Polymalic acid-based multi-functional drug delivery system

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C424S400000, C514S772300

Reexamination Certificate

active

07935677

ABSTRACT:
A structured drug system that is useful for delivering a drug payload to a specific tissue or cell type is disclosed. The system is based on purified polymalic acid. This polymer isolated from natural sources is biocompatible, biodegradable and of very low toxicity. The polymer is extremely water soluble and contains a large number of free carboxyl groups which can used to attach a number of different active molecules. In the examples disclosed N-hydroxysuccinimide esters of the carboxyl groups are used to attach such molecules. The active molecules include monoclonal antibodies to promote specific cellular uptake and specific pro-drugs such as antisense nucleic acids designed to modify the cellular metabolism of a target cell. The pro-drugs are advantageously linked by a somewhat labile bond so that they will be released under specific conditions. In addition, the system contains amide-linked valine to encourage membrane disruption under lysosomal conditions. Polyethylene glycol groups are attached to extend the drug system's circulation half-life. In addition, fluorescent reported groups can be readily included to aid in visualizing and confirming drug system targeting. The drug system can deliver treatments for a wide range of diseases and is specially advantageous for treatment of neoplasms.

REFERENCES:
patent: 6472512 (2002-10-01), LaFleur et al.
patent: 7056532 (2006-06-01), Kabanov et al.
patent: 2002/0155440 (2002-10-01), Black et al.
patent: 01/87239 (2001-11-01), None
patent: 02/059610 (2002-08-01), None
patent: 2005/028617 (2005-03-01), None
patent: 2005/055980 (2005-06-01), None
Odian, G. (1991) Principles of Polymerization, Third Edition. John Wiley and Sons, Inc.
Yu, et al. (2009) Targeted Delivery Systems for Oligonucleotide Therapeutics. The AAPS Journal, v.11(1):195-203.
Bulmus et al. (Journal of Controlled Release 93 (Nov. 18, 2003) 105-120.
Khazenzon, A.J. et al., Novel angiogenic targets for human glioma prevention and regulation of their expression, International Journal of Molecular Medicine, 2002, 10: Supplement 1, p. S41, XP008091390.
Ljubimova, J.Y. et al., A new multifunctional drug delivery system based on polymalic acid to inhibit angiogenesis and invasion of human gliomas in vitro and in vivo, European Journal of Cancer, Supplement, 2004, 2:8, p. 184, XP004640052.
Ljubimova, J.Y. et al., Development of an in vitro system to block the angiogenic target, laminin-8, in human gliomas, Proceedings of the American Association for Cancer Research Annual Meeting, Mar. 2002, vol. 43, p. 177, XP001536931.
Albini et al., A Rapid In Vitro Assay for Quantitating the Invasive Potential of Tumor Cells, Cancer Research, (Jun. 15, 1987), pp. 3239-3245, 47(12).
Andrews et al., Results of a Pilot Study Involving the Use of an Antisense Oligodeoxynucleotide Directed Against the Insulin-Like Growth Factor Type I Receptor in Malignant Astrocytomas, Journal of Clinical Oncology, (Apr. 15, 2001), pp. 2189-2200, 19(8).
Arora et al., c- Myc Antisense Limits Rat Liver Regeneration and Indicates Role for c-myc in Regulating Cytochrome P-450 3A Activity, Journal of Pharmacology and Experimental Therapeutics, (Mar. 2000), pp. 921-928, 292(3).
Astriab-Fisher et al., Antisense Inhibition of P-Glycoprotein Expression Using Peptide-Oligonucleotide Conjugates, Biochemical Pharmacology (Jul. 1, 2000), pp. 83-90, 60(1).
Belkin et al., Integrins As Receptors for Laminins, Microscopy Research and Technique, (Nov. 1, 2000), pp. 280-301, 51(3).
Bello et al., Simultaneous Inhibition of Glioma Angiogenesis, Cell Proliferation, and Invasion by a Naturally Occurring Fragment of Human Metalloproteinase-2, Cancer Research, (Dec. 15, 2001), pp. 8730-8736, 61(24).
Boado et al., Antisense-Mediated Down-Regulation of the Human Huntingtin Gene, Journal of Pharmacology and Experimental Therapy, (Oct. 2000), pp. 239-243, 295(1).
Colognato et al., Form and Function: The Laminin Family of Heterotrimers, Developmental Dynamics, (Jun. 2000), pp. 213-234, 218(2).
