NO323206B1 - Anvendelse av EGFR-tyrosinkinase-inhibitor for fremstilling av et medikament, og et medisinsk testsett som omfatter en EGFR-tyrosinkinase-inhibitor - Google Patents

Anvendelse av EGFR-tyrosinkinase-inhibitor for fremstilling av et medikament, og et medisinsk testsett som omfatter en EGFR-tyrosinkinase-inhibitor Download PDF

Info

Publication number: NO323206B1
Authority: NO; Norway
Prior art keywords: normal; epithelium; egfr; tyrosine kinase; cells
Prior art date: 1999-11-02

Application number

NO20022065A

Other languages

English (en)

Norwegian (no)

Other versions

NO20022065L (no

NO20022065D0 (no

Inventor

Nigel James Bundred

Original Assignee

Univ Manchester

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.)

1999-11-02

Filing date

2002-04-30

Publication date

2007-01-22

2002-04-30 Application filed by Univ Manchester filed Critical Univ Manchester

2002-04-30 Publication of NO20022065D0 publication Critical patent/NO20022065D0/no

2002-06-24 Publication of NO20022065L publication Critical patent/NO20022065L/no

2007-01-22 Publication of NO323206B1 publication Critical patent/NO323206B1/no

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- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO20022065A 1999-11-02 2002-04-30 Anvendelse av EGFR-tyrosinkinase-inhibitor for fremstilling av et medikament, og et medisinsk testsett som omfatter en EGFR-tyrosinkinase-inhibitor NO323206B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9925958.2A GB9925958D0 (en)	1999-11-02	1999-11-02	Therapeutic use
PCT/GB2000/004190 WO2001032155A2 (en)	1999-11-02	2000-11-01	Use of egfr tyrosine kinase inhibitors for treating breast cancer

Publications (3)

Publication Number	Publication Date
NO20022065D0 NO20022065D0 (no)	2002-04-30
NO20022065L NO20022065L (no)	2002-06-24
NO323206B1 true NO323206B1 (no)	2007-01-22

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NO20022065A NO323206B1 (no)	1999-11-02	2002-04-30	Anvendelse av EGFR-tyrosinkinase-inhibitor for fremstilling av et medikament, og et medisinsk testsett som omfatter en EGFR-tyrosinkinase-inhibitor

Country Status (21)

