Granted Patent B2

US 12,514,825 · App. 17/749,795 · Granted Jan 6, 2026

Inventors: Arturo J. Vegas (Belmont, MA); Minglin Ma (Ithaca, NY); Kaitlin M. Bratlie (Ames, IA); Daniel G. Anderson (Framingham, MA); Robert S. Langer (Newton, MA)

Assignees: Massachusetts Institute of Technology; The Children's Medical Center Corporation

A61K9/5036A61K9/0024A61K35/39A61K45/06C08B37/0084A61K9/5161

Abstract

Claims (24)

1 . A method of treating a disease or disorder in a human or animal patient, comprising:

implanting or transplanting into the human or animal patient a biological material encapsulated in a capsule comprising an unmodified alginate and an ionically crosslinked biocompatible modified alginate, wherein the modified alginate comprises one or more covalently modified monomers defined by Formula I

wherein,

X is sulfur, or NR;

R 1 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, C 3 -C 20 cyclic, substituted C 3 -C 20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group;

Y 1 and Y 2 independently are hydrogen or —PO(OR) 2 ; or

Y 2 is absent, and Y 2 , together with the two oxygen atoms to which Y 1 and Y 2 are attached form a cyclic structure as shown below

wherein n is an integer between 1 and 4; and

R 2 and R 3 are, independently, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20 cyclic, substituted C 3 -C 20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group; or

R 2 and R 3 , together with the carbon atom to which they are attached, form a 3- to 8-membered unsubstituted or substituted carbocyclic or heterocyclic ring; and

R is, independently for each occurrence, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, aroxy, substituted aroxy, alkylthio, substituted alkylthio, arylthio, substituted arylthio, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, amino, substituted amino, amido, substituted amido, polyaryl, substituted polyaryl, C 3 -C 20 cyclic, substituted C 3 -C 20 cyclic, heterocyclic, substituted heterocyclic, amino acid, poly(ethylene glycol), peptide, or polypeptide group,

wherein the ratio of guluronate to mannuronate (G/M) of the modified alginate is greater than about 1:1.

2 . The method of claim 1 , wherein the biological material is cells.

3 . The method of claim 2 , wherein (i) the disease or disorder is diabetes and the cells are pancreatic islet cells, or (ii) the cells are hepatocytes.

4 . The method of claim 1 , wherein the biological materials is encapsulated in a microcapsule comprising the modified alginate.

5 . The method of claim 1 , wherein the alginate induces a lower foreign body response in an assay than unmodified alginate, the assay comprising:

injecting the modified alginate into a laboratory animal; and

measuring the cathepsin activity induced by the modified alginate using fluorescent animal imaging.

6 . The method of claim 1 , wherein X is NR.

7 . The method of claim 1 , wherein the modified alginate is a singularly modified alginate polymer or a multiply modified alginate polymer.

8 . A method of treating a disease or disorder in a human or animal patient, comprising:

implanting or transplanting into the human or animal patient a biological material encapsulated in a capsule comprising an unmodified alginate and an ionically crosslinked biocompatible modified alginate, wherein the modified alginate is one of the following

9 . The method of claim 1 , wherein more than 15% of the monomers in modified alginate polymer are covalently modified monomers.

10 . The method of claim 1 , where the modified alginate can be ionically crosslinked using Ca 2+ , Ba 2+ , or Sr 2+ .

Assignments (2)

Continuity (7)

References Cited (112)