37 results about "Activin receptor" patented technology

The present application provides a recombinant fusion protein comprising a human activin receptor 2A extracellular domain optionally fused to an immunoglobulin heavy chain constant region via a linker wherein the human ACVR2A extracellular domain comprises a mutation from Asn (N) to Ala (A) at a site corresponding to position 24 of the sequence as shown in SEQ ID NO: 1 to remove glycosylation sites.

Provided herein, in part, is a method of treating or preventing obesity or an obesity-related disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a small molecule inhibitor of an Activin receptor Type II.

The present invention relates to compounds of formula (I) which are inhibitors of activin receptor-like kinase 5 (ALK5) and related uses.

The present invention relates to novel 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as potent inhibitors of transforming growth factor-beta receptor I (also known as activin receptor-like kinase 5) (TGFβRI) / ALK5. Other objects of the present invention are to provide processes for preparing these compounds; pharmaceutical compositions comprising an effective amount of these compounds; the use of said compounds for the preparation of a medicament for the treatment of pathological conditions or diseases which can be ameliorated by the inhibition of transforming growth factor-beta receptor I (TGFβRI) / ALK5, such as respiratory diseases, including idiopathic pulmonary fibrosis, asthma, COPD and lung cancer and skin and ocular fibrotic disorders.

The invention features polypeptides that include an extracellular ActRII chimera. In some embodiments, a polypeptide of the invention includes an extracellular ActRII chimera fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), low platelet levels (e.g., thrombocytopenia), low neutrophil levels (e.g., neutropenia), fibrosis, metabolic disorders, and / or pulmonary hypertension.

The present application relates to an activin receptor II antibody and a use. The activin receptor II antibody comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3. A mutation relative to CDRs of a parental antibody includes one or more selected from the following: a heavy chain CDR2 V54A mutation, a heavy chain CDR2 G56L mutation, a heavy chain CDR2 T58K mutation, a heavy chain CDR3 G99S mutation, a heavy chain CDR3 G99T mutation, a light chain CDR1 G24H mutation, a light chain CDR1 D28W mutation, a light chain CDR1 Y32F mutation, a light chain CDR2 P57E mutation, a light chain CDR3 S97A mutation, and a light chain CDR3 Y99N mutation. A balanced activin receptor II dual-blocking antibody that exhibits higher affinity for ActRIIA while not significantly reducing affinity for ActRIIB is obtained by screening.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of an Activin Receptor-Like Kinase 7 (ALK7) gene. The ALK7 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an ALK7 gene. Pharmaceutical compositions that include one or more ALK7 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described ALK7 RNAi agents to adipose tissue, in vivo, provides for inhibition of ALK7 gene expression and a reduction in ALK7 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including obesity, diabetes, or insulin resistance.

This application provides a heterocyclic compound, a pharmaceutical composition, an activin type II receptor inhibitor, and their applications. The heterocyclic compound is a compound of Formula I or its racemic, stereoisomer, geometric isomer, tautomer, nitride, hydrate, isotope label, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester, or pharmaceutically acceptable prodrug. This heterocyclic compound, pharmaceutical composition, and activin type II receptor inhibitor can effectively inhibit activin receptor 2B with high selectivity, showing promising application prospects in the preparation of anti-cachexia drugs, anti-muscle muscular atrophy drugs, or anti-metabolic disease drugs.

The present invention relates to compounds of formula (I) which are inhibitors of activin receptor-like kinase 5 (ALK5) and related uses.

Methods for treating obesity and related comorbidities, such as type II diabetes, by decreasing body fat mass while increasing lean mass, and thereby decreasing central adiposity, are provided. The method includes administering myostatin or activin or an activin receptor antagonist, preferably an anti-ActRII receptor antibody such as bimagrumab.

The invention features polypeptides that include an extracellular ActRII chimera. In some embodiments, a polypeptide of the invention includes an extracellular ActRII chimera fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), low platelet levels (e.g., thrombocytopenia), low neutrophil levels (e.g., neutropenia), fibrosis, metabolic disorders, and / or pulmonary hypertension.

Provided herein are antibodies and / or antigen-binding fragments thereof that bind to ActRIIA and / or ActRIIB, and methods of using the same.

Antibodies to the enzyme matriptase-2 (MTP-2) are presented. Inhibiting MTP-2 reduces uptake of dietary iron and reduces the release of iron from cellular stores in the body. Inhibitors of MTP-2 (such as antibodies to the serine protease domain) can be used to treat iron overload, which is a feature of diseases such as beta-thalassaemia and which otherwise leads to toxic accumulation of iron. Combination of an MTP-2 inhibitor with an activin receptor ligand trap, or with erythropoietin, provides additional therapeutic effects.

Provided herein are oligonucleotides for inhibiting the expression of Activin receptor 2B (ACVR2B) and methods of using the oligonucleotides for reducing ACVR2B expression in a subject.

The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

To provide polypeptides and pharmaceutical compositions comprising activin type IIB receptor variants.SOLUTION: The polypeptide of the present invention comprises an extracellular activin type IIB receptor (ActRIIB) mutant comprising an amino acid sequence consisting of a specific sequence, wherein the C-terminus of the ActRIIB mutant is fused to a human IgG1Fc domain monomer. The invention also features pharmaceutical compositions and methods of using the same to treat diseases and conditions involving muscle weakness and atrophy, bone damage, low red blood cell levels (e.g., anemia or blood loss), fibrosis, and / or pulmonary hypertension.SELECTED DRAWING: Figure 2

In certain aspects, the present disclosure provides lyophilized pharmaceutical formulations comprising a recombinant fusion protein comprising an extracellular domain (ECD) of human activin receptor type-IIA (ActRIIa) proteins or derivatives thereof linked to a constant domain of an immunoglobulin, such as human IgG1 Fc domain and one or more pharmaceutical additives and / or excipients.

