9 results about "Alternate pathway" patented technology

Provided is a CFB-targeting double-stranded RNA molecule, specifically an siRNA. The provided siRNA can effectively inhibit the CFB expression, and can be used for preventing and treating diseases caused by up-regulated CFB expression or diseases associated with abnormal activation of an alternative complement pathway.

The present invention provides an antibody or antigen-binding portion thereof that can bind to properdin (factor P). The antibody of the current invention leads to selective inhibition of alternative complement pathway while allowing the classical and lectin pathways to continue. Further, the antibody of the present invention may have modified or reduced binding to FcγRs to minimize its ADCC activity. The present invention provide an antibody that comprises an amino acid sequence to minimise its CDC activity. The antibody according to the present invention has higher FcRn binding affinity and therefore the antibody according to the present invention may have long circulating half-life in the body of the patient and it can be given at a reduced dosing frequency. The antibody according to the present invention can further be used in the preparation of a drug for treating diseases through inhibition of alternative complement pathway.

Described herein are isolated monovalent antibodies or antibody fragments thereof that bind human properdin. Such antibodies are useful in methods of treatment for diseases mediated by alternative complement pathway dysregulation.

Provided herein are methods of ameliorating a disease or disorder associated with dysregulation of the alternative complement pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

This application discloses a method for determining the functional activity of the alternative complement pathway (AP50) in animal serum and its application. The method includes: preparing a reaction buffer containing magnesium and calcium chelating agents; washing red blood cells with the reaction buffer and adjusting the red blood cell concentration to a preset range by measuring the absorbance value after complete lysis; serially diluting the animal serum to be tested with the reaction buffer, mixing it with a standardized red blood cell suspension, and incubating to induce a hemolytic reaction; after terminating the reaction, measuring the absorbance value of hemoglobin in the supernatant, calculating the hemolysis rate at each dilution, determining the serum dilution factor corresponding to 50% hemolysis, and using its reciprocal as the AP50 value. This application selectively activates the alternative pathway using a disclosed buffer formulation and eliminates batch-to-batch variability in red blood cells through absorbance standardization. It has advantages such as self-controllability, good reproducibility, low cost, and wide species adaptability, and can be widely used in immunological research and drug safety evaluation.

In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.

Described herein are isolated monovalent antibodies or antibody fragments thereof that bind human properdin. Such antibodies are useful in methods of treatment for diseases mediated by alternative complement pathway dysregulation.

The present invention discloses a piperidine-substituted benzoic acid compound, a pharmaceutical composition thereof, and its use. The piperidine-substituted benzoic acid compound of the present invention is a compound represented by Formula I, a stereoisomer thereof, a tautomer thereof, an isotope-labeled compound thereof, or a pharmaceutically acceptable salt of any of the foregoing. The compound has good inhibitory activity against complement factor B, good affinity for complement factor B, hemolytic activity in the alternative complement pathway, and inhibitory activity in the alternative complement pathway. TIFF2025541667000344.tif11998s