Patents Assigned to Sclavo, S.p.A.
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Patent number: 5622706Abstract: The cloning and sequencing of the gene which codes for a new pilinic subunit of Bordetella pertussis are described. The aminoacid sequence of the mature subunit, deduced from its necleotide sequence, is similar but not identical to that of the known pilins 2, 3 and 6. Polypeptides having the aminoacid sequence of the mature pilinic subunit or of regions thereof are particularly useful for the development of synthetic acellular vaccines against pertussis.Type: GrantFiled: November 4, 1994Date of Patent: April 22, 1997Assignees: Sclavo S.p.A., Eniricerche S.p.A.Inventors: Paola Pedroni, Barbara Riboli, Francesca De Ferra, Guido Grandi, Salvatore Toma, Beatrice Arico, Rino Rappuoli
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Patent number: 5432082Abstract: The invention provides an expression and secretion vector in yeasts which is useful for preparing heterologous proteins, comprising a synthetic oligonucleotide which directs the secretion of the heterologous protein wherein the synthetic oligonucleotide is positioned between the inducible hybrid promoter GAL-CYC and a multiple-site polylinker followed by the signals of transcription termination recognized by the RNA polymerase of the yeasts. The invention includes a hybrid plasmid obtained by cloning in one of the restriction sites of the polylinker of the vector, the DNA sequence which codes for a heterologous protein. A process is also described for the preparation of heterologous proteins which comprises cultivating in a suitable culture medium a yeast transformed with the hybrid plasmid and recovering from the culture medium the resulting heterologous proteins. The recovered proteins include hormones, lymphokines, viral antigens or immunogens useful in the therapeutical and diagnostic field.Type: GrantFiled: June 1, 1993Date of Patent: July 11, 1995Assignee: Sclavo, S.p.A.Inventors: Cesira Galeotti, Emanuela Palla, Giovanni Raugei, Giuliano Bensi, Maria L. Melli
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Patent number: 5427788Abstract: Cloning and sequencing of the Eco RI fragment of B. pertussis chromosomal DNA with 4696 base pairs, containing the genes which code for the five subunits of the pertussis toxin.A hybrid plasmid containing the DNA fragment or its further fragments and a micro-organism transformed by the hybrid plasmid and capable of expressing the cloned DNA fragment or further fragments thereof by synthesis of the pertussis toxin or one or more subunits of the pertussis toxin.The pertussis toxin or one or more subunits of the pertussis toxin so obtained are useful for the preparation of vaccines and diagnostic kits.Type: GrantFiled: June 17, 1994Date of Patent: June 27, 1995Assignee: Sclavo S.p.A.Inventors: Rino Rappuoli, Alfredo Nicosia, Maria B. Arico'
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Patent number: 5378365Abstract: A description is given of a process for the purification of factor IX, factor X, and factor II from human plasma or fractions thereof, wherein a solution containing prothrombin complex factors is purified by repeated ion exchange chromatographic separations followed by adsorption chromatography on metal ions.Type: GrantFiled: March 26, 1993Date of Patent: January 3, 1995Assignees: Sclavo S.p.A., Aima-Derivati S.p.A.Inventors: Silvana Arrighi, Francesco Norelli, Maria G. Borri, Enzo Bucci
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Patent number: 5300427Abstract: A human sera dilution buffer solution containing the enzyme collagenase is described, for use in preventing false positive indication reactions taking place when specific IgMs are sought in human sera by ELISA capture assays, in which the enzymatic conjugate consists of antibodies bound to ALP with glutaraldehyde.Type: GrantFiled: June 11, 1991Date of Patent: April 5, 1994Assignee: Sclavo S.p.A.Inventors: Paolo Fabrizi, Francesco Donnini
