Glucocerebroside treatment of pulmonary or respiratory diseases or disorders
OwnerYaron Ilan, Gadi Lalazarinventors
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Abstract
This invention relates to the use of naturally occurring mammalian intermediary metabolites, Tcell ligands or Tcell receptor ligands, preferably glycosylceramides, for the treatment or prevention of immune mediated or immune related diseases or disorders. Specifically, the present invention provides compositions and methods for the treatment or prevention of pulmonary, respiratory or airway diseases or disorders such as asthma.
Claims109
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of a one or more mammalian intermediary metabolites.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, wherein said mammalian intermediary metabolite is a T cell ligand or T cell receptor ligand.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, wherein said mammalian intermediary metabolite is a lipid, a polar lipid, or a conjugated biomolecule.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, wherein said mammalian intermediary metabolite is a glycolipid, lipoprotein, apolipoprotein, a glycoprotein other than an antibody, a cytokine or a hormone.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, wherein said mammalian intermediary metabolite is a monosaccharide ceramide, a disaccharide ceramide or a polysaccharide ceramide.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more β-galactosylceramides, β-lactosylceramides, β-glucosylceramides, analogs of β-galactosylceramide other than an α-linked analog, β-galactosylceramide derivatives, analogs of β-lactosylceramide other than an α-linked analog, derivatives of β-lactosylceramide, analogs of β-glucosylceramide other than an α-linked analog, β-glucosylceramide derivatives, sulfated glycolipids, or any combination thereof.
An in vitro screening assay for an analog or derivative of a mammalian intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- and
- (iii) an analog or derivative of said mammalian intermediary metabolite;
- and
- b) identifying a decrease in said regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analog or derivative of a mammalian intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analog or derivative of a mammalian intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- and
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analog or derivative of said mammalian intermediary metabolite;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) one or more intermediary metabolites;
- ii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- and
- c) re-administering to said subject said treated or educated cells.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) one or more intermediary metabolites;
- ii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- and
- d) administering to said subject:
- i) an effective amount of intermediary metabolite;
- ii) antigen presenting cells;
- iii) one or more antigens or epitopes associated with said disease, or one or more or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject:
- a) an effective amount of one or more intermediary metabolites;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
A therapeutic composition for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) one or more intermediary metabolites;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, the result of said administration comprising a change in the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, the result of said administration comprising the reduction, inhibition, or decrease of the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites, the result of said administration comprising the stimulation or increase of the number or function of regulatory, immune-regulatory or NKT cells.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more intermediary metabolites and antigen presenting cells, the result of said administration comprising a decrease in regulatory, immune-regulatory or NKT cell proliferation.
A method for the treatment of a pulmonary, respiratory, or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more intermediary metabolites and antigen presenting cells, the result of said administration comprising an increase in regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analog or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said assay comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (iii) analog or derivative of said intermediary metabolite;
- and
- b) identifying a decrease in said regulatory, immune-regulatory or NKT cell proliferation.
An in vitro screening assay for an analog or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said assay comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analog or derivative of an intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- and
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analog or derivative of said intermediary metabolite;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) one or more intermediary metabolites;
- ii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- and
- b) re-administering to said subject said treated or educated cells, the result of said administration comprising a change in the number of said cells.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) one or more intermediary metabolites;
- ii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- d) administering to said subject:
- i) an effective amount of one or more intermediary metabolites;
- ii) antigen presenting cells;
- iii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above;
- and
- e) the result of said administration comprising a change in the number of regulatory cells, immune-regulatory cells or NKT cells.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject:
- a) an effective amount of one or more intermediary metabolites;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above;
- e) the result of said administration comprising a change in the number of regulatory cells, immune-regulatory cells or NKT cells.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of one or more mammalian intermediary metabolites so as to modulate or change at least one component in the immune system of said subject.
