IP Library › Granted Patent US 12,533,382
Granted Patent B2
US 12,533,382 · App. 17/605,573 · Granted Jan 27, 2026

Composite including neural retina, retinal pigment epithelial cells, and hydrogel, and method for producing same

Inventors: Yuji Tanaka (Wako, JP); Michiko Mandai (Wako, JP); Masayo Takahashi (Wako, JP); Suguru Yamasaki (Kobe, JP)
Assignees: Riken; Racthera Co., Ltd.
A61K35/30A61K47/42A61L27/22A61L27/383A61L27/52A61P27/02
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,533,382
App. No.
17/605,573
Granted
Jan 27, 2026
Kind
B2
Abstract

Provided is a composite comprising a neural retina, a retinal pigment epithelial cell sheet, and a hydrogel.

Claims (23)

1 . A composite comprising a neural retina, a retinal pigment epithelial cell sheet, and a hydrogel, wherein

the neural retina and the retinal pigment epithelial cell sheet are derived from a human pluripotent stem cell respectively;

in the neural retina, a neural retinal layer including at least a photoreceptor layer is formed, wherein the photoreceptor layer comprises at least one or more cells selected from the group consisting of a photoreceptor cell, a photoreceptor precursor cell and a retinal precursor cell;

a melting point of the hydrogel is from 20° C. to 40° C.; and

the whole of the neural retina and the retinal pigment epithelial cell sheet is embedded in the hydrogel, tangent directions of the respective surfaces of the neural retina and the retinal pigment epithelial cell sheet are approximately parallel, an apical surface of the neural retina and an apical surface of the retinal pigment epithelial cell sheet face each other, and the neural retina and the retinal pigment epithelial cell sheet are separated by the hydrogel from each other without contact.

2 . The composite according to claim 1 , wherein a jelly strength of the hydrogel is from 1000 g to 2000 g.

3 . The composite according to claim 1 , wherein a concentration of the hydrogel is from 10% to 50% by weight.

4 . The composite according to claim 1 , wherein a pH of the hydrogel is from 6.5 to 7.5.

5 . The composite according to claim 1 , wherein the hydrogel has biodegradability.

6 . The composite according to claim 1 , wherein the hydrogel is a hydrogel of gelatin.

7 . The composite according to claim 6 , wherein the gelatin is alkali-treated and/or heat-treated gelatin.

8 . The composite according to claim 1 , wherein

the neural retina is a neural retina obtained from a cell aggregate obtained by differentiating a human pluripotent stem cell,

the cell aggregate comprises at least a first epithelial tissue and a second epithelial tissue, wherein the first epithelial tissue contains a human neural retina, and the second epithelial tissue has continuity of a slope of a tangent line to a surface different from continuity of a slope of a tangent line to the surface of the first epithelial tissue, and contains a cell other than a retinal cell and/or a retinal pigment epithelial cell, and

the neural retina contains a region on the first epithelial tissue most distant from the second epithelial tissue in the cell aggregate.

9 . A pharmaceutical composition comprising the composite according to claim 1 as an active ingredient.

10 . A therapeutic medication for a disease caused by a disorder of a retinal tissue or a damage of a retinal tissue, comprising the composite according to claim 1 .

11 . A composition for transplantation comprising the composite according to claim 1 .

12 . The composition for transplantation according to claim 11 , wherein the composition for transplantation is to be transplanted to the eye fundus or into the subretinal space in a patient.

13 . The composition for transplantation according to claim 12 , wherein the composition for transplantation is to be transplanted such that the composite is engrafted in a recipient patient in a condition in which the neural retina of the transplanted composite faces the neural retinal layer of the patient while the retinal pigment epithelial cell sheet of the transplanted composite faces the retinal pigment epithelial layer of the patient.

