DD273839A5 - Verfahren zur herstellung neuer insulinderivate - Google Patents

Verfahren zur herstellung neuer insulinderivate Download PDF

Info

Publication number: DD273839A5
Authority: DD; German Democratic Republic
Prior art keywords: human insulin; gln; lys; insulin; arg
Prior art date: 1986-07-21

Application number

DD87305161A

Other languages

German (de)

English (en)

Inventor

Jan Markussen

Kjeld Norris

Liselotte Langkjaer

Original Assignee

��@��@�a�k��

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.)

1986-07-21

Filing date

1987-07-20

Publication date

1989-11-29

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=8123250&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DD273839(A5) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1987-07-20 Application filed by ��@��@�a�k�� filed Critical ��@��@�a�k��

1989-11-29 Publication of DD273839A5 publication Critical patent/DD273839A5/de

Links

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Diabetes (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Endocrinology (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Obesity (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Emergency Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Zoology (AREA)
Toxicology (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

DD87305161A 1986-07-21 1987-07-20 Verfahren zur herstellung neuer insulinderivate DD273839A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DK347086A DK347086D0 (da)	1986-07-21	1986-07-21	Novel peptides

Publications (1)

Publication Number	Publication Date
DD273839A5 true DD273839A5 (de)	1989-11-29

Family

ID=8123250

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD87305161A DD273839A5 (de)	1986-07-21	1987-07-20	Verfahren zur herstellung neuer insulinderivate

Country Status (20)

