Eluting matrix and uses thereof

Patent metadata

Field	Value
Publication number	US-9849094-B2
Application number	US-201615179567-A
Country	US
Kind code	B2
Filing date	Jun 10, 2016
Priority date	Nov 7, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

CXCL12 polypeptide eluting matrices encapsulating at least one cell are described for use in the treatment of autoimmune disorders.

First claim

We claim:

1. A composition comprising at least one cell encapsulated in a CXCL12 polypeptide eluting alginate matrix, wherein the matrix is comprised of alginate polymers having an average molecular weight of about 75 kDa to about 200 kDa;
comprises a guluronic acid to mannuronic acid ratio of no more than about 1.5;
has an average pore size that excludes molecules that are greater than about 130 KD;
forms a capsule having a thickness of about 200-about 500 microns; and
is characterized by a release of the CXCL12 polypeptide at a rate of at least about 1.0 ng/mL/hr.

2. The composition of claim 1 , wherein the CXCL12 polypeptide is released at a rate of about 1.0 ng/mL/hr to about 3 ng/mL/hr.

3. The composition of claim 1 , wherein, the CXCL12 polypeptide is present in the matrix at a concentration of about 100 ng/mL.

4. The composition of claim 1 , wherein the CXLC12 polypeptide is released at a rate of about 1.75 ng/ml/hr.

5. The composition of claim 1 , wherein the concentration of CXCL12 polypeptide within the matrix is maintained at a concentration of about 1 μg/ml to about 100 ng/ml for about 3 months to about 2 years.

6. The composition of claim 5 , wherein the maintained concentration of CXCL12 polypeptide within the matrix is about 100-200 ng/ml.

7. The composition of claim 1 , wherein the at least one cell is removed.

8. The composition of claim 1 , wherein the CXCL12 polypeptide is released at a rate sufficient to repel effector T cells.

9. The composition of claim 1 , wherein the composition is characterized by an ability of repelling effector T cells in vitro in a Boyden chamber.

10. A method of providing islet cells to a subject in need thereof, said method comprising implanting the composition of claim 1 into the subject, wherein the at least one cell are islet cells, wherein the islet cells regulate blood glucose levels in the subject for a period of time, wherein the period of time is at least about 1 month.

11. The method of claim 10 , wherein the islet cells maintain the fasting serum concentration of glucose in the subject at a blood level of between about 80 mg/dl and about 120 mg/dl.

12. The method of claim 10 , wherein subject receives repeated implantation of a composition comprising at least one islet cell encapsulated in a CXCL12 polypeptide eluting matrix.

13. The method of claims 10 , wherein the matrix is not degraded by effector T-cells or macrophages.

14. The method of claim 10 , wherein regulatory T-cells are present at the site of implantation.

15. The method of claim 10 . wherein effector-T cells are absent from the site of implantation.

16. The method of claims 14 , wherein the presence of said regulatory T-cells or the absence of said effector T-cells is measured by flow cytometry or immunohistochemistry.

Assignees

• Massachusetts Gen Hospital

Inventors

• Poznansky Mark
• Chen Tao

Classifications

• A61K38/195

  Chemokines, e.g. RANTES · CPC title

• A61K2035/128

  capsules, e.g. microcapsules · CPC title

• G07F17/3244

  Payment aspects of a gaming system, e.g. payment schemes, setting payout ratio, bonus or consolation prizes · CPC title

• C08L5/04

  Alginic acid; Derivatives thereof · CPC title

• A61K38/13

  Cyclosporins · CPC title