Patents Represented by Attorney Jane R. McLaughlin
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Patent number: 5153265Abstract: A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.Type: GrantFiled: August 30, 1990Date of Patent: October 6, 1992Assignee: Cetus CorporationInventors: Paula J. Shadle, Kirston E. Koths, Margaret Moreland, Nandini Katre, Walter J. Laird, Lois Aldwin, Danute E. Nitecki, John D. Young
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Patent number: 5104650Abstract: A colony stimulating factor, CSF-1, is a lymphokine useful in overcoming the immunosuppression induced by chemotherapy or resulting from other causes. CSF-1 is obtained in usable amounts by recombinant methods, including cloning and expression of the murine and human DNA sequences encoding this protein.Type: GrantFiled: September 22, 1987Date of Patent: April 14, 1992Assignee: Cetus CorporationInventors: Peter Ralph, Mary K. Warren, Kong T. Chong, James J. Devlin, Robert Zimmerman, Ada H. C. Kung
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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: 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: 4966840Abstract: DNA plasmids are described which are selected mutants in which an altered repressor gene leads to high copy number replication. Elements in the plasmids are modified in such a way that readthrough expression of heterologous DNA inserted in the plasmid will not continue into the replication primer strand. Deletions resulting from interference with replication primer strand transcription are thereby avoided.Type: GrantFiled: June 14, 1989Date of Patent: October 30, 1990Assignee: Cetus CorporationInventor: David H. Gelfand
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Patent number: 4959314Abstract: 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: February 7, 1985Date of Patent: September 25, 1990Assignee: Cetus CorporationInventors: David F. Mark, Leo S. Lin, Shi-da Yu Lu, Alice M. Wang
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Patent number: 4952508Abstract: A method and a cloning vector are described for the controlled accumulation of cloned heterologous gene products in Bacillus subtilis. The cloning vector is capable of being replicated in B. subtilis and includes the heterologous gene located and oriented such as to be under the control of an operator, promoter, and ribosome binding site sequence. The gene codes for a protein which is under the control of a transport mechanism by which the protein is secreted by the B. subtilis. The gene product is recovered from the growth medium for the B. subtilis. The cloning vector is also capable of similar use in other bacteria such as E. coli.Type: GrantFiled: June 19, 1987Date of Patent: August 28, 1990Assignee: Cetus CorporationInventors: Shing Chang, Hing C. Wong, Vaughan P. Wittman
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Patent number: 4937191Abstract: A method producing a non-heme haloperoxidase which is substantially resistant to inactivation, at room temperature, in up to 0.3M H.sub.2 O.sub.2 for up to 25 hours, and up to 0.5mM HOCl for up to two minutes. One such haloperoxidase, isolated from Curvularia inaequalis, contains about 2 gram atoms of zinc per molecule. A halogenation reaction employing the enzyme can be performed at H.sub.2 O.sub.2 and hypohalous acid concentrations which produce rapid inactivation of heme-containing haloperoxidases.Type: GrantFiled: November 12, 1987Date of Patent: June 26, 1990Assignee: Cetus CorporationInventors: John Geigert, Te-Ning E. Liu, Thabiso N'timkulu
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Patent number: 4937192Abstract: A halogenation method using a haloperoxidase obtained from a fungus selected from the dematiaceous hyphomycetes. The enzyme has an optimum activity above about pH 5.0, and can oxidize chloride, bromide, or iodide ions.Type: GrantFiled: November 12, 1987Date of Patent: June 26, 1990Assignee: Cetus CorporationInventors: Jennie C. Hunter, Angela Belt, Lynn S. Sotos, Michelle E. Fonda
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Patent number: 4929700Abstract: A process for recovering dimeric, biologically active CSF-1 from bacterially expressed recombinant CSF1 genes is described. The process comprises recovery of the solubilized monomeric form, followed by dimerization under refolding conditions and further purification of the dimer. Heterodimers may also be produced by this process.Type: GrantFiled: April 8, 1988Date of Patent: May 29, 1990Assignee: Cetus CorporationInventors: Robert Halenbeck, Kriston Koths, Cynthia Cowgill, Walter J. Laird
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Patent number: 4847201Abstract: A colony stimulating factor, CSF-1, is a lymphokine useful in overcoming the immunosuppression induced by chemotherapy or resulting from other causes. CSF-1 is obtained in usable amounts by recombinant methods, including cloning and expression of the murine and human DNA sequences encoding this protein.Type: GrantFiled: February 9, 1988Date of Patent: July 11, 1989Assignee: Cetus CorporationInventors: Ernest S. Kaswasaki, Martha B. Ladner, Janelle N. Van Arsdell, Alice M. Wang, Peter Ralph, Mazie Y. Coyne, Mary K. Warren
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Patent number: 4822739Abstract: Methods and compositions are described which can be used to enhance the stability of genetically engineered plasmids in Gram-positive organisms. Also described are genetically engineered plasmids comprising a DNA fragment which enhances their stability and Gram-positive organisms transformed with such plasmids.Type: GrantFiled: December 24, 1985Date of Patent: April 18, 1989Assignee: Cetus CorporationInventor: Shing Chang
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Patent number: 4816396Abstract: The invention discloses a method and cloning vectors useful for the production of cloned heterologous gene products in B. subtilis. Use of the method and vector allows the host to produce the heterologous gene product as a single unfused peptide having no extraneous amino acids attached.Type: GrantFiled: March 25, 1986Date of Patent: March 28, 1989Assignee: Cetus CorporationInventor: Shing Chang
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Patent number: 4792523Abstract: The invention concerns positive retroregulatory elements, which when ligated to selected DNA sequences coding for a gene product, enhance the expression of the gene product. Plasmids carrying the positive retroregulatory element ligated to selected DNA sequence and cells transformed by such plasmids are provided AND claimed. In addition, the invention relates to a method for enhancing expression of a gene product by ligating a positive retroregulatory element to a selected DNA sequence expressionable for a desired gene product.Type: GrantFiled: August 31, 1984Date of Patent: December 20, 1988Assignee: Cetus CorporationInventors: Hing C. Wong, Shing Chang
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Patent number: 4748234Abstract: A refractile material containing a heterologous protein is recovered from a host microorganism cell culture transformed to produce the protein. One recovery process involves disrupting the cell wall and membrane of the host cell, removing greater than 99% by weight of the salts from the disruptate, redisrupting the desalted disruptate, adding a material to the disruptate to create a density or viscosity gradient in the liquid within the disruptate, and separating the refractile material from the cellular debris by high-speed centrifugation. Another version of such a recovery process comprises the further steps of solubilizing the refractile material under reducing conditions, organically extracting the solubilized refractile material, and isolating said refractile material from the extractant.Preferably the protein is recombinant IL-2 or IFN-.beta. and the salt removal step is carried out by diafiltration.Type: GrantFiled: March 25, 1986Date of Patent: May 31, 1988Assignee: Cetus CorporationInventors: Glenn Dorin, Wolfgang H. Hanisch, Leo S. Lin