Claims for Patent: 8,435,505

Summary for Patent: 8,435,505

Title:	Pharmaceutical compositions and methods for delivering such compositions
Abstract:	The present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a conjugate having a degradable linkage. The conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods for delivering such compositions are also provided.
Inventor(s):	Bentley; Michael D. (Huntsville, AL), Culbertson; Sean M. (Gurley, AL), McManus; Samuel P. (Huntsville, AL)
Assignee:	Nektar Therapeutics (San Francisco, CA)
Application Number:	13/525,068
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,435,505
Patent Claims:	1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a conjugate of the following formula: ##STR00126## wherein: POLY.sup.1 is a first water-soluble polymer; POLY.sup.2 is a second water-soluble polymer; X.sup.1 is a first spacer moiety; X.sup.2 is a second spacer moiety; H.sub..alpha. is an ionizable hydrogen atom; R.sup.1 is H or an organic radical; R.sup.2 is H or an organic radical; and Y.sup.1 is O or S; Y.sup.2 is O or S; and D is a residue of a biologically active agent. 2. The pharmaceutical composition of claim 1, wherein each of POLY.sub.1 and POLY.sup.2 is a poly(ethylene glycol). 3. The pharmaceutical composition of claim 2, wherein each poly(ethylene glycol) has a weight-average molecular weight in the range of from about 120 Daltons to about 6,000 Daltons. 4. The pharmaceutical composition of claim 2, wherein each poly(ethylene glycol) has a weight-average molecular weight in the range of from about 6,000 Daltons to about 100,000 Daltons. 5. The pharmaceutical composition of claim 1 wherein the first spacer moiety is selected from the group consisting of --C(O)--NH--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--, --NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --NH--C(O)--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --C(O)--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --NH--CH.sub.2--CH.sub.2--(OCH.sub.2CH.sub.2).sub.1-3--NH--C(O)--, --C(O)--NH--(CH.sub.2CH.sub.2O).sub.1-3--CH.sub.2--CH.sub.2--NH--, --C(O)--NH--CH.sub.2--CH.sub.2--(OCH.sub.2CH.sub.2).sub.1-3--NH--C(O)--, --C(O)--NH--(CH.sub.2CH.sub.2O).sub.1-3--CH.sub.2--CH.sub.2--NH--C(O)--, --NH--C(O)--CH.sub.2--, --CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--O--, --O--CH.sub.2--C(O)--NH--, --CH.sub.2--CH.sub.2--NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--CH.sub.2--CH.sub.2--, --O--CH.sub.2--CH.sub.2--NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH- --, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--CH.sub.2--CH.sub.2- --O--, --C(O)--NH--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--O--, and --O--CH.sub.2--CH.sub.2--NH--C(O)--, and the second spacer moiety is selected from the group consisting of --C(O)--NH--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--, --NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--NH--C(O)--, --NH--C(O)--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --C(O)--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --C(O)--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--, --NH--CH.sub.2--CH.sub.2--(OCH.sub.2CH.sub.2).sub.1-3--NH--C(O)--, --C(O)--NH--(CH.sub.2CH.sub.2O).sub.1-3--CH.sub.2--CH.sub.2--NH--, --C(O)--NH--CH.sub.2--CH.sub.2--(OCH.sub.2CH.sub.2).sub.1-3--NH--C(O)--, --C(O)--NH--(CH.sub.2CH.sub.2O).sub.1-3--CH.sub.2--CH.sub.2--NH--C(O)--, --NH--C(O)--CH.sub.2--, --CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--O--, --O--CH.sub.2--C(O)--NH--, --CH.sub.2--CH.sub.2--NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--CH.sub.2--CH.sub.2--, --O--CH.sub.2--CH.sub.2--NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH- --, --NH--C(O)--CH.sub.2--CH.sub.2--CH.sub.2--C(O)--NH--CH.sub.2--CH.sub.2- --O--, --C(O)--NH--CH.sub.2--CH.sub.2--, --CH.sub.2--CH.sub.2--NH--C(O)--, --C(O)--NH--CH.sub.2--CH.sub.2--O--, and --O--CH.sub.2--CH.sub.2--NH--C(O)--. 6. The pharmaceutical composition of claim 1, wherein R.sup.1 is H and R.sup.2 is H. 7. The pharmaceutical composition of claim 1, wherein Y.sup.1 is O and Y.sup.2 is O. 8. The pharmaceutical composition of claim 1, wherein the biologically active agent is a polypeptide. 9. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00127## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 10. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00128## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 11. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00129## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 12. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00130## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 13. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00131## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 14. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00132## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 15. The pharmaceutical composition of claim 1, wherein the conjugate corresponds to the following formula: ##STR00133## wherein each (n) is from 4 to 1500 and D is a residue of a biologically active agent. 16. The pharmaceutical composition of claim 1, in lyophilized form. 17. The pharmaceutical composition of claim 1, further comprising a liquid diluent. 18. The pharmaceutical composition of claim 17, wherein the liquid diluent is selected from the group consisting of bacteriostatic water for injection, dextrose 5% in water, phosphate-buffered saline, Ringer's solution, saline solution, sterile water, deionized water, and combinations thereof. 19. The pharmaceutical composition of claim 1, in unit dosage form. 20. The pharmaceutical composition of claim 19, housed in a glass vial. 21. A method of delivering a conjugate comprising the step of administering to a patient a therapeutically effective amount of a conjugate according to claim 1.

Details for Patent 8,435,505

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		2025-06-16