156 results about "Complement factor I" patented technology

The invention provides a complement factor B inhibitor compound, pharmaceutically acceptable salts thereof, a medicinal composition thereof and application of the complement factor B inhibitor compound in preparation of medicines related to complement factor B. The compound has a structural formula shown in a formula (I), and experimental results show that the compound has good complement factor B inhibitory activity, good in-vivo C3a level inhibition rate, bioavailability and safety. Particularly, the polypeptide has more remarkable binding capacity with target protein. # imgabs0 #

Provided are a compound as shown in general formula (I), or a stereoisomer, deuterate, solvate, prodrug, metabolite, pharmaceutically acceptable salt or co-crystal thereof, an intermediate thereof, a preparation method therefor, and the use thereof in the preparation of a drug for treating a disease associated with the activity or expression quantity of complement factor B.

The present invention relates to the technical field of nucleic acid drugs, and particularly provides a double-stranded oligonucleotide for inhibiting complement factor B (CFB) gene expression. The double-stranded oligonucleotide comprises a sense strand and an antisense strand; the sense strand contains at least fifteen consecutive nucleotides in any one sequence shown as SEQ ID NO: 1-SEQ ID NO: 255 in Table 1 or a nucleotide sequence which differs from the at least fifteen consecutive nucleotides in respect of not more than three nucleotides; and / or, the antisense strand contains at least fifteen consecutive nucleotides in any one sequence shown as SEQ ID NO: 256-SEQ ID NO: 510 in Table 1 or a nucleotide sequence which differs from the at least fifteen consecutive nucleotides in respect of not more than three nucleotides. The double-stranded oligonucleotide can inhibit CFB gene expression in cells, thereby achieving the effects of relieving, treating and / or preventing diseases or disorders mediated by abnormal CFB gene expression.

Disclosed are compounds, pharmaceutical compositions and uses thereof as complement factor D inhibitors, specifically a compound represented by formula (I), its tautomers, its stereoisomers, its prodrugs, or any one of the foregoing pharmaceutically acceptable salts, or any one of the foregoing solvates, wherein the compound has excellent inhibitory activity against complement factor D and has excellent pharmacokinetic and pharmacodynamic activity. JPEG2024533782000131.jpg47170

Disclosed in the present invention are a preparation method for a complement factor D inhibitor, an intermediate thereof, and a preparation method for an intermediate. The present invention provides a preparation method for a new complement factor D inhibitor, a new intermediate, and a preparation method for an intermediate. The selectivity of a reaction is improved by means of the new intermediate, the material conversion rate of each step of a route is high, a reaction type is common, the length of the route is moderate, and the obtained products can all be purified by means of a conventional method to obtain a target product, thereby reducing the production costs, and facilitating industrial production.

Provided is an siRNA for inhibiting the gene expression of complement factor B (CFB), or a pharmaceutical composition or conjugate containing the siRNA. The siRNA contains a sense strand and an antisense strand. Each nucleotide in the siRNA is an independent modified or unmodified nucleotide. The sense strand contains a segment of nucleotide sequence I, and the nucleotide sequence I and a nucleotide sequence show in SEQ ID NO: 1 have an equal length and differ by no more than 3 bases. The antisense strand contains a nucleotide sequence II, and the nucleotide sequence II and a nucleotide sequence shown in SEQ ID NO: 2 have an equal length and differ by no more than 3 bases. The siRNA or the pharmaceutical composition or conjugate containing the siRNA can effectively treat and / or prevent diseases related to the mRNA level of the gene expression of the CFB.

The present invention belongs to the field of biotechnology. Disclosed is a dosage composition of a complement factor B inhibitor. Specifically, the present invention provides a pharmaceutical composition comprising a compound represented by formula I, an isomer thereof, or a pharmaceutically acceptable salt thereof in a unit dosage form, wherein the mass of the compound or the pharmaceutically acceptable salt thereof is 5-1500 mg based on the free base.

The present invention provides a lipid nanoparticle comprising an entity that contains one or multiple sialic acid (SA) moieties, the entity is preferably a ganglioside, a ganglioside derivative, a ganglioside mimetic, or a combination thereof. The lipid nanoparticle of the present invention can effectively present SA moieties on the surface to bind Siglecs and complement factors to, inter alia, mitigate inflammation. The present invention also provides methods of using said lipid nanoparticle compositions described herein for pharmaceutical applications. For example, the lipid nanoparticles provided herein are useful for treating inflammatory and autoimmune diseases.

The present invention belongs to the technical field of biology. Disclosed are a crystal form of a complement factor B inhibitor, a preparation method therefor and the use thereof. Specifically, the present invention provides a crystal form of a compound represented by formula I, a preparation method therefor and the use thereof. The crystal form prepared by the present invention has good stability, for example, crystal form stability and thermal stability.

Provided herein are compounds of formula (I) and pharmaceutical compositions thereof that are useful for treating diseases or disorders mediated by complement factor B. [Formula 1] TIFF2025511100000139.tif32170

Provided are protein nanostructures that display Neisseria meningitidis factor H binding protein (fHBP). The protein nanostructure may be a two-component icosahedral nanostructure. Further provided are vaccine compositions, methods of manufacturing, and methods of use, e.g., immunizing a subject to generate a protective immune response to Neisseria meningitidis.

The present invention provides antagonizing antibodies that bind to complement factor D (CFD), conjugates thereof, and methods of using same. The anti-CFD antibodies can be used therapeutically alone or in combination with other therapeutics to treat age related macular degeneration and other diseases.

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the complement factor B (CFB) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a CFB gene and to methods of treating or preventing a CFB-associated disease in a subject.

