Patent ID: 11884747
Assignee: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC A  C

Claim 5:
6. A compound comprising:
(a) a compstatin analog peptide having an amino acid sequence:
Xaa1-Xaa2-Cys-Val-Xaa3-Gin-Xaa4-Xaa5-Gly-Xaa6-His-Xaa7-Cys-Xaa8, in which Gly between Xaa5 and Xaa6 optionally is modified to constrain the backbone conformation;
wherein:
Xaa1 is absent or is Tyr, D-Tyr or Sar;
Xaa2 is Ile, Gly or Ac-Trp;
Xaa3 is Trp or an analog of Trp, wherein the analog of Trp has increased hydrophobic character as compared with Trp;
Xaa4 is Asp or Asn;
Xaa5 is Trp or an analog of Trp comprising a chemical modification to its indole ring wherein the chemical modification increases the hydrogen bond potential of the indole ring;
Xaa6 is His, Ala, Phe or Trp;
Xaa7 is Arg or Orn;
Xaa8 is Thr, Ile, Leu, Nle, N-methyl Thr or N-methyl Ile, wherein a carboxy terminal —OH of any of the Thr, Ile, Leu, Nle, N-methyl Thr or N-methyl Ile optionally is replaced by —NH2; and
the peptide is cyclic via a Cys-Cys or thioether bond; and
(b) a terminal modification comprising an added terminal component that improves (1) the peptide's C3, iC3b, C3b or C3c binding affinity, (2) the peptide's solubility at physiological pH, and/or (3) the peptide's plasma stability and/or plasma residence time; and/or (4) the peptide's vitreous stability and/or vitreous residence time, as compared with an unmodified compstatin peptide under equivalent conditions;, wherein the added terminal component:
(i) is a C-terminal component comprising two or three lysine amino acid residues; or
(ii) is an N-terminal component comprising polyethylene glycol (PEG) having an average molecular weight of about 1 kDa to about 3 kDa; or
(iii) both (i) and (ii).