US 20120058935A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0058935 A1 Moir et al. (43) Pub. Date: Mar. 8, 2012 (54) ANTIMICROBIAL COMPOSITIONS AND Publication Classification METHODS OF USE THEREFORE (51) Int. Cl. (75) Inventors: Robert Moir, Medfield, MA (US); st 7, CR Rudolph E. Tanzi, Hull, MA (US) (2006.01) AOIP I/00 (2006.01) (73) Assignee: The General Hospital A6IP3L/2 (2006.01) Corporation, Boston, MA (US) AOIP3/00 (2006.01) AOIN 37/18 (2006.01) (21) Appl. No.: 13/256,171 A6IP3 L/10 (2006.01) (22) PCT Filed: Mar. 12, 2010 (52) U.S. Cl. ............. 514/2.6; 514/2.3: 514/24: 514/3.3: (86). PCT No.: PCT/US 10/27186 514/3.7: 514/3.4: 514/2.8: 514/2.7 S371 (c)(1), (2), (4) Date: Nov. 18, 2011 (57) ABSTRACT O O The invention features antimicrobial compositions compris Related U.S. Application Data ing B-amyloid peptides, oligomers, and analogs thereof, and (60) Provisional application No. 61/159,671, filed on Mar. methods of using them for the prevention or treatment of an 12, 2009. infection. Patent Application Publication Mar. 8, 2012 Sheet 1 of 5 US 2012/0058935 A1 Figure 1 Ot. 0. 1 OOO. i O- edia aore -- Media - A42 -- edia - 3 A 37 A. L.37 AS 37 Patent Application Publication Mar. 8, 2012 Sheet 2 of 5 US 2012/0058935 A1 Patent Application Publication Mar. 8, 2012 Sheet 3 of 5 US 2012/0058935 A1 " * p = 0.0048 50- r -0.484 10 : Temp. L. Cereb. O 25 500 750 000 A pg/mg of Protein) Patent Application Publication Mar. 8, 2012 Sheet 4 of 5 US 2012/0058935 A1 Figure 4 A IgG 60 * p = 0.0071 45 30 - 15. AD Non-AD AD Non-AD Temp, L. Cereb. Patent Application Publication Mar. 8, 2012 Sheet 5 of 5 US 2012/0058935 A1 Figure 5 -- Temp. L. lgG 90 -o- Temp. L. 6E10 -A- Cereb. * igG -e- Cereb. 6E10 10 25 40 55 70 Homogenate Dilution US 2012/0058935 A1 Mar. 8, 2012 ANTIMICROBAL COMPOSITIONS AND 0011. In various embodiments of any of the aspects delin METHODS OF USE THEREFORE eated herein, the B-amyloid peptide, oligomer, derivative or analog thereof, is formulated as a skin cleanser. In various CROSS-REFERENCE TO RELATED embodiments of any of the aspects delineated herein, the skin APPLICATION is cleansed in preparation for Surgery. 0012. In various embodiments of any of the aspects delin 0001. This application claims the benefit of the following eated herein, the microbe is a bacteria, virus, or fungus. In U.S. Provisional Application No. 61/159,671, filed Mar. 12, various embodiments of any of the aspects delineated herein, 2009, the entire contents of which are incorporated herein by microbe is one or more of Candida albicans, Escherichia reference. coli, Staphylococcus epidermidis, Streptococcus pneumo niae, Staphylococcus aureus, Listeria monocytogenes, BACKGROUND OF THE INVENTION Enterococcus faecalis, Streptococcus agalactiae Pseudomo 0002 The amyloid?-protein (AB) is believed to be the key nas aeruginosa, Streptococcus pyogenes, Streptococcus mediator of Alzheimer's disease (AD) pathology. A? is most mitis, and Streptococcus salivariu. often characterized as an incidental catabolic byproduct that 0013. In various embodiments of any of the aspects delin lacks a normal physiological role. However, AB has been eated herein, the method cleans, sanitizes, or disinfects the shown to be a specific ligand for a number of different recep Surface. In various embodiments, the Surface is a wall, floor, tors and other molecules, transported by complex trafficking ceiling, counter, machine, or other Surface or equipment pathways, modulated in response to a variety of environmen present in an industrial, commercial, or clinical setting. In tal stressors, and able to induce pro-inflammatory activities. various embodiments, the clinical setting is a hospital, medi cal office, clinic, health center, or laboratory. In other embodi ments, the Surface contacted is present in a dwelling, School, SUMMARY OF THE INVENTION office building, plane, train, automobine, restaurant, cafete 0003. As described below, the present invention features ria, or daycare center. antimicrobial compositions and methods of using them for 0014. The invention provides antimicrobial compositions the prevention or treatment of an infection. and methods of using them for the prevention or treatment of 0004. In one aspect, the invention provides a method for an infection. Compositions and articles defined by the inven treating or preventing a microbial infection in a Subject in tion were isolated or otherwise manufactured in connection need of treatment or prevention involving contacting the Sub with the examples provided below. Other features and advan ject with an effective amount of one or more of a B-amyloid tages of the invention will be apparent from the detailed peptide, oligomer, derivative or analog thereof, thereby pre description, and from the claims. venting or inhibiting a microbial infection in the Subject. 