JP2018507220A - がんの治療のための方法、組成物、及びキット - Google Patents
がんの治療のための方法、組成物、及びキット Download PDFInfo
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Abstract
Description
本出願は、図面を含むその開示の全体が出典明示によりここに援用される、2015年2月19日出願の米国仮出願第62/118350号及び2015年4月20日出願の米国仮出願第62/150235号に対して優先権を主張する。
次の本発明の説明は、本発明の様々な実施態様を例証することを単に意図したものである。而して、検討される特定の変更は、本発明の範囲を限定するものと解釈されるべきではない。当業者には、本発明の範囲から逸脱することなく様々な均等態様、変更、及び修正を実施することができることは明らかであり、そのような均等実施態様がここに含まれるべきであることが理解される。
FGFR3陽性MC38マウス結腸直腸腫瘍細胞株において、FGFR3発現を、FGFR3用の市販ELISAキットを使用して確認した。続いて、細胞株を増殖させ、1×106個のMC38腫瘍細胞を、8〜12週齢の雌C57BL/6マウスの側腹部に皮下移植した。腫瘍が80〜120mm3の平均サイズに達したところで、動物をペアマッチングさせ、表1に記載のように処置を開始した。
その後の研究において、MC38腫瘍細胞を8〜12週齢であった雌C57BL/6マウスの側腹部に皮下移植した。腫瘍が80〜120mm3の平均サイズに達したところで、動物をペアマッチングさせ、2つの処置群(1処置群につきn=6マウス)に分割した。第1群の対照マウスには週2回(「biwk」)の静脈内投与によりPBSを投与し、第2群のマウスには30mg/kgの静脈内投与により週2回B−701を投与した。処置の7日後と14日後に、各処置群からの3匹の動物を屠殺し、腫瘍を収集した。腫瘍の半分をパラフィン包埋のために処理し、第二の半分を、単個細胞懸濁液を調製するために使用し、フローサイトメトリー用に処理し、その結果を表2に示す。
FGFR3陽性のMadison109及びルイス肺癌マウスの肺がん細胞株において、FGFR3用の市販ELISAキットを使用して、FGFR3発現を確認した。続いて、細胞株を増殖させ、1×106個のルイス肺癌腫瘍細胞を、8〜12週齢であった雌C57BL/6マウスの側腹部に皮下移植した。加えて、1×106個のMadison109腫瘍細胞を、8〜12週齢であったCR雌BALB/cマウスの側腹部に皮下移植した。
(文献)
1.Bai等 Cancer Res 70:7630(2010)
2.Bumbaca等 MAbs 3:376(2011)
3.Brooks等 Clin Cancer Res 18:1855−1862(2012)
4.Grosso&Jure−Kunkel Cancer Immun 13:5(2013)
5.Lafitte等 Mol Cancer 12:83(2013)
6.Pardoll Nature Reviews Cancer 12:252−264(2012)
7.Sweiss等 “Molecular drivers of the non−T cell−inflamed tumor microenvironment in urothelial bladder cancer”J Clin Oncol (Meeting Abstracts)33(15)suppl(May20 Supplement)4511(2015)
8.Zhao等 Clin Cancer Res 16:5750(2010)
Claims (21)
- 治療上有効な量のFGFR3阻害剤を、治療上有効な量のPD1阻害剤と組み合わせて、投与することを含む、それを必要とする対象における固形腫瘍を治療する方法。
- FGFR3阻害剤が拮抗性FGFR3抗体である、請求項1に記載の方法。
- 拮抗性FGFR3抗体が、配列番号1に記載のアミノ酸配列を含むCDR−H1、配列番号2に記載のアミノ酸配列を含むCDR−H2、及び配列番号3に記載のアミノ酸配列を含むCDR−H3を含む、請求項2に記載の方法。
- 拮抗性FGFR3抗体が、配列番号7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3に記載の方法。
- 拮抗性FGFR3抗体が、配列番号4に記載のアミノ酸配列を含むCDR−L1、配列番号5に記載のアミノ酸配列を含むCDR−L2、及び配列番号6に記載のアミノ酸配列を含むCDR−L3を含む、請求項2に記載の方法。
- 拮抗性FGFR3抗体が、配列番号8に記載のアミノ酸配列を含む軽鎖可変領域を含む、請求項5に記載の方法。
- PD1阻害剤が拮抗性PD1抗体である、請求項1に記載の方法。
- 拮抗性PD1抗体が、ニボルマブ、ペンブロリズマブ、CT−011、MEDI−0680、及びRMP1−14からなる群から選択される、請求項7に記載の方法。
- PD1阻害剤が拮抗性PD1リガンド抗体である、請求項1に記載の方法。
- 拮抗性PD1リガンド抗体が、MEDI−4736、RG7446、BMS−936559、MSB0010718C、及びMPDL3280Aからなる群から選択される、請求項9に記載の方法。
- FGFR3阻害剤とPD1阻害剤を含有する薬学的組成物。
- 薬学的に許容可能な担体を更に含有する、請求項11に記載の組成物。
- FGFR3阻害剤が、拮抗性FGFR3抗体である、請求項11に記載の組成物。
- 拮抗性FGFR3抗体が、配列番号1に記載のアミノ酸配列を含むCDR−H1、配列番号2に記載のアミノ酸配列を含むCDR−H2、及び配列番号3に記載のアミノ酸配列を含むCDR−H3を含む、請求項13に記載の組成物。
- 拮抗性FGFR3抗体が、配列番号7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14に記載の組成物。
- 拮抗性FGFR3抗体が、配列番号4に記載のアミノ酸配列を含むCDR−L1、配列番号5に記載のアミノ酸配列を含むCDR−L2、及び配列番号6に記載のアミノ酸配列を含むCDR−L3を含む、請求項13に記載の組成物。
- 拮抗性FGFR3抗体が、配列番号8に記載のアミノ酸配列を含む軽鎖可変領域を含む、請求項16に記載の組成物。
