US2019151424A1PendingUtilityA1

Ceramide levels in the treatment and prevention of infections

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Assignee: ICAHN SCHOOL MED MOUNT SINAIPriority: Jun 1, 2012Filed: Nov 15, 2018Published: May 23, 2019
Est. expiryJun 1, 2032(~5.8 yrs left)· nominal 20-yr term from priority
Inventors:Edward H. SchuchmanErich GulbinsAnthony FutermanYael Pewzner-Jung
A61P 31/06A61P 31/00A61P 31/04A61K 38/50A61K 9/0073A61K 9/0014A61K 9/0019C12Y 305/01023A61K 45/06A61K 9/12
59
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Claims

Abstract

The present invention relates to a method for treating or preventing pathogenic infections in a subject having Cystic Fibrosis, COPD, and/or an open wound. This method involves selecting a subject having Cystic Fibrosis, COPD, and/or an open wound and administering to the selected subject a ceramidase under conditions effective to reduce ceramide and to treat or prevent the pathogenic infection. The method also involves the use of a ceramidase in combination with other drugs to reduce infection, reduce ceramide, or improve lung function in Cystic Fibrosis, COPD, and/or open wound patients.

Claims

exact text as granted — not AI-modified
1 .- 20 . (canceled) 
     
     
         21 . A method of administering a recombinant acid ceramidase to a subject, said method comprising:
 selecting a subject having an elevated ceramide level compared to a reference level and   administering a recombinant acid ceramidase to said subject under conditions effective to reduce ceramide in said subject.   
     
     
         22 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein. 
     
     
         23 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein and an active acid ceramidase. 
     
     
         24 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises UniProt Q13510, UniProt Q9H715, UniProt Q96AS2, OMIM 228000, NCBI Gene 427, NCBI RefSeq NP_808592, NCBI RefSeq NP_004306, NCBI RefSeq NM_177924, NCBI RefSeq NM_004315, NCBI UniGene 427, NCBI Accession Q13510, NCBI Accession AAC73009, or a combination thereof. 
     
     
         25 . The method of  claim 24 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         26 . The method of  claim 24 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592. 
     
     
         27 . The method of  claim 21 , wherein said selecting is based on ceramide level in lung epithelium, nasal epithelium, mucus, or isolated cells. 
     
     
         28 . The method of  claim 21 , wherein said administering is carried out under conditions effective to normalize ceramide levels in the subjects' respiratory epithelia, mucus, or cells. 
     
     
         29 . The method of  claim 21 , wherein one or more additional agents that reduce ceramide levels are administered in combination with said recombinant acid ceramidase. 
     
     
         30 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises an active acid ceramidase protein. 
     
     
         31 . The method of  claim 30 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         32 . The method of  claim 30 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592. 
     
     
         33 . The method of  claim 21 , wherein the recombinant acid ceramidase comprises a mature acid ceramidase protein. 
     
     
         34 . The method of  claim 33 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         35 . The method of  claim 33 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592. 
     
     
         36 . A method for treating a pathogenic infection in a subject, said method comprising:
 selecting a subject having a pathogenic infection and   administering to said selected subject a recombinant acid ceramidase under conditions effective to reduce ceramide and to treat said pathogenic infection in said selected subject.   
     
     
         37 . The method of  claim 36 , wherein said pathogenic infection comprises a bacterial pathogen, a viral pathogen, or a fungal pathogen. 
     
     
         38 . The method of  claim 36 , wherein the subject has a disease condition which predisposes the subject to pathogenic infections. 
     
     
         39 . The method of  claim 38 , wherein the disease condition is selected from the group consisting of respiratory disease, lung disease, emphysema, asthma, pulmonary fibrosis, chronic bronchitis, pneumonia, pulmonary hypertension, lung cancer, sarcoidosis, necrotizing pneumonia, asbestosis, aspergilloma, aspergillosis, acute invasive atelectasis, eosinophilic pneumonia, pleural effusion, pneumoconiosis, pneumocystosis, pneumothorax, pulmonary actinomycosis, pulmonary alveolar proteinosis, pulmonary  anthracis , pulmonary arteriovenous malformation, pulmonary edema, pulmonary embolus, pulmonary histiocytosis X (eosinophilic granuloma), pulmonary nocardiosis, pulmonary tuberculosis, pulmonary veno-occlusive disease, and rheumatoid lung disease. 
     
     
         40 . The method of  claim 36 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein. 
     
     
         41 . The method of  claim 36 , wherein the recombinant acid ceramidase comprises an acid ceramidase precursor protein and an active acid ceramidase. 
     
     
         42 . The method of  claim 36 , wherein the recombinant acid ceramidase comprises UniProt Q13510, UniProt Q9H715, UniProt Q96AS2, OMIM 228000, NCBI Gene 427, NCBI RefSeq NP_808592, NCBI RefSeq NP_004306, NCBI RefSeq NM_177924, NCBI RefSeq NM_004315, NCBI UniGene 427, NCBI Accession Q13510, NCBI Accession AAC73009, or a combination thereof. 
     
     
         43 . The method of  claim 42 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         44 . The method of  claim 42 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592. 
     
     
         45 . The method of  claim 36 , wherein said selecting is based on ceramide level in lung epithelium, nasal epithelium, mucus, or isolated cells. 
     
     
         46 . The method of  claim 36 , wherein said administering is carried out under conditions effective to normalize ceramide levels in the subjects' respiratory epithelia, mucus, or cells. 
     
     
         47 . The method of  claim 36 , wherein the recombinant acid ceramidase comprises an active acid ceramidase protein. 
     
     
         48 . The method of  claim 47 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         49 . The method of  claim 47 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592. 
     
     
         50 . The method of  claim 36 , wherein the recombinant acid ceramidase comprises a mature acid ceramidase protein. 
     
     
         51 . The method of  claim 50 , wherein the recombinant acid ceramidase comprises UniProt Q13510. 
     
     
         52 . The method of  claim 50 , wherein the recombinant acid ceramidase comprises NCBI RefSeq NP_808592.

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