37 results about "Complement inhibition" patented technology

In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

The present invention relates to methods and medicaments used for treating conditions that require axonal regeneration, e.g. in mammals affected by injury or disease of the central or peripheral nervous system. The medicaments used in these methods facilitate axonal regeneration by inhibition of the complement system. Conditions requiring axonal regeneration that may be treated in accordance with the invention include physical injuries as well as neurodegenerative disorders of the peripheral or central nervous system.

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

The present invention relates to methods and medicaments used for treating conditions that require axonal regeneration, e.g. in mammals affected by injury or disease of the central or peripheral nervous system. The medicaments used in these methods facilitate axonal regeneration by inhibition of the complement system. Conditions requiring axonal regeneration that may be treated in accordance with the invention include physical injuries as well as neurodegenerative disorders of the peripheral or central nervous system.

Paroxysmal nocturnal hemoglobinuria or other hemolytic diseases are treated using a compound which binds to or otherwise blocks the generation and / or the activity of one or more complement components, such as, for example, a complement-inhibiting antibody.

The present invention features the local administration of complement inhibitors for treatment of complement-mediated disorders. In certain embodiments the invention features inhibiting activation of one or more locally produced complement proteins. The invention provides sustained release formulations and devices comprising a complement inhibitor and methods of use thereof.

The invention discloses acylated flavonoid glycoside compounds shown as a formula I and application thereof in preparation of complement inhibitor medicines. Acylated flavonoid glycosides extracted and separated from cudweed herb are proved to inhibit hemolysis caused by activation of a complement system in a classical pathway through in vitro experiments, and have complement inhibition effect; the activity of each monomericcompound is higher than that of a total extract of cudweed herb; and the acylated flavonoid glycoside compounds are good complement inhibitors and have low effective concentration, can serve as active ingredients to prepare novel complement inhibitor medicines for treating various diseases caused by abnormal activation of complements, are low in toxicity, safe in administration and rich in raw material sources and have great clinical application value. The structure of the formula I is shown as the specifications, wherein R1 and R2 are same or different, and respectively H, OH or OCH3; and R3 and R4 are respectively H or groups shown in the specifications.

The invention belongs to the field of Chinese medicine, relates to Prunella vulgaris polysaccharide, and a preparation method and purpose thereof in preparing anticomplement medicines. The Prunella vulgaris polysaccharide including uniform polysaccharide PW-PS1 and PW-PS2 is prepared from a dry fruit aqueous extract of a labiatae plant Prunella vulgaris Linn. Through in vitro tests, the uniform polysaccharide is proved to have strong anticomplement activity and inhibition effects on classical pathway and alternative pathway of a complement system; besides, the polysaccharide does not have the anticoagulant effect influencing in vivo activity and can be used for the preparation of complement inhibition medicaments. The PW-PS1 effects on C1q, C3 and C9 components of the complement system, and the PW-PS2 effects on the C1q, C2, C3, C5 and C9 components of the complement system.

We describe a method of detecting a therapeutic exosome, the method comprising detecting an activity of an exosome. The activity may be selected from the group consisting of: (a) immunodulatory activity; (b) complement inhibition activity; (c) proteasome activity; (d) glycolytic enzyme activity; (e) anti-oxidative activity; (f) extracellular matrix (ECM) modifying activity; (g) NT5E (CD73) ecto-5'-ectonucleotidase activity; (h) ion homeostasis activity; and (i) chaperone activity. If the exosome is detected as having one or more such activities, the exosome is likely to comprise a therapeutic exosome having therapeutic activity.

In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

A method is disclosed for treating nephropathies involving undesired alternative pathway complement activation by administration of a complement inhibitory protein such as soluble complement receptor type I (sCR1).

The invention discloses a target fusion protein with the anti-inflammatory action, in particular an anti-P lectin single chain antibody target complement inhibitor ScFv-Crry and application thereof. The invention aims to provide the anti-P lectin single chain antibody target complement inhibitor ScFv-Crry with the specific targeting property and application of the ScFv-Crry to the preparation of medicines for treating organism inflammatory reactions. The anti-P lectin single chain antibody target complement inhibitor ScFv-Crry is the fusion protein which is obtained through the connection between an amino end connected with an anti-P lectin single chain antibody ScFv and a complement inhibitor Crry(1-319aa). Experiments show that the ScFv-Crry can remarkably improve the efficiency of the cell cracking mediated by an inhibiting complement, be highly aggregated at an immunity damaged position, and obviously inhibit the generation and development of inflammation. Therefore, the ScFv-Crry can be prepared into target P lectin complement inhibitor new genetic engineering target protein medicines aiming at treating inflammatory reactions. The ScFv-Crry has important contributions to the field of pharmacy and bright application prospect.

Factor H-binding peptides that binds to a region of factor H that does not impede the complement-inhibitory activity of factor H are disclosed. When immobilized onto the surface of a biomaterial, these peptides recruit factor H, resulting in a substantial inhibition of biomaterial-induced complement activation in a biological substance exposed to the biomaterial.

This disclosure relates to methods of authorizing distribution of complement-inhibiting drugs to patients who have a complement-associated disorder in a manner to ensure that the patients are aware of the possible dangers of discontinuing treatment with the drugs. A database is prepared comprising patient information including experiencing adverse clinical events after discontinuing the drug treatment. The information in the database is collected and may be reported. The patients are given a warning as to adverse events that may occur if treatment with the complement inhibiting drugs is discontinued.

The invention discloses a complement inhibitor DAF mutant, a fusion protein thereof with a complement receptor 2 mutant and use of the fusion protein in preparation of medicines treating autoimmune diseases. The DAF mutant is a molecular modification obtained by computer modeling and amino acid substitution. The fusion protein of the DAF mutant and the complement receptor 2 mutant has higher ligand binding and dissociation rates than wild-sequence fusion protein thereof, and has better ligand binding force. Biological distribution experiments prove that the fusion protein can rapidly aggregatein the arthritis position after entering a rheumatoid arthritis mouse model, and has a significant anti-adhesion / anti-inflammatory targeted inhibitory effect. In treatment for MRL / lpr lupus erythematosus mice, the fusion protein can significantly increase the survival rate of the mice, and symptoms such as proteinuria, glomerular score, interstitial inflammation, vasculitis and crescent / necrosisin the mice in the treatment group are significantly improved.

The present invention describes compositions and methods for targeting complement inhibition to sites of p-selectin expression, and compositions for inhibiting p-selectin and complement.

In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

We describe a method of detecting a therapeutic exosome, the method comprising detecting an activity of an exosome. The activity may be selected from the group consisting of: (a) immunodulatory activity; (b) complement inhibition activity; (c) proteasome activity; (d) glycolytic enzyme activity; (e) anti-oxidative activity; (f) extracellular matrix (ECM) modifying activity; (g) NT5E (CD73) ecto-5'-ectonucleotidase activity; (h) ion homeostasis activity; and (i) chaperone activity. If the exosome is detected as having one or more such activities, the exosome is likely to comprise a therapeutic exosome having therapeutic activity.

The invention discloses a complement receptor 2 variant, a fusion protein of the complement receptor 2 variant and a complement inhibitor and application of the fusion protein in preparing a medicament for treating autoimmune diseases. The complement receptor 2 variant is a molecular modified body obtained after computer modeling and amino acid replacement, has higher ligand binding and dissociation rate and better ligand binding force than a wild sequence of the complement receptor 2 variant. The biological distribution experiment proves that the fusion protein provided by the invention can rapidly and highly aggregate at an arthritis part after entering a rheumatoid arthritis mouse model, and has a remarkable anti-adhesion / anti-inflammation targeted inhibition effect. In the treatment ofMRL / lpr lupus erythematosus mice, the fusion protein can obviously improve the survival rate of the mice, and symptoms such as proteinuria, glomerular integral, interstitial inflammation, vasculitis,crescent / necrosis and the like of the mice in the treatment group are obviously improved.

The invention provides HB-NC4 recombinant protein and a preparation method and application thereof, and belongs to the technical field of biological medicines, the recombinant protein is formed by recombination of an N-terminal non-collagen structural domain 4 and an HB heparin binding structural domain of NC4 human collagen IX. The amino acid residue sequence of the recombinant protein is as shown in SEQ ID NO. 1. A nucleotide sequence for coding the recombinant protein is shown as SEQ ID NO.3 or a sequence with genetic code degeneracy. In the nucleotide sequence for coding the recombinant protein, the nucleotide sequence for coding the heparin binding domain is as shown in SEQ ID NO.4, and the nucleotide sequence for coding the N-terminal non-collagen domain 4 of the human collagen IX is as shown in SEQ ID NO.5 or has a sequence with genetic code degeneracy. The invention also discloses the preparation method of the HB-NC4 fusion protein. The HB-NC4 fusion protein retains the complement inhibition activity of the N-terminal domain 4 of collagen IX, can directly target cartilage and retain the complement inhibition activity, and the targeting property and retention time of the fusion protein are greatly improved.

The invention discloses a fusion protein scFV-CD55 of an acetylcholine receptor-resistant single-chain antibody targeted complement regulatory factor CD55. The CD55 is targeted to neuromuscular transmission through single-chain antibody to inhibit combination of the antibody of a pathogenic acetylcholine receptor and the pathogenic acetylcholine receptor, block the cascade of a complement, protect the acetylcholine receptor and eliminate immune injury caused by complement system activation, so that myasthenia gravis is treated in a targeted way. The scFv-CD55 is obtained by coupling acetylcholine receptor-resistant single-chain antibody to the amino terminal of the complement regulatory factor CD55(SCR1-4) through (G4S1)3 connecting peptide. By means of genetic engineering, soluble scFV-CD55 can be obtained through prokaryotic expression and purification. Experiments prove that: the fusion protein scFV-CD55 maintains the affinity of the acetylcholine receptor and the complement inhibition function of the CD55, the complement inhibition function of the scFV-CD55 is obviously improved in cellular experiments, and the complement deposition on immune injury parts is reduced. The invention develops a new biological agent for treating the myasthenia gravis, and the biological agent has wide application prospect.

The invention discloses an anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 and application thereof. The invention aims to provide an anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 with specific targeting and the application thereof in preparing medicaments for treating systemic inflammations. The anti-P-selectin single-chain antibody targeted complement inhibitor ScFv-CD59 is a fusion protein obtained by connecting the amino terminal of the anti-P-selectin single-chain antibody ScFv with the complement inhibitor CD59 by using a connecting peptide. The experiment proves that the ScFv-CD59 can obviously improve the efficiency of inhibiting the complement-mediated cell cracking, can achieve high-degree accumulation at the immune injury part, can obviously inhibit the occurrence and degeneration of inflammations and can obviously reduce the side effect of infection caused by the complement inhibitor. Therefore, the ScFv-CD59 can be used as an active ingredient to be prepared into a novel gene engineering targeted protein medicament with a targeted P-selectin complement inhibitor for treating inflammations. The invention plays an important role in the pharmaceutical field and has wide application prospects.

Compstatin analogues having improved binding and complement-inhibiting activity as compared to the 13 amino acid compstatin peptide (ICWQDWGHHRCT (cyclic C2-C12)) are described, in particular compstatin analogues that additionally possess useful physicochemical properties. The analogues have a thioether bond rather than a disulfide bond between the side chains of the f residues corresponding to cysteines 2 and 12 of compstatin which may increase stability. The analogues may also have 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.

The invention discloses a fusion protein of a complement receptor 2 variant and a complement inhibitor fH and an application of the fusion protein in the preparation of a drug for treating autoimmune diseases. The complement receptor 2 variant is a molecular modification obtained after computer modeling and amino acid substitution, and has higher ligand binding and dissociation rates and better ligand binding capacity than its wild-type sequence. The biological distribution experiment proves that the fusion protein provided by the present invention can rapidly and highly aggregate in the arthritis site after entering the rheumatoid arthritis mouse model, and has significant anti-adhesion / anti-inflammatory targeting inhibition effect. In the treatment of MRL / lpr lupus erythematosus mice, the fusion protein can significantly improve the survival rate of mice. Symptoms such as necrosis were significantly improved.

The invention discloses a fusion protein of a complement receptor 2 mutant and a complement inhibitor CD 59 and application thereof to preparing autoimmune disease treating drugs. The complement receptor 2 mutant is a molecular modified body obtained through computer modelling and amino acid replacement and is higher in ligand binding and dissociation rate and ligand binding force compared with wild sequences. Biological distribution test shows that the fusion protein can be highly concentrated at arthritic parts after entering mouse models with rheumatoid arthritis and achieve significant anti-adhesion / anti-inflammatory targeted inhibition effects; when applied to treating MRL / lpr (Murphy Roths large / lymphoproliferation) mice with systemic lupus erythematosus, the fusion protein can significantly improve the survival rate of the mice, and symptoms of the mice of a treatment group such as proteinuria, glomerular score, interstitial inflammation, vasculitis and crescent glomerulonephritis / necrosis can be significantly improved.

The invention discloses a targeted complement inhibitor fusion protein C3d-ScFv-CD59 of a single-chain antibody of a human anti-complement C3d molecule and a complement inhibitor CD59. The fusion protein has excellent antigen binding activity, and in-vitro inhibition experiments show that C3d-ScFv-CD59 has a more obvious inhibition effect corresponding to a single effector molecule CD59, and the effect is realized by identifying that the C3d component in a complement activation region plays a complement inhibition role. The C3d-ScFv-CD59 is used for treating influenza / bacteria co-infected mice, the survival rate is obviously increased, lung lesions are obviously relieved, the targeted complement inhibition effect is obvious, and the C3d-ScFv-CD59 has an obvious treatment effect compared with the single effector molecule CD59, and it proves that the fusion protein provided by the invention has an excellent application prospect in preparation of drugs for treating influenza virus and bacteria co-infected pneumonia.

The invention discloses a complement receptor 2 variant, a fusion protein of the complement receptor 2 variant and a complement inhibitor and application of the fusion protein in preparing a medicament for treating autoimmune diseases. The complement receptor 2 variant is a molecular modified body obtained after computer modeling and amino acid replacement, has higher ligand binding and dissociation rate and better ligand binding force than a wild sequence of the complement receptor 2 variant. The biological distribution experiment proves that the fusion protein provided by the invention can rapidly and highly aggregate at an arthritis part after entering a rheumatoid arthritis mouse model, and has a remarkable anti-adhesion / anti-inflammation targeted inhibition effect. In the treatment ofMRL / lpr lupus erythematosus mice, the fusion protein can obviously improve the survival rate of the mice, and symptoms such as proteinuria, glomerular integral, interstitial inflammation, vasculitis,crescent / necrosis and the like of the mice in the treatment group are obviously improved.

A method is disclosed for treating nephropathies involving undesired alternative pathway complement activation by administration of a complement inhibitory protein such as soluble complement receptor type I (sCR1).

The invention belongs to the field of Chinese medicine, relates to Prunella vulgaris polysaccharide, and a preparation method and purpose thereof in preparing anticomplement medicines. The Prunella vulgaris polysaccharide including uniform polysaccharide PW-PS1 and PW-PS2 is prepared from a dry fruit aqueous extract of a labiatae plant Prunella vulgaris Linn. Through in vitro tests, the uniform polysaccharide is proved to have strong anticomplement activity and inhibition effects on classical pathway and alternative pathway of a complement system; besides, the polysaccharide does not have the anticoagulant effect influencing in vivo activity and can be used for the preparation of complement inhibition medicaments. The PW-PS1 effects on C1q, C3 and C9 components of the complement system, and the PW-PS2 effects on the C1q, C2, C3, C5 and C9 components of the complement system.