Aptamers for personal health care applications
Inventors
Velasquez, Juan Esteban • Rupard, Spencer Christopher • Trejo, Amy Violet • PITZ, Adam Michael • Schmeichel, Kelly Lee • Swigart, Erin Nicole • Penner, Gregory Allen • NAMANJA-MAGLIANO, Hilda Andamiche • Wagner, Matthew Scott
Assignees
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Publication Number
US-12584137-B2
Publication Date
2026-03-24
Expiration Date
Abstract
An aptamer composition is disclosed which has one or more oligonucleotides that include at least one of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof. The aptamer composition has a binding affinity for one or more cellular membrane glycoproteins selected from the group consisting of: intercellular adhesion molecule 1 (ICAM-1), low-density lipoprotein receptor (LDLR) family members, and cadherin-related family member 3 (CDHR3), preferably intercellular adhesion molecule 1 (ICAM-1), and is configured to reduce the binding of one or more human rhinoviruses to the intercellular adhesion molecule 1 (ICAM-1).
Core Innovation
The invention provides an aptamer composition comprising at least one oligonucleotide that has binding affinity for intercellular adhesion molecule 1 (ICAM-1) and is configured to reduce the binding of one or more human rhinoviruses to ICAM-1. The oligonucleotide consists of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof, and forms a secondary structure from a 5′-end to a 3′-end comprising at least a stem, a hairpin loop, and a 3′-dangling end.
The secondary structure further comprises at least the motif GAGGYYZ, wherein Y and Z are absent or selected from guanine (G), cytosine (C), adenine (A), thymine (T) or uracil (U), and the GAGGYYZ motif is at least partially not hybridized. The document also describes a secondary-structure architecture with a 5′-dangling end and a stem formed between the hairpin loop and the dangling ends, together with motif positional constraints associated with the 3′-dangling end.
The invention further includes personal health care compositions comprising the ICAM-1-binding aptamer composition with the specified secondary-structure architecture and motif constraint. It also provides a method of inhibiting human rhinovirus infection by inhibiting binding of human rhinovirus to ICAM-1 of epithelial cells, with embodiments that narrow the epithelial-cell context to the upper respiratory tract and specify delivery by spraying.
Claims Coverage
The independent claims cover three related aspects: an aptamer composition, a personal health care composition, and a method of inhibiting infection. Across the claims, the main inventive features are an ICAM-1-binding aptamer configured to reduce human rhinovirus binding, a defined secondary-structure architecture with stem, hairpin loop, and dangling ends, and the GAGGYYZ motif constraint with the motif at least partially not hybridized.
ICAM-1 binding aptamer reducing rhinovirus binding
An aptamer composition comprising at least one oligonucleotide consisting of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof, wherein the aptamer composition has binding affinity for intercellular adhesion molecule 1 (ICAM-1) and is configured to reduce the binding of one or more human rhinoviruses to ICAM-1.
Defined 5′ to 3′ secondary structure with stem, hairpin loop, and dangling ends
The aptamer composition comprises at least one oligonucleotide forming a secondary structure from a 5′-end to a 3′-end comprising at least a stem, a hairpin loop, and a 3′-dangling end, with related claim language also reciting a 5′-dangling end and a stem formed between the hairpin loop and the dangling ends.
GAGGYYZ motif constraint with Y and Z absent or selected and at least partially not hybridized
The secondary structure comprises at least the motif GAGGYYZ, wherein Y and Z are absent or selected from guanine (G), cytosine (C), adenine (A), thymine (T) or uracil (U), and wherein the GAGGYYZ motif is at least partially not hybridized.
Personal health care composition containing the ICAM-1-binding aptamer architecture
A personal health care composition comprising the ICAM-1-binding aptamer composition with the same binding affinity for ICAM-1, the same reduction of human rhinovirus binding to ICAM-1, the same secondary-structure architecture, and the same GAGGYYZ motif constraint.
Method of inhibiting human rhinovirus infection via inhibition of binding to epithelial-cell ICAM-1
A method of inhibiting human rhinovirus infection by inhibiting binding of the human rhinovirus to ICAM-1 of epithelial cells comprising applying the aptamer composition with the same ICAM-1-binding affinity, the same reduction of human rhinovirus binding to ICAM-1, the same secondary-structure architecture, and the same GAGGYYZ motif constraint.
The claim coverage is anchored by ICAM-1-binding aptamer compositions configured to reduce binding of human rhinoviruses to ICAM-1, with a specified 5′-to-3′ secondary-structure architecture including stem, hairpin loop, and dangling ends. All independent claims require the GAGGYYZ motif with Y and Z constrained to being absent or selected from G, C, A, T, or U, and the GAGGYYZ motif is at least partially not hybridized.
Stated Advantages
Reduces binding of one or more human rhinoviruses to ICAM-1.
Inhibits human rhinovirus infection by inhibiting binding of human rhinovirus to ICAM-1 of epithelial cells.
Preferential binding to human nasal epithelial (HNEpC) cells over HEK293 cells.
Demonstrates strong ICAM-1 binding kinetics with specificity controls.
Improved ICAM-1 binding for truncated aptamer variants on HNEpC.
Temperature-dependent binding behavior is described via changes in motif hybridization and secondary structure affecting binding affinity.
Documented Applications
Inhibiting human rhinovirus infection by inhibiting binding of human rhinovirus to ICAM-1 of epithelial cells.
Use in a personal health care composition comprising the ICAM-1-binding aptamer composition.
Application in epithelial cells of the upper respiratory tract, with delivery described as spraying.
Preventing or treating rhinovirus-driven cold symptoms via upper respiratory tract delivery of the aptamer or personal health care compositions, including nasal/throat formulations and spraying.
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