SiRNA compound that inhibits complement factor B (CFB)
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Publication Number
US-12600967-B2
Publication Date
2026-04-14
Expiration Date
Abstract
Nucleic acid products that modulate, in particular interfere with or inhibit CFB gene expression, are provided. The products may be oligomeric compounds that comprise at least a first region of linked nucleosides having at least a first nucleobase sequence that is at least partially complementary to at least a portion o 5 f RNA transcribed from a CFB gene, where the first nucleobase sequence is selected from SEQ ID NOs 1 to 391, 751 and 752, or a fragment thereof.
Core Innovation
The patent content describes an siRNA compound that inhibits complement factor B (CFB), comprising 30 or 33 nucleosides and one of two directly linked pairs of nucleobase sequences. At least one sugar or internucleoside linkage may optionally be modified. The description also includes hairpin siRNA constructs, sequence and chemical modifications, and optional N-Acetyl-Galactosamine (GalNAc) conjugation.
The compounds are proposed for the treatment of complement-associated disorders and are reported to reduce CFB expression and plasma factor Bb levels. Reported activity includes reductions of plasma factor Bb of up to 74% in non-human primates. These suppressive effects are sustained for up to 13 weeks.
Claims Coverage
The claim coverage includes one inventive feature directed to an siRNA compound that inhibits complement factor B (CFB).
CFB-inhibiting siRNA compound
An siRNA compound that inhibits CFB and is 30 or 33 nucleosides long, comprising one of two specified pairs of nucleobase sequences with the first sequence linked directly to the second. At least one sugar and at least one internucleoside linkage may optionally be modified.
The claim covers a CFB-inhibiting siRNA defined by its nucleoside length and directly linked sequence-pair structure, with optional sugar or internucleoside-linkage modifications.
Stated Advantages
The reported HepG2 screening result shows CFB knockdown of 69–93% among 30 selected constructs.
In cynomolgus monkeys and non-human primates, the described constructs reduced plasma Factor Bb and CFB expression, with maximum suppression reported as 74% for construct 106-13(4) and reductions sustained through week 13.
In humanized-liver mice, both described constructs reduced CFB mRNA and protein, with construct 106-13(4) generally outperforming 13(5) and a 64% Factor Bb reduction reported at six weeks after [procedural detail omitted for safety].
Documented Applications
Treatment of age-related macular degeneration, including dry AMD and geographic atrophy; paroxysmal nocturnal hemoglobinuria; atypical hemolytic uremic syndrome; C3 glomerulopathy; Ig-mediated kidney pathologies, including IgA nephropathy and primary membranous nephropathy; and asthma.
Treatment of rheumatic and autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus, ANCA vasculitis, antiphospholipid antibody syndrome, glomerulonephritis, psoriasis, dermatomyositis, bullous pemphigoid, myasthenia gravis, and neuromyelitis optica.
Treatment of Shiga toxin E. coli-related hemolytic uremic syndrome, dense deposit disease, C3 neuropathy, cold agglutinin disease, humoral and vascular transplant rejection, graft dysfunction, myocardial infarction, sensitization towards a transplant, sepsis, complement system dysfunction, and CFB-related disorders.
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