Patents Assigned to Cetus Corporation
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Patent number: 5057410Abstract: The invention provides highly sensitive methods for detecting specific sequences contained in chimeric mRNA. The mRNA sequences are reverse transcribed into complementary DNA (cDNA), amplified by the Polymerase Chain Reaction, and detected by hybridization with a labeled sequence specific oligonucleotide probe. The method is particularly valuable for the detection of chimeric mRNAs experessed by activated oncogenes that result from aberrant genetic rearragements such as chromosomal translocations.Type: GrantFiled: August 5, 1988Date of Patent: October 15, 1991Assignee: Cetus CorporationInventors: Ernest S. Kawasaki, Francis P. McCormick, Owen O. Witto
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Patent number: 5049490Abstract: A convenient method for the quantitative determination of a DNA polymerase includes contacting an aqueous test specimen suspected of containing the enzyme with the following: a single-stranded DNA template present in a concentration of at least about 10.sup.-8 molar bases, a DNA primer complementary to the template, a source of a metal polymerase cofactor, sufficient deoxyribonucleoside triphosphates to synthesize double-stranded DNA in the presence of the polymerase, and a colorimetric or fluorescent dye which is capable of providing a detectable signal when a primed single-stranded nucleic acid is converted to double-stranded DNA by the polymerase. The rate of signal generation is then measured and can be correlated with the level of DNA polymerase in the specimen using graphical or mathematical means. The results of this method are precise, having a covariance of less than about 10%. A test kit includes the reagents needed for carrying out this method.Type: GrantFiled: February 20, 1990Date of Patent: September 17, 1991Assignees: Eastman Kodak Co., Cetus CorporationInventors: John W. H. Sutherland, Patrick J. Sheridan, Louis M. Mezei
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Patent number: 5045463Abstract: A gene having a DNA sequence complementary to that of the glucoamylase polypeptide mRNA from a fungal species, preferably Aspergillus awamori, is prepared. The mRNA is an approximately 2.2 kilobase poly A RNA obtained from fungal cells grown under conditions of glucoamylase induction. Reverse transcription of the mRNA provides a glucoamylase probe used to identify genomic digest fragments containing glucoamylase gene regions, which are sequenced to locate the introns and exons. The genomic fragments are spliced together to form a gene having a DNA sequence with altered or deleted introns which codes for fungal glucoamylase protein and is capable, when correctly combined with a cleaved DNA expression vector, of expressing a non-native protein having glucoamylase enzyme activity upon transformation of a host organism by the vector. The host is preferably bacteria or yeast. The transformed yeast host may be used to produce ethanol.Type: GrantFiled: December 19, 1988Date of Patent: September 3, 1991Assignee: Cetus CorporationInventors: Michael A. Innis, David H. Gelfand, James H. Meade
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Patent number: 5041378Abstract: Xylose isomerase (XI) muteins useful in the conversion of glucose to fructose or xylose to xylulose are obtained in usable amounts by protein structural and recombinant DNA methods, including x-ray crystallography, cloning, computer graphic modeling and site-directed mutagenesis and expression of the bacterial DNA sequences encoding native procaryotic xylose isomerase. These native sequences are altered to encode the xylose isomerase muteins having improved catalytic function and/or thermostability.Type: GrantFiled: August 11, 1987Date of Patent: August 20, 1991Assignees: Cetus Corporation, Univerity of OregonInventors: Robert J. Drummond, Will Bloch, Brian W. Matthews, Pamela L. Toy
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Patent number: 5038852Abstract: There is disclosed herein a machine for performing nucleic acid amplification under computer control. The machine utilizes any one of a number of heating and cooling systems under control of a host computer which directs the heating and cooling systems to heat and cool a reaction-chamber-containing heat exchanger at appropriate times in the process. The reaction chambers are pre-loaded with the nucleic acid(s) to be amplified, a thermostable enzyme to catalyze polymerization, specific oligonucleotide primers, and four different nucleotide triphosphates. Also disclosed is the process for the amplification chain reaction implemented by the machine, which utilizes a thermostable enzyme.Type: GrantFiled: March 14, 1990Date of Patent: August 13, 1991Assignee: Cetus CorporationInventors: Larry J. Johnson, Joseph T. Widunas
