The present disclosure relates to a novel isolated binding protein including a N-terminal pro-brain natriuretic peptide (NT-proBNP) antigen binding domain, and the preparation method therefor. The antigen-binding domain includes at least one complementarity determining region selected from the amino acid sequences as defined in the present disclosure: or; has at least 80% sequence identity with the complementarity determining region of the following amino acid sequence and has an affinity of KD≤2.26×10.sup.−8 to NT-proBNP. The binding protein may be used in the detection field of NT-proBNP protein.

The present invention is based upon the observation that inhibition of NPR-C Signaling pathway leads to the development of pulmonary arterial hypertension (PAH). Accordingly, the invention provides a mouse model for PAH, and proposes a method of using synthetic analogs of the NPR-C signaling pathway, specifically synthetic C-type atrial natriuretic factor or intermediates for, or modulators of, the NPR-C signaling pathway as anti-pulmonary vasculopathy agents. Activators of the NPR-C signaling pathway are disclosed to treat or prevent vasculopathy, including but not limited to PAH and other types of pulmonary hypertension, peripheral vascular disease, critical limb ischemia, coronary artery disease, and diabetic vasculopathy.

The present invention is based upon the observation that inhibition of NPR-C Signaling pathway leads to the development of pulmonary arterial hypertension (PAH). Accordingly, the invention provides a mouse model for PAH, and proposes a method of using synthetic analogs of the NPR-C signaling pathway, specifically synthetic C-type atrial natriuretic factor or intermediates for, or modulators of, the NPR-C signaling pathway as anti-pulmonary vasculopathy agents. Activators of the NPR-C signaling pathway are disclosed to treat or prevent vasculopathy, including but not limited to PAH and other types of pulmonary hypertension, peripheral vascular disease, critical limb ischemia, coronary artery disease, and diabetic vasculopathy.

This disclosure relates to anti-Natriuretic Peptide Receptor 1 (NPR1) antibodies including agonist antibodies which are able to activate the NPR1 receptor, pharmaceutical compositions comprising the same, and methods of treatment comprising the same.

The present invention relates to a CNP prodrug or a pharmaceutically acceptable salt thereof comprising a CNP moiety -D; and a carrier moiety —Z that is conjugated through a moiety -L.sup.2- to a reversible prodrug linker moiety -L.sup.1-, which reversible prodrug linker moiety -L.sup.1- is covalently and reversibly conjugated to -D; wherein -L.sup.2- is a chemical bond or a spacer; and —Z is a polymer having a molecular weight of at least 10 kDa. It further relates to pharmaceutical compositions comprising the CNP prodrug or a pharmaceutically acceptable salt thereof, their use as a medicament and to methods of treatment.

The present invention relates to a CNP prodrug or a pharmaceutically acceptable salt thereof comprising a CNP moiety -D; and a carrier moiety —Z that is conjugated through a moiety -L.sup.2- to a reversible prodrug linker moiety -L.sup.1-, which reversible prodrug linker moiety -L.sup.1- is covalently and reversibly conjugated to -D; wherein -L.sup.2- is a chemical bond or a spacer; and —Z is a polymer having a molecular weight of at least 10 kDa. It further relates to pharmaceutical compositions comprising the CNP prodrug or a pharmaceutically acceptable salt thereof, their use as a medicament and to methods of treatment.

The present disclosure, relates, in general, to hydrophobic salts of hydrophilic peptides that form low solubility materials in aqueous solutions and are capable of extended or sustained release of the peptide component when administered to a subject. Hydrophobic salts of C-type natriuretic peptides and uses thereof are also disclosed.

Disclosed are a novel N-terminal fusion partner, a fusion polypeptide including the fusion partner and a target polypeptide, and a method for producing a target polypeptide using the same. The novel fusion partner can enhance the yield of a target polypeptide (recombinant polypeptide) compared to the conventional fusion partners. Using the novel fusion partner is particularly beneficial in producing a target polypeptide having a relatively low molecular weight and an easily degradable amino terminus based on genetic recombination technologies. Further, the novel fusion polypeptide including the fusion partner can be expressed as inclusion bodies in a host cell and protected against proteases or the like in a host cell, which makes the target polypeptide produced stably. Therefore, in comparison to the conventional fusion partners, the novel fusion partner can be used to provide a method for producing a recombinant peptide with improved stability and yield.

Disclosed are a novel N-terminal fusion partner, a fusion polypeptide including the fusion partner and a target polypeptide, and a method for producing a target polypeptide using the same. The novel fusion partner can enhance the yield of a target polypeptide (recombinant polypeptide) compared to the conventional fusion partners. Using the novel fusion partner is particularly beneficial in producing a target polypeptide having a relatively low molecular weight and an easily degradable amino terminus based on genetic recombination technologies. Further, the novel fusion polypeptide including the fusion partner can be expressed as inclusion bodies in a host cell and protected against proteases or the like in a host cell, which makes the target polypeptide produced stably. Therefore, in comparison to the conventional fusion partners, the novel fusion partner can be used to provide a method for producing a recombinant peptide with improved stability and yield.

Analogues of an alternatively spliced form of atrial natriuretic peptide (MANP) that exhibit pGC-A gain of function and can be used to treat cardiorenal and metabolic disease are described herein.