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Patent number: 5284937Abstract: An extraction and purification process for human gamma interferon (HuIFN-gamma) from recombinant host cells producing the same in insoluble form is described, which comprises suspending the cells in a buffer solution having pH from 6.0 to 8.5, optionally complemented with an osmoprotector; disrupting the cells in conditions which do not activate the endocellular proteases; separating and solubilizing the pellet containing the insoluble HuIFN-gamma by extraction with phosphate buffer having pH comprised between 6.5 and 8.5 and finally purifying the solubilized HuIFN-gamma by one or more chromatographic techniques. Such a process allows non-degraded HuIFN-gamma to be obtained, with a biological activity and chemical-physical properties unaffected vis-a-vis the native product and in high yield and purity.Type: GrantFiled: July 23, 1991Date of Patent: February 8, 1994Assignee: Sclavo S.p.A.Inventors: Otello Protasi, Donatella Mannucci
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Patent number: 5279944Abstract: The enzyme alanine aminotransferase (ALT) is colorimetrically determined as the hydrogen peroxide obtained in the pyruvate hydrolysis reaction catalysed by the enzyme pyruvate oxidase which develops a colour read at 550 nm making use of a reagent composition buffered at pH comprised within 7.0 and 7.5 containing L-alanine, ketoglutaric acid, a source of inorganic phosphorous, the enzyme pyruvate oxidase, a system for revealing the hydrogen peroxide and optionally one or more co-factors which interact in the enzymatic reaction catalysed by the enzyme pyruvate oxidase. It is moreover described a method for the determination of the enzyme alanine aminotransferase making use of said reagent composition and of the surface antigen of the hepatitis B virus (HBsAg), by enzyme-immune assay, in the same serum specimen and in the same well of a microtitration plate.Type: GrantFiled: May 15, 1991Date of Patent: January 18, 1994Assignee: Sclavo S.p.A.Inventors: Paolo Fabrizi, Francesco Donnini, Alessandro Tabacco, Paolo Tarli, deceased
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Patent number: 5259951Abstract: A method for the purification of Factor VIII from human plasma is described, wherein a solution comprising Factor VIII is purified by using ion exchange chromatographic columns. Factor VIII obtained by said method is also described.Type: GrantFiled: June 11, 1991Date of Patent: November 9, 1993Assignee: SCLAVO S.p.A.Inventors: Silvana Arrighi, Maria G. Borri, Costante Ceccarini
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Patent number: 5244655Abstract: A process is described for the purification of recombinant human beta interferon which comprises the use of three chromatographic stages carried out in series, utilizing as stationary phases: glass particles of controlled porosity, cation exchange polymer resins and polymer resins able to complex heavy metals.Type: GrantFiled: January 17, 1992Date of Patent: September 14, 1993Assignee: Sclavo S.p.A.Inventors: Giuseppe C. Viscomi, Paolo Rappuoli
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Patent number: 5229367Abstract: The synthetic peptide of formula (I) H-Ser-His-Leu-Arg-Lys-Val-Phe-Asp-Lys-OH (SEQ ID NO. 1) and its physiologically acceptable organic or inorganic salts are novel. The synthetic peptide (I), whose amino acid sequence corresponds to that of the sequence 204-212 of human lipocortin V, shows in vitro the capability of inhibiting the prostaglandin E2 release and in vivo an antiinflammatory activity. The peptide and its organic and inorganic salts are useful as therapeutic agents for the treatment of dermatological and collagen inflammatory infections.Type: GrantFiled: January 18, 1991Date of Patent: July 20, 1993Assignee: Sclavo S.p.A.Inventors: Mauro Perretti, Cristina Becherucci, Kenneth G. Mugridge, Egle Solito, Rivo Presentini, Luca Parente
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Patent number: 5219988Abstract: This invention relates to new gem-diamino derivatives of general formula (I) ##STR1## where R is the side chain of an amino acid, of which any functional groups are suitably protected, andX is an acyl group chosen from the group consisting of 2-nitrobenzoyl, 4-chloro-butyryl, acetoacetyl, 4-bromo-butyryl, (2-nitrophenoxy)-acetyl and 2-methyl-2-(2'-nitro-phenoxy)propionyl, of use in introducing gem-diamino residues into retro-inverso peptides. The invention further relates to a method for the synthesis of retro-inverso peptides in which the gem-diamino residue or residues are introduced using the new compound (I).Type: GrantFiled: February 21, 1990Date of Patent: June 15, 1993Assignees: Eniricerche S.p.A., Sclavo S.p.A.Inventors: Laura Gazerro, Massimo Pinori, Antonio S. Verdini
