Abstract: The present invention concerns the field of conjugated peptides suitable for the production of drugs having an improved plasma half-life. In particular the present invention relates to a conjugated protein, obtained by an enzymatic reaction via microbial transglutaminase (MTGase), and an improved process for removing residual transglutaminase from peptides or recombinant proteins enzymatically conjugated by microbial transglutaminase (MTGase) to hydrophilic non-immunogenic polymer at a glutamine side-chain through an amidic linkage, allowing to obtain purified conjugated peptides or proteins which are stable against the enzymatic hydrolysis of the amidic bond between the peptide or protein moiety and the hydrophilic polymer and being free from product derived degradation displays the stability required for a drug.

Abstract: The present invention is related to glucagon-like peptide-1 (GLP-1) and analogues insulinotropic peptides, monoconjugated to biocompatible polymeric molecules by enzymatic direct and site-specific transglutamination reaction as well as their pharmaceutical formulations and delivery systems for therapeutical application in dismetabolic pathologies such as type 2 diabetes.

Abstract: The present invention is related to glucagon-like peptide-1 (GLP-1) and analogues insulinotropic peptides, monoconjugated to biocompatible polymeric molecules by enzymatic direct and site-specific transglutamination reaction as well as their pharmaceutical formulations and delivery systems for therapeutical application in dismetabolic pathologies such as type 2 diabetes.

Abstract: Novel site-specific mono-conjugates of Granulocyte Colony Stimulating Factor (G-CSF) are hereby described, with analogues and derivatives thereof, which stimulate proliferation and differentiation of progenitor cells to mature neutrophiles. These conjugates have been obtained using transglutaminase to covalently and site-specifically bind a hydrophilic, non-immunogenic polymer to a single glutamine residue of the human G-CSF native sequence and analogues thereof. These novel site-specific mono-conjugated derivatives are recommended for therapeutic use since they are stable in solution and exhibit significant biological activity in vitro and a longer bloodstream half-life, as compared to the non-conjugated protein, with a consequent prolonged pharmacological activity.

Abstract: Novel strains of genetically modified prokaryotic micro-organisms capable of expressing polypeptides having the enzyme activity of the enzymes uridine phosphorylase (UdP) and purine nucleoside phosphorylase (PNP) are described; the strains in question can be used, both in the form of whole cells and in the form of crude or purified extracts, to catalyse transglycosylation reactions between a donor nucleoside and an acceptor base with particularly high yields. The associated plasmid vectors are also described.

Abstract: Novel site-specific mono-conjugates of Granulocyte Colony Stimulating Factor (G-CSF) are hereby described, with analogues and derivatives thereof, which stimulate proliferation and differentiation of progenitor cells to mature neutrophiles. These conjugates have been obtained using transglutaminase to covalently and site-specifically bind a hydrophilic, non-immunogenic polymer to a single glutamine residue of the human G-CSF native sequence and analogues thereof. These novel site-specific mono-conjugated derivatives are recommended for therapeutic use since they are stable in solution and exhibit significant biological activity in vitro and a longer bloodstream half-life, as compared to the non-conjugated protein, with a consequent prolonged pharmacological activity.

Abstract: There are disclosed chemically active poly(ethylene glycols) and other hydrophilic polymers that are suitable for coupling to pharmaceutically or diagnostically active agents such as peptides, oligonucleotides, proteins or non-peptide molecules. The compounds are represented by the formula Poly-(X—NH—CO-A)n wherein, Poly is a hydrophilic polymer having a molecular weight of from about 300 to 100000 Daltons; A together with —NH—CO— forms a reactive group; X is a spacer moiety or a bond; n is an integer comprised between 1 and 50. The active agents of interest which may be conjugated to the disclosed compounds may be selected from hemoglobin, insulin, urokinase, alpha-interferon, G-CSF, hGH, asparaginase, adenosine deaminase, superoxide dismutase and catalase.

Abstract: The present invention relates to the expression and secretion in Saccharomyces cerevisiae of readily purifiable soluble variants of the Kex1 endopeptidase of Kluyveromyces lactis and the purification and use thereof for the in vitro processing of recombinant proteins usable in industrial applications. The soluble Kex1 endoproteases described here are free from the transmembrane domain of the native enzyme; the deletion of the transmembrane domain is achieved by removing at least 57 amino acid residues from the C-terminal.

Abstract: The present invention relates to the expression and secretion in Saccharomyces cerevisiae of readily purifiable soluble variants of the Kex1 endopeptidase of Kluyveromyces lactis and the purification and use thereof for the in vitro processing of recombinant proteins usable in industrial applications. The soluble Kex1 endoproteases described here are free from the transmembrane domain of the native enzyme; the deletion of the transmembrane domain is achieved by removing at least 57 amino acid residues from the C-terminal.

Abstract: The present invention relates to the expression and secretion in Saccharomyces cerevisiae of readily purifiable soluble variants of the Kex1 endopeptidase of Kluyveromyces lactis and the purification and use thereof for the in vitro processing of recombinant proteins usable in industrial applications. The soluble Kex1 endoproteases described here are free from the transmembrane domain of the native enzyme; the deletion of the transmembrane domain is achieved by removing at least 57 amino acid residues from the C-terminal.

