US RE50,618 E1
Anionic-core composition for delivery of therapeutic agents, and methods of making and using the same
Gerardo M. Castillo, Bothell, WA (US); Ellijah M. Bolotin, Bothell, WA (US); and Akiko Nishimoto-Ashfield, Bothell, WA (US)
Assigned to PharmaIN Corporation, Bothell, WA (US)
Appl. No. 17/519,409
Filed by PharmaIN Corporation, Bothell, WA (US)
PCT Filed Sep. 8, 2010, PCT No. PCT/US2010/048145
§ 371(c)(1), (2), (4) Date Mar. 8, 2012,
PCT Pub. No. WO2011/031771, PCT Pub. Date Mar. 17, 2011.
Application 17/519,409 is a reissue of application No. 13/395,090, filed on Sep. 8, 2010, granted, now 10,010,613, issued on Jul. 3, 2018.
Claims priority of provisional application 61/240,857, filed on Sep. 9, 2009.
Claims priority of provisional application 61/241,004, filed on Sep. 9, 2009.
Int. Cl. A61K 47/34 (2017.01); A61K 9/14 (2006.01); A61K 47/58 (2017.01); A61K 47/61 (2017.01); A61K 47/64 (2017.01)
CPC A61K 47/34 (2013.01) [A61K 9/146 (2013.01); A61K 47/58 (2017.08); A61K 47/61 (2017.08); A61K 47/645 (2017.08)] 21 Claims
 
1. A composition comprising:
(a) a polymer consisting of
(i) a polymer backbone selected from polylysine, polyornithine, polyarginine, polyglutamate, polyaspartate, polycysteine, polyserine, polythreonine, polytyrosine, chondroitin sulfate, dermatan sulfate, keratan sulfate, carageenan, pectin, fucoidan, dextran, polymethylacrylic acid, polyacrylic acid, and polyallylamine;
(ii) multiple protective chains covalently linked to the polymer backbone, wherein each protective chain is independently selected from a group consisting of a linear poly(ethyleneglycol) and a linear methoxy poly(ethyleneglycol), and each protective chain is singly terminally covalently linked to a monomeric unit on the polymer backbone via one covalent bond;
(iii) an anionic group attached to a monomeric unit on the polymer backbone by a covalent bond, wherein the anionic group is selected from the group consisting of phosphate, sulfate, sulfonate, and carboxyl, or
an anionic cluster comprising two or more anionic groups attached to a monomeric unit on the polymer backbone by a single covalent bond, wherein the anionic groups are each selected from the group consisting of phosphate, sulfate, sulfonate, and carboxyl; and
(b) a load molecule linked directly by electrostatic interaction to the anionic group or the anionic cluster of the polymer without an intermediary metal ion, wherein the load molecule
(i) comprises a cell penetrating peptide;
(ii) comprises an anionic binding domain; or
(iii) has an isoelectric point greater than 7.3;
wherein at least 85% [ 86.4% ] of the load molecule remains linked to the anionic group or the anionic cluster in the presence of 100 mM aqueous NaCl solution.