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Patent number: 5218089Abstract: New analogues of thymopentin (TP5) and of its tetrapeptide fragment (TP5.sup.1-4) containing two non-contiguous retro-inverted bonds in the peptide chain are described which are of the general formula (I) ##STR1## where R is hydrogen or an acyl radical, and R.sup.1 is an --OR.sup.2 group or an ##STR2## group where R.sup.2 is a hydrogen atom or a hydrocarbon radical, and R.sup.3 is a hydrogen atom or a hydroxyl group, and the corresponding pharmaceutically acceptable salts of acid or basic addition, possess immunomodulating activity.Type: GrantFiled: November 26, 1991Date of Patent: June 8, 1993Assignee: Sclavo S.p.A.Inventors: Sabina Mariotti, Alessandro Sisto, Luciano Nencioni, Luigi Villa, Antonio S. Verdini
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Patent number: 5206164Abstract: A synthetic peptide endowed with immunological activity is disclosed, which is capable of inducing in mammals the formation of anti-peptide antibodies capable of recognizing human alpha-fetoprotein and of reacting with it, and incapable of recognizing albumin or its degradation products, with said peptide being essentially constituted by the aminoacidic sequence of formula (I), corresponding to 38-119 region of human alpha-fetoprotein.Furthermore, the methods and means for preparing said peptide by means of the recombinant DNA techniques are reported.The synthetic peptide (I), like the polyclonal and monoclonal antipeptide antibodies are particularly suitable for the early diagnosis of hepatocellular carcinoma and of teratocarcinoma.Type: GrantFiled: February 13, 1992Date of Patent: April 27, 1993Assignee: Sclavo S.p.A.Inventors: Mario F. Tecce, Marzia M. Giuliani, Sterfano Ricci, Giulio Rttil, Benedetto Terrana
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Patent number: 5206014Abstract: The specification relates to a synthetic peptide converted into a salt comprising one or more amine groups and capable of potentiating in vivo the primary and secondary antibody response to thymo-dependent and thymo-independent antigens having low immunogenicity.Injectable preparations comprising a solution of the peptide in a pharmacologically acceptable solvent are particularly useful as adjuvants in therapy.Type: GrantFiled: February 12, 1988Date of Patent: April 27, 1993Assignee: Sclavo, S.p.A.Inventors: Luciano Nencioni, Guido Antoni, Diana Boraschi, Aldo Tagliabue
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Patent number: 5200506Abstract: New retro-inverso analogs of thymopentin (TP5) and of its tripeptide fragment (TP5.sup.1-3) of general formula (I) ##STR1## are described wherein R is hydrogen or an acyl radical, and R.sup.1 is --OR.sup.2 or ##STR2## wherein R.sup.2 is hydrogen or a hydrocarbyl radical, and the corresponding pharmaceutically acceptable acid- or base-addition salts. A process of preparing the tripeptide fragment of formula I is also described.The new compounds are enzyme-resistant immunomodulatory peptides.Type: GrantFiled: January 31, 1991Date of Patent: April 6, 1993Assignees: Eniricerche S.p.A., Sclavo S.p.A.Inventors: Alessandro Sisto, Antonio S. Verdini
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Patent number: 5130447Abstract: An improvement is described in the synthesis method for N.sup..alpha. -trityl-N.sup.G -trityl arginine within a process for preparing N.sup..alpha. -fluorenylmethoxycarbonyl-N.sup.G -trityl-arginine from arginine, comprising:a) forming N.sup..alpha. -trityl-N.sup.G -trityl-arginineb) selectively detaching the trityl group from the .alpha.-NH.sub.2 andc) introducing the fluorenylmethoxycarbonyl group in its place.The improvement consists of preparing the N.sup..alpha. -trityl-N.sup.G -trityl-arginine by solubilizing the arginine in an aprotic organic solvent by tri-alkylsilylation both of the amino nitrogen and of the carboxyl group, followed by tritylation, with trityl chloride, of the .alpha.-amino nitrogen, and of the guanidino group after deprotonating this latter with a bicyclic guanidine. The new improved process can also lead to variable quantities of the arginine analogue di-tritylated at the guanidino group, namely N.sup..alpha. -fluorenylmethoxycarbonyl-N.sup.G -di-trityl-arginine.Type: GrantFiled: May 28, 1991Date of Patent: July 14, 1992Assignee: Sclavo S.p.A.Inventors: Valerio Caciagli, Antonio S. Verdini