Country	Link
EP (1)	EP0254516B1 (pt)
JP (1)	JPS6399096A (pt)
KR (1)	KR880001701A (pt)
CN (1)	CN87104988A (pt)
AT (1)	ATE99699T1 (pt)
AU (1)	AU612324B2 (pt)
DD (1)	DD273839A5 (pt)
DE (2)	DE3788684T2 (pt)
DK (1)	DK347086D0 (pt)
ES (1)	ES2061504T3 (pt)
FI (1)	FI873185A7 (pt)
HU (1)	HU203371B (pt)
IL (1)	IL83243A (pt)
MY (1)	MY102873A (pt)
NL (1)	NL300018I1 (pt)
NO (1)	NO170978C (pt)
NZ (1)	NZ221130A (pt)
PT (1)	PT85355B (pt)
YU (1)	YU135387A (pt)
ZA (1)	ZA875295B (pt)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2053723T3 (es) *	1987-02-25	1994-08-01	Novo Nordisk As	Nuevos derivados de insulina.
DK336188D0 (da) *	1988-06-20	1988-06-20	Nordisk Gentofte	Propeptider
WO1990001038A1 (en) *	1988-07-20	1990-02-08	Nordisk Gentofte A/S	Human insulin analogs and preparations containing them
DE3827533A1 (de) *	1988-08-13	1990-02-15	Hoechst Ag	Pharmazeutische zubereitung zur behandlung des diabetes mellitus
DE3837825A1 (de) *	1988-11-08	1990-05-10	Hoechst Ag	Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung
US5716927A (en) *	1988-12-23	1998-02-10	Novo Nordisk A/S	Insulin analogs having a modified B-chain
HUT56857A (en) *	1988-12-23	1991-10-28	Novo Nordisk As	Human insulin analogues
US5514646A (en) *	1989-02-09	1996-05-07	Chance; Ronald E.	Insulin analogs modified at position 29 of the B chain
DK134189D0 (da) *	1989-03-20	1989-03-20	Nordisk Gentofte	Insulinforbindelser
DE3936876A1 (de) *	1989-11-06	1991-05-23	Hoechst Ag	Neue insulinderivate, verfahren zu deren herstellung, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung
US5474978A (en) *	1994-06-16	1995-12-12	Eli Lilly And Company	Insulin analog formulations
US5693609A (en) *	1994-11-17	1997-12-02	Eli Lilly And Company	Acylated insulin analogs
US7316999B2 (en)	2000-06-02	2008-01-08	Novo Nordisk A/S	Glucose dependent release of insulin from glucose sensing insulin derivatives
DE10114178A1 (de)	2001-03-23	2002-10-10	Aventis Pharma Gmbh	Zinkfreie und zinkarme Insulinzubereitungen mit verbesserter Stabilität
CA2464616C (en)	2001-11-19	2012-07-24	Are Bogsnes	Process for preparing insulin compounds
GB0206792D0 (en)	2002-03-22	2002-05-01	Leuven K U Res & Dev	Normoglycemia
DE10227232A1 (de)	2002-06-18	2004-01-15	Aventis Pharma Deutschland Gmbh	Saure Insulinzubereitungen mit verbesserter Stabilität
WO2005000580A1 (en)	2003-06-27	2005-01-06	Novo Nordisk A/S	High moisture barrier container for medical liquid compositions
DE602004029496D1 (de)	2003-12-22	2010-11-18	Novo Nordisk As	Offbehälter zur lagerung von pharmazeutischen flüssigkeiten
EP2033662B1 (en)	2004-01-21	2012-10-17	Novo Nordisk Health Care AG	Transglutaminase mediated conjugation of peptides
DE102006031962A1 (de)	2006-07-11	2008-01-17	Sanofi-Aventis Deutschland Gmbh	Amidiertes Insulin Glargin
DE102006031955A1 (de) *	2006-07-11	2008-01-17	Sanofi-Aventis Deutschland Gmbh	Verfahren zur Herstellung von Insulinanaloga mit dibasischem B-Kettenende
WO2008049711A1 (en)	2006-10-27	2008-05-02	Novo Nordisk A/S	Peptide extended insulins
RU2524423C2 (ru)	2008-01-09	2014-07-27	Санофи-Авентис Дойчланд Гмбх	Новые производные инсулина с чрезвычайно замедленным профилем время/действие
KR20100111683A (ko) *	2008-01-09	2010-10-15	사노피-아벤티스 도이칠란트 게엠베하	극히 지연된 시간-작용 프로필을 갖는 신규 인슐린 유도체
HUE032284T2 (en)	2008-03-18	2017-09-28	Novo Nordisk As	Protease-stabilized, acylated insulin analogues
TWI451876B (zh)	2008-06-13	2014-09-11	Lilly Co Eli	聚乙二醇化之離脯胰島素化合物
ES2570937T3 (es)	2008-08-07	2016-05-23	Biocon Ltd	Un proceso para la preparación de compuestos de insulina
PT3228320T (pt)	2008-10-17	2020-03-26	Sanofi Aventis Deutschland	Combinação de uma insulina e de um agonista do glp-1
PH12011502708B1 (en)	2009-07-06	2017-11-10	Sanofi Aventis Deutschland	Insulin preparations containing methionine
WO2011003820A1 (de) *	2009-07-06	2011-01-13	Sanofi-Aventis Deutschland Gmbh	Hitze- und schüttelstabile insulinzubereitungen
JP5832439B2 (ja)	2009-11-13	2015-12-16	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	Ｇｌｐ−１アゴニスト、インスリン及びメチオニンを含む薬学的組成物
SG10201500871TA (en)	2009-11-13	2015-04-29	Sanofi Aventis Deutschland	Pharmaceutical composition comprising a glp-1 agonist and methionine
EP2460527A1 (en)	2010-01-21	2012-06-06	Sanofi	Pharmaceutical composition for treating a metabolic syndrome
TW201141513A (en)	2010-04-14	2011-12-01	Sanofi Aventis	Insulin-siRNA conjugates
CN103179978A (zh)	2010-08-30	2013-06-26	赛诺菲-安万特德国有限公司	Ave0010用于制造供治疗2型糖尿病用的药物的用途
US9821032B2 (en)	2011-05-13	2017-11-21	Sanofi-Aventis Deutschland Gmbh	Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin
EP2548570A1 (en)	2011-07-19	2013-01-23	Sanofi	Pharmaceutical composition for treating a metabolic syndrome
JP6367115B2 (ja)	2011-08-29	2018-08-01	サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング	２型糖尿病患者の血糖コントロールに使用する組合せ医薬
TWI559929B (en)	2011-09-01	2016-12-01	Sanofi Aventis Deutschland	Pharmaceutical composition for use in the treatment of a neurodegenerative disease
EP2836508B1 (en)	2012-04-11	2016-06-29	Novo Nordisk A/S	Insulin formulations
WO2015196174A1 (en)	2014-06-20	2015-12-23	Greene Howard E	Infusion delivery devices and methods
CN107206058A (zh)	2014-12-12	2017-09-26	赛诺菲-安万特德国有限公司	甘精胰岛素/利西拉来固定比率配制剂
TWI748945B (zh)	2015-03-13	2021-12-11	德商賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患治療
TW201705975A (zh)	2015-03-18	2017-02-16	賽諾菲阿凡提斯德意志有限公司	第２型糖尿病病患之治療
ES2886837T3 (es)	2016-12-16	2021-12-21	Novo Nordisk As	Composiciones farmacéuticas que contienen insulina

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3033127A1 (de) *	1980-09-03	1982-04-08	Hoechst Ag, 6000 Frankfurt	Neue analoga des insulins
DE3327709A1 (de) *	1983-07-29	1985-02-07	Hoechst Ag, 6230 Frankfurt	Insulin-derivat-kristallsuspensionen, verfahren zu deren herstellung und deren verwendung
DE3333640A1 (de) *	1983-09-17	1985-04-25	Hoechst Ag, 6230 Frankfurt	Verfahren zur herstellung von insulin-derivaten, deren b-kette c-terminal verlaengert ist, neue basisch modifizierte insulin-derivate diese enthaltende mittel und ihre verwendung
DK113585D0 (da) *	1985-03-12	1985-03-12	Novo Industri As	Nye peptider
DK119785D0 (da) *	1985-03-15	1985-03-15	Nordisk Gentofte	Insulinpraeparat

1986
- 1986-07-21 DK DK347086A patent/DK347086D0/da not_active Application Discontinuation
1987
- 1987-07-20 PT PT85355A patent/PT85355B/pt not_active IP Right Cessation
- 1987-07-20 AU AU75916/87A patent/AU612324B2/en not_active Ceased
- 1987-07-20 NO NO873018A patent/NO170978C/no unknown
- 1987-07-20 HU HU873343A patent/HU203371B/hu not_active IP Right Cessation
- 1987-07-20 DD DD87305161A patent/DD273839A5/de not_active IP Right Cessation
- 1987-07-20 CN CN198787104988A patent/CN87104988A/zh active Pending
- 1987-07-20 FI FI873185A patent/FI873185A7/fi not_active Application Discontinuation
- 1987-07-20 YU YU01353/87A patent/YU135387A/xx unknown
- 1987-07-20 ES ES87306405T patent/ES2061504T3/es not_active Expired - Lifetime
- 1987-07-20 KR KR1019870007832A patent/KR880001701A/ko not_active Ceased
- 1987-07-20 NZ NZ221130A patent/NZ221130A/xx unknown
- 1987-07-20 ZA ZA875295A patent/ZA875295B/xx unknown
- 1987-07-20 IL IL83243A patent/IL83243A/xx not_active IP Right Cessation
- 1987-07-20 AT AT87306405T patent/ATE99699T1/de not_active IP Right Cessation
- 1987-07-20 DE DE3788684T patent/DE3788684T2/de not_active Expired - Lifetime
- 1987-07-20 DE DE2000175024 patent/DE10075024I1/de active Pending
- 1987-07-20 EP EP87306405A patent/EP0254516B1/en not_active Expired - Lifetime
- 1987-07-20 MY MYPI87001062A patent/MY102873A/en unknown
- 1987-07-21 JP JP62180168A patent/JPS6399096A/ja active Pending
2000
- 2000-09-15 NL NL300018C patent/NL300018I1/nl unknown

