＬＬ３抗体が、配列番号４０５に記載のアミノ酸配列を含む軽鎖可変領域、および、配列番号４０７に記載のアミノ酸配列を含む重鎖可変領域を含む、請求項２０に記載の抗体薬物コンジュゲート。
- （ａ）請求項１〜２３のいずれか一項に記載の抗体薬物コンジュゲート、および（ｂ）薬学的に許容されるキャリアを含む、薬学的組成物。
- １、２、３、４、５、６、７または８（各々＋／−０．４）の薬物抗体比（ＤＡＲ）を含む、請求項２４に記載の薬学的組成物。
- ２＋／−０．４のＤＡＲを含む、請求項２５に記載の薬学的組成物。
- ３０％未満の非支配的ＡＤＣ種を含む、請求項２５または２６に記載の薬学的組成物。
- （ａ）請求項１〜２３のいずれか一項に記載の抗体薬物コンジュゲートを含有する一つ以上の容器、および（ｂ）前記一つ以上の容器上にまたは容器に付随されたラベルまたは添付文書を含むキットであって、ラベルまたは添付文書が、抗体薬物コンジュゲートを癌の処置用であることを示す、キット。
- （ａ）請求項２４〜２７のいずれか一項に記載の薬学的組成物、および（ｂ）一つ以上の容器上にまたは容器に付随されたラベルまたは添付文書を含むキットであって、ラベルまたは添付文書が、抗体薬物コンジュゲートを癌の処置用であることを示す、キット。
- 請求項１〜２３のいずれか一項に記載の抗体薬物コンジュゲートまたは請求項２４〜２７のいずれか一項に記載の薬学的組成物を含む、被験体において癌を処置するための薬学的組成物。
- 癌が、小細胞肺癌、前立腺癌、甲状腺癌、または大細胞神経内分泌癌である、請求項３０に記載の薬学的組成物。
- 癌が小細胞肺癌である、請求項３０に記載の薬学的組成物。
- 請求項１〜２３のいずれか一項に記載の抗体薬物コンジュゲートまたは請求項２４〜２７のいずれか一項に記載の薬学的組成物を含む、癌を有する被験体における腫瘍開始細胞の頻度を低下させるための薬学的組成物。
- 癌が、小細胞肺癌、前立腺癌、甲状腺癌または大細胞神経内分泌である、請求項３３に記載の薬学的組成物。
- 癌が小細胞肺癌である、請求項３３に記載の薬学的組成物。
- 請求項１〜２３のいずれか一項に記載の抗体薬物コンジュゲートまたは請求項２４〜２７のいずれか一項に記載の薬学的組成物を含む、ＰＢＤを癌細胞に送達するための薬学的組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361768368P | 2013-02-22 | 2013-02-22 | |
| US61/768,368 | 2013-02-22 | ||
| PCT/US2014/017810 WO2014130879A2 (en) | 2013-02-22 | 2014-02-21 | Novel antibody conjugates and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018242172A Division JP2019069983A (ja) | 2013-02-22 | 2018-12-26 | 新規抗体コンジュゲートおよびその使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016510002A JP2016510002A (ja) | 2016-04-04 |
| JP2016510002A5 true JP2016510002A5 (ja) | 2017-05-25 |
| JP6462591B2 JP6462591B2 (ja) | 2019-01-30 |
Family
ID=51391975
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015559019A Expired - Fee Related JP6462591B2 (ja) | 2013-02-22 | 2014-02-21 | 新規抗体コンジュゲートおよびその使用 |
| JP2018242172A Pending JP2019069983A (ja) | 2013-02-22 | 2018-12-26 | 新規抗体コンジュゲートおよびその使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018242172A Pending JP2019069983A (ja) | 2013-02-22 | 2018-12-26 | 新規抗体コンジュゲートおよびその使用 |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US9968687B2 (ja) |
| EP (2) | EP3556400A1 (ja) |
| JP (2) | JP6462591B2 (ja) |
| KR (1) | KR20160037130A (ja) |
| CN (1) | CN105164159A (ja) |
| AR (1) | AR094867A1 (ja) |
| AU (2) | AU2014218730B2 (ja) |
| BR (1) | BR112015019909A2 (ja) |
| CA (1) | CA2901114C (ja) |
| CL (3) | CL2015002357A1 (ja) |
| CY (1) | CY1121907T1 (ja) |
| DK (1) | DK2958944T3 (ja) |
| ES (1) | ES2731681T3 (ja) |
| HK (1) | HK1217956A1 (ja) |
| HR (1) | HRP20191169T1 (ja) |
| HU (1) | HUE043851T2 (ja) |
| IL (1) | IL240438A0 (ja) |
| LT (1) | LT2958944T (ja) |
| ME (1) | ME03394B (ja) |
| MX (1) | MX2015010682A (ja) |
| PE (1) | PE20151901A1 (ja) |
| PH (1) | PH12015501846A1 (ja) |
| PL (1) | PL2958944T3 (ja) |
| PT (1) | PT2958944T (ja) |
| RS (1) | RS58873B1 (ja) |
| RU (2) | RU2019109456A (ja) |
| SA (1) | SA515360928B1 (ja) |
| SG (1) | SG11201506650PA (ja) |
| SI (1) | SI2958944T1 (ja) |
| TR (1) | TR201908761T4 (ja) |
| TW (1) | TWI670081B (ja) |
| WO (1) | WO2014130879A2 (ja) |
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| US8609717B2 (en) | 2010-08-18 | 2013-12-17 | Samumed, Llc | β- and γ-diketones and γ-hydroxyketones as WNT/β-catenin signaling pathway activators |
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| EP2888283B1 (en) | 2012-08-24 | 2018-09-19 | The Regents of The University of California | Antibodies and vaccines for use in treating ror1 cancers and inhibiting metastasis |
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