Musc Foundation for Research Development

University of Colorado

The United States Government As Represented by the Department of Veterans Affairs

The University of Chicago

Stephen Tomlinson

V Michael Holers

Joshua M Thurman

Baerbel Rohrer

Gary Gilkeson

Liudmila Kulik

DeAnna Adkins

Ali Alawieh

Vernon Michael Holers

Carl Atkinson

Richard J Quigg

Pablo Engel

Songqing He

Philip F Stahel

Michael V Holers

Michael Holers

The present invention describes compositions and method for improving outcomes after injury to the central nervous system wherein complement signaling is activated. In one aspect, the method comprises administering to a subject a therapeutically effective amount of a therapeutic agent comprising a targeted inhibitor molecule comprising a targeting portion and an inhibitor portion, wherein the molecule inhibits complement, and wherein therapeutic agent is administered in combination with rehabilitation therapy or thrombolytic agent.

Compositions and methods for treating central nervous system injury

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

Anti-C3d antibody conjugates and methods of detecting complement activation

Antibodies to the C3d fragment of complement component 3

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

Provided herein are methods and compositions, including pharmaceutical compositions, for stimulating liver regeneration after partial hepatectomy, massive liver resection and toxic injury, or following liver transplantation, including small-for-size liver transplantation, by inhibiting activation of complement.

Methods of stimulating liver regeneration

Disclosed is the use of agents and compositions that selectively inhibit the alternative complement pathway for the inhibiting or treating physiological damage resulting from traumatic brain injury (TBI), spinal cord injury (SCI), or related conditions. Preferred reagents for use in inhibition of damage resulting from TBI or SCI include those that inhibit factor B, with anti-factor B antibodies representing a particularly preferred agent.

Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury and related conditions

Modulation of the complement system represents a therapeutic modality for numerous pathologic conditions associated with complement activation. In a strategy to prepare complement inhibitors that are targeted to sites of complement activation and disease, compositions comprising a complement inhibitor linked to complement receptor (CR) 2 are disclosed. The disclosed are compositions can be used in methods of treating pathogenic diseases and inflammatory conditions by modulating the complement system.

Complement receptor 1 and 2 fusion proteins

Systemic suppression of the complement system has been shown to be effective to treat inflammatory disease, yet at the potential cost of compromising host defense and immune homeostasis. Herein disclosed are methods for antigen-specific targeting of complement inhibitors that show that complement inhibitors targeted to the proximal tubular epithelium protect against tubulointerstitial injury and renal dysfunction in a rat model of nephrosis. It is shown that appropriate targeting of a systemically administered complement inhibitor to a site of disease markedy enhances efficacy and obviates the need to systemically inhibit complement. Additionally, it is shown by specifically inhibiting the terminal pathway of complement, that the membrane attack complex (MAC) plays a key role in proteinuria-induced tubulointerstitial injury, thus establishing the MAC as a valid target for pharmacological intervention in proteinuric disorders. The disclosed are compositions can be used in methods of treating pathogenic diseases and inflammatory conditions by modulating the complement system.

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Mount Pleasant, SC, United States of America

Stephen Tomlinson