SI2407486T1 - Antagonistična protitelesa proti GDF-8 in uporabe pri zdravljenju ALS in drugih obolenj, povezanih z GDF-8 - Google Patents

Antagonistična protitelesa proti GDF-8 in uporabe pri zdravljenju ALS in drugih obolenj, povezanih z GDF-8 Download PDF

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SI2407486T1
SI2407486T1 SI200632239T SI200632239T SI2407486T1 SI 2407486 T1 SI2407486 T1 SI 2407486T1 SI 200632239 T SI200632239 T SI 200632239T SI 200632239 T SI200632239 T SI 200632239T SI 2407486 T1 SI2407486 T1 SI 2407486T1
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amino acid
seq
acid sequence
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antibody
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Frank S. Walsh
Margaret M. Zaleska
David S. Howland
Erika L.F. Holzbaur-Howland
Lioudmila Tchistiakova
Riyez Karim
Pamela Kelley
Xiang-Yang Tan
Seung Poon Kwak
Karen Wallace
Nicholas Weber
Menelas N. Pangalos
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Wyeth Llc
The Trustees Of The University Of Pennsylvania
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Claims (28)

  1. Antagonistična protitelesa proti GDF-8 in uporabe pri zdravljenju ALS in drugih obolenj, povezanih z GDF-8 Patentni zahtevki
    1. Humanizirano protitelo, ki specifično veže in antagonizira GDF-8 in obsega: variabilno težko (VH) regijo protitelesa, ki ima aminokislinsko sekvenco SEQ ID NO:7 ali ki se razlikuje za ne več kot 2 aminokislinska ostanka od aminokislinske sekvence SEQ ID NO:7 in variabilno lahko (VL) regijo protitelesa, ki ima aminokislinsko sekvenco SEQ ID NO:9 ali ki se razlikuje za ne več kot 2 aminokislinska ostanka od aminokislinske sekvence SEQ ID NO:9; pri čemer prvi CDR iz regije VH (H1) ima aminokislinsko sekvenco SEQ ID NO: 10, drugi CDR iz regije VH (H2) ima aminokislinsko sekvenco SEQ ID NO:11, tretji CDR iz regije VH (H3) ima aminokislinsko sekvenco SEQ ID NO: 12, prvi CDR iz regije VL (L1) ima aminokislinsko sekvenco SEQ ID NO: 13, drugi CDR iz regije VL (L2) ima aminokislinsko sekvenco SEQ ID NO:14, tretji CDR iz regije VL (L3) ima aminokislinsko sekvenco SEQ ID NO: 15, ali pri čemer ima prvi CDR iz regije VH (H1) aminokislinsko sekvenco SEQ ID NO:20, ima drugi CDR iz regije VH (H2) aminokislinsko sekvenco SEQ ID NO:21, ima tretji CDR iz regije VH (H3) aminokislinsko sekvenco SEQ ID NO:22, ima prvi CDR iz regije VL (L1) aminokislinsko sekvenco SEQ ID NO:23, ima drugi CDR iz regije VL (L2) aminokislinsko sekvenco SEQ ID NO:24, ima tretji CDR iz regije VL (L3) aminokislinsko sekvenco SEQ ID NO:25.
  2. 2. Humanizirano protitelo po zahtevku 1, ki obsega: variabilno težko (VH) regijo protitelesa, ki ima aminokislinsko sekvenco SEQ ID NO:7 ali ki se razlikuje za ne več kot 1 aminokislinski ostanek od aminokislinske sekvence SEQ ID NO:7 in variabilno lahko (VL) regijo protitelesa, ki ima aminokislinsko sekvenco SEQ ID NO:9 ali ki se razlikuje za ne več kot 1 aminokislinski ostanek od aminokislinske sekvence SEQ ID NO:9;
  3. 3. Humanizirano protitelo po zahtevku 1 ali zahtevku 2, kjer omenjena VH regija obsega aminokislinsko sekvenco SEQ ID NO:7 in omenjena regija VL obsega aminokislinsko sekvenco SEQ ID NO:9.
  4. 4. Humanizirano protitelo po zahtevkih od 1 do 3, ki dalje obsega konstantno regijo težke verige iz podtipa imunoglobulina, ki je izbran iz skupine, ki jo sestavljajo lgG1, lgG2, lgG3, lgG4, lgA1, lgA2, IgD, IgE in IgM.
  5. 5. Humanizirano protitelo po katerem koli od zahtevkov 1 do 4, ki nadalje obsega ki nadalje obsega konstantno regijo težke verige humanega lgG1.
  6. 6. Humanizirano protitelo po zahtevku 4 ali zahtevku 5, pri čemer je konstantna regija spremenjena, da modificira lastnosti protitelesa.
  7. 7. Humanizirano protitelo po zahtevku 6, pri čemer je spremenjena konstantna regija mutirana.
