University of Pennsylvania

Other

Columbia University

Ritis, Konstantinos

John D Lambris

Hongchang Qu

Daniel Ricklin

Madan Katragadda

Konstantinos Ritis

George Hajishengallis

Gary H Cohen

Roselyn J Eisenberg

Patricia G Spear

Rebecca I Montgomery

E Sander Connolly, Jr

Piet Gros

Florea Lupu

Maria Rosa Sarrias

Maciej M Markiewski

Gary Kinasewitz

Arvind K Sahu

Christoph Schmidt

Bert J C Janssen

Fletcher B Taylor

Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. The compounds comprise compstatin analogs in which the N-terminus and/or C-terminus contains an added component that improves (1) the peptide's solubility at physiological pH; (2) the peptide's plasma half-life; (3) the peptide's intraocular retention; and/or (4) the peptide's binding affinity to C3 or its fragments as compared to an unmodified compstatin peptide under equivalent conditions. Pharmaceutical compositions and methods of using the compounds are also disclosed.

Compstatin analogs with increased solubility and improved pharmacokinetic properties

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

The present disclosure describes methods for preventing or treating periodontitis or diseases associated with periodontitis. The present disclosure also describes methods of screening for compounds that can be used to prevent or treat periodontitis or diseases associated with periodontitis.

Methods of treating or preventing periodontitis and diseases associated with periodontitis

Methods for treating, preventing or delaying onset of tumor formation and other forms of cancer are disclosed. The methods involve administration of a complement inhibitor to inhibit C5a receptor signaling in the tumor microenvironment.

Administration of compstatin to an individual for the treatment of a tumor

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.

Regulator of complement activation and uses thereof

Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. These compounds display greatly improved complement activation-inhibitory activity as compared with currently available compounds. The compounds comprise compstatin analogs having a constrained backbone at position 8 (glycine) and, optionally, specific substitutions for threonine at position 13.

Modified compstatin with peptide backbone and C-terminal modifications

Methods for the treatment of sepsis with complement inhibitors are disclosed. In particular, C3 inhibitors, such as Compstatin and Compstatin analogs, are administered at various times following the onset of sepsis to alleviate tissue damage and organ failure, which are hallmarks of the second, extravascular stage of sepsis. Combination therapies for comprehensive treatment of sepsis are also disclosed. Pharmaceutical compositions and kits for use in the methods are disclosed as well.

Treatment of sepsis using complement inhibitors

Methods for treating or ameliorating the damage resulting from intracerebral hemorrhage are disclosed. The methods involve administration of a complement inhibitor to inhibit C3or C5formation or activity in the affected tissue. Pharmaceutical compositions suitable for use in the methods of the invention are also provided.

Complement inhibitors for treatment of injury from intracerebral hemorrhage

Compounds comprising peptides and peptidomimetics capable of binding C3 protein and inhibiting complement activation are disclosed. These compounds display greatly improved complement activation-inhibitory activity as compared with currently available compounds.

Potent compstatin analogs

Factor H-binding peptides that binds to a region of factor H that does not impede the complement-inhibitory activity of factor H are disclosed. When immobilized onto the surface of a biomaterial, these peptides recruit factor H, resulting in a substantial inhibition of biomaterial-induced complement activation in a biological substance exposed to the biomaterial.

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Philadelphia, PA, United States of America

John D Lambris