Modified proteases that inhibit complement activation
First Claim
1. A method of modulating complement activation, comprising contacting a non-complement protease with a target substrate(s) of a complement pathway, wherein:
- the modified non-complement protease, or a catalytically active portion thereof, comprises modifications in a scaffold protease, or a catalytically active portion of a scaffold protease, at an amino acid residue that is a determinant of substrate specificity, whereby the modified amino acid residue(s) increases one or both of specificity of the modified non-complement protease for the target substrate(s) of a complement pathway compared to the scaffold protease;
the scaffold protease is an unmodified protease that is not part of a complement pathway; and
the modified non-complement protease, or a catalytically active portion thereof, cleaves the target substrate(s) of a complement pathway such that complement activation in a pathway comprising the target substrate is modulated.
3 Assignments
0 Petitions
Accused Products
Abstract
Provided are methods for and compounds for modulating the complement system. In particular, compounds are provided that inhibit complement activation and compounds are provided that promote complement activation. The compounds are therapeutics by virtue of their effects on the complement system. Hence, the compounds that inhibit complement activation can be used for treatment of ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, inflammatory diseases and diseases with an inflammatory component, including Alzheimer'"'"'s Disease and other neurodegenerative disorder.
43 Citations
21 Claims
-
1. A method of modulating complement activation, comprising contacting a non-complement protease with a target substrate(s) of a complement pathway, wherein:
-
the modified non-complement protease, or a catalytically active portion thereof, comprises modifications in a scaffold protease, or a catalytically active portion of a scaffold protease, at an amino acid residue that is a determinant of substrate specificity, whereby the modified amino acid residue(s) increases one or both of specificity of the modified non-complement protease for the target substrate(s) of a complement pathway compared to the scaffold protease; the scaffold protease is an unmodified protease that is not part of a complement pathway; and the modified non-complement protease, or a catalytically active portion thereof, cleaves the target substrate(s) of a complement pathway such that complement activation in a pathway comprising the target substrate is modulated. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
-
Specification