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Patent number: 5037644Abstract: Stable pharmaceutical compositions suitable for parenteral administration to animals or humans are prepared comprising a therapeutically effective amount of a recombinant interleukin-2 (IL-2) protein dissolved in an inert carrier medium comprising one or more biocompatible non-ionic polymeric detergents which act as solubilizer/stabilizers for the claimed formulations.Type: GrantFiled: September 30, 1987Date of Patent: August 6, 1991Assignee: Cetus CorporationInventors: Ze'ev Shaked, Tracy Stewart, James W. Thomson, Pamela Hirtzer
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Patent number: 5034514Abstract: Bifunctional chemicals useful for linking aldehyde containing moieties to moieties containing functionalities which are or can be reactive with sulfhydryl are claimed and have the formula:L--S--(CH.sub.2).sub.n1 --CONH--SPACER--NH--XwhereinL is a leaving group selected from --H or --S--Ar, wherein Ar represents optionally substituted phenyl or pyridyl;n.sub.1 =2-4;X is selected from: --CO--Y--CONHNH.sub.2, a hydrazide; ##STR1## a hydrazine; ##STR2## a hydrazine; --CO--Y--NH--CONHNH.sub.2, a semicarbazide; and --CO--Z--NH--CSNHNH.sub.2, a thiosemicarbazide;wherein Y is alkylene or oxaalkylene and Z is alkylene or a polypeptide residue briding the N-terminal amino group and C-terminal carboxy group thereof;the SPACER is oxaalkylene or oxaalkylene substituted with hydroxyl and specifically includes residues having formulas selected froma) --(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 -- wherein each n2 is independently 2-4 andb) ##STR3## wherein n3 is 2-6.Type: GrantFiled: October 12, 1988Date of Patent: July 23, 1991Assignee: Cetus CorporationInventors: Danute E. Nitecki, Margaret Moreland
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Patent number: 5024834Abstract: Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.Type: GrantFiled: October 15, 1990Date of Patent: June 18, 1991Assignee: Cetus CorporationInventors: L. L. Houston, Lois Aldwin, Danute E. Nitecki
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Patent number: 5024947Abstract: Serum-free media which support the growth of insect cells and the production thereby of recombinant proteins and viral products are herein disclosed. The serum free media can support insect cell growth at large scale under agitated and/or sparged, preferably well-aerated conditions.The serum free medium disclosed support insect cell growth to cell densities comparable to serum-containing culture and the production of viral and recombinant products to levels equivalent to those found in serum containing culture.Type: GrantFiled: July 24, 1987Date of Patent: June 18, 1991Assignee: Cetus CorporationInventors: Duane Inlow, Brian Maiorella
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Patent number: 5013662Abstract: Method of obtaining N-terminal methionine-free proteins are described. The methods employ a novel enzyme, E. coli methionine aminopeptidase either in vitro or in vivo. For in vivo application, plasmid-borne DNA encoding the peptidase is transformed into a bacterial host which produces the desired protein.Type: GrantFiled: October 7, 1988Date of Patent: May 7, 1991Assignee: Cetus CorporationInventors: Arie Ben-Bassat, Keith A. Bauer, Shing Chang, Sheng-Yung Chang
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Patent number: 5008182Abstract: The presence or absence of a nucleic acid sequence associated with AIDS in a sample containing one or more nucleic acids and suspected of containing such sequence can be detected by amplifying the sequence using primers to form extension products as templates and detecting the amplified product if it is present. This may be accomplished by adding a labeled hybridization probe to the amplified product either free in solution or after immobilization on a solid support.Type: GrantFiled: August 15, 1989Date of Patent: April 16, 1991Assignee: Cetus CorporationInventors: John J. Sninsky, Shirley Y. Kwok, David H. Mack
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Patent number: 5004605Abstract: Stable pharmaceutical compositions suitable for parenteral administration to mammals are prepared which are in a pH range of about 2 to about 4 and comprise a therapeutically effective amount of a recombinant interferon-.beta. protein (IFN-.beta.) dissolved in an inert carrier medium comprising as a stabilizer/solubilizer an effective amount either of glycerol or of polyethylene glycol polymers having an average molecular weight from about 190 to about 1600 daltons. Further disclosed and claimed are methods for extracting IFN-.beta. from a microbial host transformed to produce it and then purifying and formulating said IFN-.beta. and methods for screening for other polyhydric non-detergent stabilizer/solubilizers or combinations thereof as solubilizer/stabilizers for pharmaceutical compositions of IFN-.beta..Type: GrantFiled: December 10, 1987Date of Patent: April 2, 1991Assignee: Cetus CorporationInventors: Susan Hershenson, Jody Thomson
