JP2019534314A - エクソン14スキッピング変異(複数可)またはエクソン14スキッピング表現型を有するがんの併用療法 - Google Patents
エクソン14スキッピング変異(複数可)またはエクソン14スキッピング表現型を有するがんの併用療法 Download PDFInfo
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Abstract
Description
METエクソン14スキッピング変異(複数可)を保有する異種移植腫瘍モデルにおけるメレスチニブ(LY2801653)とエミベツズマブ(LY2875358)との組み合わせの評価
Hs746t由来のヒト胃癌異種移植マウスモデルにおける、エミベツズマブと組み合わせたメレスチニブの有効性を決定し、いずれかの単剤療法の効果と併用効果を比較するために、本質的に以下に記載されるように実施される研究が行われ得る。Hs746tは、METエクソン14スキッピング変異(複数可)およびMET増幅を有することが知られている胃がん細胞株である(Asaoka et al.,Biochem Biophys Res Commun394:1042−1046)。
この研究では、雌胸腺欠損ヌードマウス(Envigo)を使用する。食料および水は自由に摂取可能である。いずれの実験操作の前にも動物を1週間順応させる。この研究は、AAALACの認定を受けた施設のガイドラインに従って行われる。
メレスチニブは、IC50=34nMでHs746t細胞増殖を阻害し、65〜100nMでpMETを完全に排除する。エミベツズマブは、Hs746t細胞増殖をわずかに阻害し(IC50>100nM)、10〜20%の細胞表面METを減少させ、pMET発現に対して効果を示さない(130〜650nMで)。
METエクソン14スキッピング変異(複数可)を保有する異種移植腫瘍モデルにおけるメレスチニブ(LY2801653)およびエミベツズマブ(LY2875358)の逐次投与と同時投与の評価
Hs746t由来ヒト胃癌異種移植マウスモデルにおける、エミベツズマブと逐次的および同時併用した低用量メレスチニブの有効性を決定し、より高用量のエミベツズマブ単剤療法の効果と併用効果を比較するために、本質的に以下に記載されるように実施される研究が行われ得る。
この研究では、雌胸腺欠損ヌードマウス(Envigo)を使用する。食料および水は自由に摂取可能である。いずれの実験操作の前にも動物を1週間順応させる。この研究は、AAALACの認定を受けた施設のガイドラインに従って行われる。
Hs746t異種移植モデルでは、メレスチニブ(6mg/kg、毎日、58日間)は、一過性の腫瘍退縮をもたらし、最大の退縮(30.2%)が27日目(投薬7日目)に起こり、その後、治療中に再成長し、37日目までに、腫瘍体積は約500mm3に近づく。37日目のメレスチニブ治療へのエミベツズマブ(10mg/kg、毎週、6サイクル)の逐次添加は、5/6匹の動物で腫瘍の退縮をもたらし、2/6匹の動物において、投薬完了後26日の観察期間にわたり腫瘍の退縮が完了し、再成長はない。治療後の観察中にゆっくりとした再成長を伴う一過性の腫瘍退縮は、追加の2/6匹の動物において明らかである。追加の動物では、治療後の観察中にゆっくりとした再成長を伴って約50mm3まで腫瘍の退縮が起こる。1匹の無応答動物では、コホート全体の中で、エミベツズマブ治療が開始される37日目の腫瘍のサイズが特に最大(約1200mm3)である。
<配列番号1、PRT1、人工配列>エミベツズマブLCVR
DIQMTQSPSSLSASVGDRVTITCSVSSSVSSIYLHWYQQKPGKAPKLLIYSTSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQVYSGYPLTFGGGTKVEIK
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCAGTGTCAGCTCAAGTGTATCCTCCATTTACTTGCACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGCACATCCAACTTGGCTTCTGGAGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAGTCTACAGTGGTTACCCGCTCACGTTCGGCGGAGGGACCAAGGTGGAGATCAAA
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGRVNPNRRGTTYNQKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARANWLDYWGQGTTVTVSS
CAGGTTCAGCTGGTGCAGTCTGGTGCTGAGGTGAAGAAGCCTGGTGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGTTACACCTTTACCGACTACTACATGCACTGGGTGCGTCAGGCCCCTGGTCAAGGTCTTGAGTGGATGGGTCGTGTTAATCCTAACCGGAGGGGTACTACCTACAACCAGAAATTCGAGGGCCGTGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGCGTAGCCTGCGTTCTGACGACACGGCCGTGTATTACTGTGCGCGTGCGAACTGGCTTGACTACTGGGGCCAGGGCACCACCGTCACCGTCTCC
DIQMTQSPSSLSASVGDRVTITCSVSSSVSSIYLHWYQQKPGKAPKLLIYSTSNLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQVYSGYPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCAGTGTCAGCTCAAGTGTATCCTCCATTTACTTGCACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGCACATCCAACTTGGCTTCTGGAGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATTTTGCAACTTACTACTGTCAAGTCTACAGTGGTTACCCGCTCACGTTCGGCGGAGGGACCAAGGTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGC
QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGRVNPNRRGTTYNQKFEGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARANWLDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
