US 10,512,669 B2Granted

Blockade of inflammatory proteases with cyclic peptides

AssigneeThe Regents of the University of California

InventorsMichael E. Selsted, Dat Q. Tran

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Abstract

Drug compositions for treatment of one or more inflammatory conditions can includes at least one of a θ-defensin, analog or derivative thereof. Inventive methods include researching θ-defensins, analogs or derivatives thereof for their efficacy with respect to anti-inflammatory effects, and providing such compositions to the marketplace for the purpose of treating inflammatory conditions. Of particular interest are drug compositions effective to produce clinically relevant inhibition of tumor necrosis factor alpha (TNF-α)-converting enzyme (TACE) or other proinflammatory proteases, and/or sheddases. it is contemplated that preferred compositions can be used to treat rheumatoid arthritis, inflammatory bowel disease, and other chronic inflammatory diseases, autoimmune diseases, cancer, and Alzheimer's, osteoarthritis, inflammation-related neurodegenerative and other inflammation-related diseases.

Claims13

Dependent claims

A method of screening peptides for use in treating inflammatory diseases or conditions, comprising:

obtaining a plurality of synthetic cyclic tetradecapeptide mini-θ-defensins, wherein each of the plurality of synthetic cyclic tetradecapeptide mini-θ-defensins has two disulfide bonds between respective pairs of cysteine residues, and is encoded by a polynucleotide that has between 20% and 85% sequence identity with SEQ. ID NO 1;
performing a proinflammatory protease inhibition assay utilizing a living cell for individual synthetic cyclic tetradecapeptide mini-θ-defensins of the plurality of synthetic cyclic tetradecapeptide mini-θ-defensins;
segregating a subset of candidate peptides that demonstrate a TACE inhibiting activity from the plurality of synthetic cyclic tetradecapeptide mini-θ-defensins;
and
administering individual candidate peptides from the subset of candidate peptides to an animal model of inflammatory disease or conditions to determine an anti-inflammatory effect in the animal model of inflammatory disease or condition.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/486,548Filed 1 Jun 2012 · us provisional application
Priority: 2 Jun 2011
Published: US 2013/0157964 A120 Jun 2013
Granted: 24 Dec 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification28 codes

A61K 38/1729
From mammals: cationic antimicrobial peptides, e.g. defensins
A61K 9/0053
Galenical forms characterised by the site of application: mouth and digestive tract, i.e. intraoral and peroral administration
A61K 38/10
Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof: peptides having 12 to 20 amino acids
A61K 38/12
Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof: cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins…