Amgen Inc.

Stefan I McDonough

Leslie Phillip Miranda

Kenneth William Walker

Shaw-Fen Sylvia Hu

Colin V Gegg

John Kevin Sullivan

Hung Q Nguyen

Joseph G McGivern

Justin K Murray

Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Na1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Na1.7 and/or Na1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

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Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Disclosed is a DNA encoding a composition of matter of the formula(X)&#x2014;(F)&#x2014;(X)&#x2014;(F)&#x2014;(X)&#x2003;&#x2003;(I)and multimers thereof, in which Fand Fare half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X, X, and Xare each independently -(L)-P-(L)-, and f and g are each independently 0 or 1; P is a ShK peptide analog of no more than about 80 amino acid residues in length; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. A DNA encoding the ShK peptide analog is disclosed. Also disclosed are an expression vector comprising the DNA, and a host cell comprising the expression vector.

Toxin peptide therapeutic agents

Disclosed is a composition of matter of the formula(X)&#x2014;(F)&#x2014;(X)&#x2014;(F)&#x2014;(X)&#x2003;&#x2003;(I)and multimers thereof, in which Fand Fare half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X, X, and Xare each independently -(L)-P-(L)-, and f and g are each independently 0 or 1; P is a toxin peptide of no more than about 80 amino acid residues in length, comprising at least two intrapeptide disulfide bonds; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. Linkage to the half-life extending moiety or moieties increases the in vivo half-life of the toxin peptide, which otherwise would be quickly degraded. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are a DNA encoding the inventive composition of matter, an expression vector comprising the DNA, and a host cell comprising the expression vector. Methods of treating an autoimmune disorder, such as, but not limited to, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, asthma, allergy, restinosis, systemic sclerosis, fibrosis, scleroderma, glomerulonephritis, Sjogren syndrome, inflammatory bone resorption, transplant rejection, graft-versus-host disease, and lupus and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.

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San Francisco, CA, United States of America

Stefan I McDonough