Recombinant viruses and their use for treatment of atherosclerosis and other forms of coronary artery disease and method, reagent, and kit for evaluating susceptibility to same
AssigneeAventis Pharma S.A.
InventorsPatrick BENOIT, Patrice DENEFLE, Michel PERRICAUDET
Life of this patent
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Abstract
Recombinant viruses comprising a heterologous. DNA sequence coding for a lipase involved in lipoprotein metabolism. The invention also concerns the preparation and use in therapy of said recombinant viruses, especially for the treatment or prevention of dyslipoproteinemia-related pathologies.
Claims31
1-15. (canceled)
A method for treating a patient with dyslipoproteinaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL), wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (L TR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of lipoprotein in the patient.
A method for treating a patient with hypertriglyceridaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL) wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of triglyceride in the patient.
A method for treating a patient with hypercholesterolaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL), wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (L TR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of cholesterol in the patient.
A method for treating a patient with hyperlipidaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL), wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of lipid in the patient.
A method for treating a patient with familial hypertriglyceridaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL) wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (L TR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of triglyceride in the patient.
A method for treating a patient with combined familial hyperlipidaemia and postprandial hyperlipidaemia comprising administering to the patient via intravenous injection a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active human lipoprotein lipase (LPL), wherein the nucleic acid sequence is operably linked to a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter, and wherein the nucleic acid sequence is expressed so as to cause a reduction of lipid in the patient.
A method for preventing or delaying the onset of coronary artery disease in a human individual having lipoprotein lipase enzyme in which a serine residue is present at amino acid 291 in the enzyme, comprising administering to the individual a recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a replacement lipoprotein lipase enzyme under the control of a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter, said replacement lipoprotein lipase enzyme having an asparagine residue as amino acid 291, wherein the replacement lipoprotein lipase enzyme is produced in the individual to provide a functional lipoprotein lipase enzyme.
A recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a nucleic acid sequence coding for a biologically active lipoprotein lipase (LPL) under the control of a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long teiminal repeat (LTR) promoter.
A recombinant defective adeno-associated virus, wherein the rep gene, the cap gene, or the rep and cap genes of the adeno-associated virus are deleted and replaced by a cDNA sequence coding for a biologically active lipoprotein lipase (LPL) under the control of a cytomegalovirus (CMV) or Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter.
Dependencies are inferred from the claim text.