US 12,343,353 B2
Modulating phosphatase activity in cardiac cells
Roger J. Hajjar, New York, NY (US); Federica Del Monte, Boston, MA (US); and Evangelia Kranias, Cincinnati, OH (US)
Assigned to The University of Cincinnati, Cincinnati, OH (US); and The General Hospital Corporation, Boston, MA (US)
Filed by The University of Cincinnati, Cincinnati, OH (US); and The General Hospital Corporation, Boston, MA (US)
Filed on Apr. 11, 2019, as Appl. No. 16/381,781.
Application 16/381,781 is a division of application No. 15/065,507, filed on Mar. 9, 2016, granted, now 11,213,534.
Application 15/065,507 is a continuation of application No. 14/834,406, filed on Aug. 24, 2015, abandoned.
Application 14/834,406 is a continuation of application No. 11/662,439, granted, now 9,114,148, issued on Aug. 25, 2015, previously published as PCT/US2005/032162, filed on Sep. 8, 2005.
Claims priority of provisional application 60/608,214, filed on Sep. 9, 2004.
Prior Publication US 2020/0054652 A1, Feb. 20, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 48/00 (2006.01); A01K 67/0275 (2024.01); A61K 31/66 (2006.01); C07K 14/47 (2006.01)
CPC A61K 31/66 (2013.01) [A01K 67/0275 (2013.01); C07K 14/4703 (2013.01); A01K 2217/052 (2013.01); A01K 2227/105 (2013.01); A01K 2267/0375 (2013.01); A61K 48/00 (2013.01); C12N 2799/025 (2013.01)] 12 Claims
 
1. A method of increasing cardiac contractility and reducing morphological deterioration associated with cardiac remodeling in a human subject with existing heart failure, comprising:
directly administering into the lumen of the coronary artery of the subject, an effective amount of an adeno-associated virus (AAV) vector comprising:
a nucleic acid encoding a constitutively active fragment of human phosphatase inhibitor-1 protein as set forth in SEQ ID NO: 2, wherein the constitutively active fragment is truncated at the C-terminus at amino acid 66, 61, or 54 and comprises an aspartic acid at position 35 (T35D), that inhibits human type-1 phosphatases (PP1); and
wherein said nucleic acid sequence is operably linked to a promoter capable of directing expression in the heart;
thereby expressing the constitutively active fragment of human phosphatase inhibitor-1 protein in the heart of the human subject in an amount effective to increase cardiac contractility and reduce morphological deterioration associated with cardiac remodeling in the human subject with existing heart failure, to thereby increase cardiac contractility and reduce morphological deterioration associated with cardiac remodeling in the human subject.