The Burnham Institute

La Jolla Cancer Research Foundation

Sequus Pharmaceuticals, Inc.

Other

Alza Corporation

The Ohio State University

Liposome Technology, Inc.

Miza Corporation

Shi Kun Huang

Samuel Zalipsky

Francis J Martin

Bei Jin

Edwin Kiyoshi Oto

Mohammad Hassanipour

Theresa M Allen

Martin C Woodle

Yolanda P Quinn

Wei-Ming Zhang

Robert B Chadwick

The invention provides an isolated PR Family Member (PFM) nucleic acid molecule that contains a PFM PR domain nucleotide sequence, a PFM ZF domain nucleotide sequence, or a modification thereof. The invention also provides an isolated PFM nucleic acid molecule that contains a nucleotide sequence that encodes a PFM PR domain polypeptide, or that encodes a PFM ZF domain polypeptide, or that encodes an immunologically equivalent modification thereof. Also provided are isolated PFM oligonucleotides. The invention also provides methods for detecting a PFM nucleic acid molecule in a sample. Further provided is a method of modulating cell growth by expressing an encoded PFM polypeptide in the cell. Also provided is an isolated PFM polypeptide, containing a PFM PR domain amino acid sequence, or a PFM ZF domain amino acid sequence, or a modification thereof. The invention also provides an isolated PFM peptide, containing at least 8 contiguous amino acids of a PFM polypeptide. Also provided is an antibody or antigen binding fragment thereof, which specifically binds a PFM polypeptide. Further provided is a method for detecting PFM polypeptide in a sample, by contacting the sample with a PFM antibody and detecting specifically bound antibody.

PR-domain containing nucleic acids, polypeptides, antibodies and methods

The present invention provides an isolated nucleic acid molecule encoding a PFM/SET polypeptide. Also provided is an isolated nucleic acid molecule encoding a functional fragment of a PFM/SET polypeptide that contains a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide of the invention. Further provided by the invention are PFM/SET polypeptides, and functional fragments thereof that contain a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide. The invention also provides PFM/SET antibodies, PFM/SET modulatory compounds, and related methods. The molecules of the invention can be used in methods of screening for a compound that modulates PFM/SET polypeptide histone methyltransferase activity and to modulate cell proliferation to prevent or treat proliferative disorders, including cancer. Additionally, the molecules and methods of the invention can be used to diagnose and prognose proliferative disorders.

PR/SET-domain containing nucleic acids, polypeptides, antibodies and methods of use

A liposomal composition and a method of using the same for achieving intracellular delivery of a liposome-entrapped agent is described. The liposomes are composed of a pH sensitive lipid and include a targeting ligand to direct the liposomes to a target cell. The liposomes also include a stabilizing component, such a polymer-derivatized lipid, where the polymer is attached to the lipid by a releasable linkage. Administration of the liposomes results in cellular internalization and destabilization of the liposome for intracellular delivery of the entrapped agent.

Liposome composition for improved intracellular delivery of a therapeutic agent

The invention provides a method of screening for a compound that modulates RIZ histone methyltransferase (HMT) activity, by contacting a RIZ or RIZ fragment having HMT activity with one or more candidate compounds, and determining histone methyltransferase activity of the contacted RIZ or RIZ fragment. Also provided is a method of screening for a compound that modulates progesterone receptor (PR) activity, by providing a RIZ1 modulatory compound, and determining the ability of the RIZ1 modulatory compound to modulate PR activity. Further provided is a method of identifying an individual with an estrogen receptor positive (ER+) tumor having a reduced likelihood of responding to endocrine therapy. The method involves determining the RIZ1 status of the tumor, wherein an abnormal RIZ1 status identifies the individual as an individual with a reduced likelihood of responding to endocrine therapy.

Screening, diagnostic and therapeutic methods relating to RIZ

A lipid represented by the formula:wherein each of Rand Ris an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms; n=0&#x2013;20; L is selected from the group consisting of (i) &#x2014;X&#x2014;(C&#x2550;O)&#x2014;Y&#x2014;, (ii) &#x2014;X&#x2014;(C&#x2550;O)&#x2014;, and (iii) &#x2014;X&#x2014;CH&#x2014;, wherein X and Y are independently selected from oxygen, NH, and a direct bond; and Z is a weakly basic moiety that has a pK of less than about 7.4 and greater than about 4.0 is described.

Neutral-cationic lipid for nucleic acid and drug delivery

A method of liposome-based therapy for a mammalian subject is disclosed. The method uses liposomes with outer surfaces that contain an affinity moiety effective to bind specifically to a biological surface at which the therapy is aimed, and a hydrophilic polymer coating effective to shield the affinity moiety from interaction with the target surface. The hydrophilic polymer coating is made up of polymer chains covalently linked to surface lipid components in the liposomes through releasable linkages. After a desired liposome biodistribution is achieved, a releasing agent is administered to cause cleaving of a substantial portion of the releasable linkages in the liposomes, to expose the affinity agent to the target surface.

Therapeutic liposome composition and method

The invention provides a method of inhibiting growth of a microsatellite instability (MSI)-positive tumor. The method is practiced by introducing into an MSI-positive tumor a nucleic acid molecule encoding a RIZ1 polypeptide and expressing the RIZ1 polypeptide in the tumor in an effective amount to inhibit growth of the tumor. Also provided is a method of determining the MSI status of a tumor. The method is practiced by determining in the tumor the number of adenosine (A) nucleotides in a poly(A) tract of a RIZ nucleic acid molecule in the tumor. An abnormal number of adenosine nucleotides in a RIZ poly(A) tract indicates that the tumor is MSI-positive.

Methods of detecting and treating microsatellite-instability positive tumors using RIZ

The invention provides an isolated PR Family Member (PFM) nucleic acid molecule that contains a PFM PR domain nucleotide sequence, a PFM ZF domain nucleotide sequence, or a modification thereof. The invention also provides an isolated PFM nucleic acid molecule that contains a nucleotide sequence that encodes a PFM PR domain polypeptide, or that encodes a PFM ZF domain polypeptide, or that encodes an immunologically equivalent modification thereof. Also provided are isolated PFM oligonucleotides. The invention also provides methods for detecting a PFM nucleic acid molecule in a sample. Further provided is a method of modulating cell growth by expressing an encoded PFM polypeptide in the cell.

The present invention provides mammalian retinoblastoma (Rb) protein-interacting zinc finger (RIZ) proteins, nucleic acid molecules encoding the RIZ and antibodies specific for the RIZ. The invention also provides screening assays for identifying an agent that effectively alters the association of a RIZ with a second molecule, which can bind to the RIZ. The invention also provides active fragments of RIZ containing the PR domain, which can regulate transcription. In addition, the invention provides methods for introducing a nucleic acid molecule-encoding a RIZ into a cell and for A-contacting a cell with an effective agent in order to modulate a function of a cell. Such methods are useful, for example, for inducing growth of a cardiac cell or a neuronal cell in a subject and for effecting normal growth control to a tumor cell or causing differentiation of tumor cells. The invention further provides methods for detecting a RIZ in a sample by detecting the RIZ or a nucleic acid molecule encoding the RIZ. Such methods are useful to diagnose a pathology that is characterized by an increased or decreased level of a RIZ in a cell or by expression of a mutant RIZ in a cell.

Retinoblastoma protein-interacting zinc finger proteins

The present invention provides mammalian retinoblastoma (Rb) protein-interacting zinc finger (RIZ) proteins, nucleic acid molecules encoding RIZ and antibodies specific for RIZ. The invention provides methods for identifying an agent that alters the association of a RIZ with a second molecule, which can bind to RIZ. The invention provides fragments of RIZ, PRD1-BF1, EVI-1, and egl-43. The invention provides methods for introducing a nucleic acid molecule encoding a RIZ into a cell and for contacting a cell with an effective agent in order to modulate a function of a cell. The invention further provides methods for detecting a RIZ in a sample by detecting RIZ or a nucleic acid molecule encoding RIZ.

A plasmid-liposome composition for transfection of a cell is described. The composition includes plasmid molecules condensed with a polycationic condensing agent and cationic liposomes. Also disclosed is a method for preparing the plasmid-liposome complexes.

Condensed plasmid-liposome complex for transfection

The present invention provides PR domain peptides, which are about 100 to about 120 amino acids in length and contain three highly conserved sequences of about 10 to about 12 amino acids, separated by less conserved sequences of about 20 to about 35 amino acids.

Growing community of inventors

Castro Valley, CA, United States of America

Shi Kun Huang