SMALL CATIONIC ANTI-BIOFILM AND IDR PEPTIDES

• US 20190315823A1
• Filed: 04/24/2019
• Published: 10/17/2019
• Est. Priority Date: 08/27/2013
• Status: Abandoned Application

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: Hancock, Robert E.W., Nunez, Cesar de la Fuente, Kindrachuk, Jason, Jenssen, Havard, Overhage, Joerg, Haney, Evan
• Application Number:
  US16/393,783
• Publication Number:
  US 20190315823A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/546 containing further heterocyclic rings, e.g. cephalothin
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• 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 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/14 Peptides containing saccharide radicals; Derivatives thereof , e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 14/4723 Cationic antimicrobial peptides, e.g. defensins
• CPC Class Codes: C07K 17/14 Peptides being immobilised on, or in, an inorganic carrier
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates generally to peptides and more specifically to anti-biofilm and immunomodulatory peptides.

Claims

1. An isolated antibiofilm or immunomodulatory peptide having 7 to 12 amino acids, wherein the peptide has an amino acid sequence of SEQ ID NOS:

1-663, or analogs, derivatives, enantiomers, amidated and unamidated variations and conservative variations thereof.

2. An isolated polynucleotide that encodes a peptide of claim 1.

3. The peptide of claim 1 comprising any contiguous sequence of amino acids having the formula:

AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-AA9-AA10-AA11-AA12 and containing only the residues K, R, F, L, I, A, V, W and no more than a single Q or G residue.

12. The peptide of claim 1, wherein the peptide is capable of selectively enhancing innate immunity as determined by contacting a cell containing one or more genes that encode a polypeptide involved in innate immunity and protection against an infection, with the peptide of interest, wherein expression of the one or more genes or polypeptides in the presence of the peptide is modulated as compared with expression of the one or more genes or polypeptides in the absence of the peptide, and wherein the modulated expression results in enhancement of innate immunity.

13. The peptide of claim 12, wherein the peptide:

(i) does not stimulate a septic reaction, or

(ii) stimulates expression of the one or more genes or proteins, thereby selectively enhancing innate immunity.

14. The peptide of claim 1, wherein the peptide selectively suppresses proinflammatory responses, whereby the peptide can contact a cell treated with an inflammatory stimulus and containing a polynucleotide or polynucleotides that encode a polypeptide involved in inflammation and sepsis and which is normally upregulated in response to this inflammatory stimulus, and wherein the peptides suppresses the expression of this gene or polypeptide as compared with expression of the inflammatory gene in the absence of the peptide and wherein the modulated expression results in enhancement of innate immunity.

15. The peptide of claim 14, wherein the peptide inhibits or blocks the inflammatory or septic response or inhibits the expression of a pro-inflammatory gene or molecule.

4. A polypeptide X 1-A-X2 or a functional variant or mimetic thereof, wherein A represents at least one peptide having an amino acid sequence of SEQ ID NOS:

1-749 or analogs, derivatives, enantiomers, amidated and unamidated variations and conservative variations thereof; and

wherein each X1 and X2 independently of one another represents any amino acid sequence of n amino acids, n varying from 0 to 50, and n being identical or different in X1 and X2.

5. The polypeptide of claim 4 wherein the functional variant or mimetic is a conservative amino acid substitution or peptide mimetic substitution.

6. The polypeptide of claim 4 wherein the functional variant has about 66% or greater amino acid identity.

7. The polypeptide of claim 4, wherein the amino acids are non-natural amino acid equivalents.

8. The polypeptide of claim 4 wherein the peptide has the amino acid sequence VX₁X₂X₃X₄X₅X₆X₇X₈X₉X₁₀X₁₁ wherein X₁ is F, Q, or R;

X₂ is L, W, or R;

X₃ is R, I, or W;

X₄ is R, A, V, or L;

X₅ is I or A;

X₆ is R or V;

X₇ is V, R, or W;

X₈ is W, I, or R;

X₉ is V, W, or I;

X₁₀ is I or R;

X₁₁ is R or K or the reversed sequence.

16. The peptide of claim 4, wherein the peptide is capable of selectively enhancing innate immunity as determined by contacting a cell containing one or more genes that encode a polypeptide involved in innate immunity and protection against an infection, with the peptide of interest, wherein expression of the one or more genes or polypeptides in the presence of the peptide is modulated as compared with expression of the one or more genes or polypeptides in the absence of the peptide, and wherein the modulated expression results in enhancement of innate immunity.

17. The method of claim 16, wherein the peptide does not stimulate a septic reaction, or stimulates expression of the one or more genes or proteins, thereby selectively enhancing innate immunity.

18. The peptide of claim 4, wherein the peptide selectively suppresses proinflammatory responses, whereby the peptide can contact a cell treated with an inflammatory stimulus and containing a polynucleotide or polynucleotides that encode a polypeptide involved in inflammation and sepsis and which is normally upregulated in response to this inflammatory stimulus, and wherein the peptides suppresses the expression of this gene or polypeptide as compared with expression of the inflammatory gene in the absence of the peptide and wherein the modulated expression results in enhancement of innate immunity.

19. The method of claim 18, wherein the peptide inhibits or blocks the inflammatory or septic response or inhibits the expression of a pro-inflammatory gene or molecule.

9. A method of inhibiting the growth of bacterial biofilms comprising contacting a bacterial biofilm with an inhibiting effective amount of:

(i) a peptide having an amino acid sequence of SEQ ID NOS;

1-749, or any combination thereof, or analogs, derivatives, enantiomers, amidated and unamidated variations and conservative variations thereof, and/or

ii) an isolated anti-biofilm polypeptide X1-A-X2, or a functional variant or mimetic thereof, wherein A represents at least one peptide having an amino acid sequence of SEQ ID NOS;

1-749 or analogs, derivatives, enantiomers, amidated and unamidated variations and conservative variations thereof, each X1 and X2 independently of one another represents any amino acid sequence of n amino acids, n varying from 0 to 5, and n being identical or different in X1 and X2.

10. The method of claim 9, wherein the peptide or the isolated anti-biofilm polypeptide is provided in combination with at least one antibiotic.

11. The method of claim 93, wherein the peptide is bound to a solid support or surface.

20. An isolated molecule that has anti-biofilm activity by virtue of inhibiting (p)ppGpp synthesis or causing (p)ppGpp degradation.