Abstract: The subject invention provides for novel anti-tumor and anti-retroviral compounds. More specifically, the invention relates to the sulfinic acid adducts of therapeutic C-nitroso compounds. The formation of the adducts increases the stability and more solubility of the C-nitroso compounds. These compounds include the L-cysteinesulfinic acid adducts of 6-nitroso-1,2-benzopyrone and 3-nitrosobenzamide. The invention also provides for compositions containing one or more of the compounds, and for methods of treating retroviral infections, cancer, infectious virus concentration with the subject compounds and compositions.
Abstract: Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## wherein n=1-6R=CH.sub.3, CF.sub.3, --CO.sub.2 R.sup.IV, ##STR2## R.sup.I, R.sup.II =H, F, CH.sub.3, or ##STR3## R.sup.III =H, ##STR4## or tetrazolyl R.sup.IV =H, or alkyland that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
Type:
Grant
Filed:
December 6, 1990
Date of Patent:
October 12, 1993
Assignee:
Cetus Corporation
Inventors:
Danute E. Nitecki, Lois Aldwin, Corey H. Levenson, Margaret Moreland, Irwin Braude, David F. Mark, Henry Rapoport
Abstract: This invention discloses heterobifunctional coupling agents for making a wide array of molecular conjugates. The agents contain a sterically hindered thiol, linked through a spacer arm to a second group reactive toward nucleophiles such as 1.degree. and 2.degree. amines or reactive thiols that are present on biological and organic materials. The coupling agents are useful for making conjugates containing a sterically hindered linkage.
Type:
Grant
Filed:
February 14, 1992
Date of Patent:
August 31, 1993
Assignee:
Cetus Oncology
Inventors:
Margaret Moreland, I. Lawrence Greenfield, Danute E. Nitecki
Abstract: Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
Type:
Grant
Filed:
December 6, 1990
Date of Patent:
June 1, 1993
Assignee:
Cetus Corporation
Inventors:
Danute E. Nitecki, Lois Aldwin, Corey H. Levenson, Margaret Moreland, Irwin Braude, David F. Mark, Henry Rapoport
Abstract: A high throughput apparatus and process for thermal remediation of soil contaminated with volatile organic compounds has a dryer with a high capacity heat source to volatilize and combust the compounds contained in a first lot of soil. The remediated soil is discharged and cooled. Hot gases and fines formed are drawn into a second dryer with an ignition source where a second lot of soil is used to cool the hot gases/fines mixture. A particulate control chamber is used to remove at least 75% of the fines from the gas/fines mixture. Gases containing uncombusted volatile organic compounds are directed back to the primary dryer for additional exposure to heat in order to complete combustion. Additional separation of the fines from gases is achieved in a baghouse.
Type:
Grant
Filed:
September 10, 1991
Date of Patent:
March 23, 1993
Inventors:
Charles R. Peterson, Gregory M. Peterson, Daniel C. Hopper, Trudy J. Weichlein
Abstract: Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
Type:
Grant
Filed:
December 6, 1990
Date of Patent:
December 22, 1992
Assignee:
Cetus Corporation
Inventors:
Danute E. Nitecki, Margaret Moreland, Lois Aldwin, Corey H. Levenson, Irwin Braude, David F. Mark, Henry Rapoport
Abstract: 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:
Grant
Filed:
August 30, 1990
Date of Patent:
October 6, 1992
Assignee:
Cetus Corporation
Inventors:
Paula J. Shadle, Kirston E. Koths, Margaret Moreland, Nandini Katre, Walter J. Laird, Lois Aldwin, Danute E. Nitecki, John D. Young
Abstract: A novel a selectable fusion protein having aminoglycoside phosphotransferase activity is disclosed. The marker comprises the coding sequences for aminoglycoside phosphotransferase I (APH-I) which has been modified and truncated so as to render its use in recombinant vectors more convenient. The modified, truncated sequence (mtAPH-I) gene is capable, upon expression, of conferring resistance to a number of antibiotics on the host. One of these antibiotics, G418, is toxic to eucaryotic as well as procaryotic hosts. Also disclosed are methods of constructing fusion proteins having N-terminal sequences corresponding to a desired peptide sequence, and C-terminal sequences comprising the amino acids encoded by mtAPH-I. The preferred N-terminal sequences are the first 11 amino acids of .beta.-isopropyl malate dehydrogenase, and the first 7 amino acids of yeast enolase.
Type:
Grant
Filed:
July 22, 1988
Date of Patent:
May 26, 1992
Assignee:
Cetus Corporation
Inventors:
David H. Gelfand, Frances C. Lawyer, Susanne Stoffel
Abstract: The present invention provides an improved process for the production of microbial cellulose where a cellulose-producing organism is grown under agitated conditions in the presence of a polyacrylamide-containing polymer.