Abstract: The present invention relates to the expression and secretion in Saccharomyces cerevisiae of readily purifiable soluble variants of the Kex1 endopeptidase of Kluyveromyces lactis and the purification and use thereof for the in vitro processing of recombinant proteins usable in industrial applications. The soluble Kex1 endoproteases described here are free from the transmembrane domain of the native enzyme; the deletion of the transmembrane domain is achieved by removing at least 57 amino acid residues from the C-terminal.

Abstract: Novel, genetically modified mammalian cell lines are described, which can produce glycoconjugates the oligosaccharide portions of which are more similar to the human one than those of the same glycoconjugates produced by cells which have not been genetically modified. The lines in question can be used for the production of recombinant glycoconjugates which are of therapeutic interest, in particular for the production of glycoproteins for use in human therapy, since the glycoconjugates produced in these modified lines have a lower immunogenic potential for man than corresponding glycoconjugates produced in cells which have not been genetically modified.

Abstract: The subject of the present invention is the construction of multicistronic eukaryotic plasmid expression vectors in which it is possible to express from two to four genes simultaneously and which are characterized by differently regulated bicistronic transcription units. The distinctive characteristic of these vectors is the presence of a CAP-independent translation initiation mechanism which is based on the ability of an IRES (internal ribosomal entry site) sequence to translate two proteins under the control of a single promoter. This family of multicistronic vectors can advantageously be used in various biotechnological applications in whcih the simultaneous expression of two or more genes is necessary, such as gene transfer protocols, DNA-immunization, or for the expression of different molecules in the same cell.

Abstract: Novel strains of genetically modified prokaryotic micro-organisms capable of expressing polypeptides having the enzyme activity of the enzymes uridine phosphorylase (UdP) and purine nucleoside phosphorylase (PNP) are described; the strains in question can be used, both in the form of whole cells and in the form of crude or purified extracts, to catalyse transglycosylation reactions between a donor nucleoside and an acceptor base with particularly high yields. The associated plasmid vectors are also described.

Abstract: Strains of genetically modified prokaryotic micro-organisms capable of expressing polypeptides having the enzyme activity of the enzymes uridine posphorylase (UdP) and purine nucleoside phosphorylase (PNP) are described; the strains in question can be used, both in the form of whole cells and in the form of crude or purified extracts, to catalyse transglycosylation reactions between a donor nucleoside and an acceptor base with particularly high yields. The associated plasmid vectors are also described.

Abstract: The preparation of novel biocatalysts is described; the biocatalysts are produced by the co-immobilization of the recombinant enzymes uridine phosphorylase and purine nucleoside phosphorylase by means of covalent bonds on solid substrates functionalized with epoxy groups. The novel biocatalysts are usable for successive reaction cycles, are resistant to heat and to the presence of solvents, and can advantageously be used in the industrial production of natural nucleosides and of modified analogues of pharmaceutical interest.

Abstract: The present invention relates to the expression and secretion in Saccharomyces cerevisiae of readily purifiable soluble variants of the Kex1 endopeptidase of Kluyveromyces lactis<and the purification and use thereof for the in vitro processing of recombinant proteins usable in industrial applications. The soluble Kex1 endoproteases described here are free from the trans-membrane domain of the native enzyme; the deletion of the transmembrane domain is achieved by removing at least 57 amino acid residues from the C-terminal.

Abstract: Strains of genetically modified prokaryotic micro-organisms capable of expressing polypeptides having the enzyme activity of the enzymes uridine posphorylase (UdP) and purine nucleoside phosphorylase (PNP) are described; the strains in question can be used, both in the form of whole cells and in the form of crude or purified extracts, to catalyse transglycosylation reactions between a donor nucleoside and an acceptor base with particularly high yields. The associated plasmid vectors are also described.

Abstract: New alkylthiobenzimidazole derivatives are described which belong to the class of formula: ##STR1## wherein R.sub.1 and R.sub.2 each represent a 1-3 carbon atom alkyl radical or they may form with the adjacent nitrogen atom, an optionally substituted heterocyclic ring,X represents a hydrogen atom or methyl radicaln is 1 or 2R.sub.3 represents a 4-6 carbon atom alkoxyalkyl radical, a 7 or 8 carbon atom arylalkyl radical or a 5 or 6 carbon atom cycloalkyl radical with the exception that R.sub.3 may not be an arylalkyl radical when R.sub.1 and R.sub.2 each represent a 1-3 carbon atom alkyl radicalR.sub.4 and R.sub.5 may be the same or different and each represent a hydrogen atom or a 1-2 carbon atom alkyl or they, attached at the positions 5 and 6 of the benzimidazole nucleus, may form together the ring ##STR2## The compounds (I) possess interesting antihistaminic and anti-allergic activities.

Abstract: New alkylol derivatives are described, which belong to the class having the structure formula ##STR1## where R represents a 5 or 6 membered heterocyclic ring selected among pyridine, pyrimidine, pyrazine, pyridazine, thiophene, furan, thiazole which optionally may be substituted with one or more groups selected among alkyl, alkoxy, halogen, amide, hydroxy, methylthio, trifluoromethyl, cyano, carboxy and the corresponding alkyl esters and salts with alkali metalsn is 2X and X' represent each a hydrogen atom or hydroxy group with the exception of both being hydrogen atom, and X' may be hydroxyethoxy moietym is 0 or 1and the corresponding non-toxic pharmaceutically acceptable acid addition salts. The compounds of the formula I are endowed with an interesting antitussive activity and, at their active dose, practically they are free of undesired side effects.