METHODS AND COMPOSITIONS FOR OCULAR CELL THERAPY.

Description

The present invention provides ocular cells genetically modified by a CRISPR system targeting B2M expression for ocular cell therapy. The invention further provides methods for generating an expanded population of genetically modified ocular cells, for example, limbal stem cells (LSCs) or corneal endothelial cells (CECs), wherein the cells are expanded using a LATS inhibitor and B2M expression in the cells has been reduced or eliminated. The present invention further provides cell populations, preparations, uses, and methods of therapy comprising such cells.(22) 10 / 24 / 2019 (30) 62 / 793,544 US, 01 / 17 / 2019; 62 / 754,244 US, 11 / 01 / 2018; (51) (73) ELI LILLY AND COMPANY Address: Lilly Corporate Center, Indianapolis, Indiana 46285 Country: UNITED STATES OF AMERICA (72) DANIEL CHRISTOPHER LOPES; DANIEL ANTHONY BRIERE; AVINASH MUPPIDI (74) MANUEL POLANCO FERNANDEZ (54) TYROSINE-TYROSINE PROTEIN ANALOGUES AND METHODS OF USE THEREOF (57) PYY ANALOGUES ARE DESCRIBED INCLUDING MODIFICATIONS THAT INCREASE THE HALF-LIFE COMPARED TO NATIVE HUMAN PYY, AS WELL AS ADDITIONAL MODIFICATIONS THAT INCREASE THE POTENCY AND SELECTIVITY FOR THE NPY2 RECEPTOR. PHARMACEUTICAL COMPOSITIONS ARE ALSO DESCRIBED THAT INCLUDE ONE OR MORE OF THE PYY ANALOGUES DESCRIBED HEREIN IN A PHARMACEUTICALLY ACCEPTABLE CARRIER. METHODS FOR DEVELOPING AND USING PYY ANALOGUES ARE ALSO DESCRIBED, ESPECIALLY FOR TREATING OBESITY AND OBESITY-RELATED DISEASES AND DISORDERS, SUCH AS TYPE II DIABETES MELLITUS.