DK2197903T3 - Deletioner i domæne ii af pseudomonas-eksotoksin a, der reducerer nonspecifik toksicitet - Google Patents
Deletioner i domæne ii af pseudomonas-eksotoksin a, der reducerer nonspecifik toksicitet Download PDFInfo
- Publication number
- DK2197903T3 DK2197903T3 DK08799197.2T DK08799197T DK2197903T3 DK 2197903 T3 DK2197903 T3 DK 2197903T3 DK 08799197 T DK08799197 T DK 08799197T DK 2197903 T3 DK2197903 T3 DK 2197903T3
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- residues
- seq
- sequence
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- BJXWAMLZKOXABD-UHFFFAOYSA-N CC(C)C(CC1)C=CC1C(CCC1)C1C1(CC2)C2CC1 Chemical compound CC(C)C(CC1)C=CC1C(CCC1)C1C1(CC2)C2CC1 BJXWAMLZKOXABD-UHFFFAOYSA-N 0.000 description 1
- QGVNSUJLHXLQDR-DHZHZOJOSA-N CCC(C)(C/C=C/C1C=CC=C1)C1C=CCC1 Chemical compound CCC(C)(C/C=C/C1C=CC=C1)C1C=CCC1 QGVNSUJLHXLQDR-DHZHZOJOSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/21—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Pseudomonadaceae (F)
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- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (15)
1. Isoleret, muteret Pseudomonas-eksotoksin A (PE), der omfatter en sekvens med formlen: R1,,-FCS-R2n-R3n-funktionelt PE-domæne III, hvor: n = 0 eller 1 uafhængigt for hver af R1, R2 og R3; R1 = 1 til 10 aminosyrerester; FCS = en furin-spaltningssekvens af aminosyrerester, hvilken sekvens er spaltbar ved hjælp af furin og har en aminosyreende og en carboxylende, hvor FCS: a) har formlen P4-P3-P2-P1, hvor P4 er en aminosyrerest i aminoenden, PI er en aminosyrerest i carboxylenden, PI er en arginin- eller en lysinrest, og sekvensen er spaltbar i carboxylenden af PI ved hjælp af furin; b) (i) yderligere omfatter aminosyrerester som vist ved P6-P5 i aminoenden, (ii) yderligere omfatter aminosyrerester som vist ved ΡΓ-Ρ2' i carboxylenden, (iii) yderligere hvor PI er an arginin- eller en lysinrest, er P2' tryptofan, og P4 kan være arginin, valin eller lysin, forudsat at hvis P4 ikke er arginin, så er P6 og P2 basiske rester, og (iv) sekvensen er spaltbar i carboxylenden af PI ved hjælp af furin; c) er udvalgt blandt SEQ ID NO: 12-20; d) er SEQ ID NO: 10 eller en afkortet version deraf, der omfatter RQPR (SEQ ID NO: 21); eller e) er SEQ ID NO: 11 eller en afkortet version deraf, der omfatter RSKR (SEQ ID NO: 26); R2 = 1 til 10 aminosyrer; og R3 = 1 eller flere fortløbende rester af resterne 365-394 af SEQ ID NO: 1; hvor det funktionelle PE-domæne III er resterne 395-613 af SEQ ID NO: 1, der eventuelt omfatter (i) substitutioner i en eller flere rester, der svarer til 609-613 af SEQ ID NO: 1, (ii) anvendelse af glycin, alanin, valin, leucin eller isoleucin i stedet for arginin i en position, der svarer til position 490 af SEQ ID NO: 1, (iii) anvendelse af alanin, glycin, serin eller glutamin i stedet for en eller flere rester, der svarer til rester udvalgt blandt D403, R412, R427, E431, R432, R458, D461, R467, R505, R513, E522, R538, E548, R551, R576, K590 og L597 af SEQ ID NO: 1, hvilke rester af SEQ ID NO: 1 opretholder immunogenicitet for en epitop eller subepitop i PE-domæne III, eller (iv) en kombination af hvilke som helst af (i)-(iii), hvor det muterede PE ikke inkluderer resterne 1 til 273 og 285 til 364 af SEQ ID NO: 1.
2. Muteret PE ifølge krav 1, hvor n = 0 for R3.
3. Muteret PE ifølge krav 1, hvor FCS er konjugeret eller fusioneret direkte til det funktionelle PE-domæne III.
4. Muteret PE ifølge krav 1, hvor det funktionelle PE-domæne III består af sekvensen af resterne 395-613 af SEQ ID NO: 1.
5. Muteret PE ifølge krav 1, hvor det funktionelle PE-domæne III omfatter (i) substitutioner i en eller flere rester, der svarer til 609-613 af SEQ ID NO: 1, (ii) anvendelse af glycin, alanin, valin, leucin eller isoleucin i stedet for arginin i en position, der svarer til position 490 af SEQ ID NO: 1, (iii) anvendelse af alanin, glycin, serin eller glutamin i stedet for en eller flere rester, der svarer til rester udvalgt blandt D403, R412, R427, E431, R432, R458, D461, R467, R505, R513, E522, R538, E548, R551, R576, K590 og L597 af SEQ ID NO: 1, hvilke rester af SEQ ID NO: 1 opretholder immunogenicitet for en epitop eller subepitop i PE-domæne III, eller (iv) en kombination af hvilke som helst af (i)-(iii).
6. Kimært molekyle, der omfatter (a) et cytokin, antistof eller antistoffragment, hvilket cytokin, antistof eller antistoffragment binder specifikt til et antigen eller en receptor på en celleoverflade, der er konjugeret eller fusioneret til (b) et muteret PE ifølge et hvilket som helst af kravene 1 til 5, hvor det kimære molekyle ikke inkluderer resterne 1 til 273 og 285 til 364 af SEQ ID NO: 1.
7. Kimært molekyle ifølge krav 6, hvor yderligere (a) er et antistof eller fragment deraf, der bevarer antigengenkendelsesevnen.
8. Kimært molekyle ifølge krav 7, hvor antistoffet eller fragmentet deraf binder til et målantigen, der er udvalgt blandt mesothelin og CD22.
9. Kimært molekyle til anvendelse til hæmning af væksten af en målcelle, der har et ydre, hvilket kimært molekyle omfatter: (a) et cytokin, antistof eller antistoffragment, hvilket cytokin, antistof eller antistoffragment binder specifikt til et antigen eller en receptor på det ydre af cellen, der er konjugeret eller fusioneret til (b) et muteret PE ifølge et hvilket som helst af kravene 1 til 5, hvor det kimære molekyle ikke inkluderer resterne 1 til 273 og 285 til 364 af SEQ ID NO: 1.
10. Kimært molekyle ifølge krav 9, hvor yderligere (a) er et antistof eller fragment deraf, der bevarer antigengenkendelsesevnen.
11. Kimært molekyle ifølge krav 10, hvor antistoffet eller fragmentet deraf binder til et målantigen, der er udvalgt blandt mesothelin og CD22.
12. Isoleret nukleinsyre, hvilken nukleinsyre koder for det muterede PE ifølge et hvilket som helst af kravene 1 til 5.
13. Isoleret nukleinsyre ifølge krav 12, hvor yderligere nukleinsyren koder for et cytokin, antistof eller antistoffragment, der binder specifikt til et antigen eller en receptor på en celleoverflade, hvilket cytokin, antistof eller antistoffragment er fusioneret direkte eller via en peptidlinker til det muterede PE.
14. Isoleret nukleinsyre ifølge krav 13, hvor nukleinsyren koder for et antistof eller fragment deraf, der bevarer antigenbindingsevnen.
15. Isoleret nukleinsyre ifølge krav 14, hvor antistoffet eller fragmentet deraf binder til et målantigen, der er udvalgt blandt mesothelin og CD22.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96992907P | 2007-09-04 | 2007-09-04 | |
| US1885308P | 2008-01-03 | 2008-01-03 | |
| PCT/US2008/075296 WO2009032954A1 (en) | 2007-09-04 | 2008-09-04 | Deletions in domain ii of pseudomonas exotoxin a that reduce non-specific toxicity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2197903T3 true DK2197903T3 (da) | 2015-01-05 |
Family
ID=39930583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK08799197.2T DK2197903T3 (da) | 2007-09-04 | 2008-09-04 | Deletioner i domæne ii af pseudomonas-eksotoksin a, der reducerer nonspecifik toksicitet |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8871906B2 (da) |
| EP (2) | EP2197903B9 (da) |
| AU (1) | AU2008296194B2 (da) |
| CA (1) | CA2698357C (da) |
| CY (1) | CY1115831T1 (da) |
| DK (1) | DK2197903T3 (da) |
| ES (2) | ES2642516T3 (da) |
| HR (1) | HRP20141236T1 (da) |
| PL (1) | PL2197903T3 (da) |
| PT (1) | PT2197903E (da) |
| SI (1) | SI2197903T1 (da) |
| WO (1) | WO2009032954A1 (da) |
Families Citing this family (78)
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| EP2197903B9 (en) | 2015-04-22 |
| WO2009032954A1 (en) | 2009-03-12 |
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| US20100215656A1 (en) | 2010-08-26 |
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| AU2008296194A1 (en) | 2009-03-12 |
| CA2698357A1 (en) | 2009-03-12 |
| AU2008296194B2 (en) | 2013-03-14 |
| PT2197903E (pt) | 2015-01-02 |
| US8871906B2 (en) | 2014-10-28 |
| SI2197903T1 (sl) | 2015-02-27 |
| ES2525488T3 (es) | 2014-12-23 |
| CA2698357C (en) | 2017-06-06 |
| EP2570425B1 (en) | 2017-08-23 |
| EP2197903A1 (en) | 2010-06-23 |
| PL2197903T3 (pl) | 2015-03-31 |
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