50 results about "Complement components" patented technology

The invention provides a method for detecting an anti-C1 esterase inhibitor neutralizing antibody in a biological sample, and the method mainly utilizes the characteristic that protein A resin is combined with an Fc segment of the antibody to capture the antibody (containing the anti-C1 esterase inhibitor neutralizing antibody), so that the C1 esterase inhibitor and complement component 1s (C1s) in the biological sample after thermal inactivation are removed; furthermore, an antibody (containing a neutralizing antibody) or an anti-C1 esterase inhibitor compound on the protein A resin is subjected to acid dissociation through an acidolysis solution, so that not only can the anti-C1 esterase inhibitor neutralizing antibody existing in a free form in a biological sample be detected, but also the anti-C1 esterase inhibitor neutralizing antibody existing in a combined form in the biological sample can be detected.

The present disclosure provides methods of treating an alloimmune or autoimmune disorder in an individual; the methods involve administering to the individual an effective amount of an antibody specific for complement component C1s. The present disclosure provides a method of monitoring the efficacy of a subject treatment method; the method involves detecting the level of autoantibody or alloantibody in a biological sample obtained from the individual.

According to certain embodiments, the present disclosure provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds a target antigen and a second antigen binding domain that binds a complement component. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure are capable of binding to the target antigen with an EC50 of about 10 nM or less, and / or are capable of promoting complement deposition on the target antigen with an EC50 of about 10 nM. In certain embodiments, the bispecific antigen-binding molecules of the disclosure are useful for treating diseases in which inhibition or reduction of the growth of an infectious agent or cancer cell is desired and / or therapeutically beneficial.

Provided are methods and dosage regimens for treating multifocal motor neuropathy (MMN) using an antibody that binds specifically to the C2b part of complement component 2 (C2).

Provided in the present invention are a siRNA for inhibiting the expression of complement component C5, the use thereof, and a product thereof, belonging to the technical field of small-molecule drugs and relating to the design and use of siRNA for C5 genes. The siRNA of the present invention comprises a sense strand and an antisense strand, wherein the sense strand comprises a nucleotide sequence as shown in SEQ ID NO. 1-SEQ ID NO. 546, and the antisense strand comprises a nucleotide sequence as shown in SEQ ID NO. 547-SEQ ID NO. 1092. Provided in the present invention is a brand new siRNA which can effectively inhibit the expression of complement component C5.

A method for diagnosing prostate cancer comprising: providing a saliva sample from a subject, and measuring the expression of C4B (complement component 4) in the sample. Also claimed are separate meth

The present invention relates to compounds which are capable to bind the complement component 1, subcomponent q (C1q) and to inhibit its biological activity. More in particular, the present invention discloses the usage of said compounds to prevent or treat fatigue as comorbidity in autoimmune disease.

A single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide and complement component C3 (CC3) mRNA have sufficient complementarity to mediate RNAi effect; each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and the at least one nucleotide is a fluoro-modified nucleotide; moreover, according to a direction from the 5' end to the 3' end, at least one nucleotide X is located after an eighth nucleotide and is spaced apart from the eighth nucleotide in the single-stranded oligonucleotide by 4-7 nucleotides; and each nucleotide X is a deoxynucleotide or an unmodified nucleotide. The present invention further relates to a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

The present application relates to anti-complement Cls antibodies and uses thereof. The present disclosure provides antibodies that bind complement Cls protein; and nucleic acid molecules encoding such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods of making and using such antibodies, nucleic acid molecules, and compositions. The present disclosure provides an isolated, humanized monoclonal antibody that inhibits cleavage of complement component G4, wherein the antibody does not inhibit cleavage of complement component C2. In some cases, the antibody inhibits a component of the classical complement pathway, in some cases the classical complement pathway component is Cls. In some cases, the antibody does not inhibit protease activity of Cls.

The invention relates to the field of medicines, in particular to application of a reagent for detecting a complement factor in preparation of a tinnitus diagnostic product, the complement factor is selected from a complement component, a complement regulatory protein or a complement related chemotactic factor, the complement component is selected from C3, C5 and / or C1q, and tinnitus is chronic tinnitus. The peripheral blood can be used as a sample, the chronic tinnitus can be accurately diagnosed, theoretical and experimental bases are provided for clinical diagnosis of the chronic tinnitus, diagnosis and intervention can be carried out in the early stage of tinnitus, and further deterioration is prevented.

