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:
December 21, 1984
Date of Patent:
August 1, 1989
Assignee:
Cetus Corporation
Inventors:
David F. Mark, Leo S. Lin, Shi-Da Yu Lu
Abstract: An insoluble zinc-protamine alpha interferon complex useful as an injectable sustained release dosage form for administering alpha interferon is disclosed.
Type:
Grant
Filed:
February 24, 1987
Date of Patent:
August 1, 1989
Assignee:
Schering Corporation
Inventors:
Zachary Yim, Michael A. Zupon, Imtiaz A. Chaudry
Abstract: Gamma interferon is employed in the treatment of chronic myelogenous leukemia. Patients treated in the benign stage exhibit partial and, in some cases, complete responses to gamma interferon. Successful results have also been obtained with some patients in the blast stage of the disease as well as patients who had been found to be refractory to treatment with alpha interferon.
Abstract: Novel human IL-2 polypeptide derivatives characterized by deletion of at least one amino acid from the amino acid sequence of the human IL-2 polypeptide, recombinant plasmids containing DNAs coding for the above derivatives, microorganisms harboring these plasmids and methods of producing the above derivatives in these microorganisms are provided.
Abstract: Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substituted guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functionality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.
Abstract: Stable pharmaceutical compositions comprising interferon and thimerosal which are substantially resistant to microorganism contamination and growth are disclosed.
Abstract: A method is disclosed for constructing a synthetic gene for the production of a viral protein or portion thereof. The method is useful for genes found on minus-strand RNA viral genomes, such as those of rhabdoviruses or paramyxoviruses. The protein or a portion thereof prepared by expression of the synthetic gene in a suitable host may be used for vaccine or diagnostic purposes.
Abstract: Described are modified human gamma interferons, genes coding for their synthesis and plasmids containing and capable of expressing these genes.
Abstract: Protection inducing antigens or parasites of the genus Plasmodium are described. The antigens have an apparent molecular weight of 1.8 to 2.5.times.10.sup.5 and are associated with the membranes of the erythrocytic schizont forms of the parasite. The antigens may be incorporated into vaccines and used for the inducing of immunity into susceptible vetebrate hosts including humans. Methods for the preparation of the antigens are also described.
Abstract: A method of regulating oncogene-mediated cell transformation in a mammalian host. Oncogenes having glycosylated expression products are regulated by administering an effective amount of a processing glucosidase inhibitor: a glucosidase I inhibitor, e.g., castanospermine, N-methyl-1-deoxynojirimycin, 1-deoxynojirimycin, 5-amino-5-deoxy-D-glucopyranose; or a glucosidase II inhibitor, e.g., bromoconduritol. The glucosidase I inhibitors are preferred, particularly castanospermine (CA) and N-methyl-1-deoxynojirimycin (MdN). Oncogenes having glycosylated expression products that are ultimately expressed on the plasma membrane or secreted from transformed cells are particularly susceptible to regulation by these anti-cancer drugs. Also provided is a method of regulating the immune system of a mammalian host. Administration of an effective amount of a processing glucosidase inhibitor suppresses proliferation and differentiation of monocytic and myeloblastic cells.
Type:
Grant
Filed:
July 9, 1985
Date of Patent:
June 6, 1989
Assignees:
Fred Hutchinson Cancer Research Center, Everett J. Nichols
Inventors:
Larry R. Rohrschneider, Everett J. Nichols
Abstract: Disclosed is a novel DNA which shows complementarity to human interferon-.gamma. mRNA, a recombinant plasmid containing the DNA, a microorganism containing the recombinant plasmid and a method of producing the same as well as a process for producing a polypeptide having human interferon.gamma. activity using the microorganism.
