CA2999898A1 - Method of treating malignant rhabdoid tumor of the ovary (mrto)/small cell cancer of the ovary of the hypercalcemic type (sccoht) with an ezh2 inhibitor - Google Patents
Method of treating malignant rhabdoid tumor of the ovary (mrto)/small cell cancer of the ovary of the hypercalcemic type (sccoht) with an ezh2 inhibitor Download PDFInfo
- Publication number
- CA2999898A1 CA2999898A1 CA2999898A CA2999898A CA2999898A1 CA 2999898 A1 CA2999898 A1 CA 2999898A1 CA 2999898 A CA2999898 A CA 2999898A CA 2999898 A CA2999898 A CA 2999898A CA 2999898 A1 CA2999898 A1 CA 2999898A1
- Authority
- CA
- Canada
- Prior art keywords
- smarca4
- subject
- ezh2
- ezh2 inhibitor
- sccoht
- 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.)
- Abandoned
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
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- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562233146P | 2015-09-25 | 2015-09-25 | |
| US62/233,146 | 2015-09-25 | ||
| US201562252188P | 2015-11-06 | 2015-11-06 | |
| US62/252,188 | 2015-11-06 | ||
| PCT/US2016/053673 WO2017053930A2 (en) | 2015-09-25 | 2016-09-26 | Method of treating malignant rhabdoid tumor of the ovary (mrto)/small cell cancer of the ovary of the hypercalcemic type (sccoht) with an ezh2 inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2999898A1 true CA2999898A1 (en) | 2017-03-30 |
Family
ID=58387531
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2999898A Abandoned CA2999898A1 (en) | 2015-09-25 | 2016-09-26 | Method of treating malignant rhabdoid tumor of the ovary (mrto)/small cell cancer of the ovary of the hypercalcemic type (sccoht) with an ezh2 inhibitor |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20180296563A1 (OSRAM) |
| EP (1) | EP3352761A4 (OSRAM) |
| JP (1) | JP7013369B2 (OSRAM) |
| KR (1) | KR20180054793A (OSRAM) |
| CN (2) | CN114533880B (OSRAM) |
| AU (2) | AU2016325643B2 (OSRAM) |
| CA (1) | CA2999898A1 (OSRAM) |
| EA (1) | EA201890801A1 (OSRAM) |
| IL (2) | IL258302A (OSRAM) |
| MX (2) | MX2018003663A (OSRAM) |
| SG (1) | SG10201908323TA (OSRAM) |
| WO (1) | WO2017053930A2 (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| MX376008B (es) | 2012-10-15 | 2025-03-07 | Epizyme Inc | Inhibidor de ezh2 para usarse en el tratamiento de sarcoma epiteloide. |
| MX2018002344A (es) | 2015-08-24 | 2018-07-06 | Epizyme Inc | Metodo para tratar el cancer. |
| AU2016325643B2 (en) * | 2015-09-25 | 2022-07-21 | Epizyme, Inc. | Method of treating malignant rhabdoid tumor or small cell cancer of the ovary of the hypercalcemic type |
| EP3407978A4 (en) | 2016-01-29 | 2020-01-15 | Epizyme Inc | POLYTHERAPY FOR THE TREATMENT OF CANCER |
| CA3025933A1 (en) | 2016-06-01 | 2017-12-07 | Epizyme, Inc. | Use of ezh2 inhibitors for treating cancer |
| WO2017214373A1 (en) * | 2016-06-08 | 2017-12-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| JP2019521988A (ja) | 2016-06-17 | 2019-08-08 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤 |
| EP3576729A4 (en) * | 2017-02-02 | 2021-04-14 | Epizyme, Inc. | CANCER TREATMENT MODALITIES |
| US11642346B2 (en) | 2017-03-31 | 2023-05-09 | Epizyme, Inc. | Combination therapy for treating cancer |
| JP2020522687A (ja) | 2017-06-02 | 2020-07-30 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤の使用 |
| EP3678663A4 (en) | 2017-09-05 | 2021-06-02 | Epizyme, Inc. | POLYTHERAPY FOR CANCER TREATMENT |
| CN113874013A (zh) * | 2019-03-26 | 2021-12-31 | 转化药物开发有限责任公司 | 治疗卵巢恶性横纹肌样瘤和高钙血症型卵巢小细胞癌的方法 |
| JP2022545467A (ja) * | 2019-08-22 | 2022-10-27 | ジュノー セラピューティクス インコーポレイテッド | Ｔ細胞療法とｚｅｓｔｅホモログ２エンハンサー（ＥＺＨ２）阻害剤との併用療法および関連方法 |
| CN110950834A (zh) * | 2019-11-26 | 2020-04-03 | 济南大学 | 新型eed-ezh2相互作用小分子抑制剂的确定和评价 |
| CN110960525A (zh) * | 2019-11-26 | 2020-04-07 | 济南大学 | 新型eed-ezh2相互作用抑制剂的确定和评价 |
| CN115666725A (zh) * | 2020-05-28 | 2023-01-31 | Epizyme股份有限公司 | Ezh2抑制剂用于治疗癌症的用途 |
| CN115786261B (zh) * | 2022-11-28 | 2024-12-06 | 复旦大学附属妇产科医院 | 一种卵巢高钙血症型小细胞癌细胞系及其用途 |
| CN119215165A (zh) * | 2023-06-29 | 2024-12-31 | 复旦大学附属妇产科医院 | Plk1抑制剂在制备治疗卵巢高钙血症型小细胞癌的药物中的应用 |
Family Cites Families (10)
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|---|---|---|---|---|
| PL2614369T3 (pl) * | 2010-09-10 | 2016-08-31 | Epizyme Inc | Sposób określania przydatności inhibitorów ludzkiego ezh2 w leczeniu |
| EP2709629B1 (en) * | 2011-05-16 | 2017-10-11 | Ulrike Nuber | Novel cancer therapies and methods |
| EP2825161B1 (en) * | 2012-03-12 | 2019-01-02 | Epizyme, Inc. | Inhibitors of human ezh2, and methods of use thereof |
| CN104768555B (zh) * | 2012-04-13 | 2018-10-30 | Epizyme股份有限公司 | 用于治疗癌症的联合治疗 |
| MX376008B (es) * | 2012-10-15 | 2025-03-07 | Epizyme Inc | Inhibidor de ezh2 para usarse en el tratamiento de sarcoma epiteloide. |
| US20140120083A1 (en) * | 2012-11-01 | 2014-05-01 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2015103431A1 (en) * | 2013-12-31 | 2015-07-09 | Memorial Sloan-Kettering Cancer Center | Compositions and methods for the diagnosis and treatment of ovarian cancers that are associated with reduced smarca4 gene expression or protein function |
| EA201691872A1 (ru) * | 2014-03-19 | 2017-04-28 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения для применения в лечении pi3k-гамма-опосредованных расстройств |
| MX2018002344A (es) * | 2015-08-24 | 2018-07-06 | Epizyme Inc | Metodo para tratar el cancer. |
| AU2016325643B2 (en) * | 2015-09-25 | 2022-07-21 | Epizyme, Inc. | Method of treating malignant rhabdoid tumor or small cell cancer of the ovary of the hypercalcemic type |
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- 2016-09-26 WO PCT/US2016/053673 patent/WO2017053930A2/en not_active Ceased
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- 2016-09-26 CN CN201680063541.6A patent/CN108349958B/zh active Active
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- 2016-09-26 CA CA2999898A patent/CA2999898A1/en not_active Abandoned
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2018
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2019
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2021
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| KR20180054793A (ko) | 2018-05-24 |
| US20200138825A1 (en) | 2020-05-07 |
| AU2022256115A1 (en) | 2022-11-17 |
| CN114533880A (zh) | 2022-05-27 |
| JP2018529698A (ja) | 2018-10-11 |
| CN114533880B (zh) | 2023-08-22 |
| WO2017053930A3 (en) | 2018-04-12 |
| AU2016325643A1 (en) | 2018-04-12 |
| IL280760A (en) | 2021-04-29 |
| EP3352761A4 (en) | 2019-04-24 |
| US20210121470A1 (en) | 2021-04-29 |
| CN108349958A (zh) | 2018-07-31 |
| JP7013369B2 (ja) | 2022-02-15 |
| MX2022013390A (es) | 2023-01-04 |
| WO2017053930A2 (en) | 2017-03-30 |
| EP3352761A2 (en) | 2018-08-01 |
| EA201890801A1 (ru) | 2018-09-28 |
| IL258302A (en) | 2018-05-31 |
| US20180296563A1 (en) | 2018-10-18 |
| MX2018003663A (es) | 2018-08-14 |
| SG10201908323TA (en) | 2019-10-30 |
| CN108349958B (zh) | 2022-02-15 |
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