Claims for Patent: 7,989,589

Summary for Patent: 7,989,589

Title:	Compstatin analogs with improved activity
Abstract:	Compounds comprising peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation are disclosed. These compounds display improved complement activation-inhibitory activity as compared with currently available compounds. Isolated nucleic acid molecules encoding the peptides are also disclosed.
Inventor(s):	Lambris; John D. (Bryn Mawr, PA)
Assignee:	The Trustees Of The University Of Pennsylvania (Philadelphia, PA)
Application Number:	10/528,496
Patent Claims:	1. A compound that inhibits complement activation, which comprises a peptide having a sequence: TABLE-US-00003 (SEQ ID NO: 15) Xaa1-Cys-Val-Xaa2-Gln-Asp-Trp-Gly-Xaa3-His-Arg- Cys-Xaa4; wherein: Xaa1 is Ile, Val, Leu, Ac-Ile, Ac-Val, Ac-Leu or a dipeptide comprising Gly-Ile; Xaa2 is Trp or a peptidic or non-peptidic analog of Trp; Xaa3 is His, Ala, Phe or Trp; Xaa4 is L-Thr, D-Thr, Ile, Val, Gly, or a tripeptide comprising Thr-Ala-Asn, wherein a carboxy terminal --OH of any of the L-Thr, D-Thr, Ile, Val, Gly or Asn optionally is replaced by --NH.sub.2; and the two Cys residues are joined by a disulfide bond. 2. The compound of claim 1, wherein Xaa1 is Ac-Ile. 3. The compound of claim 1, wherein Xaa3 is Ala. 4. The compound of claim 1, 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. 5. The compound of claim 4, wherein the analog of Trp is selected from the group consisting of 2-naphthylalanine, 1-naphthylalanine, 2-indanylglycine carboxylic acid, dihydrotryptophan and benzoylphenylalanine. 6. The compound of claim 1, wherein Xaa1 is Ac-Ile, Xaa2 is Trp or an analog of Trp comprising a substituted or unsubstituted indole, naphthyl or dibenzoyl component, Xaa3 is Ala and Xaa4 is L-Thr or D-Thr, wherein the carboxy terminal --OH of the L-Thr or D-Thr optionally is replaced by --NH.sub.2. 7. The compound of claim 6, having a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13. 8. The compound of claim 1, wherein Xaa1 is a dipeptide Gly-Ile, and Xaa 4 is a tripeptide Thr-Ala-Asn. 9. The compound of claim 8, comprising a peptide having SEQ ID NO:14.