Since activation of the classical pathway is associated with development of an immune response, the classical pathway is part of the acquired immune system. The classical pathway is usually triggered by antibody bound to a foreign particle (i.e., an antigen) and thus requires prior exposure to that antigen for the generation of specific antibody. No drugs have been approved for human use that specifically target and inhibit complement activation.Ĭurrently, it is widely accepted that the complement system can be activated through three distinct pathways: the classical pathway, the lectin pathway, and the alternative pathway. The growing recognition of the importance of complement-mediated tissue injury in a variety of disease states underscores the need for effective complement inhibitory drugs. Nevertheless, complement activation may be a major pathological mechanism and represents an effective point for clinical control in many of these disease states. In almost all of these conditions, complement is not the cause but is one of several factors involved in pathogenesis. The complement system has been implicated as contributing to the pathogenesis of numerous acute and chronic disease states, including: myocardial infarction, revascularization following stroke, ARDS, reperfusion injury, septic shock, capillary leakage following thermal burns, postcardiopulmonary bypass inflammation, transplant rejection, rheumatoid arthritis, multiple sclerosis, myasthenia gravis, and Alzheimer's disease. In addition, complement activation may cause the deposition of lytic complement components on nearby host cells as well as on microbial targets, resulting in host cell lysis. These activated cells are indiscriminate in their release of destructive enzymes and may cause organ damage.

For example, C3 and C5 proteolytic products recruit and activate neutrophils. While complement activation provides a valuable first-line defense against potential pathogens, the activities of complement that promote a protective inflammatory response can also represent a potential threat to the host (K. Atkinson, 1993, in Fundamental Immunology, Third Edition, edited by W. The complement system provides an early acting mechanism to initiate and amplify the inflammatory response to microbial infection and other acute insults (M. 2, 2020 and is being submitted via EFS-Web with the filing of the specification. The text file is 109 KB was created on Apr. The name of the text file containing the sequence listing is MP_1_0169_US4_Sequence_Listing_20200402.txt.

The sequence listing associated with this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into the specification. 10, 2004, all of which are hereby incorporated by reference in their entirety. 9, 2005 (now abandoned), which claims the benefit of Provisional Patent Application No. 7,919,094), and which is a continuation-in-part of U.S. 16, 2009 (now abandoned), which is a division of U.S. 1, 2010 (now abandoned), which claims the benefit of Provisional Patent Application No. 8,840,893), which is a continuation-in-part of U.S. 13, 2012, and is a continuation-in-part of U.S. 8, 2013 (now abandoned), which claims the benefit of Provisional Patent Application No. 27, 2016 (now abandoned), which is a continuation of U.S. 22, 2019, which is a continuation of U.S. This application is a continuation of pending U.S.

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