SHK-based pharmaceutical compositions and methods of manufacturing and using the same

• US 9,878,058 B2
• Filed: 08/26/2015
• Issued: 01/30/2018
• Est. Priority Date: 06/06/2011
• Status: Active Grant

• Current Assignee: TEKV Therapeutics LLC
• Original Assignee: Kv1.3 Therapeutics, Inc.
• Inventors: Iadonato, Shawn P., Tarcha, Eric J.
• Primary Examiner(s): Ahmed, Hasan
• Assistant Examiner(s): D' AMBROSIO, THEA
• Application Number:
  US14/836,700
• Publication Number:
  US 20160045627A1
• Time in Patent Office: 888 Days
• Field of Search: None
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/1767 from invertebrates
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 51/0482 chelates from cyclic ligands, e.g. DOTA
• CPC Class Codes: A61K 51/088 conjugates with carriers being peptides, polyamino acids or proteins antibodies A61K51/10
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: B01L 3/12 : Gas jars or cylinders
• CPC Class Codes: C07K 14/00 : Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• CPC Class Codes: C07K 14/43504 : from invertebrates

Abstract

Disclosed herein are pharmaceutical compositions having the sequence Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Xaa-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys (SEQ ID NO:1). The disclosed compositions can include an acid or amide at the C-terminus of SEQ ID NO: 1 and the polypeptide can be attached to an organic or inorganic chemical entity that has an anionic charge. The polypeptide can be detectably labeled for diagnostic purposes. Methods of manufacturing and using the pharmaceutical compounds are also disclosed.

Claims

1. A pharmaceutical composition comprising a pharmaceutically acceptable salt of an ShK polypeptide having the sequence of SEQ ID NO:

5, wherein the C-terminus is an amide, and wherein the pH of the pharmaceutical composition is between 5 and 7 and the pharmaceutical composition further comprises a surfactant in an amount effective to dissolve the ShK polypeptide in an aqueous carrier.

2. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition is contained in a sterile glass vial and is stored at −

70°

C.

3. The pharmaceutical composition of claim 1 formulated for subcutaneous administration.

4. The pharmaceutical composition of claim 1 wherein the pharmaceutical composition is contained in a sterile syringe.

5. A unit of manufacture for pharmaceutical use comprising:

a pharmaceutical composition comprising a pharmaceutically acceptable salt of an ShK polypeptide having the sequence of SEQ ID NO;

5, wherein the C-terminus is an amide and instructions for diluting and preparing the pharmaceutical composition for administration to a human, wherein the pH of the pharmaceutical composition is between 5 and 7 and the pharmaceutical composition further comprises a surfactant in an amount effective to dissolve the ShK polypeptide in an aqueous carrier, and wherein the pharmaceutical composition is contained in at least one glass vial prepared under sterile conditions such that the pharmaceutical composition within the at least one glass vial is stable for at least six months at −

70°

C.

6. A unit of manufacture for pharmaceutical use comprising:

a pharmaceutical composition comprising a pharmaceutically acceptable salt of an ShK polypeptide having the sequence of SEQ ID NO;

5, wherein the C-terminus is an amide and instructions for administering the pharmaceutical composition to a human, wherein the pH of the pharmaceutical composition is between 5 and 7 and the pharmaceutical composition further comprises a surfactant in an amount effective to dissolve the ShK polypeptide in an aqueous carrier, and wherein the pharmaceutical composition is contained in at least one sterile syringe.