Also Published As

Publication number	Publication date
JPS6399096A (ja)	1988-04-30
FI873185L (fi)	1988-01-22
ZA875295B (en)	1988-01-21
AU7591687A (en)	1988-01-28
NL300018I1 (nl)	2000-11-01
ATE99699T1 (de)	1994-01-15
FI873185A7 (fi)	1988-01-22
NZ221130A (en)	1990-08-28
PT85355A (en)	1987-08-01
DE3788684D1 (de)	1994-02-17
PT85355B (pt)	1990-04-30
DE10075024I1 (de)	2000-11-09
IL83243A0 (en)	1987-12-31
EP0254516A3 (en)	1990-06-27
DK347086D0 (da)	1986-07-21
NO873018L (no)	1988-01-22
FI873185A0 (fi)	1987-07-20
EP0254516B1 (en)	1994-01-05
NO170978B (no)	1992-09-28
DE3788684T2 (de)	1994-05-19
AU612324B2 (en)	1991-07-11
EP0254516A2 (en)	1988-01-27
HUT45271A (en)	1988-06-28
MY102873A (en)	1993-03-31
NO170978C (no)	1993-01-06
ES2061504T3 (es)	1994-12-16
CN87104988A (zh)	1988-03-02
KR880001701A (ko)	1988-04-26
IL83243A (en)	1993-01-14
YU135387A (en)	1988-10-31
HU203371B (en)	1991-07-29
NO873018D0 (no)	1987-07-20

Legal Events

Date	Code	Title	Description
2000-02-17	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
DE3788684T2 (de)	1994-05-19	Peptide.
DE3685668T2 (de)	1993-01-14	Peptide.
DE69722397T2 (de)	2004-04-01	Insulin-derivate und ihre verwendung
EP0132769B1 (de)	1988-01-07	Pharmazeutisches Mittel zur Behandlung des Diabetes mellitus
EP0885961B1 (de)	2004-12-01	Neue Insulinderivate mit schnellem Wirkungseintritt
EP0132770B1 (de)	1987-09-16	Neue Insulin-Derivate, Verfahren zu deren Herstellung und deren Verwendung sowie pharmazeutische Mittel zur Behandlung des Diabetes mellitus
EP2229407B1 (de)	2016-11-16	Neue insulinderivate mit extrem verzögertem zeit- / wirkungsprofil
US4946828A (en)	1990-08-07	Novel insulin peptides
DE3880346T2 (de)	1993-07-29	Insulinderivate.
EP2229406B1 (de)	2015-04-22	Neue insulinderivate mit extrem verzögertem zeit- / wirkungsprofil
NZ238718A (en)	1992-06-25	Insulin analogue and its preparation
DE102008003568A1 (de)	2009-07-16	Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil
DE102008003566A1 (de)	2009-07-16	Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil
EP0140084A1 (de)	1985-05-08	Verfahren zur Herstellung von Insulin-Derivaten, deren B-Kette C-terminal verlängert ist, neue basisch modifizierte Insulin-Derivate, diese enthaltende Mittel und ihre Verwendung
KR20160065126A (ko)	2016-06-08	인슐린 유사체의 신규한 유도체
EP0427162B1 (de)	1996-05-08	Neue Insulinderivate, Verfahren zu deren Herstellung, ihre Verwendung und eine sie enthaltende pharmazeutische Zubereitung
EP1084248A2 (de)	2001-03-21	Neue insulinanaloga mit erhöhter zinkbindung
DE102008025008A1 (de)	2009-11-26	Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil
EP0622376B1 (de)	2001-08-08	Amorphe monosphärische Formen von Insulinderivaten
DE102008025007A1 (de)	2009-11-26	Neue Insulinderivate mit extrem verzögertem Zeit-/ Wirkungsprofil