Nucleic acid molecule with anti-inflammatory and anti-coagulant and organ-protective properties

Inventors

JEDLINA, Luiza Anna

Assignees

APTAHEM AB

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Publication Number

US-11110115-B2

Patent

Publication Date

2021-09-07

Expiration Date


Abstract

The invention relates to a nucleic acid molecule or a composition comprising said molecule for use as an anti-inflammatory and/or anti-coagulant and/or organ-protective medicament. The invention also relates to a use of said nucleic acid molecule or said composition, for the manufacture of a medicament for preventing, treating, regressing, curing and/or delaying a disease or a condition wherein inflammation and/or coagulation and/or organ damage or failure occurs in an individual. Finally, the invention further relates to a method for alleviating one or more symptom(s) and/or characteristic(s) and/or for improving a parameter of a disease or condition wherein inflammation and/or coagulation and/or organ damage or failure occur in an individual, the method comprising administering to said individual said nucleic acid molecule or said composition.

Core Innovation

The document describes nucleic acid molecules comprising the nucleotide sequences set forth as SEQ ID NO:1 or SEQ ID NO:2, including nucleotide sequences at least 95% identical thereto, and pharmaceutical compositions comprising the nucleic acid molecule with a pharmaceutically acceptable carrier, adjuvant, salt, diluent and/or excipient. The nucleic acid molecule is described with SEQ ID NO:2 as fluorinated for plasma stability, including fluorinated pyrimidines (U_F, C_F). The described nucleic acid molecules are associated with addressing inflammation and/or coagulation and/or organ damage or failure in an individual.

The document positions the invention as a method for alleviating one or more symptom(s) and/or characteristic(s), and/or improving a parameter of a disease or condition, wherein inflammation and/or coagulation and/or organ damage or failure occur. It includes administering an effective amount of the nucleic acid molecule and/or a pharmaceutical composition to an individual, with disease/condition scope linked to inflammation, coagulation, and organ damage or failure. The targets include anti-inflammatory cytokines such as IL-10 and pro-inflammatory cytokines such as IL-1β, IL-6, and TNFα, along with coagulation parameters and organ injury biomarkers.

In the reported findings, the nucleic acid molecule corresponding to SEQ ID NO:2 is described in rat and mouse models and is associated with prolonged bleeding time and altered coagulation indices, reduced thrombus formation, and effects on coagulation readouts including APTT and thrombin/fibrin clot density, as well as changes in D-dimers and fibrin-related measures. The document further reports effects in inflammatory and immune readouts in a lipopolysaccharide (LPS)-induced cytokine production model, including reduced pro-inflammatory cytokines and altered immune/inflammatory markers. Survival improvement in an LPS-induced shock model and improvements in liver and kidney-related serum markers and D-dimer levels are also described.

Claims Coverage

The provided set includes three independent claims, centered on administering an effective amount of nucleic acid molecules defined by SEQ ID NO:1 or SEQ ID NO:2 (or variants with at least 95% identity) and optionally formulated in a pharmaceutical composition with pharmaceutically acceptable carriers/excipients. Across the independent claims, the inventive features concentrate on the defined nucleic acid sequences and their use in inflammation, coagulation, and organ damage or failure contexts.

Nucleic acid defined by SEQ ID NO:1 or SEQ ID NO:2 with at least 95% identity

The method administers a nucleic acid molecule comprising the nucleotide sequence set forth as SEQ ID NO:1 or a nucleotide sequence at least 95% identical thereto, or comprising the nucleotide sequence set forth as SEQ ID NO:2 or nucleotide sequence at least 95% identical thereto.

Method for alleviating symptoms and improving disease parameters

An individual receives an effective amount of the nucleic acid molecule or a pharmaceutical composition comprising it to alleviate one or more symptom(s) and/or characteristic(s) and/or improve a parameter of a disease or condition wherein inflammation and/or coagulation and/or organ damage or failure occur.

Method for preventing, treating, regressing, curing and delaying disease or condition

The method includes administering to an individual in need thereof an effective amount of a nucleic acid molecule comprising SEQ ID NO:1 or SEQ ID NO:2, or sequences at least 95% identical thereto, and/or a pharmaceutical composition comprising the nucleic acid molecule.

Inhibiting and preventing coagulation of blood

A method is directed to inhibiting and/or preventing coagulation of the blood in a subject by administering an effective amount of a nucleic acid molecule comprising SEQ ID NO:1 or SEQ ID NO:2, or at least 95% identical sequences, and a pharmaceutical composition with a pharmaceutically acceptable carrier, adjuvant, salt, diluent and/or excipient.

The independent claims rely on administering effective amounts of nucleic acid molecules defined by SEQ ID NO:1 or SEQ ID NO:2, with variants at least 95% identical, and/or related pharmaceutical compositions, for alleviating symptoms, improving parameters, preventing, treating, regressing, curing or delaying disease or condition, and inhibiting and/or preventing coagulation of blood in contexts where inflammation and/or coagulation and/or organ damage or failure occur.

Stated Advantages

Alleviation of one or more symptom(s) and/or characteristic(s) of a disease or condition.

Improving a parameter of a disease or condition where inflammation and/or coagulation and/or organ damage or failure occur.

Preventing, treating, regressing, curing and/or delaying a disease or condition involving inflammation and/or coagulation and/or organ damage or failure.

Inhibiting and/or preventing coagulation of the blood.

Documented Applications

Methods for alleviating symptoms and/or characteristics and/or improving parameters of diseases or conditions where inflammation and/or coagulation and/or organ damage or failure occur.

Preventing, treating, regressing, curing and/or delaying diseases or conditions involving inflammation and/or coagulation and/or organ damage or failure.

Inhibiting and/or preventing coagulation of blood in a subject.

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