Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

Bayer Pharmaceutical Corporation

John E Murphy

Ronald N Zuckermann

Tetsuo Uno

Chin-Yi Huang

Nathalie Dubois-Stringfellow

Michael A Innis

Fred Ehrenkranz Cohen

Varavani J Dwarki

Toshihiko Takeuchi

Robert O Ralston

Julie Rinkenberger

Mohammad Ayub Khan

This invention relates compositions and methods for increasing the uptake of polynucleotides into cells. Specifically, the invention relates to vectors, targeting ligands, and polycationic agents. The polycationic agents are capable of (1) increasing the frequency of uptake of polynucleotides into a cell, (2) condensing polynucleotides; and (3) inhibiting serum and/or nuclease degradation of polynucleotides.

Compositions and methods for polynucleotide delivery

The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP (SEQ ID NO: 118) repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP (SEQ ID NO: 118) repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP (SEQ ID NO: 119)). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.

Human antibodies that have MN binding and cell adhesion-neutralizing activity

In accordance with the present invention, there are provided lipid-conjugated polyamide compounds and related compositions and methods thereof. Lipid-conjugated polyamide compounds of the present invention are particularly useful as vehicles for delivering biologically active agents to a target site. In particular, the invention compounds are effective at facilitating the delivery of polynucleotides to cells. The present invention also provides a method for producing stable formulations of polynucleotides complexed with a delivery vehicle.

Lipid-conjugated polyamide compounds

Method of complexing a nucleic acid with a lipid-conjugated polyamide

Lipid-conjugated polyamide compounds and related compositions and methods thereof

Polycationic polymers

Cells producing recombinant retroviral particles are provided. The cells contain a first vector having a coding region encoding retroviral LTRs and a packaging signal under the control of an expression control system, a tRNA binding site located upstream from the packaging signal and origin of second strand DNA synthesis located downstream from the packaging signal. The cells also contain a second vector having a coding region encoding retroviral capsid proteins gag and pol under the control of an expression control system and a third vector having a coding region encoding a simian type D retrovirus envelope glycoprotein under the control of an expression control system.

Retroviral vectors pseudotyped with SRV-3 envelope glycoprotein sequences

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Oakland, CA, United States of America

John E Murphy