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.

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.

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.

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.

A method for purifying a long chain polypeptide includes: 1) purification step: connecting two chromatographic columns in series to separate a crude product, in which the particle size of a packing in an upstream chromatographic column is larger than that in a downstream chromatographic column; optionally, the method further includes step 2): using the upstream chromatographic column in step 1) for a salt conversion, loading the target peak product obtained in step 1) and rinsing with 95-85% of the A2 and 5-15% of the B for 15-30 min for a desalination, wherein A2 phase is an acetic acid aqueous solution with a volume ratio of 0.05%-0.2%; B phase is an organic phase acetonitrile, and the detection wavelength is 230 nm.

A method for purifying a long chain polypeptide includes: 1) purification step: connecting two chromatographic columns in series to separate a crude product, in which the particle size of a packing in an upstream chromatographic column is larger than that in a downstream chromatographic column; optionally, the method further includes step 2): using the upstream chromatographic column in step 1) for a salt conversion, loading the target peak product obtained in step 1) and rinsing with 95-85% of the A2 and 5-15% of the B for 15-30 min for a desalination, wherein A2 phase is an acetic acid aqueous solution with a volume ratio of 0.05%-0.2%; B phase is an organic phase acetonitrile, and the detection wavelength is 230 nm.

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.