ME02652B - Stabilizovana varijanta aktivin iib receptora - Google Patents
Stabilizovana varijanta aktivin iib receptoraInfo
- Publication number
- ME02652B ME02652B MEP-2016-243A MEP24316A ME02652B ME 02652 B ME02652 B ME 02652B ME P24316 A MEP24316 A ME P24316A ME 02652 B ME02652 B ME 02652B
- Authority
- ME
- Montenegro
- Prior art keywords
- polypeptide
- seq
- position corresponding
- group
- sequence
- Prior art date
Links
- 108010059616 Activins Proteins 0.000 title claims 5
- 239000000488 activin Substances 0.000 title claims 5
- 102000005606 Activins Human genes 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 claims 45
- 102000004196 processed proteins & peptides Human genes 0.000 claims 45
- 108090000765 processed proteins & peptides Proteins 0.000 claims 45
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 28
- 238000006467 substitution reaction Methods 0.000 claims 20
- 102000004169 proteins and genes Human genes 0.000 claims 16
- 108090000623 proteins and genes Proteins 0.000 claims 16
- 102000040430 polynucleotide Human genes 0.000 claims 13
- 108091033319 polynucleotide Proteins 0.000 claims 13
- 239000002157 polynucleotide Substances 0.000 claims 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims 10
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 claims 9
- 108010056852 Myostatin Proteins 0.000 claims 9
- 108010023082 activin A Proteins 0.000 claims 9
- 101710194452 Growth/differentiation factor 11 Proteins 0.000 claims 7
- 102100040898 Growth/differentiation factor 11 Human genes 0.000 claims 7
- 102000039446 nucleic acids Human genes 0.000 claims 7
- 108020004707 nucleic acids Proteins 0.000 claims 7
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 238000000034 method Methods 0.000 claims 6
- 239000000203 mixture Substances 0.000 claims 5
- 102100026818 Inhibin beta E chain Human genes 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- 210000003205 muscle Anatomy 0.000 claims 3
- 201000000585 muscular atrophy Diseases 0.000 claims 3
- 206010065687 Bone loss Diseases 0.000 claims 2
- 206010028289 Muscle atrophy Diseases 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 230000000295 complement effect Effects 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 201000001421 hyperglycemia Diseases 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 230000020763 muscle atrophy Effects 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- 208000030507 AIDS Diseases 0.000 claims 1
- 206010003694 Atrophy Diseases 0.000 claims 1
- 208000037157 Azotemia Diseases 0.000 claims 1
- 208000010392 Bone Fractures Diseases 0.000 claims 1
- 206010005949 Bone cancer Diseases 0.000 claims 1
- 208000018084 Bone neoplasm Diseases 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 208000011623 Obstructive Lung disease Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 208000001647 Renal Insufficiency Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000010399 Wasting Syndrome Diseases 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 1
- 239000003098 androgen Substances 0.000 claims 1
- 230000037444 atrophy Effects 0.000 claims 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 210000004962 mammalian cell Anatomy 0.000 claims 1
- 230000005486 microgravity Effects 0.000 claims 1
- 201000006938 muscular dystrophy Diseases 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000002035 prolonged effect Effects 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 208000001076 sarcopenia Diseases 0.000 claims 1
- 208000020431 spinal cord injury Diseases 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000002103 transcriptional effect Effects 0.000 claims 1
- 208000009852 uremia Diseases 0.000 claims 1
Classifications
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- 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
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- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
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Claims (27)
1. Izolovani protein koji sadrži stabilizovan polipeptid aktivin ITB receptora, naznačen time da je navedeni polipeptid izabran iz grupe koja se sastoji od:(a) polipeptida koji sadrži sekvencu dalje iznetu u grupi koja se sastoji od SEK ID BR: 4, 6, 12 i 14;(b) polipeptida koji ima najmanje 90% identičnosti sekvence sa (a), pri čemupolipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11, i{e) polipeptida koji imaju najmanje 95% identičnosti sekvence sa {a), pri čemupolipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11.
2. Protein prema patentnom zahtjevu l, naznačen time što je polipeptid vezan sa najmanje jednim heterolognim proteinom.
3. Protein prema patentnom zahtjevu 2, naznačen time što je heterologni polipeptid IgG Fc domena.
4. Protein prema patentnom zahtjevu 2, naznačen time što je heterologni polipeptid povezan sa polipeptidom pomoću linker sekvence.
