Patents Assigned to Cetus Corporation
  • Use of a modified soluble Pseudomonas exotoxin A in immunoconjugates
    Patent number: 4933288
    Abstract: DNA sequences encoding proteins processable by secretion leaders in recombinant hosts are described. The DNA sequences encode the NH.sub.2 -terminal region of proteins that are cleaved from a secretion leader and may be secreted through the cell membrane and, if present, cell wall in some cases. Proteins encoded by the DNA sequence have an NH.sub.2 -terminal amino acid sequence conforming to a consensus amino acid sequence that is processable by the particular secretion leader. DNA sequences encoding a consensus amino acid sequence processable by the diphterhia toxin secretion leader are disclosed. A novel Pseudomonas exotoxin and CSF-1 having NH.sub.2 -terminal sequences conforming to a consensus sequence are exemplified.
    Type: Grant
    Filed: November 21, 1986
    Date of Patent: June 12, 1990
    Assignee: Cetus Corporation
    Inventor: I. Lawrence Greenfield
  • Process for recovering microbially produced interleukin-2
    Patent number: 4931543
    Abstract: A process for recovering substantially pure rIL-2 from transformed microorganisms in which the cells are disrupted, impure insoluble rIL-2 is separated from the bulk of the cellular components, the separated impure rIL-2 is solubilized and partially purified in a reduced form, the solubilized rIL-2 is oxidized, the oxidized rIL-2 is purified to clinically acceptable levels, and the oxidized, purified IL-2 is denatured by placing it into a solution of a chaotropic agent, solids are removed from the solution and rIL-2 is renatured from the solution.
    Type: Grant
    Filed: March 25, 1988
    Date of Patent: June 5, 1990
    Assignee: Cetus Corporation
    Inventors: Robert Halenbeck, Flint Smith, Michael Kunitani
  • Succinylated interleukin-2 for pharmaceutical compositions
    Patent number: 4931544
    Abstract: A pharmaceutical composition is prepared wherein biologically active conjugated interleukin-2 is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated IL-2, which is not water soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to one or more succinyl groups by reaction with succinic anhydride.
    Type: Grant
    Filed: January 27, 1988
    Date of Patent: June 5, 1990
    Assignee: Cetus Corporation
    Inventors: Nandini Katre, Michael J. Knauf
  • Production of purified, biologically active, bacterially produced recombinant human CSF-1
    Patent number: 4929700
    Abstract: 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: Grant
    Filed: April 8, 1988
    Date of Patent: May 29, 1990
    Assignee: Cetus Corporation
    Inventors: Robert Halenbeck, Kriston Koths, Cynthia Cowgill, Walter J. Laird
  • Vinca alkaloid pharmaceutical compositions
    Patent number: 4923876
    Abstract: Disclosed herein are ready-to-use solutions comprising pharmaceutical compositions suitable for intravenous injection which are stable at room temperature. Pharmaceutical formulations of this invention comprise aqueous compositions of a pharmaceutically-acceptable vinca dimer salt, a citrate buffer and a preservative, wherein the composition pH is between 3.0 and 5.0.
    Type: Grant
    Filed: June 9, 1988
    Date of Patent: May 8, 1990
    Assignee: Cetus Corporation
    Inventors: Daniel L. Francis, Robert Kasubick
  • Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation
    Patent number: 4917888
    Abstract: A pharmaceutical composition is prepared wherein a biologically active conjugated protein which is .beta.-interferon, interleukin-2, or an immunotoxin is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated protein, which is not water-soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to a water-soluble polymer selected from polyethylene glycol homopolymers or polyoxyethylated polyols.
    Type: Grant
    Filed: December 11, 1987
    Date of Patent: April 17, 1990
    Assignee: Cetus Corporation
    Inventors: Nandini Katre, Michael J. Knauf
  • Oligonucleotide functionalizing reagents
    Patent number: 4914210
    Abstract: Oligonucleotide functionalizing reagents are disclosed which are useful in introducing sulfhydryl, amino and additional hydroxyl groups into oligonucleotides. The reagents are substantially linear in structure, at one end provided with a phosphoramidite moiety, at an opposing end provided with a sulfhydryl, amino or hydroxyl moiety, the two ends linked through a hydrophilic spacer chain. Methods of using and synthesizing the novel reagents are disclosed as well.