The present invention provides compositions and methods useful for reducing C3 gene expression and treating C3 related diseases and disorders. The present invention provides C3dsRNA agents, C3 antisense polynucleotide agents, compositions comprising C3dsRNA agents, and compositions comprising C3 antisense polynucleotide agents useful for reducing C3 expression in cells and subjects.

This invention provides anti-complement component antibodies, such as anti-C1s antibodies and anti-C1r antibodies, as well as methods for using them. [Solution] The present invention provides anti-C1s antibodies and anti-C1r antibodies, a pharmaceutical formulation containing the antibodies, and a method for treating an individual with a complement-mediated disease or disorder, comprising the step of administering the antibodies to the individual. The binding specificity and C1q dissociation-promoting function of the anti-C1s antibodies and anti-C1r antibodies have been evaluated. With respect to the antibodies, time-dependent complement neutralization function and binding to native and cleaved C1s or C1r proteins have also been demonstrated.

To provide anti-complement component-antibodies such as anti- C1s antibodies, pharmaceutical compositions comprising the same, and methods of use thereof.SOLUTION: The present invention provides antibodies that bind to C1s in a pH-dependent manner. The invention also provides pharmaceutical compositions comprising any of the antibodies, as well as methods of treating an individual with a complement-mediated disease or disorder or preventing an individual from potentially having a complement-mediated disease or disorder comprising administering any of the antibodies to the individual.SELECTED DRAWING: None

The invention discloses a kit for rapidly and efficiently diagnosing lung cancer meningeal metastasis, and relates to the technical field of medical equipment, and the key points of the technical scheme are as follows: the kit is a disposable plastic shell, and four independent chromatography channels are arranged in parallel in the kit, namely a Compleent C7 channel, a Frizzled-9 channel, an Interleukin-1 receptor protein channel and an Alpha-1-anticmotrypsin channel. Four markers can be detected at the same time, when the kit is used for diagnosing lung cancer meningeal metastasis, the dosage of cerebrospinal fluid can be reduced, the diagnosis sensitivity is improved, the detection time is shortened, the sampling frequency is reduced, and by setting an objective interpretation threshold value and an automatic analysis module, subjective judgment errors are reduced, and diagnosis consistency and repeatability are improved.

The invention provides siRNA for inhibiting expression of a complement component C5 as well as application and a product thereof, belongs to the technical field of small molecule drugs, and relates to design and application of siRNA aiming at a C5 gene. The siRNA disclosed by the invention contains a positive-sense strand and an antisense strand, the positive-sense strand contains a nucleotide sequence as shown in SEQ ID NO. 1 to SEQ ID NO. 546, and the antisense strand contains a nucleotide sequence as shown in SEQ ID NO. 547 to SEQ ID NO. 1092. The siRNA disclosed by the invention has the advantages that the siRNA can be applied to the field of biological detection, and the like. The invention provides brand new siRNA which can effectively inhibit the expression of a complement component C5.

Aspects of the disclosure provide compounds, compositions, and methods for modulating the expression or activity of complement component 3 (C3). In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of C3 mRNA in a cell or animal. In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of C3 protein in a cell or animal.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents or siRNAs, able to inhibit Complement Component C3 (C3) gene expression. Also disclosed are pharmaceutical compositions that include C3 RNAi agents and methods of use thereof. The C3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosanine, to facilitate the delivery to hepatocyte cells. Delivery of the C3 RNAi agents in vivo provides for inhibition of C3 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and / or other complement-mediated renal diseases.

Provided herein are dual-antigen binding molecules, and nucleic acid sequences encoding such molecules, that bind human complement factor D (FD) and human complement component 2 (C2). In particular embodiments, the FD binding region of the dual-antigen binding molecules comprises light and heavy chain variable regions, and the C2 binding region comprises a first single monomeric variable antibody domain (aka VHH), and optionally second single monomeric variable antibody domain. In certain embodiments, the dual-antigen binding molecules are used to treat complement-related diseases (e.g., dysregulated complement activation diseases).

