Hoffmann-La Roche Inc.

Pestka Biomedical Laboratories, Inc.

Pbl Biomedical Laboratories, Inc.

University of Medicine and Dentistry of New Jersey

Other

Genentech, Inc.

Sidney Pestka

David V Goeddel

Serguei V Kotenko

Menachem Rubinstein

Heinz-Jurgen Friesen

Hsiang-Fu Kung

Philip C Familletti

Ronald G Jubin

Robert J Donnelly

Xueli Zhu

Derhsing Lai

Stuart Emanuel

Sara Rubinstein

Jaemog Soh

David L Miller

William A Clark

Thomas M Mariano

Doranelly Koltchev

Barbara Schwartz

Michael A Skawinski

Thomas B Lavoie

Jeffry R Cook

Disclosed are interferons of Rhesus and Cynomolgus origin and methods of production and use thereof.

Interferons of rhesus and cynomolgus origin and uses thereof

The present disclosure provides isolated Interferon&#x3b1; nucleic acids and polypeptides. The disclosure also provides antibodies which specifically recognize the subject Interferon&#x3b1; polypeptides, expression vectors containing the subject nucleic acids, and host cells expressing the subject polypeptides. In addition, methods of treatment using Interferon&#x3b1; are provided.

Interferons, uses and compositions related thereto

Methods to generate modified polypeptides, modified antibodies, stably phosphorylated modified polypeptides, stably phosphorylated modified antibodies, polynucleotide sequences encoding the polypeptides, and uses thereof are provided. A computer-aided molecular modeling method is also provided to generate modified phosphorylatable polypeptides, particularly monoclonal antibodies (MAbs) for use in the diagnosis and treatment of cancers and other diseases. The corresponding MAbs contain heterologous recognition sites for polypeptide kinases and can be labeled by an identifiable label, such as radio-isotopeP. The phosphate group(s) attached to the phosphorylated polypeptide is unusually stable due to engineered intramolecular interactions between the phosphate group and its neighbouring groups. Polynucleotide sequences which encode a monoclonal antibody containing sequences encoding a putative phosphorylation site, and methods for analyzing the biochemical properties of a polypeptide by using molecular modeling tools, are also disclosed.

Phosphorylated polypeptides and uses related thereto

Modified proteins, modified interferons &agr;'s and &bgr;'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-&agr;-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable, Hu-IFN-&agr;-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-&agr;-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as Numerous uses for the phosphorylated proteins are disclosed.

Nucleic acids encoding phosphorylated fusion proteins

Modified proteins, modified interferons &agr;'s and &bgr;'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-&agr;-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-&agr;-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-&agr;-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as . Numerous uses for the phosphorylated proteins are disclosed.

Phosphorylated fusion proteins

Disclosed herein are methods and means of microbially producing, via recombinant DNA technology, mature human leukocyte interferons, useful in the treatment of viral and neoplastic diseases.

Microbial production of mature human leukocyte interferons

Expression vectors for producing modified proteins

A new class of polypeptides is disclosed, along with a method for identifying and producing such polypeptides, having the characteristic of being unique to diseased states, particularly tumors and blood-borne malignancies. These new polypeptides are active and will be useful for therapeutic purposes.

Modified interferons

Mutant human interferons

This invention relates (a) to a 540 kb YAC which encodes the necessary species-specific factor(s) and is able to substitute for human Chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens; (b) to the construction of a plasmid to integrate the selective marker for antibiotic G418 resistance into YACs and to delete some of the human DNA fragments from YACs in order to facilitate the manipulation of human genomic DNA in yeast artificial chromosome (YAC) clones; (c) to two fragmentation vectors, pSE1 and pSE2, which contain a neomycin resistance and URA3 gene, developed for targeting yeast artificial chromosomes (YACs) containing human genomic DNA; (d) to a chromosomal fragmentation procedure employed to produce a deletion set of yeast artificial chromosomes (YACs) from a parental YAC (GART D142H8) known to map to Chromosome 21q and to encode the human interferon-gamma receptor (Hu-IFN-gamma R) accessory factor gene as well as the phosphoribosylglycinamide formyltranisferase (GART) gene; and (e) to the isolation of cDNA clones that encode the necessary species-specific factor and that are able to substitute for human Chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens.

Accessory factory function for interferon gamma and its receptor

Modified proteins, modified interferons &agr;'s and &bgr;'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-&agr;-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-&agr;-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-&agr;-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as,Numerous uses for the phosphorylated proteins are disclosed.

Constructs for producing phosphorylated fusion proteins

Modified proteins, modified interferons .alpha.'s and .beta.'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-.alpha.-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-.alpha.-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-.alpha.-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as E. coli. Numerous uses for the phosphorylated proteins are disclosed.

Method of identifying proteins modified by disease states related thereto

Growing community of inventors

North Caldwell, NJ, United States of America

Sidney Pestka