Claims for Patent: 9,919,033

Summary for Patent: 9,919,033

Title:	Dry growth hormone composition transiently linked to a polymer carrier
Abstract:	The present invention relates to dry compositions of rhGH polymer prodrug containing a lyoprotectant and, optionally, one or more than one excipient. Such compositions are stable for at least 1 year, when stored at 2-8.degree. C. The invention further relates to methods of manufacturing said compositions, containers comprising such composition as well as a kit of parts.
Inventor(s):	Rasmussen; Grethe Norskov (Farum, DK), Kindermann; Susanne (Liestal, CH), Rau; Harald (Dossenheim, DE), Wegge; Thomas (Heidelberg, DE)
Assignee:	Ascendis Pharma Endocrinology Division A/S (Hellerup, DK)
Application Number:	15/340,595
Patent Claims:	1. A pen injector comprising: a cartridge comprising: a dry composition comprising: a therapeutically effective amount of a recombinant human growth hormone ("rhGH") polymer prodrug; and a lyoprotectant; wherein the rhGH is transiently linked via a reversible linker moiety to a polymer carrier, and wherein the composition is stable for at least 6 months when stored at temperatures ranging from 2 to 25.degree. C., where during such storage less than 5% of the rhGH is released from the rhGH polymer prodrug as free rhGH. 2. The pen injector according to claim 1; wherein the cartridge further comprises: a first chamber; and a second chamber. 3. The pen injector according to claim 1; wherein the cartridge is a disposable cartridge. 4. The pen injector according to claim 1; wherein the composition was dried by lyophilization. 5. The pen injector according to claim 1; wherein the dry composition is stable for at least 1 year when stored at 2-25.degree. C. 6. The pen injector according to claim 1; wherein the lyoprotectant comprises trehalose. 7. The pen injector according to claim 1; wherein the composition is provided as a single dose composition. 8. The pen injector according to claim 1; wherein the composition is provided as a multiple dose composition. 9. The pen injector according to claim 1; wherein the rhGH polymer prodrug has the chemical structure shown in (A): ##STR00040## wherein --NH-rhGH represents the rhGH residue attached to the reversible linker moiety; 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. 10. The pen injector according to claim 9; wherein the moiety PEG-X of formula (A) has the following structure: ##STR00041## wherein each c is independently an integer from 250 to 750. 11. The pen injector according to claim 1; wherein the composition further comprises at least one additional biologically active agent, either in its free form or as a prodrug, selected from the group consisting of: IGF-1, ghrelin, ghrelin-like compounds, gonadotropin releasing hormone agonists, gonadotropin releasing hormone analogs, growth hormone releasing factor, growth hormone releasing factor analogs, gonadal steroids, antiandrogens, non-steroidal aromatase inhibitors, HIV combination therapy, free fatty acid regulators, anabolic steroids, estrogen agonists, estrogen antagonists, propranolol, appetite suppressants, osteroporosis drugs, and anti-diabetic drugs. 12. The pen injector according to claim 1; wherein the rhGH polymer is sufficiently dosed in the composition to provide a therapeutically effective amount of human growth hormone ("hGH") for at least three days in on application. 13. The pen injector according to claim 12; wherein one application of the rhGH polymer prodrug is sufficient for one week. 14. The pen injector according to claim 1; wherein the composition further comprises an excipient. 15. The pen injector according to claim 1; wherein the composition comprises: rhGH polymer prodrug in an amount of 1.1-92.1% (w/w); succinic acid in an amount of 0.1-14.4% (w/w); trehalose, optionally as dehydrate, in an amount of 7.3-98.7% (w/w); and tris in an amount of 0.01-25.4% (w/w). 16. The pen injector according to claim 1; wherein the composition comprises: rhGH polymer prodrug in an amount of 7.8-85.5% (w/w); succinic acid in an amount of 0.1-8.9% (w/w); trehalose, optionally as dehydrate, in an amount of 13.6-90.3% (w/w); and tris in an amount of 0.03-15.7% (w/w). 17. The pen injector according to claim 1; wherein the composition comprises: rhGH polymer prodrug in an amount of 25.3-46.5% (w/w); succinic acid in an amount of 0.8-1.2% (w/w); trehalose, optionally as dehydrate, in an amount of 52.4-72.8% (w/w); and tris in an amount of 0.4-2.3% (w/w). 18. The pen injector according to claim 2; wherein the dry composition is arranged in the first chamber, and wherein a reconstitution solution is arranged in the second chamber. 19. The pen injector according to claim 18; wherein the reconstitution solution comprises: sterile water, and 0.7-1.1% (w/w) benzylalcohol. 20. The pen injector according to claim 18; wherein the reconstitution solution comprises 0.2-0.4% (w/w) cresol.

Details for Patent 9,919,033

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2029-12-15