CFHR-proteins – complement inhibitors

Referenznummer TO 10-00071
 

The Challenge 

The modulation of the immune system plays an essential role in fighting a variety of diseases, including infection and inflammation. The complement system is an important element of the innate immune system, it is essential to induce a protective immune response against external invaders such as microbes and modulates the adaptive immune response. Activation of the complement system occurs via three major pathways, the alternative, the classical and the lectin pathway. Each pathway is initiated by unique activators and generates a C3 convertase. Further activation results in formation of a C5 convertase, at least responsible for the generation of the membrane attack complex (MAC) causing cell lysis. To date no inhibitors are available that specifically inhibit only the alternative complement pathway. Although inhibitors of the terminal complement activation are known (Clusterin and Vitronektin), they do not allow for a sufficient level of specificity desirable to impact on the immune system only as far as necessary for therapy while avoiding side effects. Therefore there is still a demand for C5 convertase specific inhibitors that do not influence the classical and the lectin complement pathway.

Technology

The invention discloses complement factor H-related (CFHR ) proteins, in particular complement factor H-related protein 1 (CFHR-1), as new regulators of the innate immune system. CFHR proteins specifically inhibit C5 convertase activity and interfere with C5b surface deposition and MAC formation. In contrast to known C3/C5 convertase inhibitors such as complement factor H (CFH) the inventive CFHR proteins specifically inhibit only C5 convertase. CFHR proteins are useful for treatment of inflammatory diseases in which the complement system is involved, and potentially can be used to prevent complement activation during transplantations or dialyses. In addition they can be suitable for coating of devices, such as implants. Monoclonal antibodies against CFHR proteins will be useful for diagnosing inflammatory diseases. 

 

Commercial Opportunity

In-licensing or cooperation for further development of a pharmaceutical or diagnostic composition. 

 

Developmental Status

Analysis of cell and tissue samples conducted.

Patent Situation 

Priority filed September 2008, international application pending (WO 2010/034514). 

 

Further Reading

Heinen et al. 2009. Factor H–related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation. BLOOD 114 (12), 2439-2447. DOI 10.1182/blood-2009-02-205641.

 

 

 

 

 

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Kontakt:

Sabina Heim, Ph.D.
Technology Manager
Ascenion GmbH

T: +49 (0)531 6181-2090
F: +49 (0)531 6181-2098
heim@ascenion.de