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US 2024/0254166 A1Published application
Compositions and methods for inhibiting an inflammatory response and treating inflammatory diseases
AssigneeThe Regents of the University of California
InventorsSteven A. GOLDSTEIN, Ruiming Zhao
Life of this patent
Estimating the term…
Abstract
In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for inhibiting the ability of neutrophils, or polymorphonuclear leukocytes (PMNs), to release reactive oxygen species (ROS), thus also inhibiting or ameliorating neutrophil (PMN) contribution to an inflammatory response, thus also treating, ameliorating or preventing neutrophil (PMN)-meditated inflammatory-related pathologies such as acute respiratory distress syndrome (ARDS), including ARDS caused by a viral infection such as COVID-19.
Claims15
1:
- A synthetic or recombinant peptide for inhibiting activity of a voltage-gated proton channel polypeptide (Hv1), wherein the synthetic or recombinant peptide comprises:
- (a) an amino acid sequence QXHQFEXXXX (SEQ ID NO:1);
- (b) an amino acid sequence QAHQFEAXXX (SEQ ID NO:2);
- (c) an amino acid sequence QAHQFEALLL (SEQ ID NO:3), or
- (d) a homodimer or a heterodimer comprising a peptide of (a), (b), or (c),
- wherein X is any hydrophobic amino acid, and optionally the hydrophobic amino acid is glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I) or phenylalanine (F).
3 more elements
2:
- A recombinant nucleic acid encoding a synthetic or recombinant peptide of claim 1.
3:
- An expression vehicle comprising or having contained therein a recombinant nucleic acid of claim 2, wherein optionally the expression vehicle comprises or is an expression cassette, a plasmid, an expression vector or a recombinant virus.
4:
- A cell comprising or having contained therein a synthetic or recombinant peptide of claim 1.
5:
- A pharmaceutical composition comprising:
- a synthetic or recombinant peptide of claim 1.
6:
- The pharmaceutical composition of claim 4, formulated as a liposome, a dendrimer or a nanoparticle;
- or formulated as an aerosol, a lyophilate or a powder.
7:
- A method for:
- inhibiting intracellular alkalization, initiating capacitation, acrosomal reaction, and oocyte fertilization capabilities of human sperm,
- inhibiting the ability of neutrophils, or polymorphonuclear leukocytes (PMNs), to release reactive oxygen species (ROS),
- inhibiting or ameliorating neutrophil (PMN) contribution to an inflammatory response, or
- treating, ameliorating or preventing a neutrophil (PMN)-meditated inflammatory-related pathology,
- comprising:
- administering to an individual in need thereof:
- (a) a synthetic or recombinant peptide as set forth in claim 1, a recombinant nucleic acid encoding the recombinant peptide, an expression vehicle having contained therein the nucleic acid, a cell having contained therein the nucleic acid, or a pharmaceutical composition having contained therein or comprising the nucleic acid or synthetic or recombinant peptide, or
- (b) a synthetic peptide for inhibiting activity of a voltage-gated proton channel polypeptide (Hv1), wherein the synthetic peptide comprises a structure:
- (i) of about 10 to about 100 amino acids in length;
- (ii) having an amino acid sequence that comprises one or more toxin sequence elements, each of which has a length within a range of about 5 to about 18 amino acids in length;
- (iii) a peptide component has 0, 1, 2, 3, 4, 5, or 6 conserved cysteine residues of an ICK structural motif;
- (iv) has 0, 1, 2, or 3 disulfide bridges;
- and
- (v) has 0, 1, 2, or 3 beta strands,
- wherein optionally the synthetic peptide has a sequence comprising or consisting of:
- (SEQ ID NO:
- 4)
- SSTCIPSGQPCADSDDCCETFHCKWVFFTSKFMCRRVWGKD
- (also called “C6”),
- or
- (SEQ ID NO:
- 5)
- GCKWYLGDCADSDDCCETFHCKWVFFTSKFMCRRVWGKD
- (also called “C5”),
- a homodimer comprising two peptides (SEQ ID NO:4) (also called “C6”) or two peptides (SEQ ID NO:5) (also called “C5”), or a heteroduplex of (SEQ ID NO:4) and (SEQ ID NO:5),
- or a sequence as described in U.S. patent application publication no:
- US 2019 0330285 A1.
25 more elements
8:
- The method of claim 7, wherein the neutrophil (PMN)-meditated inflammatory-related pathology is acute respiratory distress syndrome (ARDS),
- and optionally ARDS caused by a viral, bacterial or fungal infection;
- a sepsis;
- pancreatitis;
- trauma or injury;
- pneumonia;
- or, aspiration into the lungs.
4 more elements
9:
- The method of claim 7, wherein the synthetic or recombinant peptide, or the recombinant nucleic acid encoding the recombinant peptide, or the cell, or the pharmaceutical composition, is formulated and/or administered as a liposome, a dendrimer or a nanoparticle;
- or formulated or administered as an aerosol, a lyophilate or a powder.
10:
- A kit comprising a synthetic or a recombinant peptide of claim 1, a recombinant nucleic acid encoding the recombinant peptide, an expression vehicle having contained therein the nucleic acid, a cell having contained therein the nucleic acid, or a pharmaceutical composition having contained therein or comprising the nucleic acid or synthetic or recombinant peptide.
(canceled)
12:
- A synthetic or a recombinant peptide for inhibiting activity of a voltage-gated proton channel polypeptide (Hv1), wherein the synthetic peptide consists of:
- (a) an amino acid sequence QXHQFEXXXX (SEQ ID NO:1);
- (b) an amino acid sequence QAHQFEAXXX (SEQ ID NO:2);
- (c) an amino acid sequence QAHQFEALLL (SEQ ID NO:3), or
- (d) a homodimer comprising a peptide of (a), (b), or (c),
- wherein X is any hydrophobic amino acid, and optionally the hydrophobic amino acid is glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I) or phenylalanine (F).
3 more elements
13:
- The method of claim 7, wherein the neutrophil (PMN)-meditated inflammatory-related pathology is caused by a viral infection, and optionally the viral infection is an influenza or a coronavirus infection, and optionally the coronavirus infection is a COVID-19 infection.
14:
- The method of claim 7, wherein the synthetic or recombinant peptide is formulated and/or administered as a liposome, a dendrimer or a nanoparticle;
- or formulated or administered as an aerosol, a lyophilate or a powder.
(canceled)
Dependencies are inferred from the claim text.