Disclosed is an engineered exosome, comprising (a) an FGF21 polypeptide, fused to a first anchoring polypeptide, (b) an IL-27 polypeptide, fused to a second anchoring polypeptide, and (c) an activin receptor type II polypeptide, fused to a third anchoring polypeptide, wherein (a), (b) and (c) are anchored on a membrane of the exosome via the first, second and third anchoring polypeptide, respectively, and wherein the FGF21 polypeptide, the IL-27 polypeptide and the activin receptor type II polypeptide are exposed on an outer surface of the membrane of the exosome. Also disclosed are compositions, nucleic acid constructs, and uses of the exosome in treating metabolic disorders.

Provided herein are Activin Receptor type 2A (ACVR2A) and Activin Receptor Type 2B (ACVR2B) RNAi agents. Also provided herein are compositions comprising the ACVR2A and / or the ACVR2B RNAi agents conjugated to human transferrin receptor (TfR) binding proteins via a linker or a direct bond. Also provided herein are methods of using ACVR2A RNAi agent(s) in separate, simultaneous, or sequential combination with ACVR2B RNAi agent(s) for treating metabolic disorders, including for example, obesity, overweight, Type 2 diabetes mellitus (T2DM), and metabolic associated steatohepatitis (MASH) in a patient

The present invention relates to the treatment of physiologic iron overload and provides antibodies against the proteolysis 2 (MTP-2). Inhibition of MTP-2 reduces dietary iron uptake and reduces iron release from cellular stores in the body. Inhibitors of MTP-2, such as antibodies against the serine protease domain, are useful in the treatment of iron overload, which is characteristic of diseases such as beta-thalassemia and which would otherwise lead to toxic accumulation of iron. Combinations of MTP-2 inhibitors with activin receptor ligand traps or with erythropoietin provide additional therapeutic effects.

The present invention relates to activin receptor IIA type variants and methods of use thereof. The present invention features a polypeptide comprising an extracellular ActRIIA variant. In some embodiments, the polypeptides of the invention comprise extracellular ActRIIA variants fused to an Fc domain monomer or part. The invention also features the treatment of diseases or conditions involving low red blood cell levels (e.g., anemia or blood loss; performing fibration; or pulmonary hypertension) pharmaceutical compositions and methods.

The invention features methods for the treatment of a cardiovascular disease using a polypeptide containing an extracellular ActRII variant, such as an ActRIIA variant, ActRIIB variant, or ActRII chimera. The polypeptide may include an extracellular ActRII variant fused to an Fc domain monomer. Treatment of a cardiovascular disease with a polypeptide described herein may reduce fibrosis, reduce inflammation, reduce cardiac remodeling, improve cardiac function, improve ventricular function, or slow or inhibit disease progression, which may reduce or delay the need for coronary revascularization, heart valve repair or replacement, implantation of a cardioverter-defibrillator, cardiac resynchronization therapy, a ventricular assist device, or a heart transplant.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of an Activin Receptor-Like Kinase 7 (ALK7) gene. The ALK7 RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of an ALK7 gene. Pharmaceutical compositions that include one or more ALK7 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described ALK7 RNAi agents to adipose tissue, in vivo, provides for inhibition of ALK7 gene expression and a reduction in ALK7 activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including obesity, diabetes, or insulin resistance. 

This disclosure provides a method for preparing a compound represented by formula (I). The method comprises reacting a first starting material represented by formula (II) and a second starting material represented by formula (III) in a reaction mixture under Negishi conditions to form a compound of formula (I). R is an amine protecting group; Y is Cl, Br, or I; and Z is a trifluoromethanesulfonate, Cl, Br, or I.

In certain aspects, the present disclosure provides stable liquid pharmaceutical formulations comprising a recombinant fusion protein and one or more pharmaceutical additives and / or excipients, the recombinant fusion protein comprises an extracellular domain (ECD) of a human activin receptor type IIA (ActRIIA) protein or a variant thereof linked to a constant domain of an immunoglobulin, such as a human IgG1 Fc domain.

The present invention relates to novel 2-(3-pyridin-2-yl-4-quinolin-4-yl-pyrazol-1-yl)-acetamide derivatives as potent inhibitors of transforming growth factor-β receptor I, (also named activin receptor-like kinase 5) (TGFβRI) / ALK5. Other objectives of the present invention are to provide a procedure for preparing these compounds; pharmaceutical compositions comprising an effective amount of these compounds; the use of the compounds for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by inhibition of transforming growth factor-β receptor I (TGFβRI) / ALK5, such as respiratory diseases including idiopathic pulmonary fibrosis, asthma, COPD and lung cancer, and dermal and ocular fibrotic conditions.

Provided herein are antibodies and / or antigen-binding fragments thereof that bind to ActRIIA and / or ActRIIB, and methods of using the same.

Antibodies against the protease 2 (MTP-2) are provided. Inhibition of MTP-2 reduces dietary iron uptake and reduces release of iron from cellular stores in the body. Inhibitors of MTP-2, such as antibodies against the serine protease domain, are useful in the treatment of iron overload, which is characteristic of diseases such as beta-thalassemia and would otherwise result in toxic accumulation of iron. Combinations of MTP-2 inhibitors with activin receptor ligand traps or with erythropoietin provide additional therapeutic effects.

To provide polypeptides that include an extracellular ActRII chimera.SOLUTION: Provided is a polypeptide of the present invention including an extracellular ActRII chimera fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), low platelet levels (e.g., thrombocytopenia), low neutrophil levels (e.g., neutropenia), fibrosis, metabolic disorders, and / or pulmonary hypertension.SELECTED DRAWING: None