DE19851675A1 - Human interleukin-10 mutant proteins - Google Patents
Human interleukin-10 mutant proteinsInfo
- Publication number
- DE19851675A1 DE19851675A1 DE19851675A DE19851675A DE19851675A1 DE 19851675 A1 DE19851675 A1 DE 19851675A1 DE 19851675 A DE19851675 A DE 19851675A DE 19851675 A DE19851675 A DE 19851675A DE 19851675 A1 DE19851675 A1 DE 19851675A1
- Authority
- DE
- Germany
- Prior art keywords
- human interleukin
- mutant proteins
- human
- muteins
- exchanges
- 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.)
- Withdrawn
Links
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 title claims abstract description 9
- 102000052620 human IL10 Human genes 0.000 title claims abstract description 9
- 102000008300 Mutant Proteins Human genes 0.000 title 1
- 108010021466 Mutant Proteins Proteins 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract 3
- 150000001413 amino acids Chemical group 0.000 claims description 3
- 102220479324 NAD(+) hydrolase SARM1_R110E_mutation Human genes 0.000 claims description 2
- 102220365941 c.325C>G Human genes 0.000 claims description 2
- 102220629702 Flap endonuclease GEN homolog 1_H109E_mutation Human genes 0.000 claims 1
- 102220644920 Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase_Y153Q_mutation Human genes 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 102200032302 rs61736602 Human genes 0.000 claims 1
- 102000003814 Interleukin-10 Human genes 0.000 description 6
- 108090000174 Interleukin-10 Proteins 0.000 description 6
- 229940076144 interleukin-10 Drugs 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007232 neuroendocrine mechanism Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5428—IL-10
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Infektionen gehören zu den häufigsten Todesursachen bei Traumapatienten. Neuro endokrine Mechanismen führen zu einer Immundepression, die mit einer erhöhten Infektionsinzidenz einhergeht. Über eine Stimulation des sympathischen Nerven systems und der Hypothalamus-Nebennieren-Achse werden Neurotransmifter, wie Catecholamine freigesetzt, die Monozyten und Makrophagen zur Produktion und Sekretion von Interleukin-10 (IL-10) stimulieren können. IL-10, als eines der wich tigsten immunsuppressiven und antiinflammatorischen Cytokine, führt zur Immun depression. IL-10 Antagonisten können folglich eingesetzt werden, um Trauma-in duzierte Immundepression zu inhibieren.Infections are one of the most common causes of death in trauma patients. Neuro endocrine mechanisms lead to immune depression, which increases with an Infection incidence is associated. Via stimulation of the sympathetic nerve systems and the hypothalamic-adrenal axis become neurotransmifters like Catecholamine released, the monocytes and macrophages for production and Can stimulate secretion of interleukin-10 (IL-10). IL-10 as one of the wich Most immunosuppressive and anti-inflammatory cytokines, leads to immune depression. IL-10 antagonists can therefore be used to trauma-in to inhibit induced immune depression.
Die Aminosäuresequenz des reifen humanen IL-10 besteht aus 160 Resten, wenn man die klonierte cDNA zugrundelegt (Moore et al. Annu. Rev. Immunol. 11, 165-190, 1993; Accession Number M57627).The amino acid sequence of the mature human IL-10 consists of 160 residues, if the cloned cDNA is used as a basis (Moore et al. Annu. Rev. Immunol. 11, 165-190, 1993; Accession Number M57627).
Die Erfindung betrifft Antagonisten des humanen Interleukin-10, ihre Zusammen setzung, Methoden zu ihrer Herstellung und ihrem Nutzen. Humanes IL-10 und IL-10 Antagonisten können in E. coli, Hefen, Insektenzellen und Säugetierzellen exprimiert werden. Die Antagonisten werden durch Einführung von Aminosäuresub stitutionen in das reife humane IL-10 hergestellt. Die cDNA, die für das humane IL-10 kodiert, wird hierfür einer gezielten Oligonukleotid-Mutagenese (Deng und Nickoloff, Anal. Biochem. 200, 81-88, 1992) oder einer PCR-Reaktion mit gezielt modifizierten Primern unterzogen, so daß an der oder den gewünschten Position(en) eine ausgewählte Aminosäure exprimiert wird.The invention relates to antagonists of human interleukin-10, their combination setting, methods for their production and their use. Human IL-10 and IL-10 antagonists can be found in E. coli, yeast, insect cells and mammalian cells be expressed. The antagonists are introduced by amino acid sub in the mature human IL-10. The cDNA, which is for the human IL-10 encoded, a targeted oligonucleotide mutagenesis (Deng and Nickoloff, anal. Biochem. 200, 81-88, 1992) or a PCR reaction with targeted modified primers so that at the desired position (s) a selected amino acid is expressed.
Die Antagonisten eignen sich zur Behandlung von:
The antagonists are suitable for the treatment of:
- - Trauma-induzierter Immundepression - Trauma-induced immune depression
- - Infektionen, die mit einem durch IL-10 induzierten Fehlen einer THl-Im munantwort einhergehen.- Infections associated with an absence of a T Hl immune response induced by IL-10.
- - B-Zell-Lymphomen.- B cell lymphomas.
Folgende Austausche des maturen humanen IL-10 sind hierfür geeignet:
The following exchanges of the mature human IL-10 are suitable for this:
- - Position 89- position 89
- - Position 109- position 109
- - Position 110- position 110
- - Position 153- heading 153
- - Position 156.- heading 156.
