Complement in action: An analysis of patent trends from 1976 through 2011

Abstract

Complement is an essential part of the innate immune response. It interacts with diverse endogenous pathways and contributes to the maintenance of homeostasis, the modulation of adaptive immune responses, and the development of various pathologies. The potential usefulness, in both research and clinical settings, of compounds that detect or modulate complement activity has resulted in thousands of publications on complement-related innovations in fields such as drug discovery, disease diagnosis and treatment, and immunoassays, among others. This study highlights the distribution and publication trends of patents related to the complement system that were granted by the United States Patent and Trademark Office from 1976 to the present day. A comparison to complement-related documents published by the World Intellectual Property Organization is also included. Statistical analyses revealed increasing diversity in complementrelated research interests over time. More than half of the patents were found to focus on the discovery of inhibitors; interest in various inhibitor classes exhibited a remarkable transformation from chemical compounds early on to proteins and antibodies in more recent years. Among clinical applications, complement proteins and their modulators have been extensively patented for the diagnosis and treatment of eye diseases (especially age-related macular degeneration), graft rejection, cancer, sepsis, and a variety of other inflammatory and immune diseases. All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent. Complement in Infection and DiseaseBecause of the essential role of complement in the defense of the host against intruders, decreased activation of the complement system or deficiency in complement components can increase the risk of infection and cause various pathological conditions (Skattum et al. 2011). For example, alcoholic cirrhosis patients with low serum C3 concentrations and decreased hemolytic complement activity have been reported to have an increased risk of infections (Homann et al. 1997). Deficiencies of components of the classical pathway such as C1q, C2, and C4 have been found to be strongly associated with systemic lupus erythematosus (SLE) (Pickering et al. 2000;Pettigrew et al. 2009). On the other hand, uncontrolled, inappropriate, or excessive complement activity can cause damage to host cells and give rise to many diseases ranging from autoimmune to inflammatory pathologies (Markiewski and Lambris 2007;Holers 2003;Ricklin and Lambris 2007; Lambris and Sahu 2001). Indeed, the dual role of complement is illustrated by several pathological conditions. For example, the early increase of complement activation during sepsis may relate to the beneficial opsonization of bacteria. However, complement activation during subsequent phases of sepsis can amplify the initial insult, leading to inflammatory activity, tissue injury, and finally t...