    Type: Grant
    Filed: October 2, 1987
    Date of Patent: April 3, 1990
    Assignee: Cetus Corporation
    Inventors: Corey Levenson, Chu-An Chang, Fred T. Oakes
  • 3'-expression enhancing fragments and method
    Patent number: 4910141
    Abstract: The invention concerns a method for extending the half-life of mRNAs. The half-life extension is conferred upon the mRNA by a co-transcribed positive retroregulatory element which is ligated to the 3' end of the DNA sequence encoding the RNA. RNAs having an extended half-life conferred by a co-transcribed positive retroregulatory element are also claimed.
    Type: Grant
    Filed: March 29, 1985
    Date of Patent: March 20, 1990
    Assignee: Cetus Corporation
    Inventors: Hing C. Wong, Shing Chang
  • Preparation of a polymer/interleukin-2 conjugate
    Patent number: 4902502
    Abstract: The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.
    Type: Grant
    Filed: January 23, 1989
    Date of Patent: February 20, 1990
    Assignee: Cetus Corporation
    Inventors: Danute E. Nitecki, Nandini Katre, Robert J. Goodson, Lois Aldwin
  • Human lymphoblastoid cell line and hybridomas derived therefrom
    Patent number: 4897466
    Abstract: A 6-thioguanine-resistant subvariant of the EBV-transformed human lymphoblastoid B cell line WI-L2 is described. The subvariant line, designated LTR228, fuses efficiently with human cells. Human.times.human hybridomas derived from LTR228 that produce monoclonal antibodies against tetanus toxin and blood group A are exemplified.
    Type: Grant
    Filed: June 6, 1986
    Date of Patent: January 30, 1990
    Assignee: Cetus Corporation
    Inventors: James W. Larrick, Andrew R. Raubitschek, Kenneth E. Truitt
  • Immunosupressive analogues and derivatives of succinylacetone
    Patent number: 4895872
    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: March 15, 1989
    Date of Patent: January 23, 1990
    Assignee: Cetus Corporation
    Inventors: Danute E. Nitecki, Margaret Moreland, Lois Aldwin, Corey H. Levenson, Irwin Braude, David F. Mark, Henry Rapaport
  • Toxin conjugates
    Patent number: 4894443
    Abstract: A novel class of polypeptides of the general formula (F-(Pro).sub.n).sub.m F, wherein F represents a flexible amino acid sequence wherein each amino acid is individually selected from the group consisting of serine, glycine, and threonine, and n is an integer from 4-8 inclusive and m is an integer from 1-4 inclusive, is disclosed. Thses polypeptides are useful in the construction of conjugates between antibodies and peptide toxins. The preparation of such conjugate toxins by linking antibodies to toxin/spacer composites prepared by recombinant techniques is also disclosed.
    Type: Grant
    Filed: September 7, 1984
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Lawrence I. Greenfield, Donald A. Kaplan, Danute E. Nitecki
  • Composition of immunotoxins with interleukin-2
    Patent number: 4894227
    Abstract: Anti-tumor activity in humans can be augmented by administering to the mammalian host a pharmacologically effective amount of mammalian IL-2 and at least one immunotoxin that binds selectively to human tumor cells. The IL-2 and immunotoxin are preferably administered separately to the host. The composition is useful for prophylactic or therapeutic treatment of such cancers as ovarian and breast cancer.
    Type: Grant
    Filed: May 29, 1987
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Paul Stevens, L. L. Houston, Kirston E. Koths, Brian Issell
  • Method of improving the yield of heterologous protein produced by cultivating recombinant bacteria
    Patent number: 4894334
    Abstract: A method for improving the yield of heterologous protein such as ricin A toxin, produced by recombinant bacteria by supplementing the nutrient medium in which the bacteria are grown with an ethanol and/or amino acid mixture during the terminal phase of the cultivation. Also disclosed is a method for improving the yield of heterologous proteins under the control of the PL promoter.
    Type: Grant
    Filed: April 6, 1987
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Arie Ben-Bassat, Glenn Dorin, Keith Bauer
  • Solubilization of proteins for pharmaceutical compositions using polyproline conjugation
    Patent number: 4894226
    Abstract: A pharmaceutical composition is prepared wherein a biologically active conjugated protein is dissolved in an aqueous carrier medium in the absence of a solubilizing agent. The unconjugated protein, which is not readily water-soluble at pH 6-8 without such solubilizing agent, is covalently conjugated to polyproline via a flexible spacer arm and exhibits substantial biological activity.