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Patent number: 5001065Abstract: A stable, continuous human cell line or progeny thereof is produced that is resistant to 6-thioguanine and ouabain, secretes less than 40 ng/ml of endogenous IgM antibodies, and grows with a doubling time of about 18 hours. The cell line, which preferably is adapted to serum-free medium, may be used as a fusion partner with an antibody-producing cell line so as to generate antibodies. In addition, it may be electroporated with a vector containing a gene of interest to produce a transformed cell line which generates a protein encoded by the gene, such as an IgG or IgM antibody.Type: GrantFiled: May 27, 1987Date of Patent: March 19, 1991Assignee: Cetus CorporationInventors: James W. Larrick, George Senyk
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Patent number: 4999339Abstract: Therapeutic treatment of malignant melanoma in humans is disclosed wherein a synergistically effective amount of DTIC in combination with IL-2 is administered to an individual having such cancer.Type: GrantFiled: March 28, 1988Date of Patent: March 12, 1991Assignee: Cetus CorporationInventors: Carolyn M. Paradise, Edward C. Bradley
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Patent number: 4994379Abstract: The invention discloses modified signal peptides derived from wild-type signal peptides of the type that are capable of forming membrane-bound lipoproteins and methods for making such modified signal peptides and DNA sequences encoding them. Modified signal peptides of the invention and DNA sequences encoding them are useful for increasing the secretion of heterologous gene products produced by transformed host organisms. The invention further discloses a method for producing recombinant DNA sequences in vivo.Type: GrantFiled: August 22, 1989Date of Patent: February 19, 1991Assignee: Cetus CorporationInventor: Shing Chang
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Patent number: 4992271Abstract: An improved process for recovering and purifying lipophilic recombinant proteins such as human .beta.-interferon and interleukin-2 from their hosts yields a protein preparation which may be formulated into a stable pharmaceutical composition having a therapeutically effective amount of the biologically active recombinant lipophilic protein dissolved in a non-toxic, inert, therapeutically compatible aqueous-based carrier medium at a pH of 6.8 to 7.8 which medium also contains a stabilizer for the protein, such as human serum albumin, normal serum albumin and human plasma protein fraction.Type: GrantFiled: September 13, 1985Date of Patent: February 12, 1991Assignee: Cetus CorporationInventors: Wolfgang H. Hanisch, Peter M. Fernandes, Terrance Taforo
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Patent number: 4985241Abstract: Damage to cells, tissue and other body parts in a mammalian host may be treated by using a lymphokine or cytotoxin in conjunction with at least one biological modifier, which may be a free radical scavenger or a metabolic inhibitor. The lymphokine or cytotoxin is preferably tumor necrosis factor and the biological modifier is preferably uric acid, buthionine sulphoximine, vitamin C, aspirin, or nordihydroguaiaretic acid. Such a combination may be used to treat, for example, cancer, infectious diseases, and damage caused by radiation therapy, high oxygen tension, and chemotherapy.Type: GrantFiled: August 25, 1989Date of Patent: January 15, 1991Assignee: Cetus CorporationInventors: Robert Zimmerman, Benedict J. Marafino, Jr.
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Patent number: 4975276Abstract: A new polypeptide, called IFN-.alpha.54, produced by E. coli transformed with a newly isolated and characterized human IFN-.alpha. gene is described. The polypeptide exhibits interferon activities such as antiviral activity, cell growth regulation, and regulation of production of cell-produced substances.Type: GrantFiled: September 2, 1982Date of Patent: December 4, 1990Assignee: Cetus CorporationInventor: Michael A. Innis
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Patent number: 4973479Abstract: A new polypeptide, called IFN-.alpha.61, produced by E. coli transformed with a newly isolated and characterized human IFN-.alpha. gene is described. The polypeptide exhibits interferon activities such as antiviral activity, cell growth regulation, and regulation of production of cell-produced substances.Type: GrantFiled: September 2, 1982Date of Patent: November 27, 1990Assignee: Cetus CorporationInventor: Michael A. Innis
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Patent number: RE33653Abstract: Muteins of biologically active proteins such as IFN-.beta. and IL-2 in which cysteine residues that are not essential to biological activity have been deleted or replaced with other amino acids to eliminate sites for intermolecular crosslinking or incorrect intramolecular disulfide bridge formation. These muteins are made via bacterial expression of mutant genes that encode the muteins that have been synthesized from the genes for the parent proteins by oligonucleotide-directed mutagenesis.Type: GrantFiled: July 26, 1989Date of Patent: July 30, 1991Assignee: Cetus CorporationInventors: David F. Mark, Leo S. Lin, Shi-da Y. Lu