Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
A61K 8/64 - ProteinsPeptidesDerivatives or degradation products thereof
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The yc-family Interleukin-2 (IL-2), Interleukin-9 (IL-9), and Interleukin-15 (IL-15) cytokines are associated with important human diseases, such as cytokine-release syndrome and cytokine storm associated disorders. Compositions, methods, and kits to modulate signaling by at least one IL-2, IL-9, or IL-15 γc-cytokine family members for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one cytokine storm related disorder are described.
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
Embodiments relate to peptide antagonists of γc-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting γc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/receptor subunit. However, success has been limited and often multiple γc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.
The γc-family Interleukin-2 (IL-2), Interleukin-9 (IL-9), and Interleukin-15 (IL-15) cytokines are associated with important human diseases, such as cytokine-release syndrome and cytokine storm associated disorders. Compositions, methods, and kits to modulate signaling by at least one IL-2, IL-9, or IL-15 γc-cytokine family members for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one cytokine storm related disorder are described.
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
A61K 8/64 - ProteinsPeptidesDerivatives or degradation products thereof
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/14 - Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 17/14 - Drugs for dermatological disorders for baldness or alopecia
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/02 - Drugs for disorders of the nervous system for peripheral neuropathies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
8.
MODULATING THE EFFECTS OF GAMMA-C-CYTOKINE SIGNALING FOR THE TREATMENT OF ALOPECIA AND ALOPECIA ASSOCIATED DISORDERS
The yc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as alopecia and alopecia associated disorders. Compositions, methods, and kits to modulate signaling by at least one yc-cytokine family member for inhibiting, ameliorating, reducing a severity of, treating, delaying the onset of, or preventing at least one alopecia related disorder are described.
Embodiments relate to peptide antagonists of γc-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting yc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/′ receptor subunit. However, success has been limited and often multiple γc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
Disclosed herein are stable peptide antagonists based on the consensus yc-subunit binding site to inhibit the activity of yc-cytokines. Such peptide antagonists are capable of inhibiting the activity of multiple yc-cytokine family members. The yc-family cytokines are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of yc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools.
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 8/64 - ProteinsPeptidesDerivatives or degradation products thereof
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
Embodiments relate to peptide antagonists of ƴc-farnily cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of ƴc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting yc-cytokine activity involve raising neutralizing antibodies against each individual ƴc-cytokine family member/' receptor subunit. However, success has been limited and often multiple ƴc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus ƴc-subunit binding site to inhibit ƴc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul -Block activity, inhibiting the activity of multiple ƴc-cytokine family members.
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
A61Q 7/00 - Preparations for affecting hair growth
A61K 47/48 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers, inert additives the non-active ingredient being chemically bound to the active ingredient, e.g. polymer drug conjugates
15.
Methods of developing selective peptide antagonists
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
G06F 19/16 - for molecular structure, e.g. structure alignment, structural or functional relations, protein folding, domain topologies, drug targeting using structure data, involving two-dimensional or three-dimensional structures
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
16.
COMPOSITIONS AND MEHTHODS FOR MODULATING GAMMA-C-CYTOKINE ACTIVITY
The vanous embodiments relate to peptide antagonists of yc-family cytokines, lnterleukin-2 (IL-2), lnterleukin-4 (IL-4), lnterieukin-7 (IL-7), lnterleukin-9 (IL-9), lnterteukin-15 (IL-15), and lnterteukin-21 (IL-21 ). The yc-cytokines are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of yc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting yc-cytokine activity involve raising neutralizing antibodies against each individual yc-cytokine family member/ receptor subunit. However, success has been limited and often multiple yc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus yc-subunit binding site to inhibit yc-cytokine activity.
patents