0005. In another aspect, the invention provides a method DEFINITIONS for treating or preventing a skin infection in a Subject involv 0015. By “B-amyloid peptide' is meant a 4.2-kD polypep ing administering to the Subject an effective amount of one or tide having a 37-43-amino acid sequence present in amyloid more of a B-amyloid peptide, oligomer, derivative or analog plaques and soluble aggregates, which accumulate in the thereof, in an amount sufficient to treat the subject. brains of patients with Alzheimer's disease. Exemplary AB 0006. In yet another aspect, the invention provides a peptides include peptides having the following amino acid method for preventing or inhibiting microbial growth on a Surface, involving contacting the Surface with an effective Sequences: amount of one or more of a B-amyloid peptide, oligomer, derivative or analog thereof, thereby preventing or inhibiting DAEFRHDSGYEVHHOKLVFFAEDWGSNKGAIIGLMVGGVWIAT microbial growth on the Surface. 0007. In still another aspect, the invention provides a (A343 ); method of sanitizing or disinfecting a body part involving contacting the body part with an effective amount of a B-amy DAEFRHDSGYEVHHOKLVFFAEDVGSNKGAIIGLMVGGVVIA (AB42) ; loid peptide, oligomer, derivative or analog thereof, thereby DAEFRHDSGYEVHHOKLVFFAEDVGSNKGAIIGLMVGGVV (AB40); sanitizing or disinfecting the body part. 0008. In one aspect, the invention provides an antimicro DAEFRHDSGYEVHHOKLVFFAEDVGSNKGAIIGLMVG (AB37). bial composition containing an effective amount of a B-amy 0016. By “anti-microbial composition' is meant any com loid peptide, oligomer, derivative or analog thereof, thereof in position that prevents, inhibits, slows, or reduces the growth, a carrier or diluent. proliferation, or Survival of a microbe (e.g., bacteria, fungus 0009. In another aspect, the invention provides a pharma (e.g., mold), protozoa, virus). ceutical pack containing a B-amyloid peptide, oligomer, 0017. By "agent' is meant any small molecule chemical derivative or analog thereof, in an individual dosage amount. compound, antibody, nucleic acid molecule, or polypeptide, 0010. In various embodiments of any of the aspects delin or fragments thereof. eated herein, the effective amount comprises 1% to 90% of a 0018. By “ameliorate” is meant decrease, suppress, B-amyloid peptide, oligomer, derivative or analog thereof, or attenuate, diminish, arrest, or stabilize the development or combinations thereof. In various embodiments of any of the progression of a disease. aspects delineated herein, the B-amyloid peptide, oligomer, 0019. By “alteration' is meant a change (increase or derivative or analog thereof, is formulated as a water soluble decrease) in the expression levels or activity of a gene or or water insoluble solid, liquid, emulsion, slurry, or powder. polypeptide as detected by standard art known methods such In various embodiments, the composition is topically admin as those described herein. As used herein, an alteration istered. includes a 10% change in expression levels, preferably a 25% US 2012/0058935 A1 Mar. 8, 2012 change, more preferably a 40% change, and most preferably 0030. By “inhibiting microbial growth' is meant prevent a 50% or greater change in expression levels.” ing, slowing, or otherwise reducing the proliferation of a 0020. By “analog is meant a molecule that is not identi microbe. Such inhibition is by at least about 5%, 10%, 25%, cal, but has analogous functional or structural features. For 50%, 75%, or 100%. example, a polypeptide analog retains the biological activity 0031. By “home antimicrobial is meant an antimicrobial of a corresponding naturally-occurring polypeptide, while composition used to clean, sanitize, or disinfect a surface with having certain biochemical modifications that enhance the a home. In various embodiments, home antimicrobials are analog's function relative to a naturally occurring polypep used in a kitchens, bathrooms, and other rooms within a tide. Such biochemical modifications could increase the ana dwelling to prevent or inhibit microbial growth on walls, log's protease resistance, membrane permeability, or half floors, carpets, ceilings, counters, appliances, food prepara life, without altering, for example, ligand binding. An analog tion or storage vessels, or other implements used in food may include an unnatural amino acid. preparation. 0021. By “body part is meant any tissue or organ of a mammalian or avian organism. Exemplary body parts 0032. By "isolated polynucleotide' is meant a nucleic acid include, but are not limited to, skin, hair, fur, epidermis, (e.g., a DNA) that is free of the genes which, in the naturally feathers, wool, hide, the oral cavity, including but not limited occurring genome of the organism from which the nucleic to, the lips, tongue, and teeth. acid molecule of the invention is derived, flank the gene. The 0022. By “dwelling' is meant any human residence. term therefore includes, for example, a recombinant DNA 0023. In this disclosure, "comprises.” “comprising.” “con that is incorporated into a vector; into an autonomously rep taining and “having and the like can have the meaning licating plasmid or virus; or into the genomic DNA of a ascribed to them in U.S.