- PD1阻害剤が拮抗性PD1抗体である、請求項11に記載の組成物。
- 拮抗性PD1抗体が、ニボルマブ、ペンブロリズマブ、CT−011、MEDI−0680、及びRMP1−14からなる群から選択される、請求項18に記載の組成物。
- PD1阻害剤が拮抗性PD1リガンド抗体である、請求項11に記載の組成物。
- 拮抗性PD1リガンド抗体が、MEDI−4736、RG7446、BMS−936559、MSB0010718C、及びMPDL3280Aからなる群から選択される、請求項20に記載の組成物。
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---|---|---|---|---|
HUE061117T2 (hu) | 2009-03-25 | 2023-05-28 | Genentech Inc | Anti-FGFR3 antitestek és eljárások alkalmazásukra |
GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
HUE053653T2 (hu) | 2014-03-26 | 2021-07-28 | Astex Therapeutics Ltd | FGFR inhibitor és IGF1R inhibitor kombinációi |
JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
EP3848034A1 (en) | 2014-03-26 | 2021-07-14 | Astex Therapeutics Limited | Cmet-inhibitors for use in delaying the emergence in resistance to fgfr inhibitors |
JOP20200201A1 (ar) | 2015-02-10 | 2017-06-16 | Astex Therapeutics Ltd | تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين |
CN108137546B (zh) | 2015-09-23 | 2021-07-27 | 詹森药业有限公司 | 双杂芳基取代的1,4-苯并二氮杂卓化合物及其用于治疗癌症的用途 |
CA2996857C (en) | 2015-09-23 | 2024-05-21 | Janssen Pharmaceutica Nv | Quinoxaline, quinoline and quinazolinone derivative compounds for the treatment of cancer |
CN110785184A (zh) * | 2017-02-06 | 2020-02-11 | 雷尼尔医疗公司 | 用于治疗癌症的方法,组合物和试剂盒 |
CN108440673B (zh) * | 2018-04-08 | 2021-08-17 | 海南医学院 | Fc融合蛋白PD1/FGFR1及其应用 |
US20200277387A1 (en) * | 2019-03-01 | 2020-09-03 | Rainier Therapeutics, Inc. | Methods and compositions for treating cancer |
CN113710244A (zh) * | 2019-06-03 | 2021-11-26 | 融合制药公司 | 用于治疗癌症的方法和组合物 |
CA3151395A1 (en) * | 2019-09-26 | 2021-04-01 | Waleed S. SHALABY | Use of fgfr inhibitors in fgfr-genetically altered cancers to enhance patient response to immune checkpoint inhibitors in sequential treatment settings |
AU2021327387A1 (en) | 2020-08-21 | 2023-05-04 | Genzyme Corporation | Fgfr3 antibodies and methods of use |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012521759A (ja) * | 2009-03-25 | 2012-09-20 | ジェネンテック, インコーポレイテッド | 抗fgfr3抗体およびこれを用いた方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI381848B (zh) * | 2008-10-20 | 2013-01-11 | Imclone Llc | 抗纖維母細胞生長因子受體-3 (fgfr-3) 抗體及包含其之醫藥組合物 |
WO2012088266A2 (en) * | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
UY34887A (es) * | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
BR112015001724A2 (pt) * | 2012-07-27 | 2018-04-03 | Genentech Inc | métodos de tratamento de condições relacionadas a fgfr3 |
MY183503A (en) * | 2013-07-16 | 2021-02-23 | Genentech Inc | Method of treating cancer using pd-1 axis binding antagonists and tigit inhibitors |
-
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- 2016-02-19 WO PCT/US2016/018634 patent/WO2016134234A1/en active Application Filing
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Non-Patent Citations (7)
