University of California

Other

City of Hope

Viagene

Memgen, Inc.

Charles E Prussak

Thomas James Kipps

Mark J Cantwell

Jian Yu

Bing Cui

George F Widhopf, Ii

Liguang Chen

Theodore Friedmann

Jiing-Kuan Yee

Atsushi Miyanohara

Shin-Tai Chen

Steven M Herrmann

The present invention relates to pharmaceutical compositions and a method of inhibiting metastasis using anti-ROR1 antibodies or antigen binding fragments, ROR1 binding peptides and ROR1 vaccines.

Antibodies and vaccines for use in treating ROR1 cancers and inhibiting metastasis

The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.

Chimeric CD154 polypeptides

The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1;, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF&#x3b1;, wherein the encoded domain or subdomain replaces a cleavage site of native TNF&#x3b1;, and a second nucleotide sequence encoding a domain or subdomain of native TNF&#x3b1; that binds to a TNF&#x3b1; receptor. The encoded chimeric TNF&#x3b1; is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF&#x3b1; receptor on the surface of a cell. The chimeric TNF&#x3b1; is therefore useful in methods for inducing apoptosis of a cell expressing a TNF&#x3b1; receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; that is expressed on the surface of the cell.

Chimeric nucleic acids encoding polypeptides comprising TNF alpha, CD70 and FAS ligand domains

Nucleic acids encoding chimeric CD154 polypeptides

The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; and chimeric TNF&#x3b1; polypeptides. The former have a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNF&#x3b1;, wherein the encoded domain or subdomain lacks a cleavage site, and a second nucleotide sequence encoding a domain or subdomain of native TNF&#x3b1; that binds to a TNF&#x3b1; receptor. The encoded chimeric TNF&#x3b1; is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNF&#x3b1; receptor on the surface of a cell. The chimeric TNF&#x3b1; is therefore useful in methods for inducing apoptosis of a cell expressing a TNF&#x3b1; receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNF&#x3b1; that is expressed on the surface of the cell.

Nucleic acid molecules encoding TNF-&#x3b1; ligand polypeptides having a CD154 domain

Methods for preserving an infectious recombinant virus for subsequent reconstitution are provided. Within one aspect, the method comprises the steps of (a) combining an infectious recombinant virus with an aqueous solution comprising a saccharide, a high molecular weight structural additive, a buffering component and water to form an aqueous suspension, thereby stabilizing the infectious virus; (b) cooling the aqueous suspension containing the virus to a temperature below the glass transition state temperature or below the eutectic point temperature of the formulation; and (c) removing water from the cooled aqueous suspension by sublimation to form a lyophilized virus having less than 10% water by weight of the lyophilized virus, the virus being capable of infecting mammalian cells upon reconstitution.

Methods for preserving recombinant retroviruses

The present invention features packaging cell lines and recombinant retroviral particles produced thereby, particularly pseudotyped retroviral particles. Preferably, the packaging cell lines are derived from HeLa, Cf2Th, D17, MDCK, or BHK cells, most preferably from Cf2Th cells. Retroviral particles are produced by inducibly expressing an envelope protein of interest (e.g., a retroviral envelope or the envelope protein of vesicular stomatitis virus (VSV G)). Inducible expression of the envelope protein is accomplished by operably linking an envelope protein-encoding nucleotide sequence to an inducible promoter (e.g., a promoter composed of a minimal promoter linked to multiple copies of tetO, the binding site for the tetracycline repressor (tetR) of the Escherichia coli, tetracycline resistance operon Tn10). Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription from the inducible promoter (e.g., a prokaryotic tetracycline repressor polypeptide (tetR)), a transcriptional activation domain, and a second ligand-binding domain (e.g., a ligand-binding domain of a steroid receptor, preferably an estrogen receptor (ER)).

Packaging cell lines for pseudotyped retroviral vectors

Methods and compositions useful for the separation of viruses, including retroviruses and vital vectors, from preparations are disclosed. Sulfated oligosaccharides with at least about 6 .mu.moles sulfate per gram of oligosaccharide are provided. In one aspect, a sulfated oligosaccharide of the present invention may be used in the purification of a virus, such as a lipid envelope virus. The present invention also discloses methods for the removal of a contaminating virus from a preparation, such as biologic therapeutics.

Growing community of inventors

San Diego, CA, United States of America

Charles E Prussak