The invention relates to nucleic acid products that interfere with complement factor B (CFB) gene expression or inhibit its expression. The nucleic acids are preferably for use in the prophylaxis or treatment of complement associated diseases, disorders or syndromes, particularly C3 glomerulopathy (C3G), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), lupus nephritis, IgA nephropathy (IgA N), myasthenia gravis (MG), and primary membranous nephropathy.

Aspects of the disclosure provide compounds, compositions, and methods for modulating the expression or activity of Complement Factor B (CFB). In certain aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB 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 CFB protein in a cell or animal.

Provided herein are methods of ameliorating a disease or condition associated with a disorder of a complement bypass pathway by administering to a subject a complement factor B (CFB) specific inhibitor.

The invention discloses application of CFB polypeptide as a target spot in preparation of diabetic nephropathy diagnosis and treatment medicines, and belongs to the technical field of biological medicines. The invention provides application of CFB (circulating fluid bed)-sourced polypeptide in preparation of a medicine for treating diabetic nephropathy and application of the CFB-sourced polypeptide as a possible target in development of a novel diabetic nephropathy biomarker. According to the invention, a complement factor B-derived polypeptide which is significantly up-regulated in diabetic nephropathy is found through deep peptidomics analysis; furthermore, a functional experiment proves that the polypeptide shows remarkable anti-fibrosis activity in kidney cells for the first time, the active oxygen level can be reduced, and an HIF-1 alpha / glycolytic pathway can be regulated and controlled.

To provide monoclonal antibodies that bind to the complement factor 5 (C5) protein, and methods of use thereof.SOLUTION: In various embodiments of the present invention, the antibodies are fully human antibodies that bind to C5 protein. In some embodiments, the antibodies of the present invention are useful for inhibiting or neutralizing C5 activity, thus providing a means of treating or preventing a C5-related disease or disorder in humans. In some embodiments, the present invention provides an anti-C5 antibody that has improved pharmacokinetic and pharmacodynamic properties, e.g., a half-life of more than 10 days.SELECTED DRAWING: None

The present disclosure provides methods for the synthesis of complement factor D inhibitors and intermediates thereof.

The present invention relates to the technical field of biology. Disclosed are a salt of a complement factor B inhibitor, a preparation method therefor and a use thereof. Specifically, the present invention provides a salt of a compound as shown in formula (A), a preparation method therefor and a use thereof.

Relates to the technical field of nucleic acid drugs, and particularly provides a double-stranded oligonucleotide for inhibiting complement factor B (CFB) gene expression, the double-stranded oligonucleotide comprises a sense strand and an antisense strand, the positive-sense strand comprises at least 15 continuous nucleotides in any sequence as shown in SEQ ID NO: 1-SEQ ID NO: 255 in a table 1 or a nucleotide sequence which is different from the at least 15 continuous nucleotides by not more than 3 nucleotides; and / or the antisense strand comprises at least 15 contiguous nucleotides in any sequence as shown in SEQ ID NO: 256-SEQ ID NO: 510 in the table 1 or a nucleotide sequence which is different from the at least 15 contiguous nucleotides by not more than 3 nucleotides. The double-stranded oligonucleotide can inhibit CFB gene expression in cells and achieve the effects of relieving, treating and / or preventing diseases or symptoms mediated by CFB gene expression abnormity.

Disclosed herein are Complement factor H (CFH) antibodies and methods of using the antibodies.

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)

Described herein is an oligonucleotide (e.g., RNAi oligonucleotide) that comprises sense and antisense strands for targeting complement factor B (CFB) mRNA.RNAi oligonucleotide can be used to inhibit CFB expression, level and / or activity in cells.Also described is a method of using oligonucleotide (e.g., RNAi oligonucleotide) for prevention or treatment of disease, disorder or condition mediated by complement pathway activation or dysregulation.

The present invention relates to the prediction and early diagnosis of acute kidney injury (AKI). The methods provide biomarkers that correlate with a patient's risk of developing AKI, or the presence of early AKI. The invention also provides devices and kits for predicting the risk of development of AKI and for diagnosing AKI.SOLUTION: A method for predicting the risk of occurrence of acute kidney injury (AKI) or for early diagnosis of AKI in a subject, the method comprising: a. determining in a sample obtained from the subject the amount of at least one biomarker selected from the group consisting of complement factor D and insulin-like growth factor binding protein 1 and combinations, isoforms, fragments and variants thereof.SELECTED DRAWING: None

Disclosed herein are C1q complement factor-engaging polypeptides with optimized C1q-binding affinity, resulting in improved complement-mediated immunological responses against target antigens. Also disclosed herein are bispecific constructs that comprises: (a) a C1q complement factor-engaging domains described herein and (b) an antigen binding moiety that binds to a target protein implicated in a disease or condition. Also disclosed herein is a method treating a disease or condition in a subject in need thereof comprising administering a bispecific construct described herein.

Aspects of the disclosure provide compounds, compositions, and methods for modulating the expression or activity of Complement Factor B (CFB). In some aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB mRNA in a cell or animal. In some aspects, the compounds, compositions, and methods of the disclosure can be used to reduce the expression of CFB protein in a cell or animal.

A pharmaceutically acceptable salt type and crystal form of a compound of formula (I), and a preparation method of the compound and an application thereof are provided.

Disclosed are compounds of formula I and II and pharmaceutically acceptable salts thereof. Also disclosed are methods of treating a neurodegenerative disorder, an inflammatory disease, an autoimmune disease, an ophthalmic disease or a metabolic disorder using the compounds disclosed herein.