Claims for Patent: 9,056,076

Summary for Patent: 9,056,076

Title:	Method of treating age-related macular degeneration comprising administering a compstatin analog
Abstract:	The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and/or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.
Inventor(s):	Deschatelets Pascal, Olson Paul, Francois Cedric
Assignee:	Potentia Pharmaceuticals, Inc.
Application Number:	US13409941
Patent Claims:	2. The method of claim 1 , wherein the compstatin analog is a compound that comprises a cyclic peptide having a core sequence of X′aa-Gln-Asp-Xaa-Gly (SEQ ID NO: 3) claim 1 , where X′aa and Xaa are selected from Trp and analogs of Trp.3. The method of claim 1 , wherein the compstatin analog is a compound that comprises a cyclic peptide having a core sequence of X′aa-Gln-Asp-Xaa-Gly-X″aa (SEQ ID NO: 4) claim 1 , where X′aa and Xaa are each independently selected from Trp and analogs of Trp and X″aa is selected from His claim 1 , Ala claim 1 , single methyl unbranched amino acids claim 1 , Phe claim 1 , Trp claim 1 , and analogs of Trp.4. The method of claim 3 , wherein the peptide has a sequence of X′aa1-X′aa2-X′aa3-X′aa-Gln-Asp-Xaa-Gly-X″aa-X″aa2-X″aa3-X″aa4-X″aa5 (SEQ ID NO: 5) claim 3 , and X′aa1 claim 3 , X′aa2 claim 3 , X′aa3 claim 3 , X″aa2 claim 3 , X″aa3-X″aa4 claim 3 , and X″aa5 are identical to the amino acids at the corresponding positions in compstatin.5. The method of claim 1 , wherein the compstatin analog is a compound that comprises a cyclic peptide having a sequence of X′aa1-X′aa2-X′aa3-X′aa4-Gln-Asp-Xaa-Gly-X″aa1-X″aa2-X″aa3-X″aa4-X″aa- 5 (SEQ ID NO: 5) claim 1 , where X′aa4 and Xaa are selected from Trp and analogs of Trp claim 1 , wherein X′aa1 claim 1 , X′aa2 claim 1 , X′aa3 claim 1 , X″aa1 claim 1 , X″aa2 claim 1 , X″aa3 claim 1 , X″aa4 claim 1 , and X″aa5 are independently selected from among amino acids and amino acid analogs claim 1 , and the peptide is cyclized via a bond between X′aa2 and X″aa4.6. The method of claim 1 , wherein the compstatin analog is a compound that comprises a cyclic peptide having a sequence: Xaa1-Cys-Val-Xaa2-Gln-Asp-Xaa2*-Gly-Xaa3-His-Arg-Cys-Xaa4 (SEQ ID NO: 6); wherein: Xaa1 is Ile claim 1 , Val claim 1 , Leu claim 1 , B-Ile claim 1 , B-Val claim 1 , B-Leu or a dipeptide comprising Gly-Ile or B-Gly-Ile claim 1 , and Brepresents a first blocking moiety; Xaa2 and Xaa2* are independently selected from Trp and analogs of Trp; Xaa3 is His claim 1 , Ala or an analog of Ala claim 1 , Phe claim 1 , Trp claim 1 , or an analog of Trp; Xaa4 is L-Thr claim 1 , D-Thr claim 1 , Ile claim 1 , Val claim 1 , Gly claim 1 , a dipeptide selected from Thr-Ala and Thr-Asn claim 1 , or a tripeptide comprising Thr-Ala-Asn claim 1 , wherein a carboxy terminal —OH of any of the L-Thr claim 1 , D-Thr claim 1 , Ile claim 1 , Val claim 1 , Gly claim 1 , Ala claim 1 , or Asn optionally is replaced by a second blocking moiety B; and the two Cys residues are joined by a disulfide bond.7. The method of claim 6 , wherein the peptide is acetylated at the N-terminus claim 6 , amidated at the C-terminus claim 6 , or both acetylated at the N-terminus and amidated at the C-terminus.8. The method of claim 6 , wherein Xaa1 is Ile claim 6 , Val claim 6 , Leu claim 6 , Ac-Ile claim 6 , Ac-Val claim 6 , Ac-Leu or a dipeptide comprising Gly-Ile or Ac-Gly-Ile; Xaa2 and Xaa2* are independently selected from Trp and analogs of Trp; Xaa3 is His claim 6 , Ala or an analog of Ala claim 6 , Phe claim 6 , Trp claim 6 , or an analog of Trp; Xaa4 is L-Thr claim 6 , D-Thr claim 6 , Ile claim 6 , Val claim 6 , Gly claim 6 , a dipeptide selected from Thr-Ala and Thr-Asn claim 6 , or a tripeptide comprising Thr-Ala-Asn claim 6 , wherein a carboxy terminal —OH of any of the L-Thr claim 6 , D-Thr claim 6 , Ile claim 6 , Val claim 6 , Gly claim 6 , Ala claim 6 , or Asn optionally is replaced by —NH.9. The method of claim 6 , wherein Xaa2 is an analog of Trp having increased hydrophobic character relative to Trp.10. The method of claim 6 , wherein Xaa2 is an analog of Trp comprising a substituted or unsubstituted bicyclic aromatic ring component or two or more substituted or unsubstituted monocyclic aromatic ring components.11. The method of claim 1 , wherein the composition is administered intravitreally.12. The method of claim 1 , wherein the compstatin analog is a compound that comprises a cyclic peptide comprising a cyclic portion 11 amino acids in length claim 1 , wherein the sequence of the peptide is at least 50% identical to the sequence of compstatin (SEQ ID NO: 8) or to the sequence of a compstatin analog that has higher activity than compstatin.13. The method of claim 12 , wherein the peptide comprises at least one non-standard amino acid.14. The method of claim 13 , wherein at least one non-standard amino acid is a singly or multiply halogenated amino acid claim 13 , N-alkyl amino acid claim 13 , or aromatic amino acid.15. The method of claim 1 , wherein the compstatin analog is a compound that comprises or consists of a sequence that is obtained by making 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 substitutions in the sequence of compstatin claim 1 , wherein the peptide is cyclized via a bond between amino acids at positions that correspond to position 2 and position 12 of compstatin.16. The method of claim 15 , wherein 1 claim 15 , 2 claim 15 , 3 claim 15 , or 4 amino acids in the sequence of compstatin is replaced by a non-standard amino acid.17. The method of claim 16 , wherein at least one non-standard amino acid is a singly or multiply halogenated amino acid claim 16 , N-alkyl amino acid claim 16 , or aromatic amino acid.18. The method of claim 1 , wherein the compstatin analog binds to substantially the same region of human C3 as does compstatin and has a C3 inhibitory activity at least 10-fold as great as that of compstatin.19. The method of claim 1 , wherein the composition is locally administered to the eye or in the vicinity of the eye.