Claims for Patent: 8,076,290

Summary for Patent: 8,076,290

Title:	Stabilizing alkylglycoside compositions and methods thereof
Abstract:	The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of a peptide, polypeptide, or variant thereof, for example insulin and Peptide T or analog thereof.
Inventor(s):	Maggio; Edward T. (San Diego, CA)
Assignee:	Aegis Therapeutics, Inc. (San Diego, CA)
Application Number:	11/937,966
Patent Claims:	1. A method for increasing the stability of parathyroid hormone (PTH), fragment PTH 1-34, or fragment PTH 3-34 comprising: admixing the parathyroid hormone, fragment PTH 1-34, or fragment PTH 3-34 and a stabilizing agent to form a composition, wherein the stabilizing agent is at least one alkylglycoside surfactant selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate and sucrose mono-tetradecanoate, thereby increasing the stability of the parathyroid hormone, fragment PTH 1-34, or fragment PTH 3-34. 2. The method of claim 1, wherein the composition further comprises a mucosal delivery-enhancing agent selected from the group consisting of an aggregation inhibitory agent, a charge-modifying agent, a pH control agent, a degradative enzyme inhibitory agent, a mucolytic or mucus clearing agent, a chitosan, and a ciliostatic agent. 3. The method of claim 2, wherein the composition further comprises benzalkonium chloride or chloroethanol. 4. The method of claim 1, wherein the composition further comprises a membrane penetration-enhancing agent selected from the group consisting of a surfactant, a bile salt, a phospholipid additive, a mixed micelle, a liposome, a carrier, an alcohol, an enamine, a nitric oxide donor compound, a long-chain amphipathic molecule, a small hydrophobic penetration enhancer, a sodium or a salicylic acid derivative, a glycerol ester of acetoacetic acid, a cyclodextrin or beta-cyclodextrin derivative, a medium-chain fatty acid, a chelating agent, an amino acid or salt thereof, an N-acetylamino acid or salt thereof, an enzyme degradative to a selected membrane component and any combination thereof. 5. The method of claim 1, wherein the composition further comprises a modulatory agent of epithelial junction physiology. 6. The method of claim 1, wherein the method further comprises lyophilizing the composition. 7. The method of claim 6, wherein the composition retains greater than 50% biological activity upon reconstitution. 8. The method of claim 1, wherein the composition is stable for at least one month when stored at temperatures from about 25 to 37 degrees Celsius. 9. The method of claim 1, wherein the composition is stable for at least one year when stored at about 4 degrees Celsius. 10. The method of claim 1, wherein the stability of the composition is determined by determining the bioactivity of the parathyroid hormone (PTH), fragment PTH 1-34, or fragment PTH 3-34 in an in vivo or in vitro assay. 11. The method of claim 1, wherein the composition further comprises a bulking agent selected from the group consisting of albumin, collagen, alginate, and mannitol. 12. The method of claim 6, wherein the composition is reconstituted. 13. A method for reducing aggregation of a parathyroid hormone (PTH), fragment PTH 1-34, or fragment PTH 3-34 comprising: admixing the parathyroid hormone (PTH), fragment PTH 1-34, or fragment PTH 3-34 and an aggregation reducing agent, wherein the aggregation reducing agent is at least one alkylglycoside surfactant selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate and sucrose mono-tetradecanoate, thereby reducing aggregation of the parathyroid hormone (PTH), fragment PTH 1-34, or fragment PTH 3-34. 14. A method for reducing immunogenicity of a parathyroid hormone (PTH), or fragment PTH 1-34, or fragment PTH 3-34 upon administration to a vertebrate, comprising: a) admixing a parathyroid hormone (PTH), or fragment PTH 1-34, or fragment PTH 3-34 and an immunogenicity reducing agent to form a composition, wherein the immunogenicity reducing agent is at least one alkylglycoside surfactant selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate and sucrose mono-tetradecanoate; and b) administering the composition to a vertebrate thereby reducing immunogenicity upon administration of the parathyroid hormone (PTH), or fragment PTH 1-34, or fragment PTH 3-34. 15. A method of manufacturing a non-aggregated aqueous solution of a parathyroid hormone (PTH), or fragment PTH 1-34, or fragment PTH 3-34 comprising: admixing the parathyroid hormone (PTH), or fragment PTH 1-34, or fragment PTH 3-34 and at least one alkylglycoside surfactant to form an aqueous solution, wherein the surfactant is selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate and sucrose mono-tetradecanoate, thereby manufacturing the non-aggregated aqueous solution.

Details for Patent 8,076,290

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2026-06-23