Granted Patent B2

US 12,735,709 · App. 19/572,773 · Granted Sep 15, 2026

Inventors: Xin Geng (Oklahoma City, OK); Chunyang Zhang (Burlington, MA); Shiyu Wang (Belmont, MA); Weimin Wang (Winchester, MA)

Assignee: Sanegene Bio USA Inc.

C12N15/113A61P37/06C12N2310/11C12N2310/14C12N2310/315C12N2310/321C12N2310/322C12N2310/351C12N2320/30

Abstract

Claims (19)

1 . A small interfering RNA (siRNA) comprising:

an antisense strand consisting of a sequence according to SEQ ID NO: 377 (5′ [mUs][fGs][fU][mC][fA][mU][fA][mA][mA][fA][mU][mU][mC][fA][mG][fG][mA][mA][mU][mUs][mCs][mC]3′), and

a sense strand consisting of a sequence according to SEQ ID NO: 388 (5′ [mAs][mAs][mU][mU][mC][fC][mU][fG][fA][fA][fU][mU][mU][mU][mA][mU][mG][mA][m C][mA][G1b][G1b][G1b]3′);

wherein:

m is a 2′-O-methyl modification,

f is a 2′-F modification,

s is a phosphorothioate linkage, and

[G1b][G1b][G1b] has the structure:

2 . A pharmaceutical composition comprising the siRNA of claim 1 , and a pharmaceutically acceptable carrier, diluent, or excipient.

3 . A method of treating a disease or disorder associated with increased expression or activity of complement factor B (CFB) in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the pharmaceutical composition of claim 2 .

4 . The method of claim 3 , wherein the disease or disorder associated with increased expression of CFB is selected from the group consisting of Paroxysmal Nocturnal Hemoglobinuria (PNH), rheumatoid arthritis, ischemia-reperfusion injuries, Multiple Sclerosis (MS), Guillain-Barre syndrome, Systemic lupus erythmatosis, C 3 Glomerulonephritis, atypical Hemolytic Uremic Syndrome (aHUS), Myasthenia Gravis (MG), Neuromyelistis Optic nerve and Spinal Cord (NMOSD), Dense Deposit Disease (DDD), Age-related Macular Degeneration (AMD), IgA nephropathy, Multifocal Motor Neuropathy (MMN), organ transplantation, and neurodegenerative diseases.

5 . The method of claim 3 , wherein the subject is a human.

6 . A method of downregulating the expression or level of complement factor B (CFB) in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the pharmaceutical composition of claim 2 .

7 . The method of claim 6 , wherein the subject is a human.

8 . A method of treating a disease or disorder associated with increased expression or activity of complement factor B (CFB) in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the siRNA of claim 1 .

9 . The method of claim 8 , wherein the disease or disorder associated with increased expression of CFB is selected from the group consisting of Paroxysmal Nocturnal Hemoglobinuria (PNH), rheumatoid arthritis, ischemia-reperfusion injuries, Multiple Sclerosis (MS), Guillain-Barre syndrome, Systemic lupus erythmatosis, C 3 Glomerulonephritis, atypical Hemolytic Uremic Syndrome (aHUS), Myasthenia Gravis (MG), Neuromyelistis Optic nerve and Spinal Cord (NMOSD), Dense Deposit Disease (DDD), Age-related Macular Degeneration (AMD), IgA nephropathy, Multifocal Motor Neuropathy (MMN), organ transplantation, and neurodegenerative diseases.

10 . The method of claim 8 , wherein the subject is a human.

11 . A method of downregulating the expression or level of complement factor B (CFB) in a subject in need thereof, wherein the method comprises administering to the subject an effective amount of the siRNA of claim 1 .

12 . The method of claim 11 , wherein the subject is a human.

Continuity (3)

References Cited (114)