DK2614077T3 - Chimeriske antigenreceptorer med en optimeret hængselregion - Google Patents
Chimeriske antigenreceptorer med en optimeret hængselregion Download PDFInfo
- Publication number
- DK2614077T3 DK2614077T3 DK11755014.5T DK11755014T DK2614077T3 DK 2614077 T3 DK2614077 T3 DK 2614077T3 DK 11755014 T DK11755014 T DK 11755014T DK 2614077 T3 DK2614077 T3 DK 2614077T3
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- DK
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- Prior art keywords
- amino acid
- cells
- domain
- leu
- protein
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Classifications
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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
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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
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
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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
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/626—Diabody or triabody
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Claims (16)
1. Protein omfattende (i) et signalpeptid; (ii) et målspecifikt genkendelsesdomæne; (iii) en linkerregion, som forbinder domænet (ii) og domænet (iv), hvor linkerregionen ikke indeholder cysteinrester og er valgt blandt vilkårlige af følgende: aminosyresekvensen ifølge SEQ ID NO. 2, en aminosyresekvens med i det mindste 95% sekvensidentitet med SEQ ID NO. 2 under den forudsætning, at aminosyreresten 48 ikke er et cystein og er et serin, og en aminosyresekvens, som afviger ved én, to eller tre aminosyrerester fra aminosyresekvensen ifølge SEQ ID NO. 2 under den forudsætning, at aminosyreresten 48 ikke er et cystein og er et serin; og (iv) et effektordomæne, som omfatter en transmembranregion og ét eller flere intra-cellulære signaleringsdomæner, hvor effektordomænet (iv) omfatter eller er en fusion af transmembran- og intracellulær-domænet af humant CD28 med det intracellulære domæne af den humane CD3 zetakæde.
2. Protein ifølge krav 1, hvor målet er en celle eller en virus, og hvor det målspecifikke genkendelsesdomæne (ii) binder et antigen, en receptor, en peptidligand eller en proteinligand for målet.
3. Protein ifølge krav 1 eller 2, hvor det målspecifikke genkendelsesdæmone (ii) omfatter et antigenbindende domæne, som er afledt af et antistof imod et antigen for målet, eller et peptid, som binder et antigen for målet, eller et peptid eller protein, som binder et antistof, som binder et antigen for målet, eller et peptid eller en proteinligand (såsom en vækstfaktor, et cytokin eller et hormon), som binder en receptor på målet, eller et domæne afledt af en receptor (såsom en vækstfaktorreceptor, en cytokinreceptor eller en hormonreceptor), som binder et peptid eller en proteinligand på målet.
4. Protein ifølge ethvert af de foregående krav, hvor antigenet for målet er et tumorassocieret overfladeantigen, et afstamningsspecifikt eller vævsspecifikt overfladeantigen eller et virusspecifikt overfladeantigen.
5. Protein ifølge ethvert af de foregående krav, hvor det antigenbindende domæne af domæne (ii) er afledt fra et antistof eller et antistoffragment, såsom et enkelt kæde Fv (scFv)-fragment, Fab-fragment, et diabody, et variabelt domæne af antistoffets tunge kæde eller antistoffets lette kæde.
6. Protein ifølge ethvert af de foregående krav, hvor effektordomænet (iv) omfatter eller er en fusion af transmembran- og intracellulærdomænet af humant CD28 med det intracellulære domæne af den humane CD3 zetakæde med aminosyresekvensen ifølge SEQ ID NO. 5; eller et funktionelt ækvivalent deraf.
7. Protein ifølge ethvert af de foregående krav, omfattende aminosyresekvensen ifølge SEQ ID NO. 7, eller en aminosyresekvens, som har i det mindste 95% sekvensidentitet med aminosyresekvensen ifølge SEQ ID NO. 7 underforudsætning af at aminosyrerest nr. 308 ikke er et cystein og er et serin.
8. Nukleinsyre, som koder for proteinet ifølge ethvert af kravene 1 til 7.
9. Nukleinsyre ifølge krav 8, omfattende nukleinsyren, som koder for aminosyresekvensen ifølge SEQ ID NO. 2 eller som omfatter nukleinsyresekvensen ifølge SEQ ID NO. 8, eller deres komplementære sekvenser eller sekvenser, som har i det mindste 95% sekvensidentitet.
10. Nukleinsyre ifølge krav 8 eller 9, omfattende nukleinsyren, som koder for aminosyresekvensen ifølge SEQ ID NO. 5 eller som omfatter nukleinsyresekvensen ifølge SEQ ID NO. 10 eller deres komplementære sekvenser eller sekvenser, som har i det mindste 95% sekvensidentitet.
11. Nukleinsyre ifølge ethvert af kravene 8 til 10, omfattende nukleinsyren, som koder for aminosyresekvensen ifølge SEQ ID NO. 7 eller nukleinsyresekvensen ifølge SEQ ID NO. 12, eller deres komplementære sekvenser eller sekvenser, som har i det mindste 95% sekvensidentitet.
12. Ekspressionskonstrukt til eksprimering af proteinet ifølge ethvert af kravene 1 til 7 i en celle, fortrinsvis yderligere omfattende promotor- og terminatorsekvenser.
13. Værtscelle, som eksprimerer et protein ifølge ethvert af kravene 1 til 7 eller som omfatter en nukleinsyre ifølge ethvert af kravene 8 til 11 eller et ekspressionskonstrukt ifølge krav 12, som er valgt blandt effektorceller for immunsystemet, og hvor effektorcellerne for immunsystemet er naturlige killer (NK)-celler, naturlige killer T (NKT)-celler eller en lymfocytpræparation, som indeholder NK-celler og NKT-celler.
14. Anvendelse "in vitro" af et protein ifølge kravene 1 til 7, en nukleinsyre ifølge kravene 8 til 11 eller et ekspressionskonstrukt ifølge krav 12 til at generere målspecifikke effektorceller.
15. Proteinet ifølge kravene 1 til 7, nukleinsyren ifølge kravene 8 til 11, ekspressions-konstruktet ifølge krav 12 eller værtscellen ifølge krav 13, til anvendelse som et medikament.
16. Proteinet ifølge kravene 1 til 7, nukleinsyren ifølge kravene 8 til 11, ekspressions-konstruktet ifølge krav 12 eller værtscellen ifølge krav 13 til anvendelse ved behandlingen af cancer eller til anvendelse ved adoptiv, målcellespecifik immunoterapi.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10009345 | 2010-09-08 | ||
| PCT/EP2011/004490 WO2012031744A1 (en) | 2010-09-08 | 2011-09-06 | Chimeric antigen receptors with an optimized hinge region |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2614077T3 true DK2614077T3 (da) | 2016-11-21 |
Family
ID=42942233
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15199344.1T DK3012268T3 (da) | 2010-09-08 | 2011-09-06 | Chimeriske antigenreceptorer med en optimeret hængselregion |
| DK11755014.5T DK2614077T3 (da) | 2010-09-08 | 2011-09-06 | Chimeriske antigenreceptorer med en optimeret hængselregion |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15199344.1T DK3012268T3 (da) | 2010-09-08 | 2011-09-06 | Chimeriske antigenreceptorer med en optimeret hængselregion |
Country Status (7)
| Country | Link |
|---|---|
| US (3) | US9212229B2 (da) |
| EP (3) | EP3012268B1 (da) |
| DK (2) | DK3012268T3 (da) |
| ES (3) | ES2656414T3 (da) |
| NO (1) | NO3012268T3 (da) |
| PT (2) | PT3012268T (da) |
| WO (1) | WO2012031744A1 (da) |
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