Tumor Necrosis Factor Patents (Class 930/144)
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Patent number: 8729027Abstract: Disclosed is a drug effective in the treatment of fibromyalgia. Basically, the disclosed therapeutic agent was created on the basis of experiments showing improvement in symptoms when etanercept was administered to patients suffering from fibromyalgia. Etanercept is known as a therapeutic agent for rheumatoid arthritis, and the JFIQ score of patients not suffering from fibromyalgia improved considerably in the preferred embodiment. In other words, a therapeutic agent for fibromyalgia is disclosed that contains etanercept as an active ingredient in an effective amount.Type: GrantFiled: July 4, 2011Date of Patent: May 20, 2014Assignee: AXIS Inc.Inventor: Kusuki Nishioka
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Patent number: 8501918Abstract: The present invention provides a method for enhancing an immune response in a mammal to facilitate the elimination of a chronic pathology. The method involves the removal of immune system inhibitors such as soluble TNF receptor from the circulation of the mammal, thus, enabling a more vigorous immune response to the pathogenic agent. The removal of immune system inhibitors is accomplished by contacting biological fluids of a mammal with one or more binding partner(s) such as TNF? muteins capable of binding to and, thus, depleting the targeted immune system inhibitor(s) from the biological fluids. Particularly useful in the invention is an absorbent matrix composed of an inert, biocompatible substrate joined covalently to a binding partner