Georgetown University

University of Hawai'i

David C Fritzinger

Reinhard Bredehorst

Carl-Wilhelm Ernst Vogel

Michael Kock

Daniel Benjamin

Carl-Wilhelm Vogel

The invention relates generally to a modified human C3 protein containing a number of single amino acid changes in the α and β-chain of human C3 protein, designed to increase the affinity of the modified protein to factor B or Bb, to decrease the affinity of the modified protein to factor H, and to reduce the immunogenicity of the modified protein as compared to the native human C3 protein, a nucleotide sequence encoding the modified C3 protein, a plasmid or viral vector containing the nucleotide sequence for expression the modified C3 protein, and a host cell containing the plasmid or viral vector. We also present a polyethylene glycol covalently bound to the modified C3 protein for reducing immunogenicity and increasing plasma half-life of the modified C3 protein; a method for depleting complement in a patient by administering the modified C3 protein to the patient in an amount effective to deplete complement; a method of ameliorating effects caused by or disease or a method of ameliorating reperfusion injury in a patient by delivering the modified C3 protein.

Modulators of complement function

A modified human complement C3 protein (C3) is disclosed comprising a substitution of a portion of a human C3 protein, with a corresponding portion of a Cobra Venom Factor protein (CVF) which results in a human C3 protein with CVF functions, but with substantially reduced immunogenicity. Advantageously, the C3 protein can be manipulated to contain at least one of the following CVF functions: increased stability of the C3 convertase and increased resistance to the actions of factors H and/or I. A large number of hybrid C3 proteins containing substitutions in the C-terminal portion of the alpha chain of C3 are presented and tested for the above functions. Methods of treatment of diseases such as reperfusion injury, autoimmune diseases, and other diseases of increased complement activation are presented as well as methods of increasing the effectiveness of gene therapeutics and other therapeutics.

Human complement C3 derivates with cobra venom factor-like function

Recombinant proCVF exhibits substantially the same activity as CVF and is useful for lowering complement activity.

Recombinant proCVF

Recombinant proCVF exhibits substantially the same activity as CVF and is useful for lowering complement activity

Recombinant procvf

DNA sequences encoding cobra C3, CVF1, and CVF2, as well as plasmids and transformed hosts comprising such DNA sequences, are provided.

Growing community of inventors

Alexandria, VA, United States of America

David C Fritzinger