A therapeutic composition for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject, the administration of said composition resulting in a change in the number of regulatory, immune-regulatory or NKT cells, said composition comprising:
- a) one or more intermediary metabolites;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease;
- or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
The use of a mammalian intermediary metabolite in the manufacture of a composition for the manipulation of regulatory, immune-regulatory or NKT cells in a mammalian subject suffering from a pulmonary, respiratory or airway disease or disorder.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of a mammalian intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject and/or a change in the peripheral/intrahepatic T cell ratio.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of a mammalian intermediary metabolite, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution in said subject and/or a change in intrahepatic CD8+ T cell trapping.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and/or antigen presenting cells, the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of an intermediary metabolite and/or antigen presenting cells, the result of said administration comprising an alteration of the function of the regulatory, immune-regulatory or NKT cell distribution.
An in vitro screening assay for an analog or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder resulting in an alteration of the regulatory, immune-regulatory or NKT cell distribution, said assay comprising:
- a) providing in vitro:
- (i) regulatory, immune-regulatory or NKT cells from said subject or another subject;
- (ii) antigen presenting cells;
- (iii) analog or derivative of said intermediary metabolite;
- and
- b) identifying a decrease in said regulatory, immune-regulatory and NKT cell proliferation.
An in vitro screening assay for an analog or derivative of an intermediary metabolite which is administered to a mammalian subject to treat a pulmonary, respiratory or airway disease or disorder resulting in an alteration of the regulatory, immune-regulatory or NKT cell distribution, said assay comprising:
- a) providing in vitro:
- i) regulatory, immune-regulatory or NKT cells and BSA in a first test tube;
- ii) regulatory, immune-regulatory or NKT cells and said analog or derivative of an intermediary metabolite in a second test tube;
- iii) regulatory, immune-regulatory or NKT cells, antigen presenting cells and BSA in a third test tube;
- iv) regulatory, immune-regulatory or NKT cells, antigen-presenting cells and an analog or derivative of said intermediary metabolite;
- b) determining the amount of regulatory, immune-regulatory or NKT cell proliferation in each of said tubes;
- and
- c) identifying the least amount of regulatory, immune-regulatory or NKT cell proliferation in said fourth tube.
A method for treating a pulmonary, respiratory, or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) intermediary metabolite;
- ii) antigens or epitopes associated with said disease, or antigens or epitopes associated with the immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- b) re-administering to said subject said treated or educated cells, the result of said administration comprising an alteration in said cell distribution.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising:
- a) obtaining cells from said subject or another subject, said cells comprising regulatory, immune-regulatory or NKT cells;
- b) treating or educating said cells ex vivo in the presence of:
- i) one or more intermediary metabolites;
- ii) one or more antigens or epitopes associated with said disease or disorder, or one or more antigens or epitopes associated with an immune-mediated inflammatory response;
- iii) antigen presenting cells;
- or
- iv) any combination of the above;
- c) re-administering to said subject said treated or educated cells;
- and
- d) administering to said subject:
- i) an effective amount of one or more intermediary metabolites;
- ii) antigen presenting cells;
- iii) one or more antigens or epitopes associated with said disease, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- iv) any combination of the above;
- and
- e) the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution.
A method for the treatment of a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject:
- a) an effective amount of an intermediary metabolite;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease or disorder, or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above;
- and
- e) the result of said administration comprising an alteration of the regulatory, immune-regulatory or NKT cell distribution.
A method for treating a pulmonary, respiratory or airway disease or disorder in a mammalian subject comprising administering to said subject an effective amount of a mammalian intermediary metabolite so as to modulate or change at least one component in the immune system of said subject.
A therapeutic composition for the treatment of a pulmonary, respiratory or airways disease or disorder in a mammalian subject, the administration of said composition resulting in an alteration of the regulatory, immune-regulatory or NKT cell distribution, said composition comprising:
- a) one or more intermediary metabolites;
- b) antigen presenting cells;
- c) one or more antigens or epitopes associated with said disease or disorder;
- or one or more antigens or epitopes associated with the immune-mediated inflammatory response;
- or
- d) any combination of the above.
The use of a mammalian intermediary metabolite in the manufacture of a composition for the manipulation of regulatory, immune-regulatory or NKT cells in a mammalian subject suffering from a pulmonary, respiratory or airway disease or disorder.
Dependencies are inferred from the claim text.