Genencor International (Danisco A/S) in the US was developing I V, In addition, there was negligible IgG antibody response to the variant interferon-β. Herceptin IgG human antibody were made and transformed into Trichoderma reesei. Genencor International, a Danisco Company. Page. GENENCOR INTERNATIONAL PALO ALTO CA Initial genetic constructs for the Herceptin IgG human antibody were made and transformed into Trichoderma.
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In certain embodiments the targeting moiety is an inhibitor for a receptor or an enzyme, in other embodiments the targeting moiety is selected from the group consisting of a growth factor, a cytokine, and a receptor ligand. A number of chemically modified enzymes having chemically conjugated carbohydrate moieties are described in Genencro Application WO entitled “Chemically modified proteins with a carbohydrate moiety.
See, for example, Sambrook, et al. A Targeting moieties for receptors. Four out of five of the GP immunized animals responded with stimulation indices of greater than 3.
DNA vaccines-challenges in delivery. Amino acid sequences of the members of this series are not entirely homologous. This is especially relevant to the design of subunit vaccines for malaria and schistosomiasis where high genwncor of high affinity antibodies are usually the best defence against invading organisms [ 111624 ].
The terms “polypeptide”, “ohgopeptide”, “peptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues. This is typically accomplished either by complexing the subject molecule with a composition to render it resistant to acidic and enzymatic hydrolysis or by packaging the chimeric molecule agent in an appropriately resistant carrier such as a liposome.
This article has been cited by other articles in PMC. Conversely, retargeted enzymes may act as catalytic antagonists, but there are retargeted enzymes that are not necessarily catalytic antagonists. Moreover, many of these enzymes provide good targets for drug in a wide variety of pathologies. Subtilisin is a serine endoprotease MWwhich is secreted in large amounts from a wide variety genencr Bacillus species.
WT-SBL causes a mere 1. Because this invention utilizes chemically coupled targeting moieties this can be accomplished with relative ease and, at most, routine experimentation. More preferably, the plasmid is an expression vector, e. Because of the high dilution of PNPP used, the reaction had to be monitored for a long time.
Such methods include, but are not limited to alanine scanning mutagenesis Cunningham and Wells Science, oligonucleotide-mediated mutagenesis Adellman et al. In the presence of decoy protein [0.
Expression of full-length immunoglobulins in Escherichia coli: Our criterion for an epitope was an average stimulation index of 3. The sequences flanking these points are evaluated for the presence of restriction sites for replacing a short gdnencor of the gene with an oligonucleotide which when expressed will encode the desired mutants.
A sequence comparison of the enzymes in the T cell epitope regions revealed that a single amino acid change could confer a T cell epitope onto the less-immunogenic protease.
Antibodies also provide useful targets for the catalytic antagonists of this invention. In preferred embodiments, the antagonists of this invention are thus catalytic in nature being effectively regenerated rendered available again after degrading each substrate molecule target.
The plates were again covered and incubated at room temperature for 1 lgg. Two weeks after the last immunization serum samples were taken and ELISAs were performed to compare titers. Notably, the first B. Frequently, one of the constituent molecules of a chimeric molecule is a “targeting molecule”.
The ability to induce improved immune responses by the subtle changes described here could have a number of potentially vital applications. Although there were previous reports of secretion of full-length antibody by yeast cells 1132the titers attained were much lower than those that we report here.
Selection of enzymes effector molecules. The vectors were shown by Southern analysis to integrate at one or more random sites in the genome and in multiple approximately three to five copies results not shown. To this end, we have characterized the immune response of igg outbred Hartley strain guinea pigs to two related bacterial proteases. Fox1 Judith A. Meerman Genencor International, Inc. Four 5 mL falcon tubes were filled according to Table 12 Table Antibody assembly and cleavage.
Five peptide regions induced average responses of approximately 2.
In certain particularly preferred embodiments, the catalytic antagonists of this invention comprise a chemically modified mutant CMM enzyme. As used herein, “subtilisin” means a naturally- occurring subtilisin or a recombinant subtilisin.
The improved antibody response measured in this paper was increased titers of guinea pig polyclonal IgG. Since approximately half of the iigg chains were shown to be nonglycosylated, it is likely that some fraction, conceivably a major fraction, of assembled antibodies had one nonglycosylated heavy chain and one glycosylated heavy chain. In still yet another embodiment this invention provides methods of genencod the activity igf an enzyme to a specific target. T cell epitope mapping of B.
The term “carbohydrate” includes mono- oligo- and poly-saccharides as well as substances derived from monosaccharides by reduction of the carbonyl group alditolsby oxidation of one or more terminal groups to carboxylic acids, or by replacement of one or more hydroxy group s by an hydrogen atom, an amino group, a thiol group or similar heteroatomic groups. After effervescence had ceased more water mL was added and the solvent removed.