Compstatin Variants as therapeutic leads for Autoimmune and Inflammatory Disease

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Princeton University Invention # 09-2488


The present invention relates to a series of novel analogues to compstatin. Based on experimental SPR (Surface Plasmon Resonance) and IC50 binding data these new analogues show greater binding affinity compared to native compstatin and are therefore potentially more potent drug candidates for diseases related to improper complement activation. Low nanomolar binding affinities similar to alternative analogues described in the literature have been achieved and, based upon testing modifications with non-natural amino acids, even greater C3c binding affinities are anticipated.


Researchers at Princeton University, Department of Chemical Engineering and University of California, Bioengineering have developed and used two de novo protein design frameworks to discover these new compstatin variants. The framework utilizes two stages: a sequences selection stage and a binding affinity calculation stage. The sequence selection stage produces a rank-ordered list of amino acid sequences with the lowest energies based upon the template structure (compstatin). The binding affinity calculation stage takes the sequences from stage one and calculates approximate binding affinities for each sequence. The sequences are then ranked according to binding affinities, elucidating sequences that have higher predicted binding affinities than the native compstatin, making them more potent inhibitors of C3c.


Although complement activation is part of a normal inflammatory response, inappropriate complement activation can cause host-cell damage, which is implicated in a number of pathological conditions, such as autoimmune diseases, stroke, heart attack, Alzheimer¿s disease and burn injuries.


Compstatin has shown highly promising results in a number of clinically relevant trials. These new compstatin analogs may offer a new second generation of complement based therapeutics leads.


Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity. Patent protection is pending.



Bellows ML, Fung HK, Taylor MS, Floudas CA, López de Victoria A, Morikis D, New Compstatin Variants through Two De Novo Protein Design Frameworks, Biophysical Journal, Vol 98, May 2010, 2337-2346


López de Victoria A, Gorham Jr RD, Bellows ML, Ling J, Lo DD, Floudas CA, Morikis D, A new Generation of Potent Complement Inhibitors of the Compstatin Family, Chemical Biology & Drug Design, Vol 77, Issue 5, May 2011


Tamamis P, Morikis D, Floudas CA, Species Specificity of the complement inhibitor compstatin investigated by all-atom molecular dynamics simulations, Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 12, Sept. 2010 pg 2655-2667


For more information on Princeton University invention # 09-2488, please contact:

Laurie Tzodikov (609) 258-7256     

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
Christodoulos Floudas (DECEASED) See Fotini P. Baba
Meghan Bellows Peterson
Dimitrios Morikis
small molecule