DK2132314T3 - Activinreceptorpolypeptidvariant og anvendelser deraf - Google Patents
Activinreceptorpolypeptidvariant og anvendelser deraf Download PDFInfo
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- DK2132314T3 DK2132314T3 DK08742032.9T DK08742032T DK2132314T3 DK 2132314 T3 DK2132314 T3 DK 2132314T3 DK 08742032 T DK08742032 T DK 08742032T DK 2132314 T3 DK2132314 T3 DK 2132314T3
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- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- 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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Claims (18)
1. Isoleret protein, der omfatter en activin-IIB-receptorpolypeptidvariant (vActRIIB), hvor polypeptidet er udvalgt fra gruppen bestående af: (a) et polypeptid, der har polypeptidsekvensen ifølge SEQ ID NO:18, bortset fra en enkelt aminosyresubstitution ved position 28, hvor substitutionen er udvalgt fra en hvilken som helst af A, F, Q, V, I, L, Μ, K, H, W og Y med E; (b) et polypeptid, der har polypeptidsekvensen ifølge aminosyrerne 19 til og med 134 ifølge SEQ ID NO:18, bortset fra en enkelt aminosyresubstitution ved position 28, hvor substitutionen er udvalgt fra en hvilken som helst af A, F, Q, V, I, L, Μ, K, H, W og Y med E; (c) et polypeptid, der har polypeptidsekvensen ifølge aminosyrerne 23 til og med 134 ifølge SEQ ID NO:18, bortset fra en enkelt aminosyresubstitution ved position 28, hvor substitutionen er udvalgt fra en hvilken som helst af A, F, Q, V, I, L, Μ, K, H, W og Y med E; (d) et polypeptid, der har polypeptidsekvensen ifølge aminosyrerne 25 til og med 134 ifølge SEQ ID NO:18, bortset fra en enkelt aminosyresubstitution ved position 28, hvor substitutionen er udvalgt fra en hvilken som helst af A, F, Q, V, I, L, Μ, K, H, W og Y med E; (e) et polypeptid, der har mindst 90 % identitet med en hvilken som helst af (a) til og med (d), hvor substitutionen ved position 28 er udvalgt fra en hvilken som helst af A, F, Q, V, I, L, Μ, K, H, W og Y med E, og hvor polypeptidet er i stand til at binde myostatin, activin A eller GDF-11.
2. Isoleret protein ifølge krav 1, hvor (i) substitutionen ved position 28 er udvalgt fra A, W eller Y med E; eller (ii) polypeptidet ifølge krav 1 (e) endvidere omfatter substitutionen A med R ved position 64.
3. Isoleret protein ifølge krav 2, hvor substitutionen ved position 28 er udvalgt fra A, W eller Y med E.
4. Isoleret protein ifølge krav 3, hvor substitutionen ved position 28 er W med E.
5. Isoleret protein ifølge et hvilket som helst af kravene 1 til 3, hvor polypeptidet har sekvensen udvalgt fra gruppen bestående af SEQ ID NO: 20, 24, 26, 28, 34, 38, 40, 42, og 87 eller 88.
6. Isoleret protein ifølge et hvilket som helst af kravene 1 til 5, hvor (i) polypeptidet er kondenseret til mindst ét heterologt polypeptid; (ii) polypeptidet er kondenseret til mindst ét heterologt polypeptid, hvor det heterologe polypeptid er et humant Fc-domæne; eller (iii) polypeptidet er kondenseret til mindst ét heterologt polypeptid, hvor det heterologe polypeptid er et humant Fc-domæne, og hvor proteinet endvidere omfatter en linker.
7. Isoleret protein ifølge krav 6, hvor (a) polypeptidet har mindst 99 % identitet med polypeptidet ifølge krav 4 og har en substitution af W med E ved position 28; og (b) polypeptidet er kondenseret til mindst ét heterologt polypeptid, hvor det heterologe polypeptid er et humant lgG2 Fc-domæne med polypeptidsekvensen ifølge SEQ ID NO: 80, og hvor proteinet endvidere omfatter hængsels-linkeren med polypeptidsekvensen ifølge SEQ ID NO: 79.
8. Isoleret protein ifølge krav 6, hvor proteinet har sekvensen udvalgt fra gruppen bestående af SEQ ID NO: 60, 62, 64, 87, 88, 91, 93, 95 og 97.
9. Farmaceutisk sammensætning, der omfatter en effektiv mængde af protein ifølge et hvilket som helst af kravene 1 til og med 8 blandet med en farmaceutisk acceptabel bærer.
