US 12,350,311 B2
Gene therapy for neurodegenerative disorders
Marco A. Passini, Northborough, MA (US); Lamya Shihabuddin, Brighton, MA (US); and Seng H. Cheng, Natick, MA (US)
Assigned to Genzyme Corporation, Cambridge, MA (US)
Filed by Genzyme Corporation, Cambridge, MA (US)
Filed on Mar. 26, 2024, as Appl. No. 18/616,511.
Application 18/616,511 is a continuation of application No. 18/046,363, filed on Oct. 13, 2022, granted, now 11,975,043.
Application 18/046,363 is a continuation of application No. 16/794,031, filed on Feb. 18, 2020, abandoned.
Application 16/794,031 is a continuation of application No. 16/449,221, filed on Jun. 21, 2019, abandoned.
Application 16/449,221 is a continuation of application No. 15/160,949, filed on May 20, 2016, granted, now 10,369,193, issued on Aug. 6, 2019.
Application 15/160,949 is a continuation of application No. 13/287,583, filed on Nov. 2, 2011, abandoned.
Application 13/287,583 is a continuation of application No. PCT/US2010/001239, filed on Apr. 27, 2010.
Claims priority of provisional application 61/268,059, filed on Jun. 8, 2009.
Claims priority of provisional application 61/174,982, filed on May 2, 2009.
Prior Publication US 2024/0350584 A1, Oct. 24, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 48/00 (2006.01); A61K 31/7088 (2006.01); A61K 38/17 (2006.01); C07K 14/47 (2006.01); C12N 7/00 (2006.01); C12N 15/86 (2006.01)
CPC A61K 38/1709 (2013.01) [A61K 31/7088 (2013.01); A61K 48/00 (2013.01); A61K 48/0008 (2013.01); A61K 48/005 (2013.01); A61K 48/0075 (2013.01); C07K 14/4702 (2013.01); C12N 7/00 (2013.01); C12N 15/86 (2013.01); C12N 2750/14121 (2013.01); C12N 2750/14133 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14171 (2013.01)] 21 Claims
 
1. A method of modulating motor function in a subject with spinal muscular atrophy (SMA) comprising administering to a subject in need thereof a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) virion comprising a self-complementary adeno-associated virus (scAAV) vector comprising a heterologous nucleic acid construct, wherein the heterologous nucleic acid construct comprises:
a. a first AAV2 inverted terminal repeat (ITR);
b. a cytomegalovirus enhancer/chicken-β actin (CBA) promoter;
c. a polynucleotide encoding a survival motor neuron (SMN) protein comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 2; and
d. a second AAV2 ITR,
wherein the rAAV virion comprises an AAV8 or AAV9 capsid, and wherein the rAAV virion is administered (i) via direct spinal cord injection, and/or (ii) via intrathecal injection.