Claims for Patent: 9,616,121

Summary for Patent: 9,616,121

Title:	Therapeutic combinations for treating Johne\'s disease
Abstract:	In alternative embodiments, the invention provides a \"triple combination\" therapy for treating, ameliorating and preventing Crohn\'s Disease (or Crohn syndrome, terminal or distal ileitis or regional enteritis) or related disorders and conditions in mammals, such as paratuberculosis in mammals, or Johne\'s disease, including genetically-predisposed and chronic disorders, where the microbial or bacterial flora of the bowel is at least one causative or symptom-producing factor; and compositions for practicing same. In alternative embodiments, methods and compositions of the invention comprise or comprise use of therapies, medications, formulations and pharmaceuticals comprising active agents that can suppress or eradicate the microbiota super-infection that causes Crohn\'s Disease or paratuberculosis infection in mammals. In alternative embodiments, the methods and uses of the invention for treating, ameliorating and preventing Crohn\'s Disease and complications of Crohn\'s Disease, or related disorders and conditions in mammals, such as paratuberculosis in mammals, or Johne\'s disease, comprises administration to an individual (human or mammal) in need thereof: (1) an anti-TNF.alpha. composition, or a composition capable of down-modulating TNF.alpha. activity; (2) a Hyperbaric Oxygen Treatment, or HBOT; and (3) an anti-Mycobacterium avium sub species paratuberculosis (MAP) (an anti-MAP) agent, composition or therapy.
Inventor(s):	Agrawal; Gaurav (Manly, AU)
Assignee:	Center for Digestive Diseases (New South Wales, AU)
Application Number:	14/405,384
Patent Claims:	1. A therapeutic combination for treating or ameliorating Johne's disease, comprising: (1) an anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity; (2) a Hyperbaric Oxygen Treatment, or HBOT, or the medical use of oxygen at a level higher than atmospheric pressure; and (3) an anti-Mycobacterium avium sub species paratuberculosis (MAP) (an anti-MAP) agent, composition, drug or therapy. 2. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the Hyperbaric Oxygen Treatment or the medical use of oxygen at a level higher than atmospheric pressure, comprises use or administration of: a pressure of about 100% oxygen, between about 90% and 100% oxygen, oxygen at about 2.5 atm absolute, or between about 2 and 3 atm absolute, or oxygen for about 90 minutes or for between about 1 hour and 2 hours per session or treatment, or any combination thereof. 3. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of: (1) a macrolide antibiotic; (2) a rifabutin and a macrolide antibiotic; (3) a rifabutin, a macrolide antibiotic, and a clofazimine; (4) a combination of a rifabutin, a clarithromycin and a clofazimine or a LAMPRENE.TM.; (5) any of (1) to (4), wherein the macrolide antibiotic is or comprises: a clarithromycin; a dirithromycin; a roxithromycin; a telithromycin; an azithromycin; a troleandomycin; or a mixture or combination thereof; (6) a nitroimidazole antibiotic, a metronidazole, a 5-nitroimidazole, or a FLAGYL.TM.; (7) a fluoroquinolone antibiotic, or a ciprofloxacin; (8) a nitroimidazole antibiotic, a metronidazole or a 5-nitroimidazole; (9) a fluoroquinolone antibiotic or a ciprofloxacin; (10) a nitroimidazole antibiotic, a metronidazole or a 5-nitroimidazole and a fluoroquinolone antibiotic or a ciprofloxacin; (11) a rifaximin, a rifamycin or a rifamycin B; (12) a rifampicin, a rifadine, a rimycin, a pyrazinamide optionally with an isoniazid; or a rifampicin, a rifadine, or a rimycin, with a pyrazinamide and/or an isoniazid; (13) an anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity; (14) a mixture or a combination of any two or several of (1) to (13). 4. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity of (1); the Hyperbaric Oxygen Treatment, or HBOT, or the medical use of oxygen at a level higher than atmospheric pressure of (2); and the anti-MAP agent, composition, drug or therapy of (3) are administered simultaneously. 5. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity of (1) is administered before, during, or after, or in between sessions of, the Hyperbaric Oxygen Treatment, or HBOT, or the medical use of oxygen at a level higher than atmospheric pressure of (2), and the anti-MAP agent, composition, drug or therapy of (3). 6. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-MAP agent, composition, drug or therapy of (3) is administered before, during, or after, or in between sessions of, the Hyperbaric Oxygen Treatment, or HBOT, or the medical use of oxygen at a level higher than atmospheric pressure of (2), and the anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity of (1). 7. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the Hyperbaric Oxygen Treatment, or HBOT, or the medical use of oxygen at a level higher than atmospheric pressure of (2) is administered before, or after, during, or in between sessions of, the anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity of (1) and the anti-MAP agent, composition, drug or therapy of (3). 8. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein: a unit dosage of an anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation is formulated as unit dosage between about 10 mg and 1100 mg, or is about 10, 20, 30, 40, 50, 60, 70, 75, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 750, 800, 900, 1000 or 1100 or more mg per unit dose. 9. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein a unit dosage of an anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation is administered or set for a bid (twice a day), tid (three times a day), four times a day, five times a day or six times a day or more. 10. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein: an anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation is formulated as a chewable delivery vehicle, a gum, a gummy, a candy, a lozenge, an ice cream or an ice, or a yogurt, or a unit dosage of an anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation is formulated as a pediatric unit dosage. 11. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation further comprises or has added to: a flavoring or a sweetening agent, an aspartamine, a stevia, monk fruit, a sucralose, a saccharin, a cyclamate, a xylitol, a vanilla, an artificial vanilla or chocolate or strawberry flavor, an artificial chocolate essence, or a mixture or combination thereof; a preservative, a benzoic acid, a potassium sorbate; at least one probiotic or prebiotic, wherein optionally the prebiotic comprises an inulin, lactulose, extracts of artichoke, chicory root, oats, barley, various legumes, garlic, kale, beans or flacks or an herb, wherein optionally the probiotic comprises a cultured or stool-extracted microorganism or bacteria, or a bacterial component, and optionally the bacteria or bacterial component comprises or is derived from a Bacteroidetes, a Firmicutes, a Lactobacilli, a Bifidobacteria, an E. coli, a Strep fecalis and equivalents; at least one congealing agent, wherein optionally the congealing agent comprises an arrowroot or a plant starch, a powdered flour, a powdered potato or potato starch, an absorbant polymer, and/or a corn flour or a corn starch; at least one an anti-inflammatory agent, wherein optionally the inflammatory agent comprises or is a 4 or a 5-amino-salicylate, an olsalazine, a mesalazine, a sulfasalazine, and/or a balsalazide, or an equivalent thereof or a combination thereof; an additive selected from one or more of a saline, a media, a defoaming agent, a surfactant agent, a lubricant, an acid neutralizer, a marker, a cell marker, a drug, an antibiotic, a contrast agent, a dispersal agent, a buffer or a buffering agent, a sweetening agent, a debittering agent, a flavoring agent, a pH stabilizer, an acidifying agent, a preservative, a desweetening agent and/or coloring agent, vitamin, mineral and/or dietary supplement, or a prebiotic nutrient; or at least one Biofilm Disrupting Compound, wherein optionally the biofilm disrupting compound comprises an enzyme, a deoxyribonuclease (DNase), N-acetylcysteine, an auranofin, an alginate lyase, glycoside hydrolase dispersin B; a Quorum-sensing inhibitor, a ribonucleic acid III inhibiting peptide, Salvadora persica extracts, Competence-stimulating peptide, Patulin and penicillic acid; peptides-cathelicidin-derived peptides, small lytic peptide, PTP-7, Nitric oxide, neo-emulsions; ozone, lytic bacteriophages, lactoferrin, xylitol hydrogel, synthetic iron chelators, cranberry components, curcumin, silver nanoparticles, Acetyl-11-keto-.beta.-boswellic acid (AKBA), barley coffee components, probiotics, sinefungin, S-adenosylmethionine, S-adenosyl-homocysteine, Delisea furanones, N-sulfonyl homoserine lactones or any combination thereof. 12. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation: is formulated as a delayed or gradual enteric release composition or formulation. 13. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation further comprises or has added to: an additional antimicrobial or an antibiotic. 14. The therapeutic combination for treating or ameliorating Johne's disease of claim 1, wherein the anti-TNF.alpha. composition or drug, or the composition or drug capable of down-modulating or down-regulating a TNF.alpha. activity, comprises a protein, a peptide or an antibody capable of specifically binding to a TNF.alpha. or a TNF.alpha.-receptor or TNF.alpha. downstream effector. 15. The therapeutic combination for treating or ameliorating Johne's disease, of claim 14, wherein the antibody is or comprises: an infliximab; an adalimumab; a certolizumab, certolizumab pegol; a golimumab; a basiliximab; a daclizumab; an omalizumab; or, any combination thereof. 