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WO 2015/161348 A1

Agents And Methods Of Treatment

Published: Oct 29, 2015
Earliest Priority: Apr 24 2014
Family: 9
Cited Works: 3
Cited by: 1
Cites: 7
Additional Info: Cited Works Full text Published

Abstract

The present disclosure relates generally to a method for controlling pathogen infestation in human and animal subjects and agents and formulations and cells including plant extracts useful for same.

Claims

A method for inhibiting growth or infestation of a pathogen in or on a human or animal subject, said method comprising contacting the pathogen with an effective amount of a combination of a plant defensin or a functional natural or synthetic derivative or variant thereof and either: (i) a proteinase inhibitor; or (ii) chemical pathogenicidic or pathogenostatic agent; in a combined amount effective to inhibit growth or infestation of the pathogen.
The method of Claim 1 wherein the combination of the defensin and the proteinase inhibitor or chemical agent is synergistic compared to the use of each alone at the same individual dose as used in the combination.
The method of Claim 1 wherein the plant defensin is a permeabilizing defensin.
The method of Claim 3 wherein the permeabilizing defensin is selected from the list consisting of NaDl, TPP3, PhDl, PhDIA, PhD2, FST, NoD173, HXL001, HXL002, HXL004, HXL007, HXL008, HXL009, HXL012, HXL013, HXL015, HXL035 and HXL036.
The method of Claim 3 wherein the permeabilizing defensin is a Solanaceous Class II defensin or a functional natural or synthetic derivative or variant thereof.
The method of Claim 5 wherein the defensin variant comprises a LooplB from a Class I defensin replacing the corresponding LooplB from a Solanaceous Class II defensin.
The method of Claim 6 wherein the defensin variant is selected from the list consisting of HXP4, HXP34, HXP35, HXP37, HXP58, HXP72, HXP91, HXP92, HXP95 and HXP107.
The method of Claim 1 wherein the proteinase inhibitor is a serine or cysteine proteinase inhibitor.
The method of Claim 8 wherein the proteinase inhibitor is selected from the list consisting of NaPI, NaCysl, NaCys2, NaCys3, NaCys4, HvCPK, SICys9, Oc-Ia, Oc-Ib, Oc-Ic, Oc-Id, StPinlA, At2g38870, CI-1B, CI-2, At2g43510 and BPTI.
The method of Claim 1 wherein the chemical agent is selected from the list consisting of ciclopirox, terbinafine, fenpropimorph, ketoconazole, intraconazole, fluconazole, amorolfine, amphotericin, azole, polyene, echinocandin, allylamine, griseofulvin, tolnaftate, benzoxaborole, aganocide, flucytosine, haloprogin, polygodial, undecylenic acid, a β-glucan synthase inhibitor and a chitin synthase inhibitor.
The method of Claim 10 wherein the echinocandin is caspofungin.
The method of Claim 1 wherein the pathogen is a fungal pathogen.
The method of Claim 12 wherein the fungal organism is selected from the list consisting of a species of Alternaeria spp, Aspergillus spp, Candida spp, Fusarium spp, Trichophyton spp, Cryptococcus spp, Histoplasma spp, Microsporum spp, Penicillium spp, Pneuocystis spp Trichosporon spp, Scedosporium spp, Paeciliomyces spp, Acremonium spp, Stachybotrys spp and Dermatiaceous molds.
The method of Claim 13 wherein the fungal organism is selected from the list consisting of Alternaria alternata, Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, Aspergillus nidulans, Aspergillus paraciticus, Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida haemulonii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida norvegensis, Candida parapsilosis, Candida tropicalis, Candida viswanathii, Fusarium oxysporum, Fusarium solani, Fusarium monoliforme, Trychophyton rubrum, Trychophyton mentagrophytes, Trychophyton inter digitales, Trychophyton tonsurans, Cryptococcus neoformans, Cryptococcus gattii, Cryptococcus grubii, Microsporum canis, Microsporum gypseum, Penicillium marneffei, Tricosporon beigelii, Trichosporon asahii, Trichosporon inkin, Trichosporon asteroides, Trichosporon cutaneum, Trichosporon domesticum, Trichosporon mucoides, Trichosporon ovoides, Trichosporon pullulans, Trichosporon loubieri, Trichosporon japonicum, Scedosporium apiospermum, Scedosporium prolificans, Paecilomyces variotii, Paecilomyces lilacinus, Acremonium stricutm, Cladophialophora bantiana, Wangiella dermatitidis, Ramichloridium obovoideum, Chaetomium atrob nneum, Dactlaria gallopavum, Bipolaris spp, Exserohilum rostratum as well as Absidia corymbifera, Apophysomyces elegans, Mucor indicus, Rhizomucor pusillus, Rhizopus oryzae, Cunninghamella bertholletiae, Cokeromyces recurvatus, Saksenaea vasiformis, Syncephalastrum racemosum, Basidiobolus ranarum, Conidiobolus coronatuslConidiobolus incongruus, Blastomyces dermatitidis, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis, Pseudallescheria boydii and Sporothrix schenckii.
The method of Claim 1 wherein the defensin and the other agent are topically applied to a human or animal.
The method of Claim 1 wherein the defensin and the other agent are non -topically applied to a human or animal.
The method of Claim 1 wherein the defensin and/or the proteinase inhibitor is produced by a genetically modified microorganism or is provided by an extract of a plant or cell.
A formulation comprising a combination of a plant defensin or a functional synthetic or natural derivative or variant thereof and either a proteinase inhibitor or a chemical agent having anti-pathogen properties and one or more pharmaceutically acceptable carriers, diluents and/or excipients.