CAGGTTCAGCTGGTGCAGTCTGGTGCTGAGGTGAAGAAGCCTGGTGCCTCAGTGAAGGTCTCCTGCAAGGCTTCTGGTTACACATTCACTGACTACTACATGCACTGGGTGCGTCAGGCCCCTGGTCAAGGTCTTGAGTGGATGGGTCGTGTTAATCCTAACCGGAGGGGTACTACCTACAACCAGAAATTCGAGGGCCGTGTCACCATGACCACAGACACATCCACGAGCACAGCCTACATGGAGCTGCGTAGCCTGCGTTCTGACGACACGGCCGTGTATTACTGTGCGCGTGCGAACTGGCTTGACTACTGGGGCCAGGGCACCACCGTCACCGTCTCCTCCGCCTCCACCAAGGGCCCATCGGTCTTCCCGCTAGCGCCCTGCTCCAGGAGCACCTCCGAGAGCACAGCCGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACGAAGACCTACACCTGCAACGTAGATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGTCCAAATATGGTCCCCCATGCCCACCCTGCCCAGCACCTGAGGCCGCCGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAACCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGACGTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTGGAGTGGGAAAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGGCAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCTGGGT
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFT
ECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFT
ECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKR
STKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLG
EIQMTQSPASLSASVGETVTITCRASENIYSYLAWYQRKQGRSPQLLVYNAKPLAEGVPSRFSGSGSGTQFSLKINSLQPEDFGTYYCQHHYGTPFTFGSGTRLEIKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC
EVQLQQSGTVLARPGASVKMSCKASGYSFTSYWMYWVKQRPGQGLEWIGGFHPRNSGTNYNQKFKGKAKLTAVTSASTAYMELSSLTNEDSAVYYCTRGYYYDGSFTYWGQGTLVTVSAAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVPSSTWPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK
また、本発明は以下を提供する。
[1]
患者におけるMETエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療する方法であって、そのような治療を必要とする患者に、有効量のメレスチニブ、またはその薬学的に許容される塩を有効量のエミベツズマブと組み合わせて投与することを含む、方法。
[2]
メレスチニブ、またはその薬学的に許容される塩が、28日サイクルで毎日約60mg〜約160mgの用量で投与され、エミベツズマブが、メレスチニブ投薬の前記28日サイクルの約1日目および約15日目に約500mg〜約2000mgの用量で投与される、[1]に記載の方法。
[3]
メレスチニブ、またはその薬学的に許容される塩が、28日サイクルで毎日約80mg〜約120mgの用量で投与され、エミベツズマブが、メレスチニブ投薬の前記28日サイクルの約1日目および約15日目に約750mgの用量で投与される、[2]に記載の方法。
[4]
メレスチニブ、またはその薬学的に許容される塩が、経口投与され、エミベツズマブが、静脈内投与される、[2]または[3]に記載の方法。
[5]
前記がんが、胃がんまたは肺がんである、[1]〜[4]のいずれか一項に記載の方法。
[6]
前記がんが、肺がんである、[1]〜[5]のいずれか一項に記載の方法。
[7]
前記がんが、非小細胞肺がんである、[6]に記載の方法。
[8]
METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんの治療における同時、個別、または逐次使用のための、有効量の化合物メレスチニブ、またはその薬学的に許容される塩と組み合わせた有効量のエミベツズマブを含む、キット。
[9]
前記がんが、胃がんまたは肺がんである、[8]に記載の使用のためのキット。
[10]
前記がんが、肺がんである、[8]または[9]に記載の使用のためのキット。
[11]
前記がんが、非小細胞肺がんである、[10]に記載の使用のためのキット。
[12]
METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんの前記治療における同時、個別、または逐次使用のための、エミベツズマブと、メリスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物。
[13]
前記がんが、胃がんまたは肺がんである、[12]に記載の使用のための組み合わせ物。
[14]
前記がんが、肺がんである、[12]または[13]に記載の使用のための組み合わせ物。
[15]
前記がんが、非小細胞肺がんである、[14]に記載の使用のための組み合わせ物。
[16]
療法における、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
[17]
METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療するための、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
[18]
METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療するための医薬を製造するための、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
[19]
前記がんが、胃がんまたは肺がんである、[16]〜[18]のいずれか一項に記載の使用。
[20]
前記がんが、肺がんである、[16]〜[18]のいずれか一項に記載の使用。
[21]
前記がんが、非小細胞肺がんにおける、[16]〜[18]のいずれか一項に記載の使用。
Claims (21)
- 患者におけるMETエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療する方法であって、そのような治療を必要とする患者に、有効量のメレスチニブ、またはその薬学的に許容される塩を有効量のエミベツズマブと組み合わせて投与することを含む、方法。
- メレスチニブ、またはその薬学的に許容される塩が、28日サイクルで毎日約60mg〜約160mgの用量で投与され、エミベツズマブが、メレスチニブ投薬の前記28日サイクルの約1日目および約15日目に約500mg〜約2000mgの用量で投与される、請求項1に記載の方法。
- メレスチニブ、またはその薬学的に許容される塩が、28日サイクルで毎日約80mg〜約120mgの用量で投与され、エミベツズマブが、メレスチニブ投薬の前記28日サイクルの約1日目および約15日目に約750mgの用量で投与される、請求項2に記載の方法。
- メレスチニブ、またはその薬学的に許容される塩が、経口投与され、エミベツズマブが、静脈内投与される、請求項2または3に記載の方法。
- 前記がんが、胃がんまたは肺がんである、請求項1〜4のいずれか一項に記載の方法。
- 前記がんが、肺がんである、請求項1〜5のいずれか一項に記載の方法。
- 前記がんが、非小細胞肺がんである、請求項6に記載の方法。
- METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんの治療における同時、個別、または逐次使用のための、有効量の化合物メレスチニブ、またはその薬学的に許容される塩と組み合わせた有効量のエミベツズマブを含む、キット。
- 前記がんが、胃がんまたは肺がんである、請求項8に記載の使用のためのキット。
- 前記がんが、肺がんである、請求項8または9に記載の使用のためのキット。
- 前記がんが、非小細胞肺がんである、請求項10に記載の使用のためのキット。
- METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんの前記治療における同時、個別、または逐次使用のための、エミベツズマブと、メリスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物。
- 前記がんが、胃がんまたは肺がんである、請求項12に記載の使用のための組み合わせ物。
- 前記がんが、肺がんである、請求項12または13に記載の使用のための組み合わせ物。
- 前記がんが、非小細胞肺がんである、請求項14に記載の使用のための組み合わせ物。
- 療法における、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
- METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療するための、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
- METエクソン14スキッピングまたはMETエクソン14スキッピング表現型を保有する腫瘍を有するがんを治療するための医薬を製造するための、エミベツズマブと、メレスチニブ、またはその薬学的に許容される塩と、を含む、組み合わせ物の使用。
- 前記がんが、胃がんまたは肺がんである、請求項16〜18のいずれか一項に記載の使用。
- 前記がんが、肺がんである、請求項16〜18のいずれか一項に記載の使用。
- 前記がんが、非小細胞肺がんにおける、請求項16〜18のいずれか一項に記載の使用。
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US201662422887P | 2016-11-16 | 2016-11-16 | |
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US201762555779P | 2017-09-08 | 2017-09-08 | |
US62/555,779 | 2017-09-08 | ||
PCT/US2017/061028 WO2018093669A1 (en) | 2016-11-16 | 2017-11-10 | Combination therapy for cancer with exon 14 skipping mutation(s) or exon 14 skipping phenotype |
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US (1) | US20210283249A1 (ja) |
EP (1) | EP3541383B1 (ja) |
JP (1) | JP6709340B2 (ja) |
CN (1) | CN109963562A (ja) |
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WO (1) | WO2018093669A1 (ja) |
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ES2420835T3 (es) | 1999-04-09 | 2013-08-27 | Kyowa Hakko Kirin Co., Ltd. | Procedimiento para controlar la actividad de las moléculas inmunofuncionales |
JP4668498B2 (ja) | 1999-10-19 | 2011-04-13 | 協和発酵キリン株式会社 | ポリペプチドの製造方法 |
US6946292B2 (en) | 2000-10-06 | 2005-09-20 | Kyowa Hakko Kogyo Co., Ltd. | Cells producing antibody compositions with increased antibody dependent cytotoxic activity |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
MXPA04003798A (es) | 2001-10-25 | 2004-07-30 | Genentech Inc | Composiciones de glicoproteina. |
US20040093621A1 (en) | 2001-12-25 | 2004-05-13 | Kyowa Hakko Kogyo Co., Ltd | Antibody composition which specifically binds to CD20 |
EA200401325A1 (ru) | 2002-04-09 | 2005-04-28 | Киова Хакко Когио Ко., Лтд. | Клетки с модифицированным геномом |
SI1572744T1 (sl) | 2002-12-16 | 2010-09-30 | Genentech Inc | Imunoglobulinske variante in njihove uporabe |
US20050106667A1 (en) | 2003-08-01 | 2005-05-19 | Genentech, Inc | Binding polypeptides with restricted diversity sequences |
US20080226635A1 (en) | 2006-12-22 | 2008-09-18 | Hans Koll | Antibodies against insulin-like growth factor I receptor and uses thereof |
TWI365185B (en) | 2008-07-24 | 2012-06-01 | Lilly Co Eli | Amidophenoxyindazoles useful as inhibitors of c-met |
PA8849001A1 (es) | 2008-11-21 | 2010-06-28 | Lilly Co Eli | Anticuerpos de c-met |
RU2013114360A (ru) | 2010-08-31 | 2014-10-10 | Дженентек, Инк. | Биомаркеры и способы лечения |
CN104334581B (zh) | 2012-05-09 | 2018-02-02 | 伊莱利利公司 | 抗‑c‑Met抗体 |
TW201622744A (zh) * | 2014-03-04 | 2016-07-01 | 美國禮來大藥廠 | 癌症之組合療法 |
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JP6709340B2 (ja) | 2020-06-10 |
EP3541383A1 (en) | 2019-09-25 |
WO2018093669A1 (en) | 2018-05-24 |
CN109963562A (zh) | 2019-07-02 |
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