D-ENANTIOMERIC PEPTIDES FOR THE THERAPY OF CHRONIC AND NEUROPATHIC PAIN

• US 20190314447A1
• Filed: 12/21/2017
• Published: 10/17/2019
• Est. Priority Date: 12/23/2016
• Status: Active Grant

• Current Assignee: Priavoid GmbH
• Original Assignee: Forschungszentrum Jã¼Lich GmbH (Bundesrepublik Deutschland)
• Inventors: WILLBOLD, Dieter, JUERGENS, Dagmar, KUTZSCHE, Janine, CASTRO, Gustavo Adolfo Guzman, JIMENEZ, Patricia Hidalgo
• Granted Patent: US 11,224,632 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/1787 for neuromediators, e.g. serotonin receptor, dopamine receptor
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/28 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
• 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: C07K 11/00 Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
• CPC Class Codes: C07K 11/02 cyclic, e.g. valinomycins ; Derivatives thereof
• CPC Class Codes: C07K 7/00 Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: C07K 7/50 Cyclic peptides containing at least one abnormal peptide link
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: C07K 9/00 Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof

Abstract

The present invention relates to a composition consisting of or containing peptides selected from the group consisting of or containing RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3 and also polymers containing or consisting of RD2/D3 homologs having at least 50% identity and derivatives of RD2 and under D3 for use as an analgesic, for use in pain therapy, for use in the treatment of chronic and/or neuropathic pain and/or for inhibiting N-type neuronal calcium channels (NCCs).

Claims

1-15. -15. (canceled)

16. A method of treating pain and/or of inhibiting N-type neuronal calcium channels (NCCs), wherein the method comprises administering to a subject in need thereof a therapeutically effective amount of a composition consisting of or comprising one or more peptides selected from RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3, and also polymers comprising or consisting of RD2, D3, homologs having at least 50% identity and derivatives of RD2 and D3.

17. The method of claim 16, wherein chronic pain is treated.

18. The method of claim 16, wherein neuropathic pain is treated.

19. The method of claim 16, wherein NCCs are blocked.

20. The method of claim 16, wherein the peptides are composed essentially of D-enantiomers.

21. The method of claim 16, wherein the one or more peptides comprise one or more peptides selected from RD2, homologs having at least 50% identity and derivatives of RD2, and also polymers comprising or consisting of RD2, homologs having at least 50% identity and derivatives of RD2.

22. The method of claim 16, wherein the one or more peptides comprise one or more peptides selected from D3, homologs having at least 50% identity and derivatives of D3, and also polymers comprising or consisting of D3, homologs having at least 50% identity and derivatives of D3.

23. The method of claim 16, wherein the peptides are administered in a dose of from 1 μ

g to 1 g per kilo of body weight.

24. The method of claim 16, wherein the composition is administered by one or more of intravenous, subcutaneous, intraperitoneal, intranasal or oral administration.

25. The method of claim 16, wherein the composition is administered orally.

26. The method of claim 19, wherein the composition has an IC₅₀ value of 1 nanomolar to 1 millimolar for N-type NCCs.

27. The method of claim 16, wherein a derivative of RD2 or D3 is administered.

28. The method of claim 27, wherein the derivative is a cyclized peptide.

29. The method of claim 27, wherein the derivative is an amidated peptide.

30. The method of claim 16, wherein the peptide is linked to one or more of amino acids, linkers, spacers, functional groups and/or further substances.

31. A method of reducing the release of neurotransmitters compared to a control in a subject in need thereof, wherein the method comprises contacting a composition consisting of or comprising peptides selected from RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3, and also polymers comprising RD2, D3, homologs having at least 50% identity and derivatives of RD2 and/or D3 for use as an analgesic in the subject in need thereof with an N-type NCC.

32. The method of claim 31, wherein a calcium influx through an NCC is reduced compared to a control.

33. The method of claim 32, wherein a function of L-type NCCs is not modified with respect to a control.

34. A method of inhibiting an N-type NCC compared to a control, wherein the method comprises contacting the N-type NCC in a subject in need thereof with a composition consisting of or comprising peptides selected from RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3, and also polymers containing RD2, D3, homologs having at least 50% identity and derivatives of RD2 and/or D3.

35. The method of claim 34, wherein a function of L-type NCCs is not modified with respect to a control.