14 . A method for treating a disease caused by a disorder of a retinal tissue or a damage of a retinal tissue, comprising the steps of:

(1) transplanting the composite according to claim 1 to the eye fundus or into the subretinal space in a patient; and

(2) engrafting the composite in vivo in the patient in a condition in which the neural retina of the transplanted composite faces the neural retinal layer of the patient while the retinal pigment epithelial cell sheet of the transplanted composite faces the retinal pigment epithelial layer of the patient.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 29, 2025
From: SUMITOMO PHARMA CO., LTD.
To: RACTHERA CO., LTD.
Reel/Frame 072399/0820 →
CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF ASSIGNEE PREVIOUSLY RECORDED AT REEL: 066212 FRAME: 0445. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Jan 25, 2024
From: SUMITOMO CHEMICAL COMPANY, LIMITED
To: SUMITOMO PHARMA CO., LTD.
Reel/Frame 066371/0053 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 23, 2024
From: SUMITOMO CHEMICAL COMPANY, LIMITED
To: SUMITOMO PHARMA CO., LTD
Reel/Frame 066212/0445 →
CHANGE OF NAME Recorded Jul 14, 2022
From: SUMITOMO DAINIPPON PHARMA CO., LTD.
To: SUMITOMO PHARMA CO., LTD
Reel/Frame 060507/0750 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 22, 2021
From: TANAKA, YUJI; MANDAI, MICHIKO; TAKAHASHI, MASAYO; YAMASAKI, SUGURU
To: RIKEN; SUMITOMO DAINIPPON PHARMA CO., LTD.; SUMITOMO CHEMICAL COMPANY, LIMITED
Reel/Frame 057874/0419 →
Priority Claims (1)
JP 2019-086199 · Apr 26, 2019 · national
Continuity (1)
Related Publication 20220249572A1 · Aug 11, 2022
References Cited (53)
US 20110004304A1 · Tao et al. · 2011 [cited by applicant]
US 20200206387A1 · Takahashi et al. · 2020 [cited by applicant]
US 20210317403A1 · Valeria Canto-Soler et al. · 2021 [cited by applicant]
CN 1720055A · 2006 [cited by applicant]
CN 102204930A · 2011 [cited by applicant]
CN 102258808A · 2011 [cited by applicant]
CN 103007355A · 2013 [cited by applicant]
CN 107109367A · 2017 [cited by applicant]
EP 2265711 · 2010 [cited by applicant]
WO 9822029A1 · 1998 [cited by applicant]
WO 2004033635A2 · 2004 [cited by applicant]
WO 2005070011A2 · 2005 [cited by applicant]
WO 2006080952A2 · 2006 [cited by applicant]
WO 2009127809A1 · 2009 [cited by applicant]
WO 2011055855A1 · 2011 [cited by applicant]
WO 2011063005A2 · 2011 [cited by applicant]
WO 2012173207A1 · 2012 [cited by applicant]
WO 2013077425A1 · 2013 [cited by applicant]
WO 2015025967A1 · 2015 [cited by applicant]
WO 2015053375A1 · 2015 [cited by applicant]
WO 2015053376A1 · 2015 [cited by applicant]
WO 2015068505A1 · 2015 [cited by applicant]
WO 2016063985A1 · 2016 [cited by applicant]
WO 2016063986A1 · 2016 [cited by applicant]
WO 2017043605A1 · 2017 [cited by applicant]
WO 2017183732A1 · 2017 [cited by applicant]
WO 2018089515A1 · 2018 [cited by applicant]
WO 2019050015A1 · 2019 [cited by applicant]
Seiler MJ, Aramant RB. Intact sheets of fetal retina transplanted to restore damaged rat retinas. Invest Ophthalmol Vis Sci. Oct. 1998;39(11):2121-31. PMID: 9761291. (Year: 1998). [cited by examiner]
Rose JB, Pacelli S, Haj AJE, Dua HS, Hopkinson A, White LJ, Rose FRAJ. Gelatin-Based Materials in Ocular Tissue Engineering. Materials (Basel). Apr. 17, 2014;7(4):3106-3135. doi: 10.3390/ma7043106. PMID: 28788609; PMCID… [cited by examiner]
Lim LT, Ah-Kee EY, Collins CE. Common eye drops and their implications for pH measurements in the management of chemical eye injuries. Int J Ophthalmol. Dec. 18, 2014;7(6):1067-8. doi: 10.3980/j.issn.2222-3959.2014.06.2… [cited by examiner]
