Use of complement inhibitors to treat ocular diseases
The present invention relates to the treatment of ocular diseases and conditions by administering a complement pathway inhibitor, particularly an alternative pathway inhibitor. Ocular diseases include age-related macular degeneration, diabetic retinopathy, and ocular angiogenesis. One embodiment comprises the administration of an anti-Factor D antibody in the form of a whole antibody, a Fab fragment or a single domain antibody. Other complement component inhibitors that may be useful in the present method include Factor H or inhibitors that block the action of properdin, factor B, factor Ba, factor Bb, C2, C2a, C3a, C5, C5a, C5b, C6, C7, C8, C9, or C5b-9.
1. A method for ameliorating macular degeneration, comprising administering an effective amount of a complement inhibitor to a subject in need thereof, wherein the complement inhibitor is an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment specifically binds to Factor D.
2. The method of claim 1 , wherein the subject requires inhibition of ocular neovascularization that affects the choroid, retinal pigmented epithelium, or retinal tissue.
3. The method according to claim 1 , wherein the antigen-binding fragment comprises a Fab, Fab′, F(ab′) 2 , Fv, a single chain Fv, a diabody, or a single domain antibody.
4. The method according to claim 1 , wherein the antibody is a monoclonal antibody.
5. The method according to claim 1 , wherein the antibody is a chimeric antibody, a multispecific antibody, a deimmunized antibody, a humanized antibody, a primatized antibody or a human antibody.
6. The method according to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a therapeutic moiety.
7. The method of claim 6 , wherein the therapeutic moiety is a cytotoxin, a therapeutic agent or a radioactive metal ion.
8. The method according to claim 1 , wherein the antibody is monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
9. The method according to claim 1 , wherein the antibody specifically binds to the same epitope as monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
10. The method according to claim 1 , wherein the antibody is a humanized monoclonal antibody derived from monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
11. The method of claim 1 , wherein the complement inhibitor is administered by parenteral administration, intradermal administration, intramuscular administration, intraperitoneal administration, intravenous administration, subantaneous administration, intranasal administration, oral administration, enteral administration, topical administration, intrathecal administration, intraventricular administration, epidural , inhalation, a biocompatible or bioerodable sustained release implant, or implantation of an infusion pump.
12. The method of claim 1 , wherein the complement inhibitor is administered locally.
13. The method of claim 1 , wherein the complement inhibitor is administered by intraocular administration, intravitreal administration, or subconjunctival administration.
14. The method according to claim 1 , wherein the complement inhibitor is administered in an eye wash solution, an eye ointment, an eye shield or an eye drop solution.
15. The method according to claim 1 , further comprising the step of administering an immunomodulatory compound, an immunosuppressive compound, an anti-inflammatory compound, or an anti-angiogenic compound, to said subject.
16. The method of claim 1 , further comprising administering to the subject an anti-angiogenesis therapy targeting vascular endothelial growth factor (VEGF).
17. The method of claim 1 , wherein the dosage of complement inhibitor administered to the subject is between 0.1 mg/kg to 100 mg/kg.
18. The method of claim 1 , wherein the macular degeneration is dry form of age-related macular degeneration.
19. The method of claim 1 , wherein the subject is human.
20. A method for inhibiting the alternative pathway activation in a subject with macular degeneration, comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment specifially binds to Factor D.
21. The method of claim 20 , wherein the subject requires inhibition of ocular neovascularization that affects the choroid, retinal pigmented epithelium, or retinal tissue.
22. The method of claim 20 , wherein the antigen-binding fragment comprises a Fab, Fab′, F(ab′) 2 , Fv, a single chain Fv, a diabody, or a single domain antibody.
23. The method of claim 20 , wherein the antibody is a monoclonal antibody.
24. The method of claim 20 , wherein the antibody is a chimeric antibody, a multispecific antibody, a deimmunized antibody, a humanized antibody, a primatized antibody or a human antibody.
25. The method of claim 20 , wherein the antibody or antigen-binding fragment thereof comprises a therapeutic moiety.
26. The method of claim 20 , wherein the antibody is monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
27. The method of claim 20 , wherein the antibody specifically binds to the same epitope as monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
28. The method according to claim 20 , wherein the antibody is a humanized monoclonal antibody derived from monoclonal antibody 166-32 produced from the hybridoma deposited with the ATCC and designated HB 12476.
29. The method of claim 20 , wherein the antibody or the antigen-binding fragment thereof is administered by parenteral administration, intradermal administration, intramuscular administration, intraperitoneal administration, intravenous administration, subantaneous administration, intranasal administration, oral administration, enteral administration, topical administration, intrathecal administration, intraventricular administration, epidural , inhalation, a biocompatible or bioerodable sustained release implant, or implantation of an infusion pump.
30. The method of claim 20 , wherein the antibody or the antigen-binding fragment thereof is administered locally.
31. The method of claim 20 , wherein the antibody or the antigen-binding fragment thereof is administered by intraocular administration, intravitreal administration, or subconjunctival administration.
32. The method according to claim 20 , wherein the antibody or the antigen-binding fragment thereof is administered in an eye wash solution, an eye ointment, an eye shield or an eye drop solution.
33. The method according to claim 20 , further comprising the step of administering an immunomodulatory compound, an immunosuppressive compound, an anti-inflammatory compound, or an anti-angiogenic compound, to said subject.
34. The method of claim 20 , further comprising administering to the subject an anti-angiogenesis therapy targeting vascular endothelial growth factor (VEGF).
35. The method of claim 20 , wherein the dosage of the antibody or the antigen-binding fragment thereof administered to the subject is between 0.1 mg/kg to 100 mg/kg.
36. The method of claim 25 , wherein the therapeutic moiety is a cytotoxin, a therapeutic agent or a radioactive metal ion.
37. The method of claim 20 , wherein the macular degeneration is dry form of age-related macular degeneration.
38. The method of claim 20 , wherein the subject is human.