14 results about "Complement inhibition" patented technology

The invention belongs to the field of immunology and pharmacology, and particularly relates to a small-molecule inhibitor as well as a preparation method and application thereof. The small-molecule inhibitor has a structure as shown in a formula (1). The small-molecule inhibitor with a specific structure provided by the invention not only can specifically target C9, but also has high binding affinity with C9, can play an efficient complement inhibition activity role, effectively blocks the formation of a membrane attack complex (MAC), reduces the attack of the MAC on normal cells, relieves immune injury and inflammatory response caused by the attack, and has a good application prospect. Therefore, a new strategy is provided for research and development of medicines for treating various complement-mediated diseases. # imgabs0 #

This application discloses the use of a biomarker in the preparation of a product for the treatment and prediction of myasthenia gravis, wherein the biomarker is one or more of OSM, CASP-8, TRAIL, TGF-α, FLT3L, IFN-γ, IL-7, and AXIN1. Through multi-omics combined analysis, this application explores the dynamic changes and molecular mechanisms of immune-inflammatory-related proteins after complement inhibition from the dual dimensions of gene transcription and protein expression, and finds a comprehensive biomarker that can systematically evaluate the dynamics of symptom improvement and the degree of disease stability, with the advantages of accurately guiding treatment adjustments and predicting disease outcomes.

A hybrid protein containing a CFH functional unit and a DAF functional unit, a mutant thereof, a nucleic acid encoding the hybrid protein, a method for treating a disease or condition associated with the complement system, and a use thereof, as well as a fusion protein constructed based on the hybrid protein mutant and an antibody that specifically binds to complement C5. Further provided are a polynucleotide encoding the fusion protein, an expression vector, and a host cell, pharmaceutical compositions thereof, and a method for treating a disease associated with C5 protein, and a use thereof.

The invention belongs to the technical field of biological medicines, and particularly relates to application of chenodeoxycholic acid in preparation of drugs for treating allergic diseases. It is found that CDCA can effectively inhibit pyroptosis and secretion of proinflammatory factors, expression of complement inhibition proteins CD46, CD55 and CD59 is remarkably up-regulated, expression of the complement inhibition proteins CD46, CD55 and CD59 is finally promoted, and occurrence and development of allergic diseases are effectively relieved. In a mouse model, CDCA can significantly improve OVA-induced food allergy symptoms, and has application prospects in treatment of allergic diseases.

The invention provides a complement protein C3C3b antigen epitope peptide as well as a related antibody and application thereof. The anti-complement protein C3 / C3b single structural domain antibody provided by the invention is combined with an MG6alpha-MG7-C345C structural domain and / or an MG6beta-MG6alpha-MG7-TED structural domain of the complement protein C3 / C3b, and can be competitively combined with a factor B to inhibit formation of C3 invertase, and the anti-complement protein C3 / C3b antibody or an antigen binding fragment thereof is small in molecular weight, high in affinity with the complement protein C3 / C3b and strong in complement inhibition activity, so that the anti-complement protein C3 / C3b single structural domain antibody or the antigen binding fragment thereof can be used for preparing the anti-complement protein C3 / C3b single structural domain antibody. Cracking of C3 and activation of a complement cascade reaction can be effectively blocked, and the compound can be potentially applied to treatment of diseases related to complement activation.

Provided are a complement protein C3C3b antigenic epitope peptide, and a related antibody thereof and the use thereof. The provided anti-complement protein C3 / C3b single-domain antibody binds to the MG6α-MG7-C345C domain and / or MG6β-MG6α-MG7-TED domain of complement protein C3 / C3b, and can compete with factor B for binding to C3b, thereby inhibiting the formation of a C3 convertase. Moreover, the anti-complement protein C3 / C3b antibody or an antigen-binding fragment thereof has a small molecular weight, exhibits a high affinity for complement protein C3 / C3b and a potent complement inhibitory activity, can effectively block the cleavage of C3 and the activation of complement cascade, and can be potentially used in the treatment of diseases associated with complement activation.

Provided are an antibody or antigen-binding fragment thereof that specifically binds to complement protein C5, a humanized anti-complement protein C5 antibody or antigen-binding fragment thereof, a composition comprising the antibody or antigen-binding fragment, and a use. The provided series of anti-complement protein C5 antibodies or antigen-binding fragments thereof have epitope diversity, and the epitopes thereof that bind to human complement protein C5 are mainly distributed in MG6α, MG7, CUBf, TED, and C345C domains. Moreover, the anti-complement protein C5 antibodies or antigen-binding fragments thereof have small molecular weights, high affinity to complement protein C5, and strong complement inhibitory activity, can effectively block the cleavage of C5 and the activation of complement cascade reactions, and can potentially be used in the treatment of diseases related to complement activation.

Compstatin analogues having improved binding and complement-inhibiting activity as compared to the 13 amino acid compstatin peptide (ICVVQDWGHHRCT (cyclic C2-C12)) (SEQ ID NO: 1) are described, in particular compstatin analogues that additionally possess useful physicochemical properties, such as increased solubility. These analogues include variants with an isoleucine residue at position 3 in place of the wild type valine residue, which provides compstatin peptides with improved binding and complement-inhibiting activity and also enables the introduction of other modifications, for example modifications that are capable of increasing solubility, such as the introduction of charged or polar amino acids at position 9 and / or the introduction of N- and / or C-terminal sequences.

Provided are a hybrid protein comprising a CFH functional unit and a DAF functional unit. an encoding nucleic acid thereof, and a method and use thereof for treating related diseases or disorders of a complement system.

Provision of RNA for complement inhibition. [Solution] RNA such as miRNA and siRNA, and their use in the treatment of complement-mediated disorders are described. In one embodiment, the disclosure features siRNA comprising an antisense strand and a sense strand, wherein the antisense strand is complementary to a nucleotide sequence that is at least 90% identical to any one of a particular set of sequences. In some embodiments, the antisense strand is complementary to a nucleotide sequence that differs from any one of a particular set of sequences by 1, 2, 3, or 4 or fewer nucleotides.

The invention provides an antibody specifically binding to complement protein C5 or an antigen binding fragment of the antibody, and a humanized anti-complement protein C5 antibody or an antigen binding fragment of the humanized anti-complement protein C5 antibody. Compositions comprising the antibodies or antigen binding fragments and uses thereof. A series of anti-complement protein C5 antibodies or antigen binding fragments thereof provided by the invention have epitope diversity, epitopes binding to human complement protein C5 are mainly distributed in MG6alpha, MG7, CUBf, TED and C345C structural domains, and the anti-complement protein C5 antibodies or antigen binding fragments thereof are small in molecular weight, high in affinity with complement protein C5 and strong in complement inhibition activity, and can be used for preparing anti-complement protein C5 antibodies or antigen binding fragments thereof. C5 cleavage and complement cascade reaction activation can be effectively blocked, and the compound can be potentially applied to treatment of diseases related to complement activation.

The present disclosure relates, inter alia, to compositions comprising a human complement inhibitor and use of the compositions in methods of treating or preventing complement-related disorders. In some embodiments, the inhibitor is administered chronically to patients. In some embodiments, the inhibitor is administered to a patient in an amount and frequency such that systemic complement inhibition is maintained and escape is prevented. In some embodiments, the composition comprises an antibody, or antigen-binding fragment thereof, which binds to the protein constituting the C5 component of human complement or to a fragment of the protein, such as C5a or C5b.

The use of urine C5b-9 (uC5b-9) as a highly accurate and superior biomarker that is well correlated to complement activity in local tissue affected by complement-mediated diseases (e.g., diseases with renal lesion components) is provided. The biomarkers may be used, for example, in the absence of systemic complement inhibition, to treat and / or monitor diseases mediated by such complements using complement inhibitors targeted to local tissue affected by such complements.

Provided herein are protein inhibitors of the complement system and methods of use thereof. In some embodiments, the protein inhibitors can reduce inflammation and tissue damage in conditions including macular degeneration. In some embodiments, the protein inhibitors comprise oligomerization domains or complement receptor domains covalently linked to CCP domains from CR1, FH, CFHR1, CFHR3 and / or CFHR5.