US 12,460,228 B2
Gene therapy for treating Wilson's disease
James M. Wilson, Philadelphia, PA (US); Jenny Agnes Sidrane, Phoenixville, PA (US); and Lakshmanan Govindasamy, Philadelphia, PA (US)
Assigned to The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed by The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed on Jul. 13, 2022, as Appl. No. 17/812,322.
Application 17/812,322 is a continuation of application No. 16/474,958, granted, now 11,473,106, previously published as PCT/US2017/068919, filed on Dec. 29, 2017.
Claims priority of provisional application 62/440,659, filed on Dec. 30, 2016.
Claims priority of provisional application 62/473,656, filed on Mar. 20, 2017.
Prior Publication US 2022/0389455 A1, Dec. 8, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/86 (2006.01); A61K 48/00 (2006.01); C07K 14/755 (2006.01)
CPC C12N 15/86 (2013.01) [A61K 48/00 (2013.01); C07K 14/755 (2013.01)] 20 Claims
 
1. A recombinant nucleic acid construct comprising a recombinant adeno-associated virus (AAV) vector genome, said vector genome comprising:
(a) an AAV 5′ inverted terminal repeat (ITR) sequence;
(b) a promoter;
(c) a codon optimized coding sequence encoding a truncated human copper-transporting ATPase 2 (ATP7B) polypeptide comprising metal-binding domains (MBD) 4-6 and comprising a deletion of MBD 1-3; and
(d) an AAV 3′ ITR sequence.
 
14. A host cell comprising a recombinant nucleic acid construct, said nucleic acid construct comprising a recombinant adeno-associated virus (AAV) vector genome, said vector genome comprising:
(a) an AAV 5′ inverted terminal repeat (ITR) sequence;
(b) a promoter;
(c) a codon optimized coding sequence encoding a truncated human copper-transporting ATPase 2 (ATP7B) polypeptide comprising metal-binding domains (MBD) 4-6 and comprising a deletion of MBD 1-3; and
(d) an AAV 3′ ITR sequence.
 
15. A method of treating a subject having Wilson's Disease, the method comprising administering to the subject a recombinant adeno-associated virus (AAV) useful as a liver-directed therapeutic for Wilson's Disease (WD), said recombinant AAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising:
(a) an AAV 5′ inverted terminal repeat (ITR) sequence;
(b) a promoter;
(c) a codon optimized coding sequence encoding a human copper-transporting ATPase 2 (ATP7B) polypeptide comprising metal-binding domains (MBD) 4-6 and comprising a deletion of MBD 1-3; and
(d) an AAV 3′ ITR sequence.