Country	Link
US (1)	US7553815B1 (de)
EP (1)	EP1272188B1 (de)
JP (1)	JP2003513035A (de)
KR (1)	KR100785359B1 (de)
CN (1)	CN1197577C (de)
AT (1)	ATE339957T1 (de)
AU (1)	AU779190B2 (de)
BR (1)	BR0015194A (de)
CA (1)	CA2389411C (de)
CY (1)	CY1106285T1 (de)
DE (1)	DE60030889T2 (de)
DK (1)	DK1272188T3 (de)
ES (1)	ES2275556T3 (de)
GB (1)	GB9925958D0 (de)
IL (1)	IL149176A0 (de)
MX (1)	MXPA02004272A (de)
NO (1)	NO323206B1 (de)
NZ (1)	NZ518696A (de)
PT (1)	PT1272188E (de)
WO (1)	WO2001032155A2 (de)
ZA (1)	ZA200203431B (de)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6949245B1 (en)	1999-06-25	2005-09-27	Genentech, Inc.	Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
KR20130056201A (ko)	2000-05-19	2013-05-29	제넨테크, 인크.	ＥｒｂＢ 길항제에 의한 암 치료요법에 대한 효과적인 반응의 가능성을 개선시키기 위한 유전자 검출 분석
WO2003000188A2 (en)	2001-06-21	2003-01-03	Ariad Pharmaceuticals, Inc.	Novel quinazolines and uses thereof
US6872715B2 (en) *	2001-08-06	2005-03-29	Kosan Biosciences, Inc.	Benzoquinone ansamycins
EP1441736A2 (de) *	2001-10-29	2004-08-04	Novartis AG	Verwendung von 7h-pyrrolo[2,3-d]pyrimidinderivaten in der behandlung solider tumore
JP4982685B2 (ja) *	2001-12-03	2012-07-25	バイエル、ファーマシューテイカルズ、コーポレイション	ヒトがんを処置するための他の細胞毒剤又は細胞増殖抑制剤と組合わせたアリール尿素化合物
US7078409B2 (en)	2002-03-28	2006-07-18	Beta Pharma, Inc.	Fused quinazoline derivatives useful as tyrosine kinase inhibitors
KR20050037510A (ko)	2002-06-05	2005-04-22	세다르스-신나이 메디칼 센터	키나제 억제제를 사용하는 암 치료 방법
WO2005017493A2 (en) *	2003-08-15	2005-02-24	Smithkline Beecham Corporation	Biomarkers in cancer
WO2005028469A1 (en)	2003-09-19	2005-03-31	Astrazeneca Ab	Quinazoline derivatives
WO2005039588A2 (en) *	2003-10-22	2005-05-06	Novartis Ag	Methods for determining the risk of developing liver and lung toxicity
US7701341B2 (en) *	2004-09-01	2010-04-20	Microsoft Corporation	Device service provider interface
CA2592177A1 (en)	2005-01-21	2006-07-27	Genentech, Inc.	Fixed dosing of her antibodies
EP1850874B1 (de)	2005-02-23	2013-10-16	Genentech, Inc.	Verzögerung des krankheitsverlauf bei eierstockkrebspatienten durch pertuzumab
CN101003514A (zh)	2006-01-20	2007-07-25	上海艾力斯医药科技有限公司	喹唑啉衍生物、其制备方法及用途
JP5133071B2 (ja)	2006-02-09	2013-01-30	第一三共株式会社	抗癌医薬組成物
CN1899616A (zh) *	2006-07-20	2007-01-24	中国人民解放军军事医学科学院生物工程研究所	非受体酪氨酸激酶c－Abl特异性抑制剂的新用途
MX2009008981A (es)	2007-03-02	2009-09-02	Genentech Inc	Prediccion de respuesta a un inhibidor her.
EP2171090B1 (de)	2007-06-08	2013-04-03	Genentech, Inc.	Genexpressionsmarker für tumorresistenz gegen behandlung mit her2-inhibitor
US9551033B2 (en)	2007-06-08	2017-01-24	Genentech, Inc.	Gene expression markers of tumor resistance to HER2 inhibitor treatment
BRPI0812682A2 (pt)	2008-06-16	2010-06-22	Genentech Inc	tratamento de cáncer de mama metastático
JP5767122B2 (ja)	2009-03-11	2015-08-19	アルデアバイオサイエンシズ，インコーポレイティド	特定の癌の治療のためのｒｄｅａ１１９／ｂａｙ８６９７６６を含む組み合わせ医薬
CN104447995A (zh)	2009-03-20	2015-03-25	霍夫曼-拉罗奇有限公司	双特异性抗-her抗体
EP2435071A1 (de)	2009-05-29	2012-04-04	F. Hoffmann-La Roche AG	Modulatoren für den her2-signalweg bei her2-exprimierenden patienten mit magenkrebs
DK2536748T3 (da)	2010-02-18	2014-10-13	Genentech Inc	Neuregulin-antagonister og anvendelse deraf ved behandling af kræft
WO2011146568A1 (en)	2010-05-19	2011-11-24	Genentech, Inc.	Predicting response to a her inhibitor
US20130245233A1 (en)	2010-11-24	2013-09-19	Ming Lei	Multispecific Molecules
JP5766296B2 (ja)	2010-12-23	2015-08-19	エフ．ホフマン−ラロシュアーゲーＦ．Ｈｏｆｆｍａｎｎ−ＬａＲｏｃｈｅＡｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ	ポリペプチド−ポリヌクレオチド複合体、およびエフェクター成分の標的化された送達におけるその使用
US20140363438A1 (en)	2011-08-17	2014-12-11	Genentech, Inc.	Neuregulin antibodies and uses thereof
WO2013063229A1 (en)	2011-10-25	2013-05-02	The Regents Of The University Of Michigan	Her2 targeting agent treatment in non-her2-amplified cancers having her2 expressing cancer stem cells
RU2014126098A (ru)	2011-11-30	2016-01-27	Дженентек, Инк.	МУТАЦИИ ErbB3 ПРИ РАКЕ
US9376715B2 (en)	2011-12-09	2016-06-28	Roche Molecular Systems, Inc	Methods for detecting mutations in the catalytic subunit of the phosphoinositol-3 kinase (PIK3CA) gene
RU2014136886A (ru)	2012-03-27	2016-05-20	Дженентек, Инк.	Диагностика и виды лечения, связанные с ингибиторами her3
KR102291355B1 (ko)	2012-11-30	2021-08-19	에프. 호프만-라 로슈 아게	Pd-l1 억제제 공동치료를 필요로 하는 환자의 식별방법
WO2017194554A1 (en)	2016-05-10	2017-11-16	Inserm (Institut National De La Sante Et De La Recherche Medicale)	Combinations therapies for the treatment of cancer