Besonders bevorzugt sind folgende Austausche:
The following exchanges are particularly preferred:
- - Ala89Asp (Glu)- Ala89Asp (Glu)
- - His109Asp (Glu)- His109Asp (Glu)
- - Arg110Glu (Asp)- Arg110Glu (Asp)
- - Tyr153Asp (Glu)- Tyr153Asp (Glu)
- - Met156Glu (Asp),- Met156Glu (Asp),
sowie Kombinationen dieser Austausche.as well as combinations of these exchanges.
Claims (5)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19851675A DE19851675A1 (en) | 1998-11-10 | 1998-11-10 | Human interleukin-10 mutant proteins |
| AU26599/00A AU2659900A (en) | 1998-11-10 | 1999-11-04 | Human interleukin 10 mutant proteins |
| PCT/EP1999/008421 WO2000027881A2 (en) | 1998-11-10 | 1999-11-04 | Human interleukin 10 mutant proteins |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19851675A DE19851675A1 (en) | 1998-11-10 | 1998-11-10 | Human interleukin-10 mutant proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19851675A1 true DE19851675A1 (en) | 2000-05-11 |
Family
ID=7887222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19851675A Withdrawn DE19851675A1 (en) | 1998-11-10 | 1998-11-10 | Human interleukin-10 mutant proteins |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2659900A (en) |
| DE (1) | DE19851675A1 (en) |
| WO (1) | WO2000027881A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021263167A3 (en) * | 2020-06-26 | 2022-04-21 | Amgen Inc. | Il-10 muteins and fusion proteins thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2020258026A1 (en) | 2019-04-19 | 2021-11-11 | Synerkine Pharma B.V. | A fusion protein comprising IL13 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0711346A1 (en) * | 1993-07-26 | 1996-05-15 | Schering Corporation | Agonists and antagonists of human interleukin-10 |
| WO1997026278A1 (en) * | 1996-01-18 | 1997-07-24 | Steeno Research Group A/S | Synthetic il-10 analogues |
-
1998
- 1998-11-10 DE DE19851675A patent/DE19851675A1/en not_active Withdrawn
-
1999
- 1999-11-04 WO PCT/EP1999/008421 patent/WO2000027881A2/en active Application Filing
- 1999-11-04 AU AU26599/00A patent/AU2659900A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021263167A3 (en) * | 2020-06-26 | 2022-04-21 | Amgen Inc. | Il-10 muteins and fusion proteins thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000027881A2 (en) | 2000-05-18 |
| WO2000027881A3 (en) | 2000-08-03 |
| AU2659900A (en) | 2000-05-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE3751406T2 (en) | Production and use of non-glycosylated IL-6. | |
| EP0181455B2 (en) | Use of preparations containing interferon-gamma (IFN-gamma) for systematically treating various human diseases at a low dosage | |
| DE69020573T2 (en) | PROCESS FOR INHIBITING STEM CELLS. | |
| DE69033700T2 (en) | Mammal IL-11 | |
| DE69839251T2 (en) | ALPHA INTERFERON-POLYMER CONJUGATES WITH INCREASED BIOLOGICAL EFFECTIVENESS AND PROCESS FOR THEIR PRODUCTION | |
| US4959455A (en) | Primate hematopoietic growth factors IL-3 and pharmaceutical compositions | |
| DE60208692T2 (en) | INTERLEUKIN -18 MUTANT PROTEINS, THEIR PREPARATION AND USE | |
| DE69206301T2 (en) | Protein with the activity of the cytokine type, encoding recombinant DNA, transformed cells and microorganisms. | |
| CA2193993A1 (en) | New hil-4 mutant proteins used as antagonists or partial agonists of human interleukin 4 | |
| DE3751677T3 (en) | NEW FAMILY OF PRIMATE HEMATOPOIETIC GROWTH FACTORS | |
| NO931141L (en) | TNF mutein | |
| DD238725A5 (en) | PROCESS FOR PREPARING A SYNERGISTIC MIXTURE OF INTERFERONS AND TUMOR NEKROSIS FACTOR | |
| DE3308030C2 (en) | Animal interferons | |
| ATE179330T1 (en) | IMPROVED ALPHA INTERFERON COMPOSITION AND METHOD FOR PRODUCING IT FROM HUMAN PERIPHERAL BLOOD LEUKOCYTES | |
| KR900701824A (en) | Compositions and methods for treating or preventing animal infections | |
| GR3034094T3 (en) | Viral recombinant vectors for expression in muscle cells. | |
| WO1988003173A3 (en) | New forms of colony stimulating factor-1 | |
| DE19535853C2 (en) | Variants of recombinant human interferon gamma, process for their preparation and their use | |
| DE4322330A1 (en) | Use of the IL-4 receptor for the therapy, prophylaxis and diagnosis of allergic, viral, parasitic and bacterial diseases as well as fungal infections | |
| AU596997C (en) | Pharmaceutical composition for the treatment of leukopenia | |
| DE4404124C2 (en) | TNF muteins, coding polynucleotide, vector, microorganism, method for producing the TNF muteins and TNF muteins containing pharmaceutical composition | |
| Andrews et al. | Molecular cloning and characterization of ovine IL-1 alpha and IL-1 beta | |
| EP0835661A3 (en) | Human interferon-Beta2A for use as a medicament | |
| DE19851675A1 (en) | Human interleukin-10 mutant proteins | |
| DE60115475T2 (en) | VARIANTS OF THE DERMATOPHAGOIDES ALLERGENS OF p 2 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |