19 results about "Complement activity" patented technology

Novel anti-C3 and anti-C5 antibodies capable of modulating complement activity by specifically binding to human complement factor C3, C3a, C3b, and / or C5 are provided. Also described herein are recombinant AAV (rAAV) comprising a variant adeno-associated virus (AAV) capsid and a transgene encoding an anti-C3 and / or anti-C5 antibody are provided. Also provided are methods of delivering the transgene to the retina and methods of treating dry age-related macular degeneration and geographic atrophy secondary to age-related macular degeneration disorders by contacting retinal cells with the rAAV)

This invention provides a pharmaceutical composition for use in a method of preventing antibody-mediated rejection (ABMR) in subjects who have undergone solid organ transplantation by preventing complement activity. [Solution] A pharmaceutical composition comprising an anti-human interleukin-6 (IL-6) antibody or an anti-human IL-6 antibody fragment for use in a method of preventing, stabilizing, or reducing complement activity in a subject who is scheduled to receive, has received, or has received a solid organ transplant, wherein the method comprises administering to a subject a prophylactic or therapeutically effective amount of the antibody or antibody fragment, the pharmaceutical composition comprising a variable light chain polypeptide containing a CDR of a specific sequence, and a variable heavy chain polypeptide containing a CDR of a specific sequence.

The invention relates to a recombinant kunitz protein of third-generation botryosphaeria formosa as well as a preparation method and application of the recombinant kunitz protein, and belongs to the technical field of fish parasite protein expression and function application research. The serine protease inhibitor of the third-generation botryosphaeria formosa is a GcKSI protein, and the amino acid sequence of the GcKSI protein is as shown in SEQ ID NO: 2. According to the invention, the amino acid sequence of the GcKSI protein is optimized, and the GcKSI recombinant protein rGcKSI is obtained through prokaryotic expression. The rGcKSI inhibits complement activity of host fish in vitro and has an obvious inhibition effect on serine protease, after injection immunization of the rGcKSI and third-generation insect infection experiments, the infection rate and the average infection intensity of the rGcKSI are obviously lower than those of a control group, and it is proved that the rGcKSI has good immunoprotectiveness on third-generation insect infection, and the rGcKSI can be used as an immunopotentiator for the third-generation insect infection of the tilapia. The GcKSI gene of the serine protease inhibitor and the GcKSI protein coded by the GcKSI gene can be used as new targets for drug research and development.

Provided are: a plasma preparation that has a reduced complement value and in which mixed viruses have been inactivated while maintaining the biological activity of plasma; and a method for producing the plasma preparation. The method includes: (1) a step for subjecting plasma to a solvent / detergent treatment (S / D treatment); and (2) a step for irradiating the S / D treated plasma with ultraviolet rays having a central wavelength of 200-260 nm from an LED light source for 10 minutes or longer such that the value of ΔA352, which corresponds to the cumulative irradiation amount and is converted by a 1% aqueous potassium iodide solution, is 0.2-0.7. The plasma preparation has a complement value (CH50) of less than 25 CH50 / mL.

Disclosed herein are methods of treating compliment mediated diseases using a crosslinked poly(allyamine) polymer comprising the residues of 2-propen-1-ylamine, or a salt thereof, 1,3-bis(allylamino)propane, or a salt thereof, and 1,2-dichloroethane.

The present invention relates to: a novel anti-C5 antibody that completely inhibits the activity of complement C5 by significantly reducing free C5 (unbound C5); and use thereof. The anti-C5 antibody according to the present invention can significantly reduce the concentration of free C5 in serum and simultaneously inhibit the classical and alternative pathways of a complement system. In addition, the anti-C5 antibody according to the present invention stably inhibited complement activity of both pathways even when the serum ratio was increased in in vitro hemolytic assays, and exhibits an excellent inhibitory effect compared to previously known antibodies, and such an inhibitory effect was consistently observed even under clinical conditions with high serum concentrations. Therefore, the anti-C5 antibody of the present invention can be effectively used for the prevention or treatment of various autoimmune diseases, including myasthenia gravis, age-related macular degeneration, and paroxysmal nocturnal hemoglobinuria.

The present application relates to a guppy trichodinid third generation recombinant kunitz protein and a preparation method and application thereof, and belongs to the technical field of fish parasite protein expression and functional application research.The serine protease inhibitor of the guppy trichodinid third generation in the present application is a GcKSI protein, and the amino acid sequence of the GcKSI protein is shown as SEQ ID NO:2.The amino acid sequence of the GcKSI protein is optimized in the present application, and a GcKSI recombinant protein rGcKSI is obtained through prokaryotic expression.rGcKSI can inhibit the complement activity of a host fish in vitro, and has an obvious inhibitory effect on serine protease.The infection rate and average infection intensity of rohu fish injected with rGcKSI and then subjected to trichodinid infection experiment are significantly lower than those of a control group, proving that rGcKSI has good immunoprotective properties for trichodinid infection, and indicating that the serine protease inhibitor GcKSI gene and the GcKSI protein encoded by the GcKSI gene can be used as a new target for drug research and development.

The present invention provides polypeptide modulators of complement activity, including cyclic polypeptide modulators. Also provided are methods of utilizing such modulators as therapeutics.

The present invention relates to a long-chain fatty acyl monoterpenoid compound, a preparation method thereof, and uses thereof in the preparation of anti-complement drugs and anti-viral pneumonia drugs. The long-chain fatty acyl monoterpenoid compound has a chemical structure with the following general structural formula: The R group is hexadecyl or tetradecyl. Through in vitro anti-complement activity tests, the results show that the above-mentioned long-chain fatty acyl monoterpenoid compound has a strong inhibitory effect on the classical pathway of the complement system (see Table 1). (3S,5R,6S,7E)-3-tetradecanoate-5,6-epoxy-β-ionone has been confirmed through in vivo animal experiments to have a good therapeutic effect on viral pneumonia in mice induced by influenza A virus H1N1.

The present invention relates to a peptide therapy to modulate the complement system. The invention provides a novel fragment of Complement Factor H Related protein 5 which restores complement regulation. Pharmaceutical compositions, medicaments and methods of treatment for use in preventing, ameliorating or treating diseases that are characterised by inappropriate complement activity are also described.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. Limited evidence suggests that antibodies can protect humans against lethal CCHFV disease, but the protective efficacy of antibodies has never been evaluated in adult animal models. Here adult mice were used to investigate the protection provided by glycoprotein-targeting neutralizing and non-neutralizing monoclonal antibodies (mAbs) against CCHFV infection. A single non-neutralizing antibody (mAb-13G8) was identified that protected adult type I interferon deficient mice >90% when treatment was initiated prior to virus exposure and >60% when administered after virus exposure. Neutralizing antibodies known to protect neonatal mice from lethal CCHFV infection, failed to confer protection regardless of IgG subclass. The target of mAb-13G8 was identified as GP38, one of multiple proteolytically-cleaved glycoproteins derived from the CCHFV glycoprotein precursor polyprotein. Robust protection required complement activity, but not Fc-receptor functionality. Consistently, it was found that GP38 previously identified as a secreted molecule also localizes to viral envelope and cellular plasma membranes. This study reveals GP38 as an important antibody target for CCHFV and lays the foundation to develop novel vaccines and immunotherapeutic against CCHFV in human.

The dosages and methods described herein provide desirable pharmacokinetic (PK) and pharmacodynamics (PD) characteristics which inhibit alternative pathway complement activity, for example at least 85% or more inhibition of AP activity in vivo at dosages from about 120 mg to 200 mg BID that provides a plasma level Ctrough at least about 65 ng / ml, which provides sufficient AP inhibition to reduce the risk of complement breakthrough. In addition, the dosage form described herein provides a significantly low Cmax, providing additional safety margin and better dosing flexibility.

Novel anti-C3 antibodies and anti-C5 antibodies are provided that are capable of modulating complement activity by specifically binding to the human complement factors C3, C3a, C3b and / or C5. Also described herein are recombinant adeno-associated virus (AAV) (rAAV) comprising a variant adeno-associated virus (AAV) capsid and a transgene encoding an anti-C3 antibody and / or an anti-C5 antibody. Also provided are methods of delivering a transgene to the retina, as well as methods of treating dry age-related macular degeneration and map-like atrophy secondary to an age-related macular degeneration disorder by contacting retinal cells with rAAV.

The present disclosure relates to proteins comprising antigen binding sites that bind to human complement C2 (C2). The present disclosure also relates to methods of inhibiting complement activity in a subject as well as methods of treating or preventing complement-mediated disorders.

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 is the use of urinary C5b-9 (uC5b-9) as a highly accurate and superior biomarker well correlated with complement activity in local tissues affected by complement-mediated diseases (e.g., those with a kidney damage component). The biomarker is useful, for example, in treating and / or monitoring such complement-mediated diseases, using complement inhibitors targeted to such local tissues affected by the diseases, without systemic complement inhibition.

The invention relates to a complement activity regulator as well as a preparation method and medical application thereof, in particular to a binding polypeptide as shown in a general formula (I) and a derivative thereof, or a medicinal salt and a pharmaceutical composition thereof, and application of the binding polypeptide and the derivative thereof in preparation of medicines for preventing or treating complement-related diseases or symptoms.

The invention belongs to the field of traditional Chinese medicine preparation, and relates to application of dicoumarin compounds daphnoretin and 3-hydroxy-6-methoxy-7, 7 '-dicoumarin ether in preparation of anticomplement drugs. According to the invention, biscoumarin compounds, namely daphnoretin and 3-hydroxy-6-methoxy-7, 7 '-biscoumarin ether, are extracted from an n-butyl alcohol extraction part of an ethanol extract of dried roots of Stellera tianshanica (Stellera tianshanica. Pored.), and the biscoumarin compounds, namely the daphnoretin and the 3-hydroxy-6-methoxy-7, 7'-biscoumarin ether are extracted from the n-butyl alcohol extraction part of the ethanol extract of the dried roots of Stellera tianshanica. An in-vitro anti-complement activity evaluation experiment proves that the compound has a relatively strong inhibition effect on both a classical pathway and a bypass pathway of a complement system. The biscoumarin compound daphnoretin and the 3-hydroxy-6-methoxy-7, 7 '-biscoumarin ether disclosed by the invention can be further used for preparing medicines for treating complement related diseases, and the complement related diseases comprise systemic lupus erythematosus, rheumatoid arthritis or acute respiratory distress syndrome.

Novel anti-C3 and anti-C5 antibodies are provided that can modulate complement activity by specifically binding to human complement factors C3, C3a, C3b, and / or C5. Recombinant AAVs (rAAVs) containing variant adeno-associated virus (AAV) capsids and transgenes encoding anti-C3 and / or anti-C5 antibodies are also described herein. Methods for delivering transgenes to the retina by contacting retinal cells with rAAVs, as well as methods for treating atrophic age-related macular degeneration and geographic atrophy secondary to age-related macular degeneration disorders, are also provided.