Title |
---|
AZIJLI, K., ET AL.: "New develoopments in the treatment of metastatic melanoma: immune checkpoint inhibitors and targeted", ANTICANCER RESEARCH, vol. 34, JPN6019047568, 2014, pages 1493 - 1506, ISSN: 0004169415 * |
CHAMPIAT, S., ET AL.: "Incorporating immune-checkpoint inhibitors into systemic therapy of NSCLC", JOURNAL OF THORACIC ONCOLOGY, vol. 9, no. 2, JPN6019047569, February 2014 (2014-02-01), pages 144 - 153, XP008173876, ISSN: 0004169410, DOI: 10.1097/JTO.0000000000000074 * |
CHEN, S., ET AL.: "Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cell in a", CANCER IMMUNOLOGY RESEARCH, vol. 3, no. 2, JPN6019047571, 11 November 2014 (2014-11-11), pages 149 - 160, XP055373998, ISSN: 0004169412, DOI: 10.1158/2326-6066.CIR-14-0118 * |
LUKE, J. J., ET AL.: "Kinase inhibitors and immune check-point blockade for the treatment of metastatic melanoma and adven", EXPERT OPINION ON PHARMACOTHERAPY, vol. 14, no. 18, JPN6019047570, 21 October 2013 (2013-10-21), pages 2457 - 2462, XP055257629, ISSN: 0004169411, DOI: 10.1517/14656566.2013.849244 * |
MOMTAZ, P., ET AL.: "Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1) receptor pathway", PHARMACOGENOMICS AND PERSONALIZED MEDICINE, vol. 7, JPN6019047567, 2014, pages 357 - 365, ISSN: 0004169414 * |
STAGG, J., ET AL.: "Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD1", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 108, no. 17, JPN6019047572, 26 April 2011 (2011-04-26), pages 7142 - 7147, XP055079201, ISSN: 0004169413, DOI: 10.1073/pnas.1016569108 * |
TYKODI, S. S.: "PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence", ONCOTARGETS AND THERAPY, vol. 7, JPN6019047573, 2014, pages 1349 - 1359, ISSN: 0004169416 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018511611A (ja) * | 2015-04-03 | 2018-04-26 | アステックス、セラピューティックス、リミテッドAstex Therapeutics Limited | 癌治療のためのfgfr/pd−1併用療法 |
JP7134628B2 (ja) | 2015-04-03 | 2022-09-12 | アステックス、セラピューティックス、リミテッド | 癌治療のためのfgfr/pd-1併用療法 |
WO2022092085A1 (ja) * | 2020-10-28 | 2022-05-05 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療用医薬組成物 |
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IL253979A0 (en) | 2017-10-31 |
JP6774421B2 (ja) | 2020-10-21 |
JP7122357B2 (ja) | 2022-08-19 |
SG11201706727XA (en) | 2017-09-28 |
CA2976638A1 (en) | 2016-08-25 |
EP3258966A4 (en) | 2018-07-25 |
EP3258966A1 (en) | 2017-12-27 |
MX2017010595A (es) | 2018-11-12 |
BR112017017700A2 (pt) | 2018-07-31 |
CN107635583A (zh) | 2018-01-26 |
WO2016134234A1 (en) | 2016-08-25 |
AU2016219917B2 (en) | 2021-12-16 |
AU2016219917A1 (en) | 2017-09-07 |
JP2021020909A (ja) | 2021-02-18 |
KR20170137717A (ko) | 2017-12-13 |
AU2022200196A1 (en) | 2022-02-10 |
US20160243228A1 (en) | 2016-08-25 |
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