TW202146024A - 包含達拉菲尼、erk抑制劑和raf抑制劑或pd-1抑制劑之三重藥物組合 - Google Patents

包含達拉菲尼、erk抑制劑和raf抑制劑或pd-1抑制劑之三重藥物組合 Download PDF

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Publication number: TW202146024A
Authority: TW; Taiwan
Prior art keywords: cancer; compound; braf; dabrafenib; pharmaceutically acceptable
Prior art date: 2020-02-28

Application number

TW110107183A

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English (en)

Chinese (zh)

Inventor

凡瑟莉娜庫克

Original Assignee

瑞士商諾華公司

Priority date (The priority date 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 date listed.)

2020-02-28

Filing date

2021-02-26

Publication date

2021-12-16

2021-02-26 Application filed by 瑞士商諾華公司 filed Critical 瑞士商諾華公司

2021-12-16 Publication of TW202146024A publication Critical patent/TW202146024A/zh

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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

TW110107183A 2020-02-28 2021-02-26 包含達拉菲尼、erk抑制劑和raf抑制劑或pd-1抑制劑之三重藥物組合 TW202146024A (zh)

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US202062983020P	2020-02-28	2020-02-28
US62/983,020		2020-02-28

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TW202146024A true TW202146024A (zh)	2021-12-16

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TW110107183A TW202146024A (zh)	2020-02-28	2021-02-26	包含達拉菲尼、erk抑制劑和raf抑制劑或pd-1抑制劑之三重藥物組合

Country Status (9)

Country	Link
EP (1)	EP4110341A2 (fr)
JP (1)	JP2023516155A (fr)
KR (1)	KR20220148846A (fr)
CN (1)	CN115279374A (fr)
AU (1)	AU2021225491A1 (fr)
CA (1)	CA3173356A1 (fr)
IL (1)	IL295626A (fr)
TW (1)	TW202146024A (fr)
WO (1)	WO2021171260A2 (fr)

Family Cites Families (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
CN101899114A (zh)	2002-12-23	2010-12-01	惠氏公司	抗pd-1抗体及其用途
DK2439273T3 (da)	2005-05-09	2019-06-03	Ono Pharmaceutical Co	Humane monoklonale antistoffer til programmeret død-1(pd-1) og fremgangsmåder til behandling af cancer ved anvendelse af anti-pd-1- antistoffer alene eller i kombination med andre immunterapeutika
BR122017025062B8 (pt)	2007-06-18	2021-07-27	Merck Sharp & Dohme	anticorpo monoclonal ou fragmento de anticorpo para o receptor de morte programada humano pd-1, polinucleotídeo e composição compreendendo o referido anticorpo ou fragmento
EP2262837A4 (fr)	2008-03-12	2011-04-06	Merck Sharp & Dohme	Protéines de liaison avec pd-1
UA103319C2 (en)	2008-05-06	2013-10-10	Глаксосмитклайн Ллк	Thiazole- and oxazole-benzene sulfonamide compounds
JP2012500855A (ja)	2008-08-25	2012-01-12	アンプリミューン、インコーポレーテッド	Ｐｄ−１アンタゴニストおよび感染性疾患を処置するための方法
AU2009290544B2 (en)	2008-09-12	2015-07-16	Oxford University Innovation Limited	PD-1 specific antibodies and uses thereof
US8552154B2 (en)	2008-09-26	2013-10-08	Emory University	Anti-PD-L1 antibodies and uses therefor
WO2011066342A2 (fr)	2009-11-24	2011-06-03	Amplimmune, Inc.	Inhibition simultanée de pd-l1/pd-l2
EP2545078A1 (fr)	2010-03-11	2013-01-16	UCB Pharma, S.A.	Anticorps pd-1
JP6072771B2 (ja)	2011-04-20	2017-02-01	メディミューン，エルエルシー	Ｂ７−ｈ１およびｐｄ−１に結合する抗体およびその他の分子
CA2840018C (fr)	2011-07-24	2019-07-16	Curetech Ltd.	Variants d'anticorps monoclonaux immunomodulateurs humanises
US9242969B2 (en)	2013-03-14	2016-01-26	Novartis Ag	Biaryl amide compounds as kinase inhibitors
SMT202100065T1 (it)	2013-05-02	2021-03-15	Anaptysbio Inc	Anticorpi diretti contro la proteina della morte programmata (pd-1)
WO2014194302A2 (fr)	2013-05-31	2014-12-04	Sorrento Therapeutics, Inc.	Protéines de liaison à l'antigène qui se lient à pd-1
US20160145355A1 (en)	2013-06-24	2016-05-26	Biomed Valley Discoveries, Inc.	Bispecific antibodies
CN112552401B (zh)	2013-09-13	2023-08-25	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
AP2016009099A0 (en)	2013-11-01	2016-03-31	Novartis Ag	Aminoheteroaryl benzamides as kinase inhibitors
SG10201804945WA (en)	2013-12-12	2018-07-30	Shanghai hengrui pharmaceutical co ltd	Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof
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
PE20170255A1 (es)	2014-01-24	2017-03-22	Dana Farber Cancer Inst Inc	Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas
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
MX2020010231A (es) *	2018-03-30	2020-10-28	Novartis Ag	Una combinacion farmaceutica triple que comprende dabrafenib, trametinib y un inhibidor de erk.

2021
- 2021-02-26 EP EP21739775.1A patent/EP4110341A2/fr not_active Withdrawn
- 2021-02-26 AU AU2021225491A patent/AU2021225491A1/en not_active Abandoned
- 2021-02-26 TW TW110107183A patent/TW202146024A/zh unknown
- 2021-02-26 WO PCT/IB2021/051641 patent/WO2021171260A2/fr not_active Ceased
- 2021-02-26 JP JP2022551299A patent/JP2023516155A/ja active Pending
- 2021-02-26 KR KR1020227032733A patent/KR20220148846A/ko not_active Withdrawn
- 2021-02-26 CA CA3173356A patent/CA3173356A1/fr active Pending
- 2021-02-26 CN CN202180017128.7A patent/CN115279374A/zh active Pending
- 2021-02-26 IL IL295626A patent/IL295626A/en unknown

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Publication number	Publication date
WO2021171260A3 (fr)	2021-10-07
JP2023516155A (ja)	2023-04-18
KR20220148846A (ko)	2022-11-07
CA3173356A1 (fr)	2021-09-02
AU2021225491A1 (en)	2022-10-20
EP4110341A2 (fr)	2023-01-04
WO2021171260A2 (fr)	2021-09-02
IL295626A (en)	2022-10-01
CN115279374A (zh)	2022-11-01

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