EP0462192A1 - Glykosilierte insuline - Google Patents
Glykosilierte insulineInfo
- Publication number
- EP0462192A1 EP0462192A1 EP19900904777 EP90904777A EP0462192A1 EP 0462192 A1 EP0462192 A1 EP 0462192A1 EP 19900904777 EP19900904777 EP 19900904777 EP 90904777 A EP90904777 A EP 90904777A EP 0462192 A1 EP0462192 A1 EP 0462192A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- insulin
- glycosylated
- phe
- human insulin
- gly
- 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.)
- Ceased
Links
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention relates to specifically glyco ⁇ sylated insulins and combinations thereof, pharmaceutical prep ⁇ arations containing such glycosylated compounds and a method for their preparation.
- insulin analogues have been suggested for the treatment of diabetes ellitus.
- the pur ⁇ pose of developing such insulin analogues has been to improve the insulin replacement therapy by making available insulin analogues with either a more rapid or a more protracted insulin action compared to especially human insulin.
- insulin has a very short half life time in circulating blood, it can not be excluded that a small amount of insulin is glycosylated in vivo not only in diabetic patients as postulated by Nakayama et al. (Nonenzymatic glyco- sylation of insulin in "Current topics in clinical and experi ⁇ mental aspects of diabetes mellitus” (1985), 201 - 204, Saka ⁇ moto, Min and Baba, Eds., Elsevier Science Publishers B.V.) but also in non-diabetics. It is therefore possible that the organ ⁇ ism has developed mechanisms to suppress the formation of anti- bodies against glycosylated insulin. It is furthermore possible that the conformational changes of the saccharide part will be able to camouflage the antigen.
- glycosylated insulin preparations will all be inhomo- geneous mixtures of glycosylated insulin molecules.
- the present insulin derivatives may in each of the three positions contain a monosaccharide or an oligosaccharide with up to three sugar residues.
- Suitable monosaccharides are glucose, mannose and galactose.
- Suitable oligosaccharides are maltose, isomaltose, lactose, maltotriose, melibiose and cello- biose.
- the specifically glycosylated insulin derivatives of this invention may be used as such for the treatment of dia- betes mellitus. With the purpose of monitoring the insulin therapy, selected mixtures of the individual specifically gly ⁇ cosylated compounds may however also be used.
- the expression insulins is meant to cover native forms of insulin such as human, bovine and porcine insulin, but also derivatives thereof wherein one or more amino acid residues have been substituted, added or deleted, compared with native insulin, for example as described in European patent applications having publication Nos. 0194864A and 0214826A.
- native insulins have three poten ⁇ tial glycosylation sites, namely the two N-terminal amino acid residues in the A- and B-chain and the lysine residue in posi ⁇ tion B29.
- the chain structure is the reactive component
- insulin 1 deoxy-D-fructosyl insulin (glucose insulin) "insulin" designates desamino insulin.
- Gly(Al) ,Phe(Bl) ,Lys(B29) triglucose human insulin
- Gly(Al) ,Phe(Bl) ,Lys(B29) trimaltose human insulin Gly(Al) ,Phe(Bl) ,Lys(B29) trilactose human insulin
- Gly(Al) ,Phe(Bl) ,Lys(B29) trimannose human insulin
- Gly(Al) ,Phe(Bl) ,Lys(B29) triisomaltose human insulin Phe(Bl) glucose [Asp B1 °] human insulin
- the duration of the reaction and the composition of the reaction mixture will depend on whether a mono-, di- or triglycosylated end product is desired.
- the reaction may con- veniently be followed by reversed phase high pressure liquid chromatography (hereinafter designated RP HPLC) to determine the point of maximum formation of each of the individual glyco ⁇ sylated products.
- RP HPLC reversed phase high pressure liquid chromatography
- the insulin preparation of the present invention can be used similarly to the use of the known insulin preparations.
- the amino acid analysis showed the presence of one less Phe and one less Gly residue proving a substitution in po- sition Al and Bl.
- the molecular weight measured was 6132 (calculated: 6132) .
- the subcutaneous absorption was measured in pigs by injection of 125 l labelled Phe(Bl) ,Gly(Al) diglucose insulin prepared using the iodate method essentially as described (J ⁇ r- gensen et al., Diabetologia JL9 (1980), 546 - 554).
