The present invention provides anti-Activin A antibodies, and antigen-binding fragments thereof, as well as methods of use of such antibodies, or antigen-binding fragments thereof, for treating a subject having pulmonary arterial hypertension (PAH).

Provided in the present disclosure are a bifunctional protein which can bind to PD-1 (programmed death receptor-1) and TGF-β (transforming growth factor-β), the medical use of the bifunctional protein, and a preparation method therefor.

A fusion protein including a GDF15 variant having increased physiological activity and in vivo stability, and a pharmaceutical composition containing the same are disclosed. The GDF15 variant or long-acting GDF15 fusion protein is superior to conventional GDF15 variants in terms of in vitro efficacy, binding affinity for GDF15 receptors, and body weight loss effect. Therefore, a pharmaceutical composition containing, as an active ingredient, the GDF15 variant, the long-acting GDF15 fusion protein, or a dimer of the fusion protein, causes appetite suppression, and thus can be effectively used as a therapeutic agent for metabolic diseases or obesity. Furthermore, the pharmaceutical composition can be used in combination therapy or the like with chemical drugs and other therapeutic agents for metabolic diseases, and can be effectively used in combination therapy with conventional therapeutic agents for metabolic diseases or obesity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

Methods are provided for treating osteoarthritis by administering αKlotho protein and sTGFβ-R2 protein to a site within a mammal exhibiting symptoms of osteoarthritis, such as a knee joint. The αKlotho protein and the sTGFβ-R2 protein are both present at the osteoarthritic site.

An agent capable of promoting proliferation and differentiation of granulosa cells is disclosed which comprises a growth and differentiation factor-9 (GDF9) protein comprising a modified GDF9 polypeptide monomer which includes at least one amino acid substitution that enhances binding to and/or activation of activin-like kinase 4 and/or 5 receptor (ALK4/5). The agent is preferably provided in a mature dimeric form (eg comprising two monomers of the same modified GDF9 polypeptide monomer) and/or in a pro/mature complex form. The agent may be suitable for, inter alia, promoting oocyte maturation in vitro for use in assisted reproductive technologies.

The current invention provides a method of activating fibroblast and myofibroblast apoptosis in a tissue of a mammal, comprising administering to the tissue a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGFB1 protein in a mammalian cell, an siRNA molecule that binds to an mRNA that codes for COX-2 protein in a mammalian cell, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable histidine-lysine polymer. The invention also provides additional methods for using this composition.

The disclosure describes global transcriptome profiling in human vascular endothelial cells upon THSD1 knockdown and identification from these studies of specific genes and pathways that are THSD1. The analysis highlights a role for THSD1 in regulating endothelial to mesenchymal transition and other pathways. The analysis also demonstrates that endothelial cell injury is the first event of an intracranial aneurysm. The disclosure provides novel cell lines and reagents used for better understanding the molecular mechanism of THSD1 biology.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.