	US 12,453,778 B2
	Incremental dose finding in controlled-release PTH compounds
David Brian Karpf, Mountain View, CA (US); Kennett Sprogøe, Holte (DK); Lars Holten-Andersen, Vanløse (DK); Felix Cleemann, Mainz (DE); Guillaume Maitro, Mannheim (DE); Mathias Krusch, Hirschhorn (DE); Thomas Wegge, Heidelberg (DE); and Joachim Zettler, Heidelberg (DE)
Assigned to ASCENDIS PHARMA BONE DISEASES A/S, Hellerup (DK)
Appl. No. 16/337,803
Filed by Ascendis Pharma Bone Diseases A/S, Hellerup (DK)
PCT Filed Sep. 28, 2017, PCT No. PCT/EP2017/074593 § 371(c)(1), (2) Date Mar. 28, 2019, PCT Pub. No. WO2018/060311, PCT Pub. Date Apr. 5, 2018.
Claims priority of application No. 16191453 (EP), filed on Sep. 29, 2016.
Prior Publication US 2019/0224329 A1, Jul. 25, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/59 (2017.01); A61K 9/00 (2006.01); A61K 38/29 (2006.01); A61K 47/10 (2017.01); A61K 47/18 (2017.01); A61K 47/22 (2006.01); A61K 47/60 (2017.01); A61P 5/18 (2006.01)

CPC A61K 47/593 (2017.08) [A61K 9/0019 (2013.01); A61K 38/29 (2013.01); A61K 47/10 (2013.01); A61K 47/18 (2013.01); A61K 47/22 (2013.01); A61K 47/60 (2017.08); A61P 5/18 (2018.01)]

8 Claims

1. A method of treating a patient having hypoparathyroidism, with parathyroid hormone (PTH), wherein the method comprises the step of administering a pharmaceutical composition comprising a controlled-release PTH compound to the patient in accordance with a dosage regimen in which dose adjustment in response to hypocalcemia or hypercalcemia is performed in increments of no more than 25%; wherein the controlled-release PTH compound is of formula (Ia) or a pharmaceutically acceptable salt thereof:

Z-(L²-L¹-D)_x (Ia);

wherein —Z comprises a branched PEG polymer with a molecular weight of about 40 kDa,

-L²-L¹- has the formula:

wherein the unmarked dashed line indicates attachment by an amide bond to a nitrogen of

-D, and the dashed line marked with an asterisk indicates attachment to —Z, wherein -D is PTH (1-34) (SEQ ID NO: 51) and x is 1.