  8. 8. Humanizirano protitelo po zahtevku 6 ali zahtevku 7,pri čemer je konstantna regija spremenjena, da poveča ali zmanjša vezavo receptorja Fc.
  9. 9. Protitelo po zahtevku 5, pri čemer konstantna regija obsega aminokislinsko sekvenco SEQ ID NO:19.
  10. 10. Protitelo po zahtevku 7, pri čemer konstantna regija humanega lgG1 obsega aminokislinsko sekvenco SEQ ID NO:19, ki je mutirana pri enem ali več ostankih 117 in 120 le-teh.
  11. 11. Protitelo po katerem koli od zahtevkov 1 do 10, ki dalje obsega konstantno regijo lahke verige protitelesa, ki je izbrana iz skupine, ki jo sestavljata kappa in lambda.
  12. 12. Polinukleotid, ki kodira protitelo po katerem koli od zahtevkov od 1 do 11.
  13. 13. Polinukleotid po zahtevku 12, ki je funkcionalno vezan na ekspresijsko kontrolno sekvenco.
  14. 14. Vektor, ki obsega polinukleotid po zahtevku 12 ali zahtevku 13 kot antagonist GDF-8.
  15. 15. Gostiteljska celica, ki obsega vektor po zahtevku 14, ali obsega polinukleotid po zahtevku 12 ali zahtevku 13 kot antagonist GDF-8.
  16. 16. Metoda proizvodnje protitelesa, ki specifično veže GDF-8 obsega korak gojenja gostiteljske celice po zahtevku 15 in pridobivanje protitelesa, ki je bil z njim proizveden.
  17. 17. Protitelo po katerem koli od zahtevkov od 1 do 11, ki je proizvedeno z metodo po zahtevku 16.
  18. 18. Sestavek, ki obsega protitelo po katerem koli od zahtevkov od 1 do 11 in 17 ter farmacevtsko sprejemljiv nosilec.
  19. 19. Sestavek po zahtevku 18 za uporabo pri zdravljenju obolenja pri sesalskem posamezniku, pri čemer je obolenje izbrano iz skupine, ki jo sestavljajo: mišično obolenje, nevromišično obolenje, degenerativno obolenje kosti, adipozno obolenje, presnovna bolezen okostja, inducirana bolezen kosti, obolenje presnove glukoze in z insulinom-povezano obolenje.
  20. 20. Sestavek za uporabo po zahtevku 19, pri čemer je omenjeno obolenje nadalje izbrano iz skupine obolenj, ki jo sestavljajo: mišična distrofija, Duchennova mišična distrofija, mišična atrofija, atrofija organa, krhkost, sindrom karpalnega kanala, kongestivna obstruktivna pljučna bolezen, amiotrofična lateralna skleroza (ALS), sarkopenija, kaheksija, sindrom izgube mišične mase, osteoporoza, z osteoporozo povezani zlomi, osteopenija, osteoartritis, nizka kostna masa, motena toleranca na glukozo, insulinska rezistenca, diabetes tipa 2, debelost in metabolični sindrom.
  21. 21. Sestavek za uporabo po zahtevku 20, pri čemer je omenjeno obolenje Duchennova mišična distrofija.
  22. 22. Sestavek za uporabo po zahtevku 20, pri čemer je omenjeno obolenje ALS.
  23. 23. Sestavek za uporabo po zahtevku 20, pri čemer je omenjeno obolenje kaheksija ali sarkopenija.
  24. 24. Sestavek po zahtevku 18 za uporabo pri zdravljenju obolenja z izgubljanjem mišične mase pri sesalskem posamezniku.
  25. 25. Sestavek za uporabo po zahtevku 24, pri čemer je obolenje z izgubljanjem mišične mase sindrom izgubljanja mišične mase ali s HIV povzročeno izgubljanje mišične mase.
  26. 26. Sestavek za uporabo po katerem koli od zahtevkov od 19 do 25, pri čemer je omenjeni sesalski posameznik človek.
  27. 27. Uporaba protitelesa po katerem koli od zahtevkov 1 do 11, in vitro, v diagnostični metodi.
  28. 28. Protitelo po katerem koli od zahtevkov od 1 do 11 za uporabo in vivo v diagnostični metodi.
SI200632239T 2005-08-19 2006-08-14 Antagonistična protitelesa proti GDF-8 in uporabe pri zdravljenju ALS in drugih obolenj, povezanih z GDF-8 SI2407486T1 (sl)

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SI200631905T SI1915397T1 (sl) 2005-08-19 2006-08-14 Antagonistična protitelesa proti GDF-8 in uporabe pri zdravljenju ALS in drugih obolenj, povezanih z GDF-8

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US (7) US7888486B2 (sl)
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