JP2016520082A - 抗folr1免疫複合体投与計画 - Google Patents
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Abstract
Description
FOLR1は、大部分の卵巣癌、並びに多くの子宮癌、子宮内膜癌、膵癌、腎癌、肺癌及び乳癌に過剰発現し、正常組織でのFOLR1の発現は、腎臓近位尿細管、肺の肺胞肺細胞、膀胱、精巣、脈絡叢及び甲状腺中の上皮細胞の頂端膜に限局される。(Weitman SD, et al., Cancer Res 52:3396−3401(1992);AntonyAC,Annu Rev Nutr16:501−521(1996);Kalli KR,et al.Gynecol Oncol 108:619−626(2008))。 FOLR1のこの発現パターンにより、FOLR1は、FOLR1指向性癌療法の所望の標的となる。
I.定義
II.FOLR1結合剤
III免疫複合体
III.FOLR1−結合剤の投与方法
* * *
実施例1
ヒト癌患者におけるIMGN853投与治験
実施例2
注入反応のためのIMGN853ステロイド系予防
****
配列
配列番号1−ヒト葉酸受容体1
MAQRMTTQLLLLLVWVAVVGEAQTRIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPWRKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQVDQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHFYFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAMSGAGPWAAWPFLLSLALMLLWLLS
配列番号2−ヒト葉酸受容体1核酸配列
atggctcagcggatgacaacacagctgctgctccttctagtgtgggtggctgtagtaggggaggctcagacaaggattgcatgggccaggactgagcttctcaatgtctgcatgaacgccaagcaccacaaggaaaagccaggccccgaggacaagttgcatgagcagtgtcgaccctggaggaagaatgcctgctgttctaccaacaccagccaggaagcccataaggatgtttcctacctatatagattcaactggaaccactgtggagagatggcacctgcctgcaaacggcatttcatccaggacacctgcctctacgagtgctcccccaacttggggccctggatccagcaggtggatcagagctggcgcaaagagcgggtactgaacgtgcccctgtgcaaagaggactgtgagcaatggtgggaagattgtcgcacctcctacacctgcaagagcaactggcacaagggctggaactggacttcagggtttaacaagtgcgcagtgggagctgcctgccaacctttccatttctacttccccacacccactgttctgtgcaatgaaatctggactcactcctacaaggtcagcaactacagccgagggagtggccgctgcatccagatgtggttcgacccagcccagggcaaccccaatgaggaggtggcgaggttctatgctgcagccatgagtggggctgggccctgggcagcctggcctttcctgcttagcctggccctaatgctgctgtggctgctcagc
配列番号:3−huMov19 vHC
QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS
配列番号4−huMov19 vLCv1.00
DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLNISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKR
配列番号:5−huMov19 vLCv1.60
DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKR
配列番号:6−huMov19 vLC CDR1
KASQSVSFAGTSLMH
配列番号:7−huMov19 vLC CDR2
RASNLEA
配列番号:8−huMov19 vLC CDR3
QQSREYPYT
配列番号:9−huMov19 vHC CDR1
GYFMN
配列番号:10−huMov19 vHC CDR2−Kabat定義
RIHPYDGDTFYNQKFQG
配列番号:11−huMov19 vHC CDR2−Abm定義
RIHPYDGDTF
配列番号:12−huMov19 vHC CDR3
YDGSRAMDY
配列番号:13−huMov19 HCアミノ酸配列
QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
配列番号:14−huMov19 LCv1.00
DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLNISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
配列番号:15−huMov19 LCv1.60
DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
配列番号:16−muMov19 vHC CDR2−Kabat定義
RIHPYDGDTFYNQNFKD
Claims (26)
