US 11,952,585 B2
Methods of treating phenylketonuria
Omar L. Francone, Waltham, MA (US); Deborah A. Kinch, Bedford, MA (US); Diana Lamppu, Roslindale, MA (US); Albert Barnes Seymour, Westborough, MA (US); and Teresa Leah Wright, Lexington, MA (US)
Assigned to HOMOLOGY MEDICINES, INC., Bedford, MA (US)
Filed by HOMOLOGY MEDICINES, INC., Bedford, MA (US)
Filed on Jan. 13, 2021, as Appl. No. 17/147,974.
Claims priority of provisional application 63/110,251, filed on Nov. 5, 2020.
Claims priority of provisional application 62/960,498, filed on Jan. 13, 2020.
Prior Publication US 2021/0261983 A1, Aug. 26, 2021
Int. Cl. C12N 15/864 (2006.01); A61K 48/00 (2006.01); C12N 7/00 (2006.01); C12N 7/01 (2006.01); C12N 9/02 (2006.01); C12N 15/52 (2006.01); C12N 15/86 (2006.01); A61K 31/573 (2006.01)
CPC C12N 15/86 (2013.01) [C12N 7/00 (2013.01); C12N 9/0071 (2013.01); A61K 31/573 (2013.01); C12N 2750/14143 (2013.01); C12N 2830/008 (2013.01); C12N 2830/50 (2013.01); C12Y 114/16001 (2013.01)] 17 Claims
 
1. A method for treating a subject having phenylketonuria (PKU), the method comprising administering to the subject an rAAV at a dose of about 6e13 vg/kg to about 1e14 vg/kg, wherein the rAAV comprises:
(a) an AAV capsid comprising:
a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 203-736 of SEQ ID NO:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 is R;
a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 138-736 of SEQ ID NO:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 is R; and/or
a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 1-736 of SEQ ID NO:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 is R; and
(b) a transfer genome comprising a silently altered PAH coding sequence operably linked to a transcriptional regulatory element, wherein the silently altered PAH coding sequence comprises a nucleotide sequence having at least 95% sequence identity to the sequence set forth in SEQ ID NO: 1, and encodes the amino acid sequence set forth in SEQ ID NO:13.