US2008064652A1PendingUtilityA1

Methods and compositions for treating hypercholesterolemia

37
Individually held — no corporate assignee on recordPriority: Sep 7, 2004Filed: Sep 7, 2007Published: Mar 13, 2008
Est. expirySep 7, 2024(expired)· nominal 20-yr term from priority
Inventors:Vassilis ZannisKypreos Kyriakos
A61P 9/10C07K 14/775A61K 38/1709
37
PatentIndex Score
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Cited by
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References
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Claims

Abstract

The present invention provides methods and compositions for treating hypercholesterolemia using therapeutic apoE proteins. A therapeutic apoE protein is a naturally-occurring apoE protein (e.g., apoE1, apoE2, apoE2*, apoE2**, apoE3, and apoE4) that has one or more amino acid substitutions in the carboxy-terminal region which, when administered to a mammal having hypercholesterolemia, reduces the plasma cholesterol levels without inducing hypertriglyceridemia. The invention also provides a method for reducing plasma cholesterol using low doses of naturally-occurring apoE proteins.

Claims

exact text as granted — not AI-modified
1 - 36 . (canceled)  
     
     
         37 . A method for reducing plasma cholesterol in a mammal, without inducing hypertriglyceridemia, said method comprising administering to said mammal an effective amount of a nucleic acid encoding a therapeutic apoE protein, operably linked to a promoter that, when expressed in the target cells, is capable of expressing said therapeutic apoE protein, and wherein said therapeutic apoE protein comprises a naturally-occurring apoE protein having at least one amino acid substitution in the carboxy-terminal region.  
     
     
         38 . The method of  claim 37 , wherein said nucleic acid is associated with a liposome.  
     
     
         39 . The method of  claim 37 , wherein said nucleic acid is administered by intravenous injection.  
     
     
         40 . The method of  claim 37 , wherein said nucleic acid comprises a recombinant viral vector.  
     
     
         41 . The method of  claim 40 , wherein said vector is an adeno-associated vector, a lentiviral vector, a herpes viral vector, or a retroviral vector.  
     
     
         42 . The method of  claim 37 , wherein said nucleic acid is administered to the liver.  
     
     
         43 . The method of  claim 37 , wherein said therapeutic apoE protein comprises at least one amino acid substitution selected from the group consisting of L261X, W264X, F265X, L268X, and V269X, wherein X is any amino acid.  
     
     
         44 . The method of  claim 43 , wherein X is alanine.  
     
     
         45 . The method of  claim 37 , wherein said therapeutic apoE protein comprises at least one amino acid substitution selected from the group consisting of L261A, W264A, F265A, L268A, and V269A.  
     
     
         46 . The method of  claim 45 , wherein said therapeutic apoE protein comprises the amino acid substitutions L261A, W264A, F265A, L268A, and V269A.  
     
     
         47 . The method of claims  37 , wherein said naturally-occurring apoE protein is selected from the group consisting of apoE1, apoE2, apoE2*, apoE2**, apoE3, and apoE4 protein.  
     
     
         48 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE2[L261A/W264A/F265A/L268A/V269A].  
     
     
         49 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE3[L261A/W264A/F265A/L268A/V269A].  
     
     
         50 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE4[L261A/W264A/F265A/L268A/V269A].  
     
     
         51 . The method of  claim 37 , wherein said therapeutic apoE protein comprises at least one amino acid substitution selected from the group consisting of W276X, L279X, V283X, V287X, and V293X, wherein X is any amino acid.  
     
     
         52 . The method of  claim 51 , wherein X is alanine.  
     
     
         53 . The method of  claim 37 , wherein said therapeutic apoE protein comprises at least one amino acid substitution selected from the group consisting of W276A, L279A, V283A, V287A, and V293A.  
     
     
         54 . The method of  claim 53 , wherein said therapeutic apoE protein comprises the amino acid substitutions W276A, L279A, V283A, V287A, and V293A.  
     
     
         55 . The method of  claim 51 , wherein said therapeutic apoE protein is a therapeutic apoE1, apoE2, apoE2*, apoE2**, apoE3, or apoE4 protein.  
     
     
         56 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE2[W276A/L279A/V283A/V287A/V293A].  
     
     
         57 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE3[W276A/L279A/V283A/V287A/V293A].  
     
     
         58 . The method of  claim 37 , wherein said therapeutic apoE protein is apoE4[W276A/L279A/V283A/V287A/V293A].  
     
     
         59 . A nucleic acid encoding a therapeutic apoE protein comprising a naturally-occurring apoE protein having at least one amino acid substitution in the carboxy-terminal region.  
     
     
         60 . A nucleic acid encoding the therapeutic apoE protein of claim  20 .  
     
     
         61 - 63 . (canceled)

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