University of Colorado

Musc Foundation for Research Development

Alexion Pharmaceuticals, Inc.

Johns Hopkins University

National Jewish Health

Taligen Therapeutics, Inc.

Alexion Cambridge Corporation

V Michael Holers

Joshua M Thurman

Stephen Tomlinson

Gary Gilkeson

Baerbel Rohrer

Liudmila Kulik

Peter Flynn

Woodruff Emlen

Martin Gilbert Pomper

Erwin W Gelfand

Catherine Anne Foss

Xiaojiang Chen

Christian Taube

Conrad Stoldt

Natalie Serkova

Nirmal Kumar Banda

Antonio M Risitano

Brian Larsen

Pablo Engel

James M Kovacs

Jonathan P Hannan

James Kovacs

The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting diagnostic, prophylactic and therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response.

Antibodies to the C3D fragment of complement component 3

Provided herein are compositions, including pharmaceutical compositions, and methods for modulating, i.e., stimulating or inhibiting, activity of the alternative complement pathway, and methods of identifying factor H-binding proteins.

Modulating the alternative complement pathway

Provided herein, inter alia, are compositions and methods of using the same for detecting complement activation.

Anti-C3d antibody conjugates and methods of detecting complement activation

The presently disclosed subject matter provides compositions and kits comprising light-emitting versions of the monoclonal antibody to C3d (mAB 3d29) for imaging and methods of use thereof for detecting infectious and inflammatory cells in vivo. The presently disclosed subject matter also provides methods for detecting and/or monitoring a() infection in a subject, as well as methods of treating ainfection in a subject.

Light-emitting versions of the monoclonal antibody to C3D (MAB 3D29) for imaging

The disclosure provides compositions and methods relating to the treatment of pain, such as pain from rheumatoid arthritis. By creating conjugates of antibodies that target C5aR and siRNA's that target C5 expression, a dual mode therapeutic that targets two different aspects of C5's inflammatory signaling.

Antibody-siRNA conjugates and uses therefor

Methods for treating subjects having complement-mediated hemolytic disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and other hemolytic anemias, the method comprising administering an effective amount of a composition that inhibits the activity of the complement alternative pathway.

Treatment of paroxysmal nocturnal hemoglobinuria, hemolytic anemias and disease states involving intravascular and extravascular hemolysis

Antibodies to the C3d fragment of complement component 3

Provided herein are compositions and methods directed to soluble proteins which can selectively deliver modulators of complement activity. Targeted delivery of these modulators is accomplished by selectively mutating particular amino acids in a targeting protein portion of the composition corresponding to at least the first two N-terminal SCR domains of CR2. Depending on the particular combination of mutations introduced into the targeting portion, a complement activity modulator can be selectively delivered to particular ligands of CR2 at sites where complement system activation or suppression is desired.

Complement receptor 2 (CR2) targeting groups

The invention provides a CR2-FH molecule comprising a CR2 portion comprising CR2 protein or a fragment thereof and a FH portion comprising a factor H protein or a fragment thereof, and pharmaceutical compositions comprising a CR2-FH molecule. Also provided are methods of using the compositions for treatment diseases in which the alternative complement pathway is implicated, such as age-related macular degeneration, rheumatoid arthritis, and ischemia reperfusion.

Targeting complement factor H for treatment of diseases

This invention relates to humaneered anti-factor B antibodies and antigen-binding fragments thereof with reduced immunogenicity. The humaneered anti-factor B antibodies and antigen-binding fragments thereof are derived from murine monoclonal antibody 1379, which binds factor B in the third short consensus repeat ('SCR') domain and selectively inhibits activation of the alternative complement pathway by preventing formation of the C3bBb complex. The invention also relates to methods of treating diseases or disorders in which activation of the alternative complement pathway plays a role, and methods of selectively inhibiting activation of the alternative complement pathway in an individual in need thereof.

Humaneered anti-factor B antibody

Disclosed is a crystalline human CR2 protein in complex with C3d, and the three dimensional structure of the crystalline complex. Also disclosed are methods of use of the structure, particularly for structure-based identification of compounds that bind to CR2 and inhibit or enhance the binding of CR2 to a natural ligand, that bind to CR2 and agonize or antagonize the receptor, that bind to CR2 and inhibit or enhance CR2 dimerization, or that use the C3-binding ability of CR2 as a drug delivery vehicle. Also disclosed are therapeutic compounds obtained by such methods and uses for such compounds.

Three-dimensional structure of complement receptor type 2 and uses thereof

Methods of non-invasive imaging of complement-mediated inflammation are provided. Compositions including CR-targeted ultrasmall superparamagnetic nanoparticles or aggregates thereof for use with those methods are also provided.

Growing community of inventors

Denver, CO, United States of America

V Michael Holers