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU661533B2 (en)	1992-01-20	1995-07-27	Astrazeneca Ab	Quinazoline derivatives
US5795910A (en) *	1994-10-28	1998-08-18	Cor Therapeutics, Inc.	Method and compositions for inhibiting protein kinases
MX9707453A (es) *	1995-03-30	1997-12-31	Pfizer	Derivados de quinazolina.
GB9508538D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
GB9508565D0 (en) *	1995-04-27	1995-06-14	Zeneca Ltd	Quiazoline derivative
ATE247469T1 (de) *	1995-06-07	2003-09-15	Pfizer	Heterocyclische kondensierte pyrimidin-derivate
MX9800215A (es) *	1995-07-06	1998-03-31	Novartis Ag	Pirrolopirimidas y procesos para su preparacion.
KR20010071271A (ko) *	1998-05-15	2001-07-28	존 비. 랜디스	방사선 및 성장 인자 수용체 티로신 키나아제 억제제에의한 사람 종양의 치료법
WO2008026150A1 (en)	2006-08-28	2008-03-06	Koninklijke Philips Electronics N.V.	Method and apparatus for image enhancement

1999
- 1999-11-02 GB GBGB9925958.2A patent/GB9925958D0/en not_active Ceased
2000
- 2000-11-01 MX MXPA02004272A patent/MXPA02004272A/es active IP Right Grant
- 2000-11-01 NZ NZ518696A patent/NZ518696A/xx not_active IP Right Cessation
- 2000-11-01 KR KR1020027005551A patent/KR100785359B1/ko not_active Expired - Fee Related
- 2000-11-01 WO PCT/GB2000/004190 patent/WO2001032155A2/en not_active Ceased
- 2000-11-01 IL IL14917600A patent/IL149176A0/xx not_active IP Right Cessation
- 2000-11-01 CA CA002389411A patent/CA2389411C/en not_active Expired - Fee Related
- 2000-11-01 CN CNB00815290XA patent/CN1197577C/zh not_active Expired - Fee Related
- 2000-11-01 ES ES00973002T patent/ES2275556T3/es not_active Expired - Lifetime
- 2000-11-01 BR BR0015194-7A patent/BR0015194A/pt not_active Application Discontinuation
- 2000-11-01 JP JP2001534360A patent/JP2003513035A/ja active Pending
- 2000-11-01 AT AT00973002T patent/ATE339957T1/de not_active IP Right Cessation
- 2000-11-01 AU AU11559/01A patent/AU779190B2/en not_active Ceased
- 2000-11-01 DK DK00973002T patent/DK1272188T3/da active
- 2000-11-01 US US10/111,390 patent/US7553815B1/en not_active Expired - Fee Related
- 2000-11-01 DE DE60030889T patent/DE60030889T2/de not_active Expired - Lifetime
- 2000-11-01 PT PT00973002T patent/PT1272188E/pt unknown
- 2000-11-01 EP EP00973002A patent/EP1272188B1/de not_active Expired - Lifetime
2002
- 2002-04-30 NO NO20022065A patent/NO323206B1/no not_active IP Right Cessation
- 2002-04-30 ZA ZA200203431A patent/ZA200203431B/xx unknown
2006
- 2006-12-11 CY CY20061101772T patent/CY1106285T1/el unknown

