IP Library Granted Patent US 11,655,343
Granted Patent B2
US 11,655,343 · App. 16/086,405 · Granted May 23, 2023

Alginate hydrogel compositions

Inventors: Venkata R. Garigapati (Southborough, MA); Tetsuo Hoshino (Arlington, MA); Amit Garle (Lowell, MA)
Assignee: Takeda Pharmaceutical Company Limited
C08J3/075C08B37/0084C08J3/245C08L5/04C08L71/02C12N5/0018C08J2305/04C08L2203/02C12N5/0636C12N5/0644C12N5/0662
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Quick Facts
Patent No.
US 11,655,343
App. No.
16/086,405
Granted
May 23, 2023
Kind
B2
Abstract

The present application provides a semi-permeable hydrogel composition comprising an alginate matrix that is covalently crosslinked in its periphery to a multi-armed water soluble polymer, along with related methods and uses thereof.

Claims (24)

1. A semi-permeable hydrogel composition comprising an alginate that forms an alginate matrix comprising a periphery, wherein the periphery of the alginate matrix is covalently crosslinked to a multi-armed water soluble polymer that comprises polyethylene glycol or poly(2-methacryloyloxy ethyl phosphorylcholine), wherein the multi-armed water soluble polymer forms a covalently crosslinked surface layer on the alginate matrix, and wherein the covalent crosslink of the multi-armed water soluble polymer and the alginate comprises a linkage that is a product of a first click-reactive functional group of the multi-armed water soluble polymer and a second click-reactive functional group of the alginate.

2. The semi-permeable hydrogel composition of claim 1 , wherein the hydrogel composition further comprises 1-20 surface layers of alginate that is covalently crosslinked to the multi-armed water soluble polymer.

3. The semi-permeable hydrogel composition of claim 1 , wherein the hydrogel composition further comprises a biocompatible surface layer, wherein the biocompatible surface layer is covalently bonded to the semi-permeable hydrogel composition.

4. The hydrogel composition of claim 1 , wherein the hydrogel composition is stable for at least 30 days at 40° C. in 1 mM phosphate buffered saline.

5. The hydrogel composition of claim 4 , wherein the composition is characterized by a first tan delta value determined at the time the composition is subjected to storage at 40° C. in 1 mM phosphate buffered saline (day 0), and a second tan delta value determined after the composition has been stored for 30 days at 40° C. in 1 mM phosphate buffered saline; and wherein the first tan delta value and the second tan delta value are the same or differ by no more than about 0.05.

6. The hydrogel composition of claim 4 , wherein the hydrogel maintains its semi-permeability after storage for 30 days at 40° C. in 1 mM phosphate buffered saline.

7. The semi-permeable hydrogel composition of claim 1 , wherein the composition is permeable to molecular species that have a molecular weight of up to about 100 kDa, and is impermeable to larger molecular species.

8. The hydrogel composition of claim 1 , wherein the alginate is in a matrix comprising a divalent cation selected from the group consisting of Ca 2+ , Cu 2+ , Ba 2+ , Sr 2+ , Mg 2+ , and combinations thereof.

9. The hydrogel composition of claim 1 , wherein the multi-armed water soluble polymer is a multi-armed polyethylene glycol having from 3 to 10 arms, and wherein:

i) the multi-armed water soluble polymer has a weight average molecular weight in a range from about 1,000 to about 100,000 Daltons; or

ii) the alginate has a weight average molecular weight in a range from about 10,000 to about 300,000 g/mol.

10. The hydrogel composition of claim 1 , wherein

i) about 3 mol % to about 50 mol % of the alginate comprises the second functional group; and

ii) the second functional group is selected from azide and tetrazine; the first functional group is selected from a dibenzyl cyclooctyne amine and norbornene; and the covalent crosslinks are formed by virtue of a cycloaddition reaction between the first and second functional groups.

11. The hydrogel composition of claim 1 , wherein the alginate is in a matrix further comprising within the matrix, a pharmacologically active material.

12. The hydrogel composition of claim 11 , wherein the pharmacologically active material is selected from the group consisting of proteins, polynucleotides, and small molecules.

13. The hydrogel composition of claim 1 , wherein the alginate is in a matrix further comprising living cells within the matrix, wherein:

i) the living cells are autologous cells, allogeneic cells or xenogeneic cells;

ii) the living cells are induced pluripotent stem-cell derived cells, induced pluripotent stem-cell derived pancreatic progenitor cells, platelets, T-Cells, CAR-T cells, cardiac myoblasts, genetically modified APRE-19 cells, pancreatic cells or dermal cells; or

iii) the living cells are hormone, cytokine, or growth factor secreting cells.

14. The hydrogel composition of claim 1 , in a form selected from the group consisting of a bead, capsule, sheet, membrane, thread, fiber, filament, particle, sponge, mesh, foam, scaffold and composites of any of the foregoing.

15. The semi-permeable hydrogel composition of claim 1 , wherein the multi-armed water soluble polymer comprises poly(2-methacryloyloxy ethyl phosphorylcholine).

16. The semi-permeable hydrogel composition of claim 1 , wherein the multi-armed water soluble polymer comprises a copolymer of (2-methacryloyloxyethyl phosphorylcholine) and lysine methacrylamide.

17. A semi-permeable hydrogel composition comprising an alginate that forms an alginate matrix comprising a periphery, wherein the periphery of the alginate matrix is covalently crosslinked to a multi-armed water soluble polymer that is polyethylene glycol or poly(2-methacryloyloxy ethyl phosphorylcholine), wherein the multi-armed water soluble polymer forms a covalently crosslinked surface layer on the alginate matrix, wherein the covalent crosslink of the multi-armed water soluble polymer and the alginate comprises a linkage that is a product of a first click-reactive functional group of the multi-armed water soluble polymer and a second click-reactive functional group of the alginate, wherein the hydrogel composition is stable for at least 30 days at 40° C. in 1 mM phosphate buffered saline, wherein the composition is characterized by a first tan delta value determined at the time the composition is subjected to storage at 40° C. in 1 mM phosphate buffered saline (day 0), and a second tan delta value determined after the composition has been stored for 30 days at 40° C. in 1 mM phosphate buffered saline; and wherein the first tan delta value and the second tan delta value are the same or differ by no more than about 0.05.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 30, 2021
From: MILLENNIUM PHARMACEUTICALS, INC.
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 056729/0503 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2018
From: HOSHINO, TETSUO
To: TAKEDA PHARMACEUTICAL COMPANY LIMITED
Reel/Frame 047561/0622 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2018
From: GARLE, AMIT; GARIGAPATI, VENKATA R.
To: MILLENNIUM PHARMACEUTICALS, INC.
Reel/Frame 047561/0632 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 21, 2018
From: TAKEDA PHARMACEUTICAL COMPANY LIMITED
To: MILLENNIUM PHARMACEUTICALS, INC.
Reel/Frame 047561/0642 →
Continuity (2)
Provisional Application 62312998 · Mar 24, 2016
Related Publication 20190100628A1 · Apr 4, 2019
Cited By (2)
US 12,338,330 US 12,364,791