5. Protein prema patentnom zahtjevu 4, naznačen time što je linker sekvenca izabrana iz grupe koja se sastoji od sekvenci dalje iznetih u: SEK ID BR: 25, SEK ID BR: 27, SEK ID BR: 38, SEK ID BR: 40, SEK ID BR: 42, SEK ID BR: 44, SEK ID BR: 45, SEK ID BR: 46, SEK ID BR: 48, SEK ID BR: 49 i SEK ID BR: 50.
6. Protein prema patentnom zahtjevu 3, naznačen time što protein sadrži polipeptid izabran iz grupe koja se sastoji od: (a) polipeptida koji sadrži sekvencu dalje iznetu u grupi koja se sastoji od SEK ID BR: 8, 10, 16 i 18; (b) polipeptida koji ima najmanje 90% identičnosti sekvence sa (a), pri čemu polipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR:2, pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11, i (c) polipeptida koji imaju najmanje 95% identičnosti sekvence sa (a), pri čemu polipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR:2, pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11.
7. Izolovani protein sadrži sekvencu dalje iznetu u SEK ID BR: 10 l EP 2 370 463 Bl
8. Izolovani proteina sadrži stabilizovani aktivin Im receptora polipeptid (svActRIIB) naznačen time što je navedeni polipeptid izabran iz grupe koja se sastoji od: (a) polipeptida koji sadrži sekvencu dalje iznetu u SEK ID BR: 2, osim pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je supstitucija na položaju 28 odabrana iz grupe koji se sastoji od W i Y, i supstitucija na položaju 44 je T; (b) polipeptida koji sadrži sekvencu dalje iznetu u aminokiselinama 19 do 134 iz SEK ID BR: 2, osim pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je supstitucija na položaju 28 odabrana iz grupe koji se sastoji od W i Y i supstitucija na položaju 44 je T; (e) polipeptida koji sadrži sekvencu dalje iznetu u aminokiselinama 23 do 134 iz SEK ID BR: 2, osim pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i pojedinačne aminokiselinske supstituciju na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je supstitucija na položaju 28 odabrana iz grupe koji se sastoji od W i Y i supstitucija na položaju 44 je T; (d) polipeptida koji sadrži sekvencu dalje iznetu u aminokiselinama 25 do 134 iz SEK ID BR: 2, osim pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je supstitucija na položaju 28 odabrana iz grupe koji se sastoji od W i Y i supstitucija na položaju 44 je T; (e) polipeptida koji ima najmanje 80% identičnosti sekvence sa bilo kojom od (a) do (d), osim pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i pojedinačne aminokiselinske supstitucije na položaju koji odgovara položaju 44 iz SEK ID BR: 2, pri čemu je supstitucija na položaju 28 odabrana iz grupe koji se sastoji od W i Y i supstitucija na položaju 44 je T, pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11.
9. Izolovani molekul nukleinske kiseline koji sadrži polinukleotid koji kodira polipeptid prema patentnom zahtjevu 8.
10. Izolovani molekul nukleinske kiseline koji sadrži polinukleotid izabran iz grupe koja se sastoji od: (a) polinukleotida koji kodira polipeptid koji sadrži sekvencu dalje iznetu u grupi koja se sastoji od SEK ID BR: 4, 6, 12 i 14;(b) polinukleotida koji kodira polipeptid koji ima najmanje 90% identičnosti sekvence sa (a), pri čemu polipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR: 2; i pri čemu je je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-ll ; i (e) polinukleotida koji kodira polipeptid koji ima najmanje 95% identičnosti sekvence sa (a), pri čemu polipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovara položaju 44 iz SEK ID BR: 2 i pri čemu je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-11.
11. Moleku!nukleinske kiseline prema patentnom zahtjevu 10, naznačen time što polinukleotid ima sekvencu izabranu iz grupe koja se sastoji od sekvence dalje iznete u SEK ID BR: 3, 5, ll i 13 ili njenog komplementa.
12. Molekul nukleinske kiseline prema patentnom zahtjevu 10, naznačen time što polinukleotid dalje sadrži polinukleotid koji kodira najmanje jedan heterologni protein.