- 患者に有効量の、FOLR1ポリペプチドと結合する免疫複合体を投与することを含む、癌を有するヒト患者の治療方法であって、前記投与により、Cmaxが約100〜150μg/mLとなる、前記方法。
- 前記免疫複合体は、投与量約3mg/kg〜約6mg/kgで投与される、請求項1に記載の方法。
- 前記免疫複合体は、投与量約3.0mg/kgで投与される、請求項2に記載の方法。
- 前記免疫複合体は、投与量約3.3mg/kgで投与される、請求項2に記載の方法。
- 前記免疫複合体は、投与量約5.0mg/kgで投与される、請求項2に記載の方法。
- 前記免疫複合体は、投与量約5.5mg/kgで投与される、請求項2に記載の方法。
- 前記免疫複合体は、投与量約6.0mg/kgで投与される、請求項2に記載の方法。
- 前記免疫複合体は、投与量約6.5mg/kgで投与される、請求項1に記載の方法。
- 前記免疫複合体は、約1回/週投与される、請求項1〜8のいずれか一項に記載の方法。
- 前記患者に有効量の、FOLR1ポリペプチドと結合する免疫複合体を投与することを含む、癌を有するヒト患者の治療方法であって、前記免疫複合体は、約6mg/kgの投与量で、約1回/週投与される、前記方法。
- 前記患者に有効量の、FOLR1ポリペプチドと結合する免疫複合体を投与することを含む、癌を有するヒト患者を対象にした治療方法であって、前記免疫複合体は、約6.5mg/kgの投与量で、約1回/週投与される、前記方法。
- 前記免疫複合体は、配列番号6を含む軽鎖CDR1、配列番号7を含む軽鎖CDR2、配列番号8を含む軽鎖CDR3、配列番号9を含む重鎖CDR1、配列番号10または11を含む重鎖CDR2、及び配列番号12を含む重鎖CDR3を含有する抗体を含む、請求項1〜11のいずれか一項に記載の方法。
- 前記免疫複合体は、配列番号5を含む可変軽鎖及び配列番号3を含む可変重鎖含有抗体を含む、請求項12に記載の方法。
- 前記免疫複合体はIMGN853である、請求項13に記載の方法。
- 前記免疫複合体は、静脈内投与される、請求項1〜14のいずれか一項に記載の方法。
- 癌は、卵巣癌、脳腫瘍、乳癌、子宮癌、子宮内膜癌、膵癌、腎癌及び肺癌からなる群から選択される、請求項1〜15のいずれか一項に記載の方法。
- 前記肺癌は非小細胞肺癌または細気管支−肺胞癌である、請求項16に記載の方法。
- 前記卵巣癌は上皮性卵巣癌である、請求項16に記載の方法。
- 前記卵巣癌は白金耐性、再発性または難治性である、請求項18に記載の方法。
- 前記癌は、FOLR1プロペプチドまたは核酸を発現させる、請求項1〜19のいずれか一項に記載の方法。
- 前記FOLR1発現レベルは、免疫組織化学(IHC)によって測定される、請求項20に記載の方法。
- 前記患者にステロイドを投与することを更に含む、請求項1〜21のいずれか一項に記載の方法。
- 前記ステロイドはデキサメタゾンである、請求項22に記載の方法。
- 前記投与により、腫瘍径が減少する、請求項1〜22のいずれか一項に記載の方法。
- 前記癌は卵巣癌であり、前記投与によりCA125が減少する、請求項1〜16及び請求項18〜25のいずれか一項に記載の方法。
- 前記投与により、副作用が減少する、請求項1〜25のいずれか一項に記載の方法。
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PCT/US2014/037911 WO2014186403A2 (en) | 2013-05-14 | 2014-05-13 | Anti-folr1 immunoconjugate dosing regimens |
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JP2021062774A Withdrawn JP2021102648A (ja) | 2013-05-14 | 2021-04-01 | 抗folr1免疫複合体投与計画 |
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JP2023145920A Pending JP2023162436A (ja) | 2013-05-14 | 2023-09-08 | 抗folr1免疫複合体投与計画 |
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KR (4) | KR20160020421A (ja) |
CN (1) | CN105308072A (ja) |
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BR (1) | BR112015028244A2 (ja) |
CA (1) | CA2911499A1 (ja) |
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RU (1) | RU2015149285A (ja) |
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IL299620A (en) | 2012-08-31 | 2023-03-01 | Immunogen Inc | Tests and diagnostic kits for the detection of folate receptor 1 |
SG10201907501QA (en) | 2013-08-30 | 2019-10-30 | Immunogen Inc | Antibodies and assays for detection of folate receptor 1 |
CN106164093A (zh) * | 2013-10-08 | 2016-11-23 | 伊缪诺金公司 | 抗folr1免疫偶联物给药方案 |
