Claims for Patent: 8,226,949

Summary for Patent: 8,226,949

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 parathyroid hormone (PTH) or PTH analogs, amylin, a monoclonal antibody, insulin, Peptide T or analog thereof, gastrin, gastrin releasing peptides, gastrin releasing peptide-like (GRP) proteins, epidermal growth factor or analog thereof.
Inventor(s):	Maggio; Edward T. (San Diego, CA)
Assignee:	Aegis Therapeutics LLC (San Diego, CA)
Application Number:	12/618,558
Patent Claims:	1. A pharmaceutical composition for increasing the stability, reducing aggregation or reducing immunogenicity of a monoclonal antibody comprising: a monoclonal antibody; and a stabilizing agent comprising at least one alkylglycoside. 2. The composition of claim 1, wherein the monoclonal antibody is selected from the group consisting of abagovomab, afelimomab, anatumomab mafenatox, arcitumomab, bectumomab, besilesomab, capromab, edobacomab, edrecolomab, elsilimomab, enlimomab, enlimomab pegol, epitumomab cituxetan, ibritumomab tiuxetan, imciromab, inolimomab, mitumomab, oregovmab, satumomab, sulesomab, technetium (.sup.99mTc) nofetumomab merpentan, tositurnomab, vepalimomab, zolimomab aritox, adalimumab, adecatumumab, belimumab, bertilimumab, denosumab, efungumab, golimumab, ipilimumab, iratumumab, lerdelimumab, lexatumumab, mapatumumab, metelimumab, ofatumumab, panitumumab, pritumumab, raxibacumab, sevirumab, stamulumab, ticilimumab, tuvirumab, votumumab, zalutumumab, zanolimumab, abciximab, basiliximab, bavituximab, cetuximab, ecromeximab, galiximab, infliximab, keliximab, lumiliximab, pagibaximab, priliximab, rituximab, teneliximab, volociximab, alemtuzumab, apolizumab, aselizumab, bapineuzumab, bevacizumab, bivatuzumab, cantuzumab mertansine, certolizumab pegol, daclizumab, eculizumab, efalizurnab, epratuzumab), fontolizumab, gemtuzumab, inotuzumab ozogamicin, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, natalizumab, nimotuzumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pertuzumab, pexelizumab, ranibizumab, reslizumab, rovelizumab, ruplizumab, sibrotuzumab, siplizumab, sontuzumab, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, trastuzumab, tucotuzumab celmoleukin, urtoxazumab, visilizumab, yttrium .sup.90Y tacatuzumab tetraxetan, and IgG. 3. The composition of claim 2, wherein the monoclonal antibody is IgG. 4. The composition of claim 1, further comprising a buffering agent. 5. The composition of claim 1, wherein the alkylglycoside has an alkyl chain and wherein the alkyl chain has between about 10 to 16 carbon atoms. 6. The composition of claim 1, wherein the alkylglycoside is selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate, and sucrose mono-tetradecanoate. 7. The composition of claim 1, wherein the alkylglycoside has a critical micelle concentration (CMC) of less than about 1 mM. 8. The composition of claim 7, wherein the alkylglycoside has a CMC of less than about 0.5 mM. 9. The composition of claim 1, further comprising 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. 10. The composition of claim 9, wherein the mucosal delivery-enhancing agent is a chitosan. 11. The composition of claim 9, wherein the mucosal delivery-enhancing agent is a ciliostatic agent. 12. The composition of claim 1, further comprising benzalkonium chloride or chloroethanol. 13. The composition of claim 1, further comprising 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. 14. The composition of claim 1, further comprising a modulatory agent of epithelial junction physiology. 15. The composition of claim 1, further comprising a vasodilator agent. 16. The composition of claim 1, further comprising a selective transport-enhancing agent. 17. The composition of claim 1, wherein the composition is in a lyophilized form. 18. The composition of claim 17, wherein the lyophilized composition retains greater than 50% biological activity upon reconstitution. 19. The composition of claim 1, wherein the composition is stable to denaturation as determined by lack of increased light scatter for at least one week upon agitation at 150 RPM at temperatures from about 25 to 37 degrees Celsius. 20. The composition of claim 19, wherein the composition is stable to denaturation as determined by lack of increased light scatter for at least two weeks upon agitation at 150 RPM at temperatures from about 25 to 37 degrees Celsius. 21. The composition of claim 1, wherein the composition is stable to denaturation as determined by lack of increased light scatter for at least one year when stored at about 4 degrees Celsius. 22. The composition of claim 1, wherein the stability of the composition is determined by determining the bioactivity of the monoclonal antibody in an in vivo or in vitro assay. 23. The composition of claim 18, wherein the lyophilized composition further comprises a bulking agent selected from the group consisting of albumin, collagen, alginate, and mannitol. 