- the absorp- tion rate after subcutaneous injection into pigs of 1 J -2 ⁇ "5 J ⁇ human insulin and 125I Phe(Bl) ,Gly(Al) diglucose human insulin is shown in Table 1, below.
- the T 75 , T 50 and T 5 values given in Table 1 are the time (in hours) elapsed from the moment of in- 10
- Table 2 shows the fast action of diglucose insulin compared with human insulin.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK1114/89 | 1989-03-08 | ||
DK111489A DK111489D0 (da) | 1989-03-08 | 1989-03-08 | Peptider |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0462192A1 true EP0462192A1 (de) | 1991-12-27 |
Family
ID=8101165
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19900904777 Ceased EP0462192A1 (de) | 1989-03-08 | 1990-03-06 | Glykosilierte insuline |
Country Status (19)
Country | Link |
---|---|
EP (1) | EP0462192A1 (de) |
JP (1) | JPH04504117A (de) |
KR (1) | KR920701249A (de) |
CN (1) | CN1045586A (de) |
AU (1) | AU638701B2 (de) |
CA (1) | CA2049937A1 (de) |
CS (1) | CS114290A3 (de) |
DD (1) | DD296933A5 (de) |
DK (1) | DK111489D0 (de) |
FI (1) | FI914226A0 (de) |
GR (1) | GR1000604B (de) |
HU (1) | HUT59942A (de) |
IL (1) | IL93674A0 (de) |
NO (1) | NO913517L (de) |
NZ (1) | NZ232808A (de) |
PT (1) | PT93366A (de) |
WO (1) | WO1990010645A1 (de) |
YU (1) | YU45490A (de) |
ZA (1) | ZA901737B (de) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2385879C2 (ru) | 2004-01-21 | 2010-04-10 | Ново Нордиск Хелс Кеа Аг | Способ конъюгации пептидов, опосредованной трансглутаминазой |
US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
WO2010088268A1 (en) | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Exogenously triggered controlled release materials and uses thereof |
CA2750269A1 (en) | 2009-01-28 | 2010-08-05 | Smartcells, Inc. | Crystalline insulin-conjugates |
US9050370B2 (en) | 2009-01-28 | 2015-06-09 | Smartcells, Inc. | Conjugate based systems for controlled drug delivery |
WO2010107520A1 (en) | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Soluble non-depot insulin conjugates and uses thereof |
CA2754950A1 (en) | 2009-03-20 | 2010-09-23 | Smartcells, Inc. | Terminally-functionalized conjugates and uses thereof |
CA2806399A1 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
JP2013542915A (ja) | 2010-07-28 | 2013-11-28 | スマートセルズ・インコーポレイテツド | 薬物−リガンドコンジュゲート、その合成およびその中間体 |
CA2805902A1 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinant lectins, binding-site modified lectins and uses thereof |
US9624287B2 (en) | 2012-07-17 | 2017-04-18 | Case Western Reserve University | O-linked carbohydrate-modified insulin analogues |
EP2877200B1 (de) * | 2012-07-17 | 2019-05-08 | Case Western Reserve University | O-verknüpfte kohlenhydratmodifizierte insulinanaloga |
US9700599B2 (en) | 2012-11-13 | 2017-07-11 | Adocia | Rapid-acting insulin formulation comprising a substituted anionic compound |
JP6735561B2 (ja) | 2012-12-03 | 2020-08-05 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | O−グリコシル化カルボキシ末端部分(ctp)ペプチド系のインスリンおよびインスリン類似体 |
EP2970124B1 (de) | 2013-03-14 | 2019-05-22 | The Board of Trustees of the Leland Stanford Junior University | Mitochondriale aldehyd-dehydrogenase-2-modulatoren und verfahren zur verwendung davon |
CA2924743A1 (en) | 2013-10-04 | 2015-04-09 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
FR3020947B1 (fr) | 2014-05-14 | 2018-08-31 | Adocia | Composition aqueuse comprenant au moins une proteine et un agent solubilisant, sa preparation et ses utilisations |
US9795678B2 (en) | 2014-05-14 | 2017-10-24 | Adocia | Fast-acting insulin composition comprising a substituted anionic compound and a polyanionic compound |
