Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
1998-06-11
2001-03-27
LeGuyader, John L. (Department: 1633)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C435S320100, C435S325000, C435S455000, C435S458000, C514S04400A
Reexamination Certificate
active
06207195
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
This invention is related to the delivery of drugs and genes to cells via nanoparticles.
BACKGROUND OF THE INVENTION
Cystic Fibrosis (CF) is a single gene, recessive disorder characterized by a defective cAMP stimulated chloride conductance across epithelia surfaces, especially in the lung and pancreatic duct. Clinically, this defect results in decreased mucocilliary clearance in lung airways, leading to chronic bacterial infections and inflammation. As a result, patients have a life expectancy of less than 30 years. Clinical trials have thus far focused on either gene or drug therapies for the pulmonary treatment of cystic fibrosis [7,8].
The most common CF mutation, &Dgr;F508, results in failure of the CFTR protein to reach the plasma membrane, likely due to protein trafficking error. The action of 4PBA has been shown to restore CFTR chloride conductance on the plasma membrane of &Dgr;F508 bronchial epithelial cells in vitro [10].
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a solid nanosphere for treating cystic fibrosis.
Another object of the invention is to provide a solid nanosphere for gene delivery.
Another object of the invention is to provide a method of treating cystic fibrosis.
Another object of the invention is to provide a method of treating tumors.
Another object of the invention is to provide a method of treating urea cycle disorders.
It is yet another object of the invention to provide methods of treating a &bgr;-hemoglobinopathy.
These and other objects of the invention are achieved by one or more embodiments of the invention. In one embodiment of the invention a solid nanosphere for treating cystic fibrosis is provided. The nanosphere comprises sodium 4-phenylbutyrate (4-PBA).
In another embodiment of the invention a solid nanosphere is provided for treating cystic fibrosis. The nanosphere comprises:
a wild-type CFTR-encoding nucleic acid; and
a drug which activates &Dgr;F508 mutant CFTR proteins.
In still another embodiment of the invention a solid nanosphere is provided for gene delivery. The nanosphere comprises:
sodium 4-phenylbutyrate (4-PBA) and a nucleic acid construct, wherein the construct comprises a promoter operatively linked to a gene coding sequence, wherein the promoter is 4-PBA-inducible.
In yet another embodiment of the invention a method of treating cystic fibrosis is provided. The method comprises the step of:
administering an aerosolized medicament to a lung of a cystic fibrosis patient wherein the medicament comprises a solid nanosphere comprising 4-PBA.
In still another embodiment of the invention a method of treating tumors is provided. The method comprises the step of:
administering a medicament to a tumor, wherein the medicament comprises a solid nanosphere comprising 4-PBA.
According to another aspect of the invention a method of treating a urea cycle disorder is provided. The method comprises the step of:
administering a medicament to the liver of a patient with a urea cycle disorder, wherein the medicament comprises a solid nanosphere comprising 4-PBA.
According to still another aspect of the invention a method is provided for treating a &bgr;-hemoglobinopathy. The method comprises the step of:
administering a medicament to the bone marrow of a patient with a &bgr;-hemoglobinopathy, wherein the medicament comprises a solid nanospher 4-PBA.
In still another embodiment of the invention another method is provided for treating a &bgr;-hemoglobinopathy. The method comprises the step of:
administering a medicament to a patient with a &bgr;-hemoglobinopathy, wherein the medicament comprises a solid nanosphere comprising 4-PBA.
The invention thus provides the art with formulations and methods for treating a variety of human diseases, including cystic fibrosis, urea cycle disorders, cancers, and &bgr;-hemoglobinopathies.
REFERENCES:
patent: 94/04671 (1994-03-01), None
patent: 96/29998 (1996-10-01), None
patent: 97/46588 (1997-12-01), None
S.M. Walsh et al. “Combination fo Drug and Gene Delivery by Gelatin Nanospheres for the Treatment of Cystic Fibrosis” Proceedings of the 24th International Symposium on Controlled Release of Bioactive Materials, Stockhom, Jun. 14, 19, 1997, pp. 75-76.
R.C. Rubenstein et al. “In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta. F508-CFTR” J. Clin. Invest., vol. 100, No. 10, Nov. 15, 1997, pp. 2457-2465.
H. Koy et al. “The Cystic Fibrosis Transmembrane Conductance Regulator Overexpression, Purification, and Characterization of Wild Type and Delta F508 Mutant Forms of the First Nucleotide Binding Fold in Fusion with the Maltose-Binding Protein” J. Biol. Chem., vol. 268, No. 32, Nov. 15, 1993, pp. 24330-24338.
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Leong Kam W.
Rubenstein Ronald
Walsh Scott
Zeitlin Pam
Banner & Witcoff , Ltd.
Kaushal Sumesh
LeGuyader John L.
The Johns Hopkins University
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