# US 12,600,967 B2 · SiRNA compound that inhibits complement factor B (CFB)

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- Number: US 12,600,967 B2
- Document ID: US12600967B2
- Status: Granted
- Kind: B2
- Application number: 17/867,404
- Filed: 2022-07-18
- Published: 2023-05-04
- Granted: 2026-04-14
- Earliest claimed: 2021-07-17
- Assignees: Sirnaomics, Inc.
- Applicants: Sirnaomics, Inc.
- Inventors: Dmitry Samarsky
- Web page: https://patentgrep.com/patent/US12600967B2

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/712: Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/315: Phosphorothioates
- C12N 2310/351: Conjugate
- C12N 2310/531: Stem-loop; Hairpin
- C12N 2320/11: for the determination of target sites, i.e. of active nucleic acids
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 1

An siRNA compound that inhibits complement factor B (CFB), comprising
(a) a first nucleobase sequence that is SEQ ID NO:251 linked directly to a second nucleobase sequence that is SEQ ID NO:503, or
(b) a first nucleobase sequence that is SEQ ID NO:252 linked directly to a second nucleobase sequence that is SEQ ID NO:504;
wherein said compound is 30 or 33 nucleosides long,
wherein optionally at least one sugar in the siRNA is modified, and
wherein optionally at least one internucleoside linkage is modified.

### Claim 2 (depends on 1)

The siRNA according to claim 1, having the sequence of SEQ ID NO:755.

### Claim 3 (depends on 1)

The siRNA according to claim 1, having the sequence of SEQ ID NO:756.

### Claim 4 (depends on 1)

The siRNA according to claim 1, which further comprises one or more ligands, wherein said ligand optionally comprises at least one carbohydrate.

### Claim 5 (depends on 4)

The siRNA according to claim 4, wherein said one or more carbohydrates comprise one or more N-Acetyl-Galactosamine moieties.

### Claim 6 (depends on 1)

The siRNA according to claim 1, wherein sugars of the nucleosides at any of positions 2 and 14 downstream from the first nucleoside of the 5′ end do not contain 2′-O-methyl modifications.

### Claim 7 (depends on 1)

The siRNA according to claim 1, wherein sugars of the nucleosides at any of positions 9 to 11 downstream from the first nucleoside of the 5′ end contain 2′-F modifications.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, and a physiologically acceptable excipient.

### Claim 9 (depends on 1)

A method of treating a disease or disorder, comprising administering to a subject suffering from said disorder an effective amount of a compound according to claim 1, wherein said disease or disorder is selected from autoimmune disease, complement system dysfunction including aberrant upregulation of complement components such as CFB, age-related macular degeneration (AMD) including dry AMD and geographic atrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), Ig-mediated kidney pathologies such as IgA nephropathy and primary membranous nephropathy, asthma, rheumatic disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, antiphospholipid antibody syndrome (APS), glomerulonephritis, psoriasis, dermatomyositis bullous pemphigoid, Shiga toxin E. coli-related hemolytic uremic syndrome, myasthenia gravis (MG), neuromyelistis optica (NMO), dense deposit disease, C3 neuropathy, cold agglutinin disease, humoral and vascular transplant rejection, graft dysfunction, myocardial infarction, sensitization towards a transplant, and sepsis.