FR3043557B1 (fr) | 2015-11-16 | 2019-05-31 | Adocia | Composition a action rapide d'insuline comprenant un citrate substitue |
CN105597080A (zh) * | 2016-01-29 | 2016-05-25 | 程潜 | 一种用于治疗尿毒症和尿蛋白的药物 |
CN105535927A (zh) * | 2016-01-29 | 2016-05-04 | 山东中海制药有限公司 | 一种用于治疗流感、上呼吸道感染、病毒性肺炎的药物 |
CN105709207A (zh) * | 2016-01-29 | 2016-06-29 | 徐宝贞 | 一种用于治疗痛风的药物 |
BR112018074716A2 (pt) | 2016-06-02 | 2019-03-12 | Sanofi | conjugados de um agente farmacêutico e porção capaz de ligar-se a uma proteína sensível à glicose |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3847890A (en) * | 1971-11-01 | 1974-11-12 | A Green | Acidic monosaccharide-substituted proteins |
US4444683A (en) * | 1982-11-17 | 1984-04-24 | University Of Utah | Glycosylated insulin derivatives |
EP0119650A3 (de) * | 1983-03-21 | 1987-09-30 | THE PROCTER & GAMBLE COMPANY | Galactosyl-Insulin-Konjugate für die Behandlung von Zuckerkranken |
HU906340D0 (en) * | 1986-10-13 | 1991-04-29 | Sandoz Ag | Synthesis in solid phase for producing peptonic alcohols |
-
1989
- 1989-03-08 DK DK111489A patent/DK111489D0/da not_active Application Discontinuation
-
1990
- 1990-03-06 WO PCT/DK1990/000062 patent/WO1990010645A1/en not_active Application Discontinuation
- 1990-03-06 KR KR1019910701014A patent/KR920701249A/ko not_active Application Discontinuation
- 1990-03-06 HU HU8727A patent/HUT59942A/hu unknown
- 1990-03-06 EP EP19900904777 patent/EP0462192A1/de not_active Ceased
- 1990-03-06 JP JP2504720A patent/JPH04504117A/ja active Pending
- 1990-03-06 CA CA002049937A patent/CA2049937A1/en not_active Abandoned
- 1990-03-06 AU AU52807/90A patent/AU638701B2/en not_active Expired - Fee Related
- 1990-03-06 NZ NZ232808A patent/NZ232808A/en unknown
- 1990-03-07 YU YU00454/90A patent/YU45490A/xx unknown
- 1990-03-07 DD DD90338488A patent/DD296933A5/de not_active IP Right Cessation
- 1990-03-07 PT PT93366A patent/PT93366A/pt not_active Application Discontinuation
- 1990-03-07 ZA ZA901737A patent/ZA901737B/xx unknown
- 1990-03-07 GR GR900100159A patent/GR1000604B/el unknown
- 1990-03-07 CN CN90101282A patent/CN1045586A/zh active Pending
- 1990-03-07 IL IL93674A patent/IL93674A0/xx unknown
- 1990-03-08 CS CS901142A patent/CS114290A3/cs unknown
-
1991
- 1991-09-06 FI FI914226A patent/FI914226A0/fi not_active Application Discontinuation
- 1991-09-06 NO NO91913517A patent/NO913517L/no unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9010645A1 * |
Also Published As
Publication number | Publication date |
---|---|
KR920701249A (ko) | 1992-08-11 |
CA2049937A1 (en) | 1990-09-09 |
YU45490A (en) | 1991-10-31 |
NO913517D0 (no) | 1991-09-06 |
ZA901737B (en) | 1990-11-28 |
DD296933A5 (de) | 1991-12-19 |
AU5280790A (en) | 1990-10-09 |
DK111489D0 (da) | 1989-03-08 |
WO1990010645A1 (en) | 1990-09-20 |
GR900100159A (en) | 1990-07-31 |
CN1045586A (zh) | 1990-09-26 |
AU638701B2 (en) | 1993-07-08 |
HU902787D0 (en) | 1991-11-28 |
JPH04504117A (ja) | 1992-07-23 |
IL93674A0 (en) | 1990-12-23 |
NZ232808A (en) | 1992-04-28 |
PT93366A (pt) | 1990-11-07 |
GR1000604B (el) | 1992-08-26 |
HUT59942A (en) | 1992-07-28 |
NO913517L (no) | 1991-11-06 |
CS114290A3 (en) | 1992-02-19 |
FI914226A0 (fi) | 1991-09-06 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19910822 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE |
|
RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: HALSTROM, JOHN, BOBERG |
|
17Q | First examination report despatched |
Effective date: 19930118 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
|
18R | Application refused |
Effective date: 19941020 |