Last Updated: June 18, 2026

Claims for Patent: 11,389,510

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Summary for Patent: 11,389,510

Title:	Controlled-release CNP agonists with low initial NPR-B activity
Abstract:	The present invention relates to a controlled-release CNP agonist from which CNP agonist is released with a release half-life of at least 6 hours under physiological conditions and which controlled-release CNP agonist has an EC50 that is at least 20-fold higher than the EC50 of the corresponding free CNP agonist and which released CNP agonist has an EC50 that is at most 3-fold higher than the EC50 of the corresponding free CNP agonist; to pharmaceutical compositions comprising said controlled-release CNP agonist; their use; and to methods of treatment.
Inventor(s):	Kennett Sprogøe, Harald Rau, Felix Cleemann, Ulrich Hersel, Caroline Elisabeth Rasmussen
Assignee:	Ascendis Pharma Endocrinology Division AS
Application Number:	US16/066,058
Patent Claims:	1. A controlled-release CNP agonist comprising a CNP moiety comprising a ring moiety (−D), wherein the ring moiety has the amino acid sequence of SEQ ID NO:96, the ring moiety being between two cysteine residues forming a disulfide bridge, and being conjugated to a polymer via a linker cleavable in aqueous buffer at pH 7.4 and 37° C. in the absence of enzymes with a half-life of up to six months, wherein the polymer is water-soluble and conjugated via the linker to an amino group side chain of a lysine of SEQ ID NO:96 or the polymer is water-insoluble, wherein D-H is released from the controlled-release CNP agonist by cleavage of the linker with a release half-life of at least 6 hours in aqueous buffer at pH 7.4 and 37° C. in the absence of enzymes and which controlled-release CNP agonist has an EC50 that is at least 20-fold higher than the EC50 of the D-H. 2. The controlled-release CNP agonist of claim 1, wherein the controlled-release CNP agonist has an EC50 that is at least 50-fold higher than the EC50 D-H. 3. The controlled-release CNP agonist of claim 1, wherein the controlled-release CNP agonist has an EC50 that is at least 100-fold higher than the EC50 D-H. 4. The controlled-release CNP agonist of claim 1, wherein the release half-life is at least 24 hours. 5. The controlled-release CNP agonist of claim 1, wherein the release half-life is at least 168 hours. 6. A pharmaceutical composition comprising the controlled-release CNP agonist of claim 1 and at least one excipient.

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