13. ji od:opolinukleotida koji kodira polipeptid koji sadrži sekvencu dalje iznetu u grupi koja se sastoji od SEKR: 8, 10, 16, i 18;b) polinukleotida koji kodira polipeptid koji ima najmanje 90% identičnosti sekvence sa (a), pri čem olipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovar oložaju 44 iz SEK ID BR: 2 i pri čemu je je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-ll ;(e) polinukleotida koji kodira polipeptid koji ima najmanje 95% identičnosti sekvence sa (a), pri čem olipeptid ima W ili Y na položaju koji odgovara položaju 28 iz SEK ID BR: 2 i T na položaju koji odgovar oložaju 44 iz SEK ID BR: 2 i pri čemu je je polipeptid sposoban da veže miostatin, aktivin A, ili GDF-l l.
14. Moleku!l nukleinske kiseline prema patentnom zahtjevu 13, naznačen time što polinukleotid ima sekvencu izabranu iz grupe koja se sastoji od sekvence dalje iznete u SEK ID BR: 7, 9, 15 i 17, ili njenog komplementa.
15. Molekul nukleinske kiseline prema patentnom zahtjevu 10, naznačen time, što je polinukleotid operativno vezan sa transkripcionom ili translacionom regulatornom sekvencom.
16. Rekombinantni vektor koji sadrži moleku! nukleinske kiseline prema patentnom zahtjevu l0.
17. Ćelija domaćin koja sadrži rekombinantni vektor prema patentnom zahtjevu 16.
18. Ćelija domaćin prema patentnom zahtjevu 17, gde je ćelija domaćin ćelija sisara.
19. Postupak proizvodnje svActRiffi proteina koji obuhvata kultivisanje ćelije domaćina prema patentnom zahtjevu 17, pod uslovima koji promovišu ekspresiju proteina i oporavak proteina.
20. Farmaceutska kompozicija koja sadrži efikasnu količinu proteina prema bilo kom od patentnih zahtjeva 1-8 u smeši sa farmaceutski prihvatljivim nosačem.
21. Kompozicija prema patentnom zahtjevu 20 za upotrebu kao lijek.
22. Kompozicija prema patentnom zahtew 20 za upotrebu u postupku liječenja mišićne atrofije ili metaboličkog poremećaja izabranog od dijabetesa, gojaznosti, hiperglikemije ili gubitka koštane mase kod subjekta kome je potreban takav tretman.
23. Kompozicija za upotrebu prema patentnom zahtjew 22, pri čemu je mišićna atrofija usled bolesti gubitka mišićne mase izabrana od mišićne distrofije, amiotrofue lateralne skleroze, kongestivne opstruktivne bolesti pluća, hronične srčane insuficijencije, kaheksije usled kancera, AIDS-a, bubrežne insuficijencije, uremije, reumatoidnog artritisa, sarkopenije uzrokovane starenjem, atrofije organa, sindroma karpalnog tunela, gubitka androgena, opekotina, dijabetesa i atrofije mišića usled dugotrajnog ležanja u krevetu, povrede kičmene moždine, šloga, preloma kostiju, starenja ili izloženosti mikrogravitaciji.
24. Kompozicija prema patentnom zahtjew 20 za upotrebu u postupku liječenja oboljenja u kome je aktivin prekomemo eksprimiran kod subjekta kome je potreban takav tretman i gde je oboljenje kancer.
25. Vektor prema patentnom zahtjew 16 za upotrebu u postupku liječenja gubitka mišićne mase ili metaboličkog poremećaja izabranog od dijabetesa, gojaznosti, hiperglikemije ili gubitka koštane mase ili kancera u kome je aktivin prekomerno eksprimiran kod subjekta kod koga postoji potreba za takvim tretmanom, naznačen time da je vektor sposoban da usmerava ekspresiju svActRIIB polipeptida kod subjekta.
26. Kompozicija za upotrebu prema patentnom zahtjew 24 ili vektor za upotrebu prema patentnom zahtjevu 25, naznačena time što je kancer kancer ovarijuma.
27. Upotreba proteina prema bilo kom od patentnih zahtjeva 1-8 u postupku za povećanje mišićne mase ili povećanje odnosa posne mišićne mase u odnosu na masu masti, pri čemu postupak nije postupak za lečenje ljudskog ili životinjskog tela pomoću terapije.
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