    Type: Grant
    Filed: November 14, 1986
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Lois Aldwin, Danute E. Nitecki
  • Combination therapy using antitumor immunotoxins with tumor necrosis factor
    Patent number: 4894225
    Abstract: Tumor necrosis factor and a suitable immuotoxin when administered simultaneously or in tandem produce a synergistic effect in treating tumor burden in warm-blooded animals. Methods and protocols for obtaining this syneristic effect are disclosed, as well as compositions effective in this treatment.
    Type: Grant
    Filed: March 2, 1987
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventor: Robert Zimmerman
  • Purification of recombinant beta-interferon incorporating RP-HPLC
    Patent number: 4894330
    Abstract: Improved RP-HPLC methods for purifying recombinant betainterferon are disclosed. Said RP-HPLC methods employ wide pore silica gel reverse-phase columns and solvent systems containing acetonitrile as the organic modifier and either heptafluorobutyric acid or trifluoroacetic acid as the organic acid.The invention further concerns processes for purifying recombinant IFN-.beta. incorporating said improved RP-HPLC methods.The invention further concerns recombinant IFN-.beta. purified by said RP-HPLC methods, or recovered and/or purified by processes incorporating said RP-HPLC.
    Type: Grant
    Filed: December 23, 1986
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Susan Hershenson, Ze'ev Shaked
  • N-terminal derivatives of tumor necrosis factor purified by microporous PTFE membranes
    Patent number: 4894439
    Abstract: A process is disclosed for the purification of recombinantly produced biologically active proteins in which a solution containing a mixture of materials, including the biologically active protein, is passed through a continuous porous hydrophobic membrane, and the fraction enriched in the biologically active protein is recovered. Hydrophobic proteins such as TNF and recombinant ricin toxin A chain may be purified according to the process. Conditions for enhanced recovery of purified TNF using the process are disclosed. A highly purified TNF comprising 95% or greater TNF as determined by SDS-PAGE analysis, with an endotoxin content of less than 0.1 ng/mg TNF which is substantially free of pyrogens by the USP rabbit pyrogen test at a dosage range of 1.0 to 2.4.times.10.sup.5 U/kg, is obtained.
    Type: Grant
    Filed: May 22, 1986
    Date of Patent: January 16, 1990
    Assignee: Cetus Corporation
    Inventors: Glenn Dorin, Wolfgang H. Hanisch, James W. Thomson, Sidney N. Wolfe, Leo S. Lin
  • Purified thermostable enzyme
    Patent number: 4889818
    Abstract: A purified thermostable enzyme is obtained that has unique characteristics. Preferably the enzyme is isolated from the Thermus aquaticus species and has a molecular weight of about 86,000-90,000 daltons. The thermostable enzyme may be native or recombinant and may be used in a temperature-cycling chain reaction wherein at least one nucleic acid sequence is amplified in quantity from an existing sequence with the aid of selected primers and nucleotide triphosphates. The enzyme is preferably stored in a buffer of non-ionic detergents that lends stability to the enzyme.
    Type: Grant
    Filed: June 17, 1987
    Date of Patent: December 26, 1989
    Assignee: Cetus Corporation
    Inventors: David H. Gelfand, Susanne Stoffel, Frances C. Lawyer, Randall K. Saiki
  • Treatment of infections with lymphokines
    Patent number: 4879111
    Abstract: Infections in mammalian hosts may be treated therapeutically or prophylactically with an effective amount of at least one lymphokine before or after host infection, the amount being sufficient to achieve at least 50% protection of the host. Preferably, the lymphokine is IL-2 or a combination of TNF and IL-2 or TNF and IFN-.gamma.. Also, preferably the infection is bacterial and is being treated prophylactically. The combination of TNF and IL-2 or TNF and IFN-.gamma. is administered in synergistically effective amounts.
    Type: Grant
    Filed: April 17, 1986
    Date of Patent: November 7, 1989
    Assignee: Cetus Corporation
    Inventor: Kong-Teck Chong