Treatment of age-related macular degeneration using RNA complexes that target MyD88 or TLR3
Inventors
Lee, Dong-Ki • Hong, Sun Woo • Hong, Isu • Hwang, Jihye
Assignees
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Publication Number
US-10590423-B2
Publication Date
2020-03-17
Expiration Date
Abstract
In certain aspects, provided herein are RNA complexes that inhibit Myeloid differentiation primary response gene 88 (MyD88) and/or Toll-like receptor 3 (TLR3) and are useful in the treatment of age-related macular degeneration (AMD). In certain aspects, provided herein are pharmaceutical compositions comprising such RNA complexes and methods of using such RNA complexes and pharmaceutical compositions.
Core Innovation
The invention relates to a method of treating age-related macular degeneration (AMD) in a subject by administering an RNA duplex. The RNA duplex includes an antisense strand of at least 19 nucleotides in length and a sense strand of 16 nucleotides in length, where the antisense strand comprises SEQ ID NO: 54 or SEQ ID NO: 56 and the sense strand is SEQ ID NO: 53 or SEQ ID NO: 55.
In the RNA duplex complex, the 5′ end of the antisense strand and the 3′ end of the sense strand form a blunt end. A cholesterol moiety is attached to the 3′ end of the sense strand, and the duplex is configured as an antisense/sense RNA duplex complex for AMD treatment.
The invention further describes RNA duplexes and related compositions as RNA complexes that inhibit MyD88 and/or TLR3, including MyD88 mRNA and TLR3 mRNA knockdown and corresponding MyD88 protein and TLR3 protein knockdown outcomes. The document also describes optional chemical modifications such as 2′-O-methylated nucleosides and phosphorothioate bonds, and provides eye-targeted pharmaceutical compositions for treating wet and/or dry AMD, including optional combination with an anti-VEGF therapeutic.
Claims Coverage
The partial content provided includes one independent claim (clm-00001). The independent claim focuses on a treating method for AMD using a specific RNA duplex architecture and strand composition, including defined strand identities and end structure, plus a cholesterol moiety attachment.
Cholesterol-modified blunt-ended antisense/sense RNA duplex for AMD treatment
Administering to a subject an RNA duplex comprising an antisense strand of at least 19 nucleotides and a sense strand of 16 nucleotides, wherein the antisense strand comprises SEQ ID NO: 54 or SEQ ID NO: 56, the sense strand is SEQ ID NO: 53 or SEQ ID NO: 55, a cholesterol moiety is attached to the 3′ end of the sense strand, and the antisense 5′ end and sense 3′ end form a blunt end.
Based on the provided independent claim, inventive coverage is centered on administering a specific cholesterol-modified RNA duplex having defined antisense/sense SEQ ID selections and a blunt-end complex architecture for treating age-related macular degeneration.
Stated Advantages
Documented Applications
Treating wet and/or dry age-related macular degeneration (AMD) by administering a cholesterol-modified antisense/sense RNA duplex (intravitreal and/or topical eye-targeted pharmaceutical compositions).
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