To provide anti-complement component antibodies, such as anti-C1s antibodies and anti-C1r antibodies, and to provide methods of use thereof.SOLUTION: Provided are an anti-C1s antibody and an anti-C1r antibody; a pharmaceutical formulation comprising the antibody; and a method for treating an individual with a complement-mediated disease or disorder comprising a step of administering the antibody to the individual. The binding specificity and C1q dissociation promotion function of the anti-C1s antibody and the anti-C1r antibody have been evaluated. Time-dependent complement neutralization function and binding to native and truncated C1s or C1r proteins have also been demonstrated for the antibody.SELECTED DRAWING: None

A method for diagnosing facioscapulohumeral muscular dystrophy (FSHD) using one or more biomarkers is provided. More particularly, provided is a method for diagnosing FSHD in a subject, the method comprising detecting the presence of a biomarker or change in level of a biomarker in a biological sample from the subject, wherein the biomarker is wherein the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), lumican (LUM), phosphatidylinositol-glycan-specific phospholipase D (GPLD1 ), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, LUM, GPLD1, C4BPB, CNDP1, or IGKV2-30. In some aspects, when the change in level of the biomarker is an increase in the level of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, and / or LUM, or a combination of any thereof, the subject is diagnosed as having FSHD. In some aspects, when the change in level of the biomarker is a decrease in the level of GPLD1, C4BPB, CNDP1, and / or IGKV2-30, or a combination of any thereof, the subject is diagnosed as having FSHD. Also provided is a method for determining efficacy of a therapeutic treatment for FSHD in a subject, the method comprising measuring the level of a biomarker in a biological sample from the subject before and after the treatment, and determining that the treatment is effective in treating FSHD if the level of the biomarker is decreased or increased relative to a reference level or to the level of the biomarker in the sample from the subject before treatment, wherein when the biomarker is mannose binding lectin 2 (MBL2), junction plakoglobin (JUP), desmoplakin (DSP), tetranectin (CLEC3B), complement component 7 (C7), complement component 9 (C9), tenascin C (TNG), or lumican (LUM), or a combination of any two or more of MBL2, JUP, DSP, CLEC3B, C7, C9, TNG, or LUM, the treatment is effective when the level of the biomarker decreases, or wherein when the biomarker is phosphatidylinositol-glycan-specific phospholipase D (GPLD1), complement component 4 binding protein, beta chain (C4BPB), carnosine dipeptidase (CNDP1), or immunoglobulin kappa variable 2-30 (IGKV2-30), or a combination of any two or more of GPLD1, C4BPB, CNDP1, or IGKV2-30, the treatment is effective when the level of the biomarker increases. In various aspects, the method further comprises treating the subject diagnosed with FSHD.

Provided herein are methods for expression of anti-C3 molecule by administering a recombinant adeno-associated virus (rAAV) virion in an amount capable of blocking C3 activity in the eye.

The present disclosure relates to the development and application of a complement inhibitor, which is an antibody or antigen-binding portion thereof that binds to MASP-2. The disclosed antibody binds to MASP-2 with high affinity and specifically recognizes the enzymatically active domains CCP1-CCP2-SP of human, monkey, mouse, and rat MASP-2. It effectively inhibits the production of complement components C4b and C3 convertase C4b2b at low concentrations, with blocking activity 50-200 times higher than that of known antibodies. Furthermore, the MASP-2 antibody is well tolerated, exhibits no toxicity, and exhibits superior efficacy and safety compared to similar antibodies.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents or siRNAs, able to inhibit Complement Component C3 (C3) gene expression. Also disclosed are pharmaceutical compositions that include C3 RNAi agents and methods of use thereof. The C3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the C3 RNAi agents in vivo provides for inhibition of C3 gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by C3 gene expression, including IgA nephropathy, C3 glomerulopathy, paroxysmal nocturnal hemoglobinuria, and / or other complement-mediated renal diseases.

