Abstract: A polypeptide is provided that excludes (a) a full-length mature TGF-.beta. molecule or precursor TGF-.beta. molecule or deletion variants of mature or precursor TGF-.beta. molecules in which from about 1 to 10 amino acid residues have been deleted, (b) a polypeptide of the sequence: Cys-Val-Arg-Gln-Leu-Tyr-Ile-Asp-Phe-Arg-Lys-Asp-Leu-Gly-Trp-Lys, and (c) a polypeptide of the sequence: Arg Asn-Leu-Glu-Glu-Asn-Cys-Cys-Val-Arg-Pro-Leu-Tyr-Ile-Asp-Phe-Arg-Gln-Asp-Le u, said polypeptide comprising an amino acid sequence that is based on conserved sequences in the family of TGF-.beta. molecules. Such polypeptides are particularly useful therapeutically as immunosuppressive agents when coupled to carrier proteins or crosslinked to form polymers.
Abstract: Methods and compositions are provided for the treatment or prophylaxis of septic shock caused by bacteremic infection. Therapeutically and prophylactically effective doses of transforming growth factor-beta are administered to patients, either alone or in combination with another therapeutic or prophylactic agent for treating this pathologic condition. Preferably, the transforming growth factor-beta is human transforming growth factor-beta, and most preferably TGF-.beta..sub.1, TGF-.beta..sub.2, or TGF-.beta..sub.3.
Type:
Grant
Filed:
June 27, 1989
Date of Patent:
October 8, 1991
Assignee:
Genentech, Inc.
Inventors:
Michael A. Palladino, Stephen A. Sherwin
Abstract: Enzyme-catalyzed synthetic reactions having otherwise unfavorable equilibria are facilitated by recovery of polypeptides by electrodialysis. A process of preparing polypeptides is provided that can be operated continuously to produce high yields of enriched polypeptides without recourse to post-synthetic product manipulations heretofore employed that are expensive and present a risk of residual toxic by-products. The invention is applied to advantage in the preparation of alpha-L-aspartyl-L-phenylalanine lower alkyl esters.
Abstract: Described herein is the secretion from yeast of heterologous protein via a preprotein in which the heterologous protein is fused to the signal peptide of a yeast protein. The preprotein is processed by the cells to produce and secrete mature heterologous protein.
Type:
Grant
Filed:
June 20, 1990
Date of Patent:
April 23, 1991
Assignee:
Genentech, Inc.
Inventors:
Chung N. Chang, Ronald A. Hitzeman, Mark D. Matteucci
Abstract: 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.
Abstract: 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:
Grant
Filed:
September 13, 1985
Date of Patent:
February 12, 1991
Assignee:
Cetus Corporation
Inventors:
Wolfgang H. Hanisch, Peter M. Fernandes, Terrance Taforo
Abstract: 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:
Grant
Filed:
August 25, 1989
Date of Patent:
January 15, 1991
Assignee:
Cetus Corporation
Inventors:
Robert Zimmerman, Benedict J. Marafino, Jr.
Abstract: DNA constructs are prepared which operably link human interferon genes, selective, eukaryotic marker genes, and promoter and expression control sequences for the expression of human interferon in Chinese hamster ovary (CHO) cells or progeny thereof. The human recombinant interferon so produced contains glycans which are a subset of the population of glycans which are contained in the native counterpart, and may be used in therapeutic formulations. The CHO cells yield high levels of human interferon with no detectable amounts of host IFN, either constitutive or inductive.
Type:
Grant
Filed:
July 31, 1985
Date of Patent:
October 30, 1990
Assignee:
Cetus Corporation
Inventors:
Francis P. McCormick, Michael A. Innis, Gordon M. Ringold
Abstract: A process for amplifying any target nucleic acid sequence contained in a nucleic acid or mixture thereof comprises treating separate complementary strands of the nucleic acid with a molar excess of two oligonucleotide primers and extending the primers with a thermostable enzyme to form complementary primer extension products which act as templates for synthesizing the desired nucleic acid sequence. The amplified sequence can be readily detected. The steps of the reaction can be repeated as often as desired and involve temperature cycling to effect hybridization, promotion of activity of the enzyme, and denaturation of the hybrids formed.
Type:
Grant
Filed:
June 17, 1987
Date of Patent:
October 23, 1990
Assignee:
Cetus Corporation
Inventors:
Kary B. Mullis, Henry A. Erlich, David H. Gelfand, Glenn Horn, Randall K. Saiki
Abstract: A method for producing factor VIII in recombinant mammalian host cells utilizing an expression vector containing a selectable marker DNA and an amplifiable marker DNA. The initial selection is based upon the selectable marker and subsequent amplification of factor VIII DNA and amplifiable marker DNA is conducted in cells not deficient in the amplifiable marker.
Type:
Grant
Filed:
August 7, 1987
Date of Patent:
October 23, 1990
Assignee:
Genentech, Inc.
Inventors:
Daniel J. Capon, Richard M. Lawn, Arthur D. Levinson, Gordon A. Vehar, William I. Wood
Abstract: DNA isolates coding for enkephalinase and methods of obtaining such DNA are provided, together with expression systems for recombinant production of enkephalinase for use in therapeutic or diagnostic compositions. Enkephalinase assays are facilitated by novel enkephalinase substrates.
Type:
Grant
Filed:
January 12, 1987
Date of Patent:
October 2, 1990
Assignee:
Genentech, Inc.
Inventors:
Bernard Malfroy-Camine, Peter R. Schofield
Abstract: Metallothionein transcription control sequences, promoters or inducing regions, free of DNA encoding metallothionein, are used to inducibly express genes encoding polypeptides of interest. Vectors and host expression systems using the transciption control sequences, promoters and/or inducing regions are provided.
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.
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.
Abstract: Shuttle vector systems are provided for the regulated expression of subject genes in transformed hosts. A promoter/operator which does not originate with the transformed host cell controls expression of the subject gene and a repressor, which also does not originate with the host cell, regulates the promoter/operator. According to this invention, promoter/operator--repressor functionalities from one bacterium are used in other bacteria, thereby obviating the need to locate homologous expression regulatory sequences for each bacterial host.
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
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
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.
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.
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.