24. The composition of claim 17, wherein the lyophilized composition is reconstituted prior to administering to a mammalian subject. 25. The composition of claim 1, wherein the composition is formulated for parenteral, intransal, pulmonary, or buccal delivery. 26. A method for increasing the stability of a monoclonal antibody comprising: admixing the monoclonal antibody, a stabilizing agent and a buffering agent to form a composition, wherein the stabilizing agent is at least one alkylglycoside surfactant, thereby increasing the stability of the monoclonal antibody. 27. The method of claim 26, wherein the monoclonal antibody is selected from the group consisting of: abagovomab, afelimomab, anatumomab mafenatox, arcitumomab, bectumomab, besilesomab, capromab, edobacomab, edrecolomab, elsilimomab, enlimomab, enlimomab pegol, epitumomab cituxetan, ibritumomab tiuxetan, imciromab, inolimomab, mitumomab, oregovomab, satumomab, sulesomab, technetium (.sup.99mTc) nofetumomab merpentan, tositumomab, vepalimomab, zolimomab aritox, adalimumab, adecatumumab, belimumab, bertilimumab, denosumab, efungumab, golimumab, ipilimumab, iratumumab, lerdelimumab, lexatumumab, mapatumumab, metelimumab, ofatumumab, panitumumab, pritumumab, raxibacumab, sevirumab, stamulumab, ticilimumab, tuvirumab, votumumab, zalutumumab, zanolimumab, abciximab, basiliximab, bavituximab, cetuximaba ecromeximab, galiximab, infliximab, keliximab, lumiliximab, pagibaximab, priliximab, rituximab, teneliximab, volociximab, alemtuzumab, apolizumab, aselizumab, bapineuzumab, bevacizumab, bivatuzumab, cantuzumab mertansine, certolizumab pegol, daclizumab, eculizumab, efalizumab, epratuzumab), fontolizumab, gemtuzumab, inotuzumab ozogamicin, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, natalizumab, nimotuzumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pertuzumab, pexelizumab, ranibizumab, reslizumab, rovelizumab, ruplizumab, sibrotuzumab, siplizumab, sontuzumab, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, trastuzumab, tucotuzumab celmoleukin, urtoxazumab, visilizumab , yttrium .sup.90Y tacatuzumab tetraxetan, IgG-1, IgG-2, IgG-3, and IgG-4. 28. The method of claim 27, wherein monoclonal antibody is IgG-3. 29. The method of claim 26, wherein the alkylglycoside is selected from the group consisting of dodecyl maltoside, tridecyl maltoside, tetradecyl maltoside, sucrose mono-dodecanoate, sucrose mono-tridecanoate and sucrose mono-tetradecanoate. 30. The method of claim 26, wherein the alkylglycoside has a critical micelle concentration (CMC) of less than about 1 mM. 31. The method of claim 30, wherein the alkylglycoside has a CMC of less than about 0.5 mM. 32. The method of claim 26, 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. 33. The method of claim 32, wherein the mucosal delivery-enhancing agent is a chitosan. 34. The method of claim 32, wherein the mucosal delivery-enhancing agent is a ciliostatic agent. 35. The method of claim 26, wherein the composition further comprises benzalkonium chloride or chloroethanol. 36. The method of claim 26, 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. 37. The method of claim 26, wherein the composition further comprises a modulatory agent of epithelial junction physiology. 38. The method of claim 26, wherein the composition further comprises a vasodilator agent. 39. The method of claim 26, wherein the composition further comprises a selective transport-enhancing agent. 40. The method of claim 26, wherein the composition is in a lyophilized form. 41. The method of claim 40, wherein the composition retains greater than 50% biological activity upon reconstitution. 42. The method of claim 26, wherein the composition is stable to denaturation as determined by lack of increased light scatter for least one week when stored at temperatures from about 25 to 37 degrees Celsius. 43. The method of claim 42, wherein the composition is stable to denaturation as determined by lack of increased light scatter for at least two weeks when stored at temperatures from about 25 to 37 degrees Celsius. 44. The method of claim 26, wherein the composition is stable to denaturation as determined by lack of increased light scatter for at least one year when stored at about 4 degrees Celsius. 45. The method of claim 26, wherein the stability of the composition is determined by determining the bioactivity of the monoclonal antibody in an in vivo or in vitro assay. 46. The method of claim 26, wherein the composition further comprises a bulking agent selected from the group consisting of albumin, collagen, alginate, and mannitol. 47. The method of claim 40, wherein the composition is reconstituted prior to administering to a mammalian subject. 48. The method of claim 26, wherein the stability of the composition is determined by light scatter.

Details for Patent 8,226,949

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2026-06-23
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2026-06-23
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