10. Isoleret nukleinsyremolekyle, der består af en polynukleotidsekvens, der koder for protein ifølge et hvilket som helst af kravene 1 til 8.
11. Isoleret nukleinsyremolekyle ifølge krav 10, hvilket molekyle omfatter et polynukleotid udvalgt fra gruppen bestående af: (a) et polynukleotid med sekvensen udvalgt fra gruppen bestående af SEQ ID NO:19, 23, 25, 27, 33, 37, 39, 41, 59, 61, 63, 92, 94, og 96 eller komplementet heraf; og (b) et polynukleotid, der koder for et polypeptid, der har aminosyresekvensen udvalgt fra gruppen bestående af SEQ ID NO:20, 24, 26, 28, 34, 38, 40, 42, 60, 62, 64, 87, 88, 91,93, 95 og 97.
12. Rekombinant ekspressionsvektor, der omfatter nukleinsyren ifølge krav 10 eller 11.
13. Værtscelle omfattende den rekombinante vektor ifølge krav 12.
14. Fremgangsmåde til fremstilling af protein ifølge et hvilket som helst af kravene 1 til og med 8, hvilken fremgangsmåde omfatter dyrkning af værtscellen ifølge krav 13, hvorved proteinet udtrykkes.
15. Protein ifølge et hvilket som helst af kravene 1 til 8 eller sammensætning ifølge krav 9 til anvendelse (i) til hæmning af myostatinaktivitet eller øgning af mager muskelmasse eller øgning af forholdet mellem mager muskelmasse og fedtmasse hos et individ med behov for en sådan behandling; (ii) ved behandling af en muskelsvindssygdom eller metabolisk forstyrrelse hos et individ med behov for en sådan behandling; eller (iii) ved behandling af en sygdom, hvor activin er overudtrykt hos et individ med behov for en sådan behandling.
16. Protein eller sammensætning til anvendelse ifølge krav 15, hvor muskelsvindssygdommen eller metabolisk forstyrrelse er udvalgt fra muskeldystrofi, amyotrofisk lateral sklerose, kongestiv obstruktiv lungesygdom, kronisk hjerteinsufficiens, cancerkakeksi, AIDS, kakeksi på grund af nyreinsufficiens, uræmi, kakeksi på grund af rheumatoid arthritis, aldersrelateret sarcopeni, organatrofi, karpaltunnelsyndrom, androgen deprivation, kakeksi på grund af forbrændingsskader, diabetisk nefropati og muskelsvind på grund af længerevarende sengeleje, rygmarvslæsion, apopleksi, knoglef raktur, ældning, eksponering for minimal indvirkning af tyngdekraft, diabetes, fedme, hyperglykæmi og knogletab.
17. Protein eller sammensætning til anvendelse ifølge krav 15, hvor den sygdom, hvori activin er overudtrykt, er cancer.
18. Protein eller sammensætning til anvendelse ifølge krav 17, hvor canceren er ovariecancer.
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US6547408P | 2008-02-11 | 2008-02-11 | |
PCT/US2008/003119 WO2008109167A2 (en) | 2007-03-06 | 2008-03-06 | Variant activin receptor polypeptides and uses thereof |
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DK08742032.9T DK2132314T3 (da) | 2007-03-06 | 2008-03-06 | Activinreceptorpolypeptidvariant og anvendelser deraf |
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EP (2) | EP2132314B1 (da) |
JP (1) | JP5496682B2 (da) |
KR (5) | KR20090127146A (da) |
CN (2) | CN101679980B8 (da) |
AR (1) | AR065611A1 (da) |
AU (1) | AU2008223338C9 (da) |
BR (1) | BRPI0808332A2 (da) |
CA (1) | CA2679841C (da) |
CL (2) | CL2008000664A1 (da) |
CR (2) | CR11054A (da) |
CY (1) | CY1118857T1 (da) |
DK (1) | DK2132314T3 (da) |
EA (2) | EA201490822A1 (da) |
ES (1) | ES2613043T3 (da) |
HR (1) | HRP20170323T1 (da) |
HU (1) | HUE032260T2 (da) |
IL (2) | IL200605A (da) |
LT (1) | LT2132314T (da) |
MX (2) | MX348286B (da) |
NZ (1) | NZ579369A (da) |
PE (3) | PE20130615A1 (da) |
PH (1) | PH12013502308A1 (da) |
PL (1) | PL2132314T3 (da) |
PT (1) | PT2132314T (da) |
RS (1) | RS55726B1 (da) |
SI (1) | SI2132314T1 (da) |
TW (3) | TWI573802B (da) |
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