US 12,442,020 B2
Materials and methods for treatment of pain related disorders
Ante Sven Lundberg, Cambridge, MA (US); Samarth Kulkarni, Cambridge, MA (US); Lawrence Klein, Cambridge, MA (US); and Hari Kumar Padmanabhan, Cambridge, MA (US)
Assigned to Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed by VERTEX PHARMACEUTICALS INCORPORATED, Boston, MA (US)
Filed on Oct. 3, 2022, as Appl. No. 17/959,089.
Application 17/959,089 is a continuation of application No. 16/315,547, granted, now 11,459,587, previously published as PCT/IB2017/054086, filed on Jul. 6, 2017.
Claims priority of provisional application 62/461,874, filed on Feb. 22, 2017.
Claims priority of provisional application 62/358,763, filed on Jul. 6, 2016.
Prior Publication US 2023/0279439 A1, Sep. 7, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/90 (2006.01); A61K 35/30 (2015.01); A61K 38/46 (2006.01); A61K 48/00 (2006.01); A61P 25/00 (2006.01); A61P 25/02 (2006.01); A61P 25/04 (2006.01); A61P 29/00 (2006.01); A61P 43/00 (2006.01); C07K 14/47 (2006.01); C07K 14/705 (2006.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/113 (2010.01); C12N 15/86 (2006.01)
CPC C12N 15/907 (2013.01) [A61K 35/30 (2013.01); C07K 14/705 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12N 15/1138 (2013.01); C12N 2310/20 (2017.05); C12N 2800/80 (2013.01)] 18 Claims
 
1. A method for editing a Sodium Voltage-Gated Channel Alpha Subunit 9 (SCN9A) gene in a cell by genome editing comprising: introducing into the cell (a) one or more S. pyogenes Cas9 (spCas9) endonuclease or one or more polynucleotide encoding the one or more spCas9 endonuclease and (b) one or more gRNA or sgRNA or one or more nucleic acid encoding the one or more gRNA or sgRNA, wherein the one or more gRNA or sgRNA comprises a spacer sequence that targets a sequence within or near the SCN9A gene to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the SCN9A gene or SCN9A regulatory elements that results in one or more permanent insertions, deletions or mutations of at least one nucleotide within or near the SCN9A gene, thereby reducing or eliminating the expression or function of SCN9A gene products, wherein the spacer sequence of the one or more gRNA or sgRNA is about 20 to 60 nucleotides in length and comprises an RNA sequence corresponding to any one of SEQ ID NO: 46832, 49122, 49431, 47474, 47446, 28779, 29821, 28146, 49436, 47224, 47462, 47240, 27323, 27522, 27893, 47261, 28137, 49367, 47232, 47445, 49313, 47267, 30622, 47231, 26766, 28139, 46079, 48091, 46833, 26765, 27876, 47241, 47248, 30051, 30111, 28760, 28085, 27254, 30163, 49303, 28083, 49344, 47245, 48090, 28132, 27328, 46078, 28773, 46496, 27885, 29928, 27933, 46039, 47439, 28774, 47455, 30020, 47236, 28089, 26813, 47464, 28091, 29908, 27892, 28776, 28783, 27252, 29930, or 47625.