De Diesbach et al., Identification, Purification and Partial Characterisation of an Oligonucleotide Receptor in Membranes of HepG2 Cells, Nucleic Acids Research, (Feb. 15, 2000), pp. 868-874, 28(4).
Dias et al., Antisense Oligonucleotides : Basic Concepts and Mechanisms, Molecular Cancer Therapy, (Mar. 2002), pp. 347-355, 1(5).
Fujiwara et al., Purification and Characterization of Human Laminin-8. Laminin-8 Stimulates Cell Adhesion and Migration Through a3β1 and a6p, Integrins, Journal of Biological Chemistry, (May 18, 2001), pp. 17550-17558, 276(20).
Gonzalez et al., Complex Interactions Between the Laminin a4 Subunit and Integrins Regulate Endothelial Cell Behavior In Vitro and Angiogenesis In Vivo, Proceedings of the National Academy of Sciences USA, (Dec. 10, 2002), pp. 16075-16080, 99(25).
Hayashi et al., Identification and Recombinant Production of Human Laminin a4 Subunit Splice Variants, Biochemical and Biophysical Research Communications, (Dec. 6, 2002), pp. 498-504, 299(3).
Herold-Mende et al., Clinical Impact and Functional Aspects of Tenascin-C Expression During Glioma Progression, International Journal of Cancer, (Mar. 20, 2002), pp. 362-369, 98(3).
Jansen et al., Chemosensitisation of Malignant Melanoma by BCL2 Antisense Therapy, Lancet, (Nov. 18, 2000), pp. 1728-1733, 356(9243).
Kachra et al., Expression of Matrix Metalloproteinases and Their Inhibitors in Human Brain Tumors, Clinical and Experimental Metastasis, (1999), pp. 555-566, 17(7).
Kleinman et al., Basement Membrane Complexes With Biological Activity, Biochemistry, (Jan. 28, 1986), pp. 312-318, 25(2).
Knott et al., Stimulation of Extracellular Matrix Components in the Normal Brain by Invading Glioma Cells, International Journal of Cancer, (Mar. 16, 1998), pp. 864-872, 75(6).
Komata et al., Combination Therapy of Malignant Glioma Cells With 2-5A-Antisense Telomerase RNA and Recombinant Adenovirus p53, Gene Therapy, (Dec. 2000), pp. 2071-2079, 7(24).
Kondraganti et al., Selective Suppression of Matrix Metalloproteinase-9 in Human Glioblastoma Cells by Antisense Gene Transfer Impairs Glioblastoma Cell Invasion, Cancer Research, (Dec. 15, 2000), pp. 6851-6855, 60(24).
Kulla et al., Tenascin Expression Patterns and Cells of Monocyte Lineage: Relationship in Human Gliomas, Modern Pathology, (Jan. 2000), pp. 56-87, 13(1).
Lacerra et al., Restoration of Hemoglobin A Synthesis in Erythroid Cells From Peripheral Blood of Thalassemic Patients, Proceedings of the National Academy of Sciences USA, (Aug. 15, 2000), pp. 9591-9596, 97(17).
Lal et al., A Public Database for Gene Expression in Human Cancers. Cancer Research, (Nov. 1, 1999), pp. 5403-5407, 59(21).
Ljubimov et al., Human Corneal Basement Membrane Heterogeneity: Topographical Differences in the Expression of Type IV Collagen and Laminin Isoforms, Lab Investigation, (Apr. 1995), pp. 461-473, 72(4).
Ljubimova et al., Gene Array Analysis of Differentially Expressed Genes in Human Glial Tumors. International Journal of Oncology, (2001), pp. 287-295, 18.
Ljubimova et al., Overexpression of a4 Chain-Containing Laminins in Human Glial Tumors Identified by Gene Microarray Analysis, Cancer Research (Jul. 15, 2001), pp. 5601-5610, 61(14).
MacDonald et al., Urokinase Induces Receptor Mediated Brain Tumor Cell Migration and Invasion, Journal of Neuro-Oncology, (Dec. 1998), pp. 215-226, 40(3).
McKean et al., FAK Induces Expression of Prx1 to Promote Tenascin-C-Dependent Fibroblast Migration, Journal of Cell Biology, (Apr. 28, 2003), pp. 393-402, 161(2).
Minakawa et al., In Vitro Interaction of Astrocytes and Pericytes With Capillary-Like Structures of Brain Microvessel Endothelium, Lab Investigation, (Jul. 1991), pp. 32-40, 65(1).
Miner et al., The Laminin Alpha Chains: Expression, Developmental Transitions, and Chromosomal Locations of A1-5, Identification of Heterotrimeric Laminins 8-11, and Cloning of a Novel a3 Isoform, Journal of Cell Biology, (May 5, 1997), pp. 685-701, 137(3).
Nielsen et al., Peptide Nucleic Acid Targeting of Double-Stranded DNA. Methods in Enzymology, 2001, pp. 329-340, 340.
Patarroyo et al., Laminin Isoforms

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