US 12,031,144 B2
Oxidation-resistant AAT gene therapy
Ronald G. Crystal, New York, NY (US); Katie Stiles, Bronx, NY (US); Meredith Sosulski, New York, NY (US); Stephen M. Kaminsky, Bronx, NY (US); Dolan Sondhi, New York, NY (US); Bishnu De, New Hyde Park, NY (US); and Jonathan Rosenberg, Cranbury, NJ (US)
Assigned to Cornell University, Ithaca, NY (US)
Appl. No. 16/498,592
Filed by Cornell University, Ithaca, NY (US)
PCT Filed Mar. 29, 2018, PCT No. PCT/US2018/025183
§ 371(c)(1), (2) Date Sep. 27, 2019,
PCT Pub. No. WO2018/183705, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/478,357, filed on Mar. 29, 2017.
Prior Publication US 2020/0102575 A1, Apr. 2, 2020
Int. Cl. A61K 48/00 (2006.01); C12N 15/86 (2006.01)
CPC C12N 15/86 (2013.01) [A61K 48/00 (2013.01); C12N 2750/14141 (2013.01)] 19 Claims
OG exemplary drawing
 
8. A method to inhibit cathepsin G and neutrophil elastase under conditions of oxidative damage or oxidative stress in a lung of a mammal having emphysema, COPD, respiratory distress syndrome or fibrotic interstitial lung disease comprising: administering to a pleura of the mammal, an amount of an adeno-associated viral gene therapy vector comprising an expression cassette coding for a human oxidation-resistant alpha 1-antitrypsin (AAT) that has a leucine at position 358 and a valine at position 351, wherein expression of the oxidation-resistant AAT from the vector in the lung of the mammal results in inhibition of cathepsin G and neutrophil elastase under conditions of the oxidative damage or stress in the lung as a result of increased levels of the oxidation-resistant AAT in the mammal after administration, and wherein the mammal prior to administration of the vector has serum AAT levels of less than 11 μM.