IL295626A - קומבינצית תרופות משולשת הכוללת dabrafenib, מעכב erk ומעכב raf - Google Patents
קומבינצית תרופות משולשת הכוללת dabrafenib, מעכב erk ומעכב rafInfo
- Publication number
- IL295626A IL295626A IL295626A IL29562622A IL295626A IL 295626 A IL295626 A IL 295626A IL 295626 A IL295626 A IL 295626A IL 29562622 A IL29562622 A IL 29562622A IL 295626 A IL295626 A IL 295626A
- Authority
- IL
- Israel
- Prior art keywords
- braf
- dabrafenib
- compound
- seq
- pharmaceutic
- Prior art date
Links
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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- A—HUMAN NECESSITIES
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- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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PCT/IB2021/051641 WO2021171260A2 (en) | 2020-02-28 | 2021-02-26 | A triple pharmaceutical combination comprising dabrafenib, an erk inhibitor and a raf inhibitor or a pd-1 inhibitor |
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IL295626A true IL295626A (he) | 2022-10-01 |
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IL (1) | IL295626A (he) |
TW (1) | TW202146024A (he) |
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---|---|---|---|---|
IL129299A0 (en) | 1999-03-31 | 2000-02-17 | Mor Research Applic Ltd | Monoclonal antibodies antigens and diagnosis of malignant diseases |
IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
ATE514713T1 (de) | 2002-12-23 | 2011-07-15 | Wyeth Llc | Antikörper gegen pd-1 und ihre verwendung |
NZ563193A (en) | 2005-05-09 | 2010-05-28 | Ono Pharmaceutical Co | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
EP2170959B1 (en) | 2007-06-18 | 2013-10-02 | Merck Sharp & Dohme B.V. | Antibodies to human programmed death receptor pd-1 |
US8168757B2 (en) | 2008-03-12 | 2012-05-01 | Merck Sharp & Dohme Corp. | PD-1 binding proteins |
UA103319C2 (en) | 2008-05-06 | 2013-10-10 | Глаксосмитклайн Ллк | Thiazole- and oxazole-benzene sulfonamide compounds |
CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
EP2342229A1 (en) | 2008-09-12 | 2011-07-13 | ISIS Innovation Limited | Pd-1 specific antibodies and uses thereof |
CA2998281C (en) | 2008-09-26 | 2022-08-16 | Dana-Farber Cancer Institute, Inc. | Human anti-pd-1 antobodies and uses therefor |
US20130017199A1 (en) | 2009-11-24 | 2013-01-17 | AMPLIMMUNE ,Inc. a corporation | Simultaneous inhibition of pd-l1/pd-l2 |
EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
CN103608040B (zh) | 2011-04-20 | 2017-03-01 | 米迪缪尼有限公司 | 结合b7‑h1和pd‑1的抗体和其他分子 |
CA2840018C (en) | 2011-07-24 | 2019-07-16 | Curetech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
US9242969B2 (en) | 2013-03-14 | 2016-01-26 | Novartis Ag | Biaryl amide compounds as kinase inhibitors |
SG11201508528TA (en) | 2013-05-02 | 2015-11-27 | Anaptysbio Inc | Antibodies directed against programmed death-1 (pd-1) |
CA3175360C (en) | 2013-05-31 | 2024-05-28 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind pd-1 |
US20160145355A1 (en) | 2013-06-24 | 2016-05-26 | Biomed Valley Discoveries, Inc. | Bispecific antibodies |
CN112457403B (zh) | 2013-09-13 | 2022-11-29 | 广州百济神州生物制药有限公司 | 抗pd1抗体及其作为治疗剂与诊断剂的用途 |
SI3063143T1 (sl) | 2013-11-01 | 2018-09-28 | Novartis Ag, | Aminoheteroaril benzamidi kot inhibitorji kinaze |
HUE046249T2 (hu) | 2013-12-12 | 2020-02-28 | Shanghai hengrui pharmaceutical co ltd | PD-1 antitest, antigén-kötõ fragmense, és gyógyászati alkalmazása |
TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
AU2017329090B9 (en) * | 2016-09-19 | 2019-09-05 | Novartis Ag | Therapeutic combinations comprising a RAF inhibitor and a ERK inhibitor |
US20210121460A1 (en) * | 2018-03-30 | 2021-04-29 | Novartis Ag | A triple pharmaceutical combination comprising dabrafenib, trametinib and an erk inhibitor |
-
2021
- 2021-02-26 AU AU2021225491A patent/AU2021225491A1/en not_active Abandoned
- 2021-02-26 IL IL295626A patent/IL295626A/he unknown
- 2021-02-26 TW TW110107183A patent/TW202146024A/zh unknown
- 2021-02-26 WO PCT/IB2021/051641 patent/WO2021171260A2/en unknown
- 2021-02-26 JP JP2022551299A patent/JP2023516155A/ja active Pending
- 2021-02-26 EP EP21739775.1A patent/EP4110341A2/en active Pending
- 2021-02-26 CN CN202180017128.7A patent/CN115279374A/zh active Pending
- 2021-02-26 KR KR1020227032733A patent/KR20220148846A/ko unknown
- 2021-02-26 CA CA3173356A patent/CA3173356A1/en active Pending
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KR20220148846A (ko) | 2022-11-07 |
WO2021171260A3 (en) | 2021-10-07 |
CN115279374A (zh) | 2022-11-01 |
TW202146024A (zh) | 2021-12-16 |
EP4110341A2 (en) | 2023-01-04 |
CA3173356A1 (en) | 2021-09-02 |
AU2021225491A1 (en) | 2022-10-20 |
JP2023516155A (ja) | 2023-04-18 |
WO2021171260A2 (en) | 2021-09-02 |
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