The invention discloses a system for evaluating the ADE effect of Middle East respiratory coronavirus based on a complement-mediated pathway and application of the system. The system is selected from any one of the following (1)-(3): (1) the system comprises a Middle East Respiratory Syndrome Coronavirus pseudovirus, a complement component C1q and a cell over-expressing CD93; (2) the system comprises an antibody targeting the Middle East Respiratory Syndrome Coronavirus, a complement component C1q and a cell overexpressing CD93; and; and (3) the system comprises an antibody targeting the Middle East Respiratory Syndrome Coronavirus, a Middle East Respiratory Syndrome Coronavirus pseudovirus, a complement component C1q and a cell overexpressing CD93. The system provided by the invention has the advantages of high sensitivity, high detection peak value and wide detection range, can provide reference for research and development or use of MERS-CoV prevention, alleviation and / or treatment drugs, and has wide application prospects.

According to certain embodiments, the present disclosure provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds a target antigen and a second antigen binding domain that binds a complement component. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure are capable of binding to the target antigen with an EC50 of about 10 nM or less, and / or are capable of promoting complement deposition on the target antigen with an EC50 of about 10 nM. In certain embodiments, the bispecific antigen-binding molecules of the disclosure are useful for treating diseases in which inhibition or reduction of the growth of an infectious agent or cancer cell is desired and / or therapeutically beneficial.

This invention belongs to the field of biotechnology diagnostics and discloses protein biomarkers for early pregnancy diagnosis in sows and their applications. From the perspective of early pregnancy diagnosis strategies in sows, this invention, through bioinformatics analysis and screening of differentially expressed proteins, identifies porcine complement component 5a receptor 1 (C5aR1), porcine lysosomal acid phosphatase 2 (ACP2), and porcine tetrahexine 7 (TSPAN7) as biomarkers involved in the development and progression of sow pregnancy, which can be used to indicate whether a sow is pregnant. This invention can improve the risk prediction ability of sows after artificial insemination based on known risk factors. In production, it can be used for precise stratification after artificial insemination, improving sow parity and reproductive efficiency, and reducing non-productive days in sows.

The present disclosure reports that a calcium-dependent serine protease, complement component is (C1s) has been identified as a protease responsive for cleavage of exogenous polypeptides expressed in mammalian cell lines such as CHO cells. These CHO cell lines provide for increased yield of antigenically correct, uncleaved exogenous polypeptide as compared to unmodified CHO cells expressing the active C1s protease. C1s-deficient cell lines and methods for use of same for producing exogenous polypeptides, e.g., human immunodeficiency virus (HIV) envelope glycoprotein polypeptides, such as, gp120 or human Factor VIII are provided.

The present invention relates to complement component C1q binders ("C1q binders") comprising a peptide that binds to a globular head domain of complement component C1q and by this can either activate or inhibit complement. Further disclosed are pharmaceutical compositions and kits comprising the C1q binders according to the invention. The invention also relates to the medical uses of such C1q binders and compositions. In particular, the C1q binders or compositions of the invention may be used in the treatment, prevention and diagnosis of diseases or disorders. The invention also relates to nucleic acids encoding the peptides.

There is a need to identify solid forms of Compound 1 that can improve important biological characteristics such as solubility, dissolution rate, and bioavailability without sacrificing stability and efficacy. The present disclosure addresses these needs and provides further related advantages.SOLUTION: Provided herein is an amorphous form of complement-component 5a receptor having the formula of Compound 1. Also provided herein are pharmaceutical compositions and methods of treatment using the amorphous form of Compound 1 described herein.SELECTED DRAWING: Figure 2

The invention discloses a biomarker for auxiliary diagnosis or evaluation of epilepsy related to nodular sclerosis and application of the biomarker. The biomarker comprises any one or a combination of at least two of a complement component 7, N-acetylgalactosamine transferase 3, an ecological virus integration site 5, a hemoglobin subunit theta 1 or leukotriene A4 hydrolase. The invention provides a protein biomarker combination which is low in invasiveness and easy to quantify and can be used for preoperative evaluation, postoperative prognosis judgment and curative effect monitoring and a detection method thereof, and the accuracy and reliability of nodular sclerosis related epilepsy diagnosis and risk evaluation are remarkably improved.