16. The therapeutic combination for treating or ameliorating Johne's disease, of claim 12, wherein the formulation comprises a gastro-resistant coating designed to dissolve at a pH of 7 in the terminal ileum, or an active ingredient is coated with an acrylic based resin or equivalent, or a poly(meth)acrylate, or a methacrylic acid copolymer B, NF, which dissolves at pH 7 or greater, which optionally comprises a multimatrix (MMX) formulation. 17. The therapeutic combination for treating or ameliorating Johne's disease, of claim 13, wherein the additional antimicrobial or an antibiotic comprises: an ampicillin, a sulbactama tetracycline, a cephalosporin, a carbapenem, an imipenem, a meropenem, a monobactam, a lincosamide, a clindamycin, a quinolone, a fluoroquinolone, a sulphonamide, a fradicin, a nitroimidazole, a metronidazole, a tinidazole, an anti-clostridial agent, or a ramoplanan, an aminoglycoside antibiotic, a gentamycin, a neomycin, a streptomycin, a paromomycin, a verdamicin, a mutamicin, a sisomicin, a netilmicin, a retymicin, a kanamycin, an amphenicol, an ansamycin, a beta-lactam (.beta.-lactam) antibiotic, a carbapenem, a cephalosporin, a cephamycin, a monobactam, an oxacephem, a lincosamide antibiotic, a clindamycin, or a lincomycin, a glycopeptide antibiotic, a vancomycin, a teicoplanin, a telavancin, a bleomycin, a ramoplanin, a decaplanin, a polypeptide antibiotic, an actinomycin, an actinomycin D, a bacitracin, a bacitracin, a tetracycline, a 2,4-diaminopyrimidine class antibiotic, a clavacin, a clairformin, a claviform, an expansine, a clavatin, an expansin, a gigantin, a leucopin, a patuline or a patulin, or an equivalent thereof or a combination thereof. 18. The therapeutic combination for treating or ameliorating Johne's disease, of claim 9, wherein the unit dosage and daily dosage are adjusted to be: (a) about 1000 mg/70 kg a day, or about 14 mg/kg a day, for an adult median dose per day or five times a day for adult use, or for a 70 kg individual would be 200 mg per unit dose; or, (b) for a pediatric dosage about 350 mg/25 kg a day, or about 15 to 16 mg/kg, a day; or equivalent, or, five times a day for pediatric use, or for a 25 kg individual, would be 70 mg per unit dose. 19. The therapeutic combination for treating or ameliorating Johne's disease, of claim 8, wherein a unit dosage of an anti-MAP or an anti-TNF.alpha. composition, drug, formulation, pharmaceutical or pharmaceutical preparation is formulated or administered for a daily or once a day dosage of about 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 750, 800, 900, 1000 or 1100 or more mg per day, or between about 100 and 1100 mg per day. 20. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a macrolide antibiotic. 21. The therapeutic combination for treating or ameliorating Johne's disease, of claim 20, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a rifabutin and a macrolide antibiotic. 22. The therapeutic combination for treating or ameliorating Johne's disease, of claim 21, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a rifabutin, a macrolide antibiotic, and a clofazimine. 23. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a nitroimidazole antibiotic, a metronidazole, a 5-nitroimidazole, or a FLAGYL.RTM.. 24. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a fluoroquinolone antibiotic or a ciprofloxacin. 25. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a nitroimidazole antibiotic, a metronidazole or a 5-nitroimidazole. 26. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a fluoroquinolone antibiotic or a ciprofloxacin. 27. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a nitroimidazole antibiotic, a metronidazole or a 5-nitroimidazole and a fluoroquinolone antibiotic or a ciprofloxacin. 28. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a rifaximin, a rifamycin or a rifamycin B. 29. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of a rifampicin, a rifadine, a rimycin, a pyrazinamide optionally with an isoniazid; or a rifampicin, a rifadine, or a rimycin, with a pyrazinamide and/or an isoniazid. 30. The therapeutic combination for treating or ameliorating Johne's disease, of claim 1, wherein the anti-Mycobacterium avium sub species paratuberculosis (MAP) agent, composition, drug or therapy, comprises administration of an anti-TNF.alpha. composition or drug, or a composition or a drug capable of down-modulating or down-regulating a TNF.alpha. activity.

Details for Patent 9,616,121

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2032-06-04
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	05/12/1998		2032-06-04
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	01/02/2003		2032-06-04
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2032-06-04
Genentech, Inc.	XOLAIR	omalizumab	For Injection	103976	06/20/2003		2032-06-04
Genentech, Inc.	XOLAIR	omalizumab	Injection	103976	09/28/2018		2032-06-04