88 results about "Complement components" patented technology

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, Pemphigus, e.g., Pemphigus vulgaris (PV) and Pemphigus foliaceus (PF), and C3 glomerulopathy.

The present disclosure provides methods of treating a complement-mediated disease or disorder in an individual, and methods of inhibiting activation of complement component C4 in an individual in need thereof. The methods comprise administering to the individual an anti-C1s antibody. The methods also comprise administering an anti-C1s antibody in a fixed dose, e.g., 5.5 g, 6.5 g, or 7.5 g. The methods also comprise administering an effective dose of an anti-C1s antibody to the individual to achieve a minimum serum level of anti-C1s antibody for therapeutic effect.

The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., Alzheimer's disease, atherosclerosis, or inflammation of the choroid plexus (ChP).

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 disclosure provides engineered polypeptides that specifically bind to human complement component C5 and / or serum albumin. The disclosure also provides fusion proteins comprising such engineered polypeptides, wherein such fusion proteins may be multivalent and multi-specific fusion proteins. The disclosure further provides nucleic acid molecules that encode such engineered polypeptides or fusion proteins, and methods of making such engineered polypeptides or fusion proteins. The disclosure further provides pharmaceutical compositions that comprise such engineered polypeptides or fusion proteins, and methods of treatment using such engineered polypeptides or fusion proteins.

Compositions and methods useful to reduce expression of C3 gene and for treatment of C3-associated diseases and conditions are provided. Provided are C3 dsRNA agents, C3 antisense polynucleotide agents, compositions comprising C3 dsRNA agents, and compositions comprising C3 antisense polynucleotide agents that can be used to reduce C3 expression in cells and subjects.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting a complement component C3 (C3) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), atypical hemolytic uremic syndrome (aHUS), neuromyelitis optica (NMO), multifocal motor neuropathy (MMN), myasthenia gravis (MG), C3 glomerulonephritis, or systemic lupus erythmatosis.

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.

The present disclosure relates to the development and application of a complement inhibitor, which is an antibody or an antigen-binding portion thereof that binds to MASP-2. The antibody disclosed herein can bind to MASP-2 with high affinity, can specifically recognize the enzymatic domains CCP1-CCP2-SP of human, monkey, mouse and rat MASP-2, and can effectively inhibit the generation of complement component C4b and C3 convertase C4b2b under low concentration conditions, and its blocking activity is 50-200 times higher than that of known antibodies, and the MASP-2 antibody is well tolerated without any toxic reactions, and its efficacy and safety are better than similar antibodies.

The present invention provides anti-complement component antibodies, such as anti-C1s antibodies and anti-C1r antibodies, and methods of using the same. The invention also provides pharmaceutical formulations comprising the antibodies, and methods of treating a subject having a complement-mediated disease or disorder comprising administering the antibodies to the subject. And evaluating the binding specificity and C1q substitution function of the anti-C1s antibody and the anti-C1r antibody. The time dependent complement neutralizing function of the antibodies as well as binding to native and truncated C1s or C1r proteins are also shown.

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.

Isolated monoclonal antibodies that bind to human complement component C6 and related antibody-based compositions and molecules are disclosed. Also disclosed are therapeutic methods for using the antibodies.

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.

To provide an anti-C5 antibody for treatment of neuromyelitis optica spectrum disorder.SOLUTION: Provided are methods for clinical treatment of neuromyelitis optica spectrum disorder (NMOSD) using an anti-C5 antibody, or antigen binding fragment thereof. The present disclosure provides a method of treating neuromyelitis optica spectrum disorder (NMOSD) in a subject in need thereof by administering an antibody that specifically binds to a complement component 5 (C5). In certain embodiments, the antibody that specifically binds to the C5 reduces a rate at which the C5 is cleaved in vivo into C5a and C5b. In other embodiments, the antibody that specifically binds to the C5 binds to one or both of the C5a and / or C5b fragments. In any of these embodiments, the antibody that specifically binds to the C5 reduces a complement cascade at the C5, thereby reducing release of proinflammatory mediators and formation of a cytolytic pore.SELECTED DRAWING: None

Provided herein are methods for treating a subject with PNH comprising administering to a subject a therapeutically effective amount of complement component C5 (C5) inhibitor, complement component C3 (C3) inhibitor, or complement factor B (CFB) inhibitor in combination with a therapeutically effective amount of small molecule complement factor D (CFD) inhibitor of Formula I or Formula II, or a pharmaceutically acceptable salt thereof.

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.

The invention relates to a siRNA double-stranded molecule targeting complement factor B (CFB) mRNA, a siRNA-GalNAc delivery carrier conjugate and application of the siRNA double-stranded molecule and the siRNA-GalNAc delivery carrier conjugate. And using such siRNA example compositions to inhibit expression of CFB mRNA and treat diseases associated with abnormal expression of complement components.

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.

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).

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.

Provided are agents and methods for the detection of complement-mediated thrombotic microangiopathy (CM-TMA) biomarkers. The agents may specifically bind to CM-TMA biomarkers, preferably a proteolytic fragment of complement component factor B (Ba) and soluble C5b9 (sC5b9) and can be used in methods of diagnosis and treatment of CM-TMA, e.g., treatment with an anti-C5 antibody such as ravulizumab (ALXN1210).

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.