US 12,226,457 B2
Dry growth hormone composition transiently linked to a polymer carrier
Grethe Nørskov Rasmussen, Farum (DK); Susanne Kindermann, Liestal (CH); Harald Rau, Dossenheim (DE); and Thomas Wegge, Heidelberg (DE)
Assigned to Ascendis Pharma Endocrinology Division A/S, Hellerup (DK)
Filed by Ascendis Pharma Endocrinology Division A/S, Hellerup (DK)
Filed on May 5, 2020, as Appl. No. 16/866,764.
Application 16/866,764 is a continuation of application No. 15/901,350, filed on Feb. 21, 2018, granted, now 10,682,395.
Application 15/901,350 is a continuation of application No. 15/340,595, filed on Nov. 1, 2016, granted, now 9,919,033.
Application 15/340,595 is a continuation of application No. 13/515,621, granted, now 9,511,122, issued on Dec. 6, 2016, previously published as PCT/EP2010/069710, filed on Dec. 15, 2010.
Claims priority of application No. 09179335 (EP), filed on Dec. 15, 2009.
Prior Publication US 2020/0261544 A1, Aug. 20, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 38/27 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 9/19 (2006.01); A61K 45/06 (2006.01); A61K 47/10 (2017.01); A61K 47/12 (2006.01); A61K 47/18 (2017.01); A61K 47/26 (2006.01); A61K 47/60 (2017.01); A61M 5/19 (2006.01)
CPC A61K 38/27 (2013.01) [A61K 9/0019 (2013.01); A61K 9/08 (2013.01); A61K 9/19 (2013.01); A61K 45/06 (2013.01); A61K 47/10 (2013.01); A61K 47/12 (2013.01); A61K 47/18 (2013.01); A61K 47/26 (2013.01); A61K 47/60 (2017.08); A61M 5/19 (2013.01)] 39 Claims
 
1. A dry composition comprising a therapeutically effective amount of a rhGH polymer prodrug and one or more cytoprotectants, wherein the growth hormone is transiently linked to a polymer carrier,
wherein the rhGH polymer prodrug has the chemical structure shown in (A):

OG Complex Work Unit Chemistry
wherein —HN-rhGH represents a rhGH residue attached to a transient linker; wherein R1, R2, R3, R4, and R5 are selected independently from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tertiary butyl;
wherein PEG represents a PEGylation residue attached to the transient linker; wherein n=1 or 2; and
wherein X is selected from C1 to C8 alkyl or C1 to C12 heteroalkyl,
characterized in that it contains one or more additional biologically active agents, either in its free form or as a prodrug, and wherein the one or more additional biologically active agents are selected from the group consisting of IGF-1, ghrelin or ghrelin-like compounds, gonadotropin releasing hormone agonists and/or analogs, growth hormone releasing factor and analogs, gonadal steroids, antiandrogens, non-steroidal aromatase inhibitors, HIV combination therapy, free fatty acid regulators, anabolic steroids, estrogen agonists/antagonists, propranolol, appetite suppressants osteoporosis drugs including bisphosphonates, bone formation agents, estrogens, parathyroid hormones, and selective receptor modulators, and/or anti-diabetic drugs, alpha-glucosidase inhibitors and amylin analogues.