Cangene Corporation

Connaught Laboratories Limited

Robert T Garvin

Lawrence T Malek

Joel E Haynes

Eric A James

Eric James

A novel conjugated protein produced by recombinant DNA techniques comprises a low molecular weight carrier protein portion that is normally self-aggregating to an immunogenic higher molecular weight proteinaceous material and a hapten portion wich is a peptide fraction that contains an epitope for an antigen for a pathogenic disease attached to the low molecular weight carrier portion. On aggregation of the self-aggregating protein, the hapten is on the surface of the viral particle, allowing for recognition of the hapten by the immune system. Upon introduction in vivo, the viral protein produces antibodies to both the self-aggregating protein and the hapten. A plurality of the conjugated proteins having different haptens can be combined into a viral protein to provide multi specific vacicines conferring immunity to a variety of pathogenic agents.

Multispecific antigenic proteins

A gene expression system is used to produce heterologous biologically active proteins, in particular bioactive granulocyte macrophage colony stimulating factor ('GM-CSF'), secreted from a host selected from the Streptomyces genera. The gene expression system includes a regulatory nucleotide sequence linked to a second nucleotide sequence encoding the heterologous protein. The regulatory sequence, encodes a peptide which directs the secretion of the heterologous protein in bioactive form from a host selected from the Streptomyces genera. The regulatory sequence includes a signal sequence and a promoter sequence. The second nucleotide sequence, which encodes GM-CSF or a biologically active derivative of GM-CSF, may be either natural or synthetic. In particular, the invention relates to an expression system for secreting bioactive, non-glycosylated, oxidized, therapeutically useful GM-CSF from a host selected from the Streptomyces genera. Also disclosed are similar constructs for expression of interleukin 3 (IL-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF.alpha.), human stem cell factor (SCF), interleukin 7 (IL-7), erythropoietin (EPO) and interleukin 2 (IL-2). Novel signal peptides of these constructs include hybrids of the signal peptides of Streptomyces griseus protease B and Escherichia coli omp A, hybrids of Streptomyces griseus protease B and Streptomyces limosus .alpha.-amylase signal peptide.

Expression system for the secretion of bioactive human granulocyte

A DNA signal sequence initially isolated from Streptomyces griseus encodes a signal peptide which directs the secretion, via a fused intermediate, of a protein from the cell within which the DNA signal sequence is expressed. The signal sequence is derived from genes encoding protease A and protease B of S. griseus. The DNA signal sequence encodes a thirty-eight amino acid signal peptide. A DNA construct, including the DNA signal sequence and a gene sequence encoding a protein, when transformed into a living cell by a suitable vector, results in the signal peptide correctly directing the secretion of a mature protein of desired structure, particularly from prokaryotic genera selected for their ability to display enzymatic activity of a type typified by, but not exclusive to, that of protein disulphide oxidoreductase, EC 5.3.4.1, more particularly in the genera Streptomyces, and most particularly in Streptomyces lividans 66.

Expression system comprising DNA encoding the signal peptide of protease

A gene expression system is used to produce heterologous biologically active proteins, in particular bioactive granulocyte macrophage colony stimulating factor ('GM-CSF'), secreted from a host selected from the Streptomyces genera. The gene expression system includes a regulatory nucleotide sequence linked to a second nucleotide sequence encoding the heterologous protein. The regulatory sequence, encodes a peptide which directs the secretion of the heterologous protein in bioactive form from a host selected from the Streptomyces genera. The regulatory sequence includes a signal sequence and a promoter sequence. The second nucleotide sequence, which encodes GM-CSF or a biologically active derivative of GM-CSF, may be either natural or synthetic. In particular, the invention relates to an expression system for secreting bioactive, non-glycosylated, oxidized, therapeutically useful GM-CSF from a host selected from the Streptomyces genera.

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Toronto, Canada

Robert T Garvin