Claims for Patent: 11,759,504

Summary for Patent: 11,759,504

Title:	PTH compounds with low peak-to-trough ratios
Abstract:	The present invention relates to a pharmaceutical composition comprising a PTH compound, wherein after subcutaneous administration the pharmacokinetic profile of the PTH compound exhibits a peak to trough ratio of less than 4 within one injection interval.
Inventor(s):	Kennett Sprogøe, Lars Holten-Andersen, David Brian Karpf, Felix Cleemann, Guillaume Maitro, Mathias Krusch, Thomas Wegge, Joachim Zettler
Assignee:	Ascendis Pharma Bone Diseases AS
Application Number:	US16/337,955
Patent Claims:	1. A pharmaceutical composition comprising a parathyroid hormone (PTH) compound, wherein the pharmaceutical composition is suitable for subcutaneous administration, and wherein after subcutaneous administration to a mammal the PTH compound has a pharmacokinetic profile exhibiting a peak to trough ratio of free PTH of less than 4 in plasma within one daily injection interval at steady state; wherein the PTH compound is a water-soluble controlled-release PTH compound of formula (Ia) or a pharmaceutically acceptable salt thereof wherein -D is a PTH moiety, which has the sequence of SEQ ID NO:51; -L2-L1- has the formula: wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond; and the dashed line marked with an asterisk indicates attachment to —Z; —Z comprises a polyethylene glycol polymer of about 40 kDa; x is 1; and the PTH moiety is released with a release half-life of at least 12 hours. 2. The pharmaceutical composition of claim 1, wherein the subcutaneous administration is via subcutaneous injection. 3. The pharmaceutical composition of claim 1, wherein the subcutaneous administration occurs with a pen device. 4. The pharmaceutical composition of claim 1, wherein the peak to trough ratio is less than 3. 5. The pharmaceutical composition of claim 1, wherein the administration is to a non-human primate. 6. The pharmaceutical composition of claim 5, wherein the non-human primate is a cynomolgus monkey. 7. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a pH ranging from and including pH 3 to pH 8. 8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a pH ranging from and including pH 4 to pH 5. 9. The pharmaceutical composition of claim 1, wherein the mammal is a human. 10. The pharmaceutical composition of claim 1, wherein —Z comprises a branched polyethylene glycol polymer. 11. The pharmaceutical composition of claim 1, wherein —Z has one branching point. 12. The pharmaceutical composition of claim 10, wherein -L2-L1 is attached to the N-terminal amine functional group of -D.