AU2016323968B2 (en) | 2015-09-17 | 2023-07-06 | Immunogen, Inc. | Therapeutic combinations comprising anti-FOLR1 immunoconjugates |
US20180236098A1 (en) | 2016-08-12 | 2018-08-23 | L.E.A.F. Holdings Group Llc | Alpha and gamma-d polyglutamated antifolates and uses thereof |
CN109789212A (zh) | 2016-08-12 | 2019-05-21 | L.E.A.F.控股集团公司 | 聚谷氨酸化抗叶酸剂及其用途 |
EP3684814A1 (en) | 2017-09-18 | 2020-07-29 | Sutro Biopharma, Inc. | Anti-folate receptor alpha antibody conjugates and their uses |
US11730738B2 (en) | 2018-02-07 | 2023-08-22 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated pralatrexate and uses thereof |
US11779584B2 (en) | 2018-02-07 | 2023-10-10 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated pemetrexed and uses thereof |
US12048766B2 (en) | 2018-02-14 | 2024-07-30 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated tetrahydrofolates and uses thereof |
WO2019160734A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated lometrexol and uses thereof |
CA3090753A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated pralatrexate and uses thereof |
CN115925952A (zh) | 2018-03-13 | 2023-04-07 | 东莞凡恩世生物医药有限公司 | 抗叶酸受体1抗体及其用途 |
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JP2022530524A (ja) | 2019-04-29 | 2022-06-29 | イミュノジェン, インコーポレイテッド | バイパラトピックFR-α抗体及びイムノコンジュゲート |
CN112794911B (zh) * | 2021-04-14 | 2021-08-03 | 上海偌妥生物科技有限公司 | 人源化抗叶酸受体1抗体及其应用 |
WO2023116911A1 (zh) * | 2021-12-24 | 2023-06-29 | 百奥泰生物制药股份有限公司 | 抗FRα抗体及其抗体药物偶联物和用途 |
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MX2019008028A (es) | 2019-09-06 |
RU2015149285A (ru) | 2017-06-19 |
MX2015015735A (es) | 2016-03-31 |
KR20220054700A (ko) | 2022-05-03 |
JP2018197249A (ja) | 2018-12-13 |
CN105308072A (zh) | 2016-02-03 |
KR20240068778A (ko) | 2024-05-17 |
SG11201509043RA (en) | 2015-12-30 |
IL268180A (en) | 2019-09-26 |
AU2019250121A1 (en) | 2019-10-31 |
US20170239367A1 (en) | 2017-08-24 |
JP2021102648A (ja) | 2021-07-15 |
KR20230066648A (ko) | 2023-05-16 |
US20140363451A1 (en) | 2014-12-11 |
US20220378694A1 (en) | 2022-12-01 |
JP2023162436A (ja) | 2023-11-08 |
CA2911499A1 (en) | 2014-11-20 |
HK1222340A1 (zh) | 2017-06-30 |
EP2997044A2 (en) | 2016-03-23 |
AU2021250837A1 (en) | 2021-11-04 |
SG10201701096UA (en) | 2017-03-30 |
WO2014186403A2 (en) | 2014-11-20 |
US20200046634A1 (en) | 2020-02-13 |
AU2014265587A1 (en) | 2015-11-19 |
KR20160020421A (ko) | 2016-02-23 |
BR112015028244A2 (pt) | 2017-09-19 |
EP2997044A4 (en) | 2017-03-22 |
WO2014186403A3 (en) | 2015-01-08 |
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