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Patent number: 5130415Abstract: A synthetic peptide endowed with immunological activity is disclosed, which is capable of inducing in mammals the formation of anti-peptide antibodies capable of recognizing human alpha-fetoprotein and of reacting with it, and incapable of recognizing albumin or its degradation products, with said peptide being essentially constituted by the aminoacidic sequence of formula (I), corresponding to 38-119 region of human alpha-fetoprotein.Furthermore, the methods and means for preparing said peptide by means of the recombinant DNA techniques are reported.The synthetic peptide (I), like the polyclonal and monoclonal antipeptide antibodies are particularly suitable for the early diagnosis of hepatocellular carcinoma and of teratocarcinoma.Type: GrantFiled: July 24, 1989Date of Patent: July 14, 1992Assignee: Sclavo S.p.A.Inventors: Mario F. Tecce, Marzia M. Giuliani, Stefano Ricci, Giulio Ratti, Benedetto Terrana
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Patent number: 5116947Abstract: A method of synthesis of a partially retro-inverso peptide incorporating at least one malonyl residue of formula (III) ##STR1## wherein R represents the side chain of an .alpha.-amino acid, is described which is characterized in that said malonyl residue is incorporated by condensing a 5-substituted-2,2-dimethyl-1,3-dioxane-4,6-dione of formula (IV) ##STR2## wherein R' is the side-chain R wherein the functional groups, if any, are suitably protected, with an amino acid, amino acid amide, peptide fragment, or pseudo-peptide fragment wherein the terminal carboxyl group, if present, and the possible side-chain functionalities are suitably protected and the reactive amino group is tri-alkyl-silylated.The new compounds of formula (VI) and a process for the preparation of a partially retro-inverso tuftsin analog which involves use of said method and said intermediate are also described and claimed.Type: GrantFiled: August 9, 1991Date of Patent: May 26, 1992Assignee: Sclavo S.p.A.Inventors: Massimo Pinori, Felice Centini, Antonio S. Verdini
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Patent number: 5112996Abstract: A method is described for substituting at least one hydrogen atom originally present in the guanidino group of a compound of general formula (I) ##STR1## where R is any substituted or unsubstituted residue, by a group R.sub.1 where R.sub.1 is an unsubstituted or substituted, linear or branched alkyl, consisting of:a) silylating the guanidino group and any other silylatable functional groups present within the R group andb) alkylating the product obtained in step a) with a mixture consisting of the alkyl halide R.sub.1 -X and an organic base containing a tertiary nitrogen.Type: GrantFiled: August 28, 1990Date of Patent: May 12, 1992Assignee: Sclavo S.p.A.Inventor: Valerio Caciagli
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Patent number: 5088493Abstract: A multiple wavelength light spectrophometer for non-invasive monitoring of a body organ in vivo comprising: a single pulsed light source, optical fibers for transmitting to and receiving the infrared radiation from the organ, a radiation detector capable of branching received radiation into several different wavelengths, an amplifier, and a data acquisition system including a microprocessor capable of compensating for light diffusion effects by employing a specific algorithm.Type: GrantFiled: February 16, 1988Date of Patent: February 18, 1992Assignee: Sclavo, S.p.A.Inventors: Ivo Giannini, Marco Ferrari, Amilcare C. de Resmini, Paolo Fasella