Also Published As

Publication number	Publication date
DK1272188T3 (da)	2007-01-29
BR0015194A (pt)	2002-06-18
CN1197577C (zh)	2005-04-20
NO20022065L (no)	2002-06-24
MXPA02004272A (es)	2003-08-20
EP1272188B1 (de)	2006-09-20
NZ518696A (en)	2004-12-24
CA2389411C (en)	2009-09-01
KR100785359B1 (ko)	2007-12-18
KR20020064306A (ko)	2002-08-07
JP2003513035A (ja)	2003-04-08
WO2001032155A2 (en)	2001-05-10
IL149176A0 (en)	2002-11-10
EP1272188A2 (de)	2003-01-08
PT1272188E (pt)	2007-01-31
ATE339957T1 (de)	2006-10-15
CN1387437A (zh)	2002-12-25
DE60030889D1 (de)	2006-11-02
CY1106285T1 (el)	2011-10-12
NO20022065D0 (no)	2002-04-30
ES2275556T3 (es)	2007-06-16
AU1155901A (en)	2001-05-14
GB9925958D0 (en)	1999-12-29
US7553815B1 (en)	2009-06-30
WO2001032155A3 (en)	2002-05-10
CA2389411A1 (en)	2001-05-10
ZA200203431B (en)	2003-02-26
DE60030889T2 (de)	2007-04-05
AU779190B2 (en)	2005-01-13

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2011-06-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO323206B1 (no)	2007-01-22	Anvendelse av EGFR-tyrosinkinase-inhibitor for fremstilling av et medikament, og et medisinsk testsett som omfatter en EGFR-tyrosinkinase-inhibitor
Li et al.	2019	Cornulin is induced in psoriasis lesions and promotes keratinocyte proliferation via phosphoinositide 3-kinase/Akt pathways
Auriemma et al.	2020	The interplay between prolactin and reproductive system: focus on uterine pathophysiology
Scaling et al.	2014	GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast
User et al.	2003	Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction
Su et al.	2013	Ovarian cancer risk is reduced by prolonged lactation: a case-control study in southern China
Huang et al.	2014	Oestrogen‐induced angiogenesis promotes adenomyosis by activating the S lug‐VEGF axis in endometrial epithelial cells
Schwertfeger et al.	2001	Mammary gland involution is delayed by activated Akt in transgenic mice
Sutherland et al.	1998	Estrogen and progestin regulation of cell cycle progression
Laidlaw et al.	1995	The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone
Rose et al.	2012	The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression
De Lima et al.	2003	Effects of low dose tamoxifen on normal breast tissue from premenopausal women
Xu et al.	2007	Lysophosphatidic acid promoting corneal epithelial wound healing by transactivation of epidermal growth factor receptor
Sun et al.	2019	Establishment and comparison of different intrauterine adhesion modelling procedures in rats
Kuchtey et al.	2008	Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor
Cramer	2023	Incessant ovulation: a review of its importance in predicting cancer risk
Wiley et al.	2024	Oral hypoxia-inducible factor 2α inhibitor belzutifan in ocular von Hippel-Lindau disease: subgroup analysis of the single-arm phase 2 LITESPARK-004 Study
Nacci et al.	2011	Sex hormone receptors in vocal fold tissue: a theory about the influence of sex hormones in the larynx
Zhao et al.	2024	Apelin-13 alleviates intrauterine adhesion by inhibiting epithelial–mesenchymal transition of endometrial epithelial cells and promoting angiogenesis
Gandhi et al.	2000	Effects of a pure antiestrogen on apoptosis and proliferation within human breast ductal carcinoma in situ
Jing et al.	2024	Silencing METTL3 increases HSP70 expression and alleviates fibrosis in keratocytes
Benda	1992	Clomiphene's effect on endometrium in infertility
Klaassens et al.	2006	Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen
Shen et al.	2025	Jiawei Qingxin Zishen Decoction mitigates granulosa cell apoptosis and enhances ovarian reserve through Netrin/UNC5B signaling pathway
Tower et al.	2009	AFPep, a novel drug for the prevention and treatment of breast cancer, does not disrupt the estrous cycle or fertility in rats