Type:
Grant
Filed:
December 3, 1987
Date of Patent:
May 30, 1989
Assignees:
New York University & Juridical Foundation, Japanese Foundation for Cancer Research
Inventors:
Tadatsugu Taniguchi, Haruo Sugano, Tatsunari Nishi, Jan T. Vilcek, Yum K. Yip
Abstract: Partial sequences of human-.gamma.-interferon, comprising aminoacid sequences 5 to 127, 1 to 127 and 5 to 146, having biological activity. These partial sequences can be obtained by a genetic engineering process, for which purpose the appropriate DNA sequences are chemically synthesized. The DNA sequences are incorporated in hybrid plasmids, and the latter are introduced into host organisms and their expression is induced there. The biologically active polypeptides are suitable, as is human-.gamma.-interferon, for medicaments.
Type:
Grant
Filed:
March 4, 1985
Date of Patent:
May 23, 1989
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Joachim Engels, Michael Leineweber, Eugen Uhlmann, Wolfgang Ulmer
Abstract: Recombinant vectors which are effective in expressing DNA sequences encoding specific fragments of diphtheria toxins at high levels in recombinant host cells are disclosed. Both a fragment consisting of the enzymatically active A chain of diphtheria toxin and a fragment consisting of both the A portion and a B portion partial sequence are constructed by use of this recombinant vector.
Type:
Grant
Filed:
February 9, 1984
Date of Patent:
May 16, 1989
Assignee:
Cetus Corporation
Inventors:
David H. Gelfand, Lawrence I. Greenfield, Frances C. Lawyer
Abstract: A process for purifying a protein and particularly the purification of a protein, such as gamma interferon, that forms highly insoluble aggregates during the growth of host cells transformed with DNA sequence coding for the protein.
Type:
Grant
Filed:
February 4, 1986
Date of Patent:
May 9, 1989
Inventors:
Chrisopher P. Prior, Garance M. Ducommun
Abstract: TNF or LT qualitatively and quantitatively potentiates the anti-viral activity of interferons, thus permitting the use of lower interferon doses to protect uninfected cells from interferon sensitive and relatively insensitive viruses and to selectively kill virus-infected cells.
Abstract: A method of purifying a polypeptide having a physiological activity such as one having interferon activities from a culture mixture of a microorganism obtained by a recombinant DNA technique and capable of producing the polypeptide is disclosed. The method comprises subjecting the cultured cells to extraction and purification in the presence of a salt of zinc or copper and polyethyleneimine thereby inhibiting decomposition and denaturation of the polypeptide. The extracted polypeptide can be further purified by column chromatographies using a column containing an anion exchange resin, column containing a cation exchange resin and column containing a gel filtration resin.
Type:
Grant
Filed:
October 10, 1986
Date of Patent:
May 9, 1989
Inventors:
Naoki Higashi, Shunjiro Sugimoto, Masafumi Tsujimoto, Hounai Shirasawa, Tsutomu Okada, Kazumori Yamamoto, Tattanahalli L. Nagabhushan, Paul P. Trotta
Abstract: A composition containing an antiviral and an antitumor agent is useful when topically applied for the treatment of tumors and cancers, particularly for the treatment of viral or cancerous skin disorders and skin manifestations thereof. Interferon is usefully employed in these compositions in combination with the antitumor agent. Antitumor agents which are useful include interleukin, such as Interleukin II, tumor necrosis factor (TNF), target cell lysis factor (TCLF) and carcino-breaking factor (CBF). These compositions are especially usefully applied by topical application to the skin manifestation of the viral or cancerous skin disorder.
Abstract: A biologically active interferon can be administered to an animal in conjunction with the administration of a vaccine to improve the vaccine efficiency and allow the use of a smaller vaccination dose. This procedure will cause a less severe vaccine infection in the animal than if no interferon was administered.
Abstract: A pharmaceutical composition containing IL-2 or IFN-.beta. dissolved in a suitable carrier medium at pH 7.0 to 8.0 stabilized with sodium laurate is suitable for parenteral injection into humans or animals. This formulation may be prepared by adding to either protein, after its recovery from a transformed organism, an effective amount of sodium laurate at a pH of 9 to 9.5 and then adjusting the pH of the formulation to between 7.0 and 8.0.