WO 2015025967 A1—English translation (Year: 2014). [cited by examiner]
Kuwahara et al., , “Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue,” Nature Communications, 6: 6286 (2015). [cited by applicant]
Taylor et al., “The epidemiology of infection in trachoma,” Investigative Ophthalmology & Visual Science, 30 (8): 1823-1833 (1989). [cited by applicant]
M'Barek et al., “Human ESC-derived retinal epithelial cell sheets potentiate rescue of photoreceptor cell loss in rats with retinal degeneration,” Science Translational Medicine, 9 (421): 1-12 (2017). [cited by applicant]
Seiler et al., “Cell replacement and visual restoration by retinal sheet transplants,” Progress in Retinal Eye Research, 31(6): 661-687 (2012). [cited by applicant]
Lamba et al., “Generation, Purification and Transplantation of Photoreceptors Derived from Human Induced Pluripotent Stem Cells,” PLoS One, 5 (1): e8763 (2010). [cited by applicant]
Meyer et al., “Optic Vesicle-like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment,” Stem Cells, 29 (8): 1206-1218 (2011). [cited by applicant]
Reichman et al., “From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium”, PNAS, 111 (23): 8518-8523 (2014). [cited by applicant]
Zhong et al., “Generation of three dimensional retinal tissue with functional photoreceptors from human iPSCs”, Nature Communications, 5: 4047 (2015). [cited by applicant]
Kamao et al., “Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application,” Stem Cell Reports, 2(2): 205-218 (2014). [cited by applicant]
Nakano et al., “Self-Formation of Optic Cups and Storable Stratified Neural Retina from Human ESCs,” Cell Stem Cell, 10 (6): 771-785 (2012). [cited by applicant]
Haruta et al., “In Vitro and In Vivo Characterization of Pigment Epithelial Cells Differentiated from Primate Embryonic Stem Cells,” Investigative Ophthalmology & Visual Science, 45 (3): 1020-1025 (2004). [cited by applicant]
Okamoto et al., “Induction of Retinal Pigment Epithelial Cells from Monkey iPS Cells,” Investigative Ophthalmology & Visual Science, 52 (12): 8785-8790 (2011). [cited by applicant]
Osakada et al., “In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction”, Cell Science, 122 (17): 3169-3179 (2009). [cited by applicant]
Gamm et al., “A Novel Serum-Free Method for Culturing Human Prenatal Retinal Pigment Epithelial Cells,” Investigative Ophthalmology & Visual Science, 49 (2): 788-799 (2008). [cited by applicant]
Nakagawa et al., “A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells,” Scientific Reports, 4: 3594 (2014). [cited by applicant]
Aramant et al, “Successful cotransplantation of intact sheets of fetal retina with retinal pigment epithelium,” Investigative Ophthalmology & Visual Science, 40 (7): 1557-1564 (1999). [cited by applicant]
Tu et al., “Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration,” EBioMedicine, 39: 562-574 (2018). [cited by applicant]
Arakawa et al., “Development of novel therapies using human iPS cell-derived retinal pigment epithelia,” Folia Pharmacologica Japonica, 148: 217 (2016). [cited by applicant]
Akiba et al., “Toward establishment of regenerative cell Full therapy for retinitis pigmentosa using iPS cell derived retinal sheet,” Folia Pharmacologica Japonica, 155: 93-98 (2020). [cited by applicant]
International Search Report issued in corresponding International Patent Application No. PCT/JP2020/017635 dated Jun. 30, 2020. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion issued in corresponding International Patent Application No. PCT/JP2020/017635 dated Nov. 4, 2021. [cited by applicant]