Type:
Grant
Filed:
October 26, 1990
Date of Patent:
May 19, 1992
Assignee:
Weyerhaeuser Company
Inventors:
Arie Ben-Bassat, Kent D. Coddington, Donald C. Johnson
Abstract: Compositions useful for detecting ras gene proteins are described consisting of GTP and a protein having an apparent reduced molecular weight of about 115,000-120,000 daltons, or fragments derived therefrom, that stimulate ras protein guanosine triphosphatase activity. Also described are methods whereby the compositions are used to identify cancer therapeutics.
Type:
Grant
Filed:
July 8, 1988
Date of Patent:
April 14, 1992
Assignee:
Cetus Corporation
Inventors:
Francis P. McCormick, Kirston E. Koths, Robert F. Halenbeck, Mary M. Trahey
Abstract: Methods for enhancing the immune response to vaccination in animals, including humans, comprise administering interleukin-2 (IL-2) as part of the vaccination regimen, preferably for 5 to 14 days post-vaccination. In addition, compositions for enhancing the immune response of an animal to a vaccine employ IL-2 as an active ingredient, preferably human IL-2.
Type:
Grant
Filed:
June 30, 1989
Date of Patent:
March 31, 1992
Assignee:
Cetus Corporation
Inventors:
Michael V. Doyle, Arthur D. Newell, Jack H. Nunberg, Thomas J. White, Gary A. Anderson
Abstract: Anti-tumor activity in mammals can be augmented by administering to the mammalian host a synergistically effective amount of TNF and IL-2 or of TNF and IFN-.beta., or of TNF, IL-2 and IFN-.beta. in combination. The composition of TNF and IL-2 and/or IFN-.beta. may be prepared in vitro or administered separately to the host. If the TNF and IL-2 are administered sequentially, the TNF must be administered prior to the IL-2 to obtain synergy. The composition is useful for treating such cancers as mastocytoma, melanoma, leukemia, lymphoma, mammary adenocarcinoma, and pharyngeal squamous cell carcinoma.
Type:
Grant
Filed:
June 26, 1989
Date of Patent:
March 24, 1992
Assignee:
Cetus Corporation
Inventors:
Robert Zimmerman, Jeffrey L. Winkelhake
Abstract: Ricin B muteins, ricin and ricin precursors having at least one amino acid of at least one galactoside binding site altered to decrease the binding of ricin B to galactosides are claimed. DNA sequences encoding the ricin B muteins, ricin and ricin precursor in which the B chain thereof is the ricin B mutein are claimed. Recombinant expression vectors effective in expressing the DNA sequences of the ricin B muteins, ricin and ricin precursors are claimed. Host cells transformed with the foregoing expression vectors are also claimed. Conjugates comprising binding moieties such as antibodies, hormones, and lymphokines bound to the ricin B mutein and ricin wherein the B chain thereof is the mutein is also claimed.
Type:
Grant
Filed:
March 12, 1987
Date of Patent:
January 7, 1992
Assignee:
Cetus Corporation
Inventors:
Michael Piatak, Jr., L. L. Houston, Anne W. Emerick
Abstract: 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:
Grant
Filed:
September 30, 1987
Date of Patent:
August 6, 1991
Assignee:
Cetus Corporation
Inventors:
Ze'ev Shaked, Tracy Stewart, James W. Thomson, Pamela Hirtzer
Abstract: 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.
Abstract: 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:
Grant
Filed:
October 15, 1990
Date of Patent:
June 18, 1991
Assignee:
Cetus Corporation
Inventors:
L. L. Houston, Lois Aldwin, Danute E. Nitecki
Abstract: A pharmaceutical composition is prepared wherein a biologically active conjugated plasminogen activator is selectively conjugated to at least one heparin fragment having a terminal 2,5-anhydro-D-mannose residue which has an aldehyde not involved in intramolecular hemiacetal formation. The resulting conjugate has a prolonged half-life as compared to native tissue plasminogen activator and is able to deliver heparin to the site of clot dissolution to prevent reocclusion.
Abstract: 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:
Grant
Filed:
October 7, 1988
Date of Patent:
May 7, 1991
Assignee:
Cetus Corporation
Inventors:
Arie Ben-Bassat, Keith A. Bauer, Shing Chang, Sheng-Yung Chang
Abstract: 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:
Grant
Filed:
July 26, 1989
Date of Patent:
July 30, 1991
Assignee:
Cetus Corporation
Inventors:
David F. Mark, Leo S. Lin, Shi-da Y. Lu
Abstract: Serotype-specific human anti-Pseudomonas monoclonal antibodies which bind to determinants of the cell wall lipopolysaccharides of P. aeruginosa are prepared from hybrid cell lines. The antibodies may be of any isotype. These antibodies may be used to treat infections caused by P. aeruginosa.
Type:
Grant
Filed:
April 26, 1985
Date of Patent:
June 1, 1993
Assignee:
Cetus Corporation
Inventors:
James W. Larrick, Andrew A. Raubitschek