The formulation of Claim 18 wherein the plant defensin is a permeabilizing defensin.
The formulation of Claim 18 wherein the permeabilizing defensin is a Class II Solanaceous defensin or a functional natural or synthetic derivative or variant thereof.
The formulation of Claim 18 wherein the formulation is a topical formulation.
The formulation of Claim 18 wherein the proteinase inhibitor is selected from NaPI, NaCysl, NaCys2, NaCys3, NaCys4, HvCPK, SICys9, Oc-Ia, Oc-Ib, Oc-Ic, Oc-Id, StPinlA, At2g38870, CI-1B, CI-2, At2g43510, and BPTI
The formulation of Claim 18 wherein the chemical agent is ciclopirox, terbinafine, fenpropimorph, ketoconazole, intraconazole, fluconazole, amorolfine, amphotericin, azole, polyene, echinocandin, allylamine, griseofulvin, tolnaftate, benzoxaborole, aganocide, flucytosine, haloprogin, polygodial, undecylenic acid, a β-glucan synthase inhibitor and a chitin synthase inhibitor.
The formulation of Claim 18 wherein the echinocandin is caspofungin.
The formulation of Claim 18 comprising a cell or plant extract as a source of defensin and/or proteinase inhibitor.
Use of a formulation of any one of Claims 18 to 25 in the manufacture of a medicament for the treatment or prophylaxis of a pathogen of a human or animal subject.
A method for inhibiting growth or infestation of a pathogen, the method comprising contacting the pathogen with an effective amount of combination of a plant defensin selected from the list consisting of NaDl, TPP3, PhDl, PhDIA, PhD2, FST, NoD173, HXL001, HXL002, HXL004, HXL007, HXL008, HXL009, HXL012, HXL013, HXL015, HXL035 and HXL036 or a variant or derivative of a defensin selected from the list consisting of HXP4, HXP34, HXP35, HXP37, HXP58, HXP72, HXP91, HXP92, HXP95 and HXP107 and a proteinase inhibitor or chemical agent having anti -pathogen properties, the combination of the defensin and either a proteinase inhibitor or chemical agent facilitates anti-pathogen activities compared to the use of each alone at the same individual dose as used in the combination.
A method for inhibiting growth or infestation of a pathogen, the method comprising contacting the pathogen with an effective amount of combination of a plant defensin selected from the list consisting of NaDl, TPP3, PhDl, PhDIA, PhD2, FST, NoD173, HXL001, HXL002, HXL004, HXL007, HXL008, HXL009, HXL012, HXL013, HXL015, HXL035 and HXL036 or a variant or derivative of a defensin selected from the list consisting of HXP4, HXP34, HXP35, HXP37, HXP58, HXP72, HXP91, HXP92, HXP95 and HXP107 and either a proteinase inhibitor selected from the list consisting of NaPI, NaCysl, NaCys2, NaCys3, NaCys4, HvCPK, SICys9, Oc-Ia, Oc-Ib, Oc-Ic, Oc-Id, StPinlA, At2g38870, CI-1B, CI-2, At2g43510 and BPTI or a chemical agent selected from the list consisting of ciclopirox, terbinafine, fenpropimorph, ketoconazole, intraconazole, fluconazole, amorolfine, amphotericin, azole, polyene, echinocandin, allylamine, griseofulvin, tolnaftate, benzoxaborole, aganocide, flucytosine, haloprogin, polygodial, undecylenic acid, a β-glucan synthase inhibitor and a chitin synthase inhibitor, the combination of the defensin and the other agent facilitates anti-pathogen activity compared to the use of each alone at the same individual dose as used in the combination.
A method for inhibiting growth or infestation of a fungal pathogen, the method comprising contacting the fungal pathogen with an effective amount of combination of a plant defensin selected from the list consisting of NaDl, TPP3, PhDl, PhDIA, PhD2, FST, NoD173, HXL001, HXL002, HXL004, HXL007, HXL008, HXL009, HXL012, HXL013, HXL015, HXL035 and HXL036 or a variant or derivative of a defensin selected from the list consisting of HXP4, HXP34, HXP35, HXP37, HXP58, HXP72, HXP91, HXP92, HXP95 and HXP107 and either a proteinase inhibitor selected from the list consisting of NaPI, NaCysl, NaCys2, NaCys3, NaCys4, StPinlA, HvCPK, SICys9, Oc-Ia, Oc-Ib, Oc- Ic, Oc-Id, At2g38870, CI-1B, CI-2, At2g43510 and BPTI or a chemical agent selected from the list consisting of ciclopirox, terbinafine, fenpropimorph, ketoconazole, intraconazole, fluconazole, amorolfine, amphotericin, azole, polyene, echinocandin, allylamine, griseofulvin, tolnaftate, benzoxaborole, aganocide, flucytosine, haloprogin, polygodial, undecylenic acid, a β-glucan synthase inhibitor and a chitin synthase inhibitor, in a combination of the defensin and the other agent which facilitates inhibition or growth of the pathogen.
The method of Claim 27 or 29 wherein the echinocandin is caspofungin.
The method of any one of Claims 27 to 30 wherein the combination is synergi

Applicants

Hexima Ltd
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Inventors

Van Der Weerden Nicole
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Anderson Marilyn Anne
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Payne Jennifer
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IPC Classifications

A61K38/16
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A01N37/18
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A01N63/02
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A01N65/38
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C07K14/415
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Document History

Publication: Oct 29, 2015
WO 2015/161348 A1
Application: Apr 24, 2015
AU 2015/050195 W
Priority: Apr 24, 2014
AU 2014/901480 A

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