DK2817332T3 - Sekvenssymmetriske modificerede bispecifikke IgG4-antistoffer. - Google Patents
Sekvenssymmetriske modificerede bispecifikke IgG4-antistoffer. Download PDFInfo
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- DK2817332T3 DK2817332T3 DK13705504.2T DK13705504T DK2817332T3 DK 2817332 T3 DK2817332 T3 DK 2817332T3 DK 13705504 T DK13705504 T DK 13705504T DK 2817332 T3 DK2817332 T3 DK 2817332T3
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- antibody
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- heavy chain
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/53—Hinge
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (22)
1. Symmetrisk bispecifikt antistof af klassen IgG4 omfattende to tunge kæder, som hver omfatter et variabelt domæne, et CHl-domæne og en hængselregion, hvor det for hver tung kæde gælder, at: cysteinen i position 127, nummereret efter Kabat-nummereringssystemet, i CH1-domænet, som danner en disulfidbinding mellem kæderne med en cystein i en let kæde, er substitueret med en ikke-thiolholdig aminosyre; og en eller flere af aminosyrerne placeret i den øvre hængselregion er substitueret med cystein, hvor sekvensen af den konstante region i hver tung kæde er ligeartet eller identisk, og den variable region i hver tung kæde er forskelligartet.
2. Symmetrisk bispecifikt antistof ifølge krav 1, hvor hængselregionen er et hængsel af IgGl-typen.
3. Symmetrisk bispecifikt antistof ifølge krav 1 eller 2, hvor antistoffet er isoleret.
4. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 1 til 3, hvor den ene eller de flere aminosyrer placeret i den øvre hængselregion i den første tunge kæde, der er substitueret med cystein, er udvalgt blandt S227, K228, Y229 og G230, nummeret ifølge Kabat-nummereringssystemet.
5. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 1 til 4, hvor cysteinen i position 239 og cysteinen i position 242, nummereret ifølge Kabat-nummereringssystemet, er substitueret med en ikke-thiolholdig aminosyre i den ene eller begge tunge kæder.
6. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 1 til 5, hvor cysteinen i position 239, nummereret ifølge Kabat-nummereringssystemet, i den første tunge kæde er substitueret med en ikke-thiolholdig aminosyre.
7. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 1 til 6, hvor cysteinen i position 242, nummereret efter Kabat-nummereringssystemet, i den første tunge kæde er substitueret med en ikke-thiolholdig aminosyre.
8. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 5 til 7, hvor den ikke-thiolholdige aminosyre er serin.
9. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor cysteinen i position 127 er substitueret med serin.
10. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor den ene eller begge tunge kæder er muteret således, at der er indsat tre aminosyrer mellem aminosyrerne 226-243, nummereret efter Kabat-nummereringssystemet.
11. Symmetrisk bispecifikt antistof ifølge krav 10, hvor den ene eller begge tunge kæder er muterede således, at der er indsat tre aminosyrer mellem 238 og 239, nummereret efter Kabat-nummereringssystemet.
12. Symmetrisk bispecifikt antistof ifølge krav 11, hvor tre alaniner er indsat mellem positionerne 238 og 239 i den første tunge kæde nummereret efter Kabat-nummereringssystemet.
13. Symmetrisk bispecifikt antistof ifølge krav 11, hvor en threonin, en histidin og en yderligere threonin er indsat mellem positionerne 238 og 239 i den ene eller begge tunge kæder nummereret efter Kabat-nummereringssystemet.
14. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor serinen i position 241 i den ene eller begge tunge kæder nummereret efter Kabat-nummereringssystemet er substitueret med prolin.
15. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor det for den ene eller begge tunge kæder gælder, at glycinen i position 230 er substitueret med cystein, serinen i position 227 er substitueret med prolin, tyrosinen i position 229 er substitueret med serin, prolinen i position 237 er substitueret med asparaginsyre, prolinen i position 238 er substitueret med lysin, aminosyresekvensen threonin-histidin-threonin er indsat mellem positionerne 238 og 239, og serinen i position 241 er substitueret med prolin.
16. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor begge tunge kæder omfatter et CH2-domæne og/eller et CH3-domæne.
17. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af de foregående krav, hvor hængselregionen i hver af de tunge kæder er identisk.
18. Symmetrisk bispecifikt antistof ifølge et hvilket som helst af kravene 1 til 17, hvor hver tung kæde omfatter en øvre hængselregion og kerneregion på 12 til 17 aminosyrer i længden, for eksempel 15 aminosyrer i længden.
19. Ekspressionsvektor omfattende en sekvens, som koder for et antistof som defineret i et hvilket som helst af kravene 1 til 18.
20. Værtscelle omfattende en vektor som defineret i krav 19.
21. Antistof som defineret i et hvilket som helst af kravene 1 til 18 til anvendelse i behandling af en sygdom eller lidelse.
22. Fremgangsmåde til dannelse af et symmetrisk bispecifikt antistof, hvilken fremgangsmåde omfatter trinnet at blande et første IgG4-antistof med et andet IgG4-antistof ex vivo under reducerende betingelser, der leder til tungkædeudveksling, hvor antigenspecificiteten af de variable regioner i det første antistof er forskellig fra antigenspecificiteten af de variable regioner i det andet antistof, og det første IgG4-antistof og det andet IgG4-antistof omfatter hver især et CHl-domæne og en hængselregion som defineret i et hvilket som helst af kravene 1 til 18.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1203051.6A GB201203051D0 (en) | 2012-02-22 | 2012-02-22 | Biological products |
| PCT/EP2013/053614 WO2013124450A1 (en) | 2012-02-22 | 2013-02-22 | Sequence symmetric modified igg4 bispecific antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2817332T3 true DK2817332T3 (da) | 2016-11-07 |
Family
ID=45940018
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK16180209.5T DK3156416T3 (da) | 2012-02-22 | 2013-02-22 | Sekvenssymmetriske modificerede bispecifikke igg4-antistoffer |
| DK13705504.2T DK2817332T3 (da) | 2012-02-22 | 2013-02-22 | Sekvenssymmetriske modificerede bispecifikke IgG4-antistoffer. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK16180209.5T DK3156416T3 (da) | 2012-02-22 | 2013-02-22 | Sekvenssymmetriske modificerede bispecifikke igg4-antistoffer |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US10221251B2 (da) |
| EP (2) | EP3156416B1 (da) |
| JP (2) | JP6308952B2 (da) |
| KR (2) | KR102077331B1 (da) |
| CN (2) | CN104321341B (da) |
| AU (2) | AU2013224003B2 (da) |
| CA (1) | CA2864439C (da) |
| DK (2) | DK3156416T3 (da) |
| EA (1) | EA035050B1 (da) |
| ES (2) | ES2599503T3 (da) |
| GB (1) | GB201203051D0 (da) |
| HK (1) | HK1202563A1 (da) |
| IL (1) | IL234102B (da) |
| MX (1) | MX356288B (da) |
| SG (1) | SG11201404789XA (da) |
| WO (1) | WO2013124450A1 (da) |
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