University of Pennsylvania

Daniel Ricklin

John D Lambris

Hongchang Qu

Christoph Schmidt

Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. The compounds comprise compstatin analogs in which the N-terminus contains an added or substituted component that improves (1) the peptide's binding affinity to C3 or its fragments, (2) the peptide's solubility in aqueous liquids, (3) the peptide's plasma stability, (4) the peptide's in vivo retention and/or (5) the peptide's bioavailability, as compared with an unmodified compstatin peptide under equivalent conditions. Pharmaceutical compositions and methods of using the compounds are also disclosed.

Compstatin analogs with improved pharmacokinetic properties

Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. The compounds include a modified compstatin peptide or analog thereof, comprising an added N-terminal component that improves (1) the binding affinity of the peptide to C3, C3b or C3c and/or (2) the plasma stability and/or plasma residence time of the peptide, as compared with an unmodified compstatin peptide under equivalent conditions. Methods of improving the C3 binding of compstatin or compstatin analogs are also disclosed, as well as methods of designing compstatin analogs with improved C3 binding.

Compstatin analogs with improved potency and pharmacokinetic properties

A potent complement regulator is disclosed. The complement regulator comprises a complement regulatory region connected by a flexible linker to a multifunctional binding region that enables binding to C3b activation/inactivation products and/or oxidation end products, as well as to polyanionic surface markers on host cells. An embodiment of the invention utilizes factor H SCRs 1-4 as the complement regulatory region and factor H SCRs 19 and 20 as the multifunctional binding region, linked together by a poly-Gly linker at least 12 residues in length. Pharmaceutical compositions comprising the complement regulator and methods of using the complement regulator are also disclosed.

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Daniel Ricklin