IP Library Granted Patent US 9,649,340
Granted Patent B2
US 9,649,340 · App. 12/857,866 · Granted May 16, 2017

Methods for producing enriched populations of human retinal pigment epithelium cells

Inventors: Irina V. Klimanskaya (Upton, MA); Robert P. Lanza (Clinton, MA)
Assignee: Astellas Institute for Regenerative Medicine
A61K35/30A61K9/0048A61K35/44C12N5/062C12N5/0621A61K35/12C12N2501/01C12N2501/115C12N2501/15C12N2501/155C12N2501/33C12N2506/02
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Quick Facts
Patent No.
US 9,649,340
App. No.
12/857,866
Granted
May 16, 2017
Kind
B2
Abstract

This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

Claims (22)

1. A method of treating retinal disease or condition in an human subject, comprising transplanting into the eye of said subject a composition comprising an allogeneic human pigmented cell population comprising bestrophin+/CRALBP+ cells obtained by in vitro differentiation of human pluripotent cells that express Oct-4, alkaline phosphatase, SSEA-3, SSEA-4, TRA-I-60, and TRA-I-81, wherein the human pigmented cell population has a normal karyotype.

2. The method of claim 1 , wherein said human pigmented cell population comprises cells that are bestrophin+, CRALBP+, PEDF+, and express RPE65.

3. The method of claim 1 , wherein said human pigmented cell population comprises cells that are Pax6+.

4. The method of claim 1 , wherein said retinal disease or condition is a disease of retinal degeneration.

5. The method of claim 1 , wherein the retinal disease or condition comprises pathologic myopia, retinitis pigmentosa, RPE detachment, retinal dysplasia, retinal atrophy, retinopathy, macular dystrophy, cone dystrophy, cone-rod dystrophy, Malattia Leventinese, Doyne honeycomb dystrophy, Sorsby's dystrophy, Stargardt disease, pattern/butterfly dystrophies, Best vitelliform dystrophy, North Carolina dystrophy, central areolar choroidal dystrophy, angioid streaks, or a toxic maculopathy.

6. The method of claim 1 , which comprises transplantation of the human pigmented cell population by vitrectomy surgery into the subretinal space of the eye of said human subject.

7. The method of claim 1 , wherein said human pigmented cell population is transplanted into the eye of said human subject in a suspension format or on a substrate or matrix having said human pigmented cell population disposed thereon.

8. The method of claim 1 , wherein the retinal disease or condition is macular degeneration.

9. The method of claim 1 , wherein the retinal disease or condition is Stargardt disease.

10. The method of claim 1 , wherein the retinal disease or condition is age-related macular degeneration.

11. The method of claim 1 , wherein the retinal disease or condition is retinitis pigmentosa.

12. The method of claim 1 , wherein said human pigmented cell population comprises pigmented cells that exhibit a cobblestone, polygonal appearance characteristic of epithelial cells in culture.

13. The method of claim 1 , wherein said human pigmented cell population is prepared by a method comprising:

a) allowing hES cell cultures to overgrow on MEF and form a thick multilayer of cells, or forming an embryoid body (EB) from hES cells;

b) culturing the multilayer of cells or EB for a sufficient time for the appearance of pigmented cells; and

c) isolating and culturing the pigmented cells from the resultant cell cultures, thereby obtaining a human pigmented cell population comprising CRALBP+/bestrophin+cells.

14. The method of claim 13 , wherein said culturing in step (b) comprises culturing the hES cells in a medium lacking exogenously added FGF, lacking exogenously added LIF and lacking exogenously added PLASMANATE® (an aqueous solution containing 5 g plasma proteins per 100 mL, buffered with sodium carbonate and stabilized with 0.005 M sodium caprylate and 0.004 M acetyltryptophan, said plasma proteins comprising approximately 88% normal human albumin, 12% alpha and beta globulins, and not more than 1% gamma globulin, and containing sodium 145 mEq/L, potassium 0.25 mEq/L, and chloride 100 mEq/L).

15. The method of claim 13 , wherein the duration of culturing in step (b) is at least 6 weeks.

16. The method of claim 13 , wherein the duration of culturing in step (b) is between about 6 weeks and about 8 weeks.

17. The method of claim 13 , wherein the duration of culturing in step (b) is between about 3 months and about 5 months.

18. The method of claim 1 , wherein the method restores visual acuity in the subject.

19. The method of claim 18 , wherein visual acuity is restored to a moderate level.

Assignments (7)
CONFIRMATORY ASSIGNMENT Recorded Apr 5, 2024
From: ASTELLAS INSTITUTE FOR REGENERATIVE MEDICINE
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 067024/0057 →
CHANGE OF NAME Recorded Jul 27, 2016
From: OCATA THERAPEUTICS, INC.
To: ASTELLAS INSTITUTE FOR REGENERATIVE MEDICINE
Reel/Frame 039493/0166 →
CHANGE OF NAME Recorded Jan 7, 2015
From: ADVANCED CELL TECHNOLOGY, INC.
To: OCATA THERAPEUTICS, INC.
Reel/Frame 034749/0622 →
RELEASE OF SECURITY INTEREST Recorded Nov 24, 2014
From: CAMOFI MASTER LDC; CAMHZN MASTER LDC
To: ADVANCED CELL TECHNOLOGY, INC.; MYTOGEN, INC.
Reel/Frame 034421/0863 →
CONFIRMATORY ASSIGNMENT Recorded Oct 23, 2014
From: LANZA, ROBERT
To: ADVANCED CELL TECHNOLOGY, INC.
Reel/Frame 034038/0172 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 23, 2014
From: KLIMANSKAYA, IRINA V.
To: ADVANCED CELL TECHNOLOGY, INC.
Reel/Frame 034023/0115 →
SECURITY AGREEMENT Recorded Jan 25, 2013
From: ADVANCED CELL TECHNOLOGY, INC.; MYTOGEN, INC.
To: CAMOFI MASTER LDC; CAMHZN MASTER LDC
Reel/Frame 029698/0001 →
Continuity (4)
Continuation 11490953 · Jul 21, 2006
Continuation PCTUS2005002273 · Jan 24, 2005
Provisional Application 60538964 · Jan 23, 2004
Related Publication 20110117062A1 · May 19, 2011