US 11,807,868 B2
Adeno-associated variants, formulations and methods for pulmonary delivery
Melissa Kotterman, Emeryville, CA (US); Peter Francis, Emeryville, CA (US); Melissa Calton, Emeryville, CA (US); Johnny Gonzales, Emeryville, CA (US); Roxanne Croze, Emeryville, CA (US); and Christopher Schmitt, Emeryville, CA (US)
Assigned to 4D Molecular Therapeutics Inc., Emeryville, CA (US)
Filed by 4D MOLECULAR THERAPEUTICS INC., Emeryville, CA (US)
Filed on Oct. 6, 2022, as Appl. No. 17/938,641.
Application 17/938,641 is a continuation of application No. PCT/US2021/029253, filed on Apr. 26, 2021.
Claims priority of provisional application 63/088,432, filed on Oct. 6, 2020.
Claims priority of provisional application 63/016,246, filed on Apr. 27, 2020.
Prior Publication US 2023/0257772 A1, Aug. 17, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/86 (2006.01); C07K 14/005 (2006.01); A61K 9/12 (2006.01); A61K 9/00 (2006.01); C07K 14/47 (2006.01); A61P 11/00 (2006.01)
CPC C12N 15/86 (2013.01) [A61K 9/0078 (2013.01); A61K 9/12 (2013.01); A61P 11/00 (2018.01); C07K 14/005 (2013.01); C07K 14/4712 (2013.01); C12N 2750/14121 (2013.01); C12N 2750/14122 (2013.01); C12N 2750/14141 (2013.01); C12N 2750/14142 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14151 (2013.01)] 28 Claims
 
1. A method of delivering a heterologous nucleic acid to a lung cell in a primate comprising administering to the primate a composition comprising a recombinant adeno-associated virus (rAAV) vector, said rAAV vector comprising (i) a capsid comprising a capsid protein comprising the amino acid sequence set forth as SEQ ID NO:12 or an amino acid sequence at least 90% identical to SEQ ID NO:12 and comprising a Thr at amino acid 469 and an Ala at amino acid 598 based on the amino acid numbering set forth in SEQ ID NO: 12 and (ii) a heterologous nucleic acid comprising a nucleotide sequence encoding a gene product, wherein the step of administering comprises pulmonary, endobronchial, intranasal, intratracheal, and/or intrabronchial administration.
 
16. A nucleic acid sequence comprising a nucleotide sequence set forth in SEQ ID NO:43 or a sequence at least 80% identical thereto.
 
18. A pharmaceutical composition comprising an rAAV vector, said rAAV vector comprising (i) a capsid comprising a capsid protein of SEQ ID NO:12 or an amino acid sequence at least 90% identical to SEQ ID NO:12 and comprising a Thr at amino acid 469 and an Ala at amino acid 598 based on the amino acid numbering set forth in SEQ ID NO: 12 and (ii) a heterologous nucleic acid comprising a nucleotide sequence encoding a CFTR or a biologically active truncated CFTR protein lacking amino acids 708-759 of the human CFTR protein sequence, said nucleotide sequence operably linked to an expression control sequence.
 
23. A pharmaceutical composition comprising an rAAV virus, wherein the rAAV virus is formulated in a buffer comprising about 10 mM to about 50 mM citrate, about 70 mM to about 150 mM NaCl and a surfactant and having a pH of about 5.0 to about 7.0.
 
27. A method of treating cystic fibrosis in a primate comprising administering to the primate a pharmaceutical composition according to claim 18, wherein the step of administering comprises pulmonary, endobronchial, intranasal, intratracheal, and/or intrabronchial administration.