Georgetown University

Other

Aventis Pharma Deutschland, Gmbh

Kathleen F Pirollo

Esther H Chang

Eugen Uhlmann

Liang Xin Xu

Anuschirwan Peyman

David William Will

Antonina Rait

The present application provides methods of preventing and treating the toxic effects of exposure to organophosphate agents. In embodiments, targeted cationic liposome complexes delivering nucleic acid molecules encoding butyrylcholinesterase and a polyproline rich peptide are administered. Suitably, the administration is via inhalation or via aerosol. Also provided are cationic liposome complexes and methods of making the complexes for such administration.

Treatment for exposure to nerve agent

A method of preparing an antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex comprises the steps of (a) preparing an antibody or antibody fragment; (b) mixing said antibody or antibody fragment with a cationic liposome to form a cationic immunoliposome or with a cationic polymer to form a polyplex; and (c) mixing said cationic immunoliposome or said polyplex with a therapeutic or diagnostic agent to form said antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex.

Preparation of antibody or an antibody fragment targeted immunoliposomes for systemic administration of therapeutic or diagnostic agents and uses thereof

The present invention provides methods of preparing an antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex comprising (a) preparing an antibody or antibody fragment; (b) mixing said antibody or antibody fragment with a cationic liposome to form a cationic immunoliposome or with a cationic polymer to form a polyplex; and (c) mixing said cationic immunoliposome or said polyplex with a therapeutic or diagnostic agent to form said antibody- or antibody fragment-targeted cationic immunoliposome or polymer complex. The present invention also provides cationic immunoliposome or polymer complexes produced by such methods and compositions comprising such complexes. The present invention also provides methods for treating various diseases and disorders, including cancers, by administering the complexes and compositions of the invention to a patient.

Preparation of antibody or an antibody fragment-targeted immunoliposomes for systemic administration of therapeutic or diagnostic agents and uses thereof

Provided herein is an antibody- or antibody fragment-targeted cationic immunoliposome complex prepared by a method comprising the steps of (a) preparing an antibody or antibody fragment; (b) mixing the antibody or antibody fragment with a cationic liposome and to form a cationic immunoliposome wherein the antibody or antibody fragment is complexed with the cationic liposome, but is not chemically conjugated to the cationic liposome and wherein said antibody or antibody fragment does not comprise a lipid tag; and (c) mixing the cationic immunoliposome with a therapeutic or diagnostic agent to form the antibody- or antibody fragment-targeted cationic immunoliposome. Also provided is an antibody- or antibody fragment-targeted cationic immunoliposome comprising an antibody or antibody fragment; a cationic liposome, wherein the antibody or antibody fragment is complexed with the cationic liposome, but is not chemically conjugated to the cationic liposome and wherein said antibody or antibody fragment does not comprise a lipid tag and a therapeutic or diagnostic agent.

Simplified and improved method for preparing an antibody or an antibody fragment targeted immunoliposome for systemic administration of a therapeutic or diagnostic agent

The present invention is in the fields of drug delivery, cancer treatment and diagnosis and pharmaceuticals. This invention provides a method of making antibody- or antibody fragment-targeted immunoliposomes for the systemic delivery of molecules to treat and image diseases, including cancerous tumors. The invention also provides immunoliposomes and compositions, as well as methods of imaging various tissues. The liposome complexes are useful for encapsulation of imaging agents, for example, for use in magnetic resonance imaging. The specificity of the delivery system is derived from the targeting antibodies or antibody fragments.

Tumor-targeted nanodelivery systems to improve early MRI detection of cancer

Provided are antisense oligonucleotides directed against the raf-1 gene, Ha-ras gene and HER-2 gene, components of a signal transduction pathway involving oncogenes and their normal counterparts and leading to the phenotype of cellular radioresistance. Administration of these antisense oligonucleotides is shown to reverse the radioresistance phenotype in cells overexpressing HER-2 or a mutant form of Ha-ras. Methods and compositions for reversing radiation resisting among other conditions involving these genes are disclosed.

Compositions and methods for reducing radiation and drug resistance in cells

Targeted ligand-liposome-therapeutic molecule complexes (vectors) for the systemic delivery of the therapeutic molecule to various target cell types including cancer cells such as squamous cell carcinoma of the head and neck, breast and prostate tumors. The preferred ligands, folate and transferrin, target the liposome complex and facilitate transient gene transfection. The systemic delivery of complexes containing DNA encoding wild-type p53 to established mouse xenografts markedly sensitized the tumors to radiotherapy and chemotherapy. The combination of systemic p53 gene therapy and conventional radiotherapy or chemotherapy resulted in total tumor regression and long tern inhibition of recurrence. This cell-specific delivery system was also used in vivo to successfully deliver, via intravenous administration, small DNA molecules (oligonucleotides) resulting in chemosensitivity and xenograft growth inhibition. Other therapeutic molecules, including intact viruses, can be encapsulated in a complex and targeted in accordance with the invention.

Targeted liposome gene delivery

The invention relates to a specific modified oligonucleotide complementary to a section of the human Ha-ras gene and mRNA, and its use to specifically regulate, modulate or inhibit expression of the HA-ras gene, and its use as a pharmaceutical for the treatment of conditions arising from the abnormal expression of the Ha-Ras gene, in particular in combination with chemotherapy and radiotherapy. The modified oligodeoxynucleotide according to the invention has the sequence 5&prime;-TxAxTxTxCxCxGxTxCxAxT-3&prime;-O&mdash;PO &mdash;O&mdash;R (SEQ ID NO:1), wherein X is an internucleotide linkage of type o or s, with the proviso that x is an s linkage at least 4 times and at most 9 times, and o means a phosphodiester internucleoside linkage, s means a phosphorothioate internucleoside linkage, R means a C -C alkyl group, &mdash;(CH &mdash;CH O)n-(CH ) &mdash;CH , or &mdash;CH &mdash;CH(OH)CH O&mdash;(CH ) &mdash;CH wherein n is an integer from 1 to 6, m is an integer from 0 to 20 and q is an integer from 7 to 20 and A is 2&prime;-deoxyadenosine, G is 2&prime;-deoxyguanosine, C is 2&prime;-deoxycytidine and T is thymidine.

Modified antisense nucleotides complementary to a section of the human Ha-ras gene

Provided are antisense oligonucleotides directed against the raf-1 gene, Ha-ras gene and HER-2 gene, components of a signal transduction pathway involving oncogenes and their normal counterparts and leading to the phenotype of cellular radioresistance. Administration of these antisense oligonucleotides is shown to reverse the radioresistance phenotype in cells overexpressing HER-2 or a mutant form of Ha-ras. Methods and compositions for reversing radiation resistance among other conditions involving these genes are disclosed.

Growing community of inventors

Rockville, MD, United States of America

Kathleen F Pirollo