Claims for Patent: 10,500,256

Summary for Patent: 10,500,256

Title:	Polymers for delivery of therapeutic proteins
Abstract:	In some aspects, improved hydrogel copolymers (e.g., comprising itaconic acid and N-vinylpyrrolidone) are provided and may be used, e.g., for oral delivery of a therapeutic protein. In some embodiments, improved methods for loading a therapeutic protein (e.g., a high isoelectric point protein) into a hydrogel copolymer are provided, and may comprise incubating the therapeutic protein and the hydrogel in a reduced ionic strength loading solution. In some embodiments, use of the reduced ionic strength loading solution can result in hydrogel copolymer-therapeutic protein compositions that display improved pharmacokinetic attributes, e.g., improved loading and/or release of a therapeutic protein.
Inventor(s):	Koetting; Michael (Austin, TX), Peppas; Nicholas (Austin, TX)
Assignee:	BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM (Austin, TX)
Application Number:	14/870,807
Patent Claims:	1. A polymer comprising: a) a copolymer comprising itaconic acid, methacrylic acid, and/or N-vinylpyrrolidone; wherein the copolymer is at least partially crosslinked; and b) a therapeutic protein wherein the therapeutic protein has been loaded into the copolymer using a solution having an ionic strength of less than about 100 mM PBS at about pH 7.4. 2. The polymer of claim 1, wherein the therapeutic protein is a high isoelectric point protein having an isoelectric point of greater than 7. 3. The polymer of claim 2, wherein the therapeutic protein has an isoelectric point of greater than 7.4. 4. The polymer of claim 2, wherein the therapeutic protein has an isoelectric point of from 7.6 to 9.2. 5. The polymer of claim 2, wherein the therapeutic protein has an isoelectric point of from 8.2 -9.2. 6. The polymer of claim 3, wherein the therapeutic protein has an isoelectric point of greater than 8. 7. The polymer of claim 2, wherein the therapeutic protein is calcitonin, an antibody, a fusion protein, a peptide, or an enzyme. 8. The polymer of claim 7, wherein the therapeutic protein is an antibody, wherein the antibody is adalimumab, infliximab, rituximab, bevacizumab, trastuzumab, ranibizumab, cetuximab, palivizumab, alemtuzumab, ibritumomab tiuxetan, arcitumomab, muromonab, basiliximab, daclizumab or tositumomab. 9. The polymer of claim 7, wherein the therapeutic protein is calcitonin. 10. The polymer of claim 1, wherein the solution has an ionic strength of from about 15 mM PBS to 100 mM PBS at about pH 7.4. 11. The polymer of claim 1, wherein the solution has an ionic strength of less than about 15 mM PBS at about pH 7.4. 12. The polymer of claim 1, wherein one component of said copolymer is itaconic acid. 13. The polymer of claim 1, wherein one component of said copolymer is N-vinylpyrrolidone. 14. The polymer of claim 1, wherein the copolymer further comprises poly(ethylene glycol). 15. The polymer of claim 1, wherein at least about 75% of the copolymer comprises itaconic acid and/or N-vinylpyrrolidone. 16. The polymer of claim 15, wherein at least about 90% of the copolymer comprises itaconic acid and/or N-vinylpyrrolidone. 17. The polymer of claim 16, wherein at least about 95% of the copolymer comprises itaconic acid and/or N-vinylpyrrolidone. 18. The polymer of claim 17, wherein at least about 99% of the copolymer comprises itaconic acid and/or N-vinylpyrrolidone. 19. The polymer of claim 1, wherein the copolymer is poly(itaconic acid-co-N-vinylpyrrolidone), poly(itaconic acid-co-N-vinylpyrrolidone-co-methacrylic acid), poly(itaconic acid-g-poly(ethylene glycol)), poly(methacrylic acid-g-poly(ethylene glycol)), poly(methacrylic acid-co-N-vinylpyrrolidone), or poly(itaconic acid-co-N-vinylpyrrolidone-co-methyl methacrylate). 20. The polymer of claim 19, wherein the copolymer is poly(itaconic acid-co-N-vinylpyrrolidone). 21. The polymer of claim 20, wherein the ratio of itaconic acid:N-vinylpyrrolidone is from about 1:1 to about 1:9. 22. The polymer of claim 20, wherein the ratio of itaconic acid:N-vinylpyrrolidone is from about 1:1 to about 1:4. 23. The polymer of claim 21, wherein the ratio of itaconic acid:N-vinylpyrrolidone is about 1:2. 24. The polymer of claim 1, wherein the polymer is further defined as a hydrogel, wherein the hydrogel at least partially swells at a pH above about 5. 25. The polymer of claim 1, wherein the copolymer is from about 1 to about 10% crosslinked. 26. The polymer of claim 25, wherein the copolymer is crosslinked using tetra(ethylene glycol) dimethacrylate (TEGDMA), poly(ethylene glycol) dimethacrylate (PEGDMA), a peptide, or ethylene glycol dimethacrylate. 27. A method of producing a copolymer comprising a therapeutic protein, comprising: (a) admixing the copolymer and the therapeutic protein in a solution with an ionic strength of less than 100 mM PBS at about pH 7.4; and (b) allowing the copolymer and the therapeutic protein to remain in the solution for a period of time sufficient to allow for incorporation or diffusion of the therapeutic protein into the copolymer; wherein the copolymer comprises itaconic acid, methacrylic acid, and/or N-vinylpyrrolidone; and wherein the copolymer is at least partially crosslinked; thereby producing the polymer of claim 1. 28. The polymer of claim 11, solution having an ionic strength of less than 2 mM PBS at pH 7.4. 29. The polymer of claim 1 wherein the solution has an ionic strength of less than 60 mM PBS at about pH 7.4. 30. The polymer of claim 29, wherein the solution has an ionic strength of less than 40 mM PBS at about pH 7.4. 31. The polymer of claim 30, wherein the solution has an ionic strength of less than 30 mM PBS at about pH 7.4. 32. The polymer of claim 31, wherein the solution has an ionic strength of less than 20 mM PBS at about pH 7.4.

Details for Patent 10,500,256

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2034-09-30
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2034-09-30
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	05/12/1998		2034-09-30
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	01/02/2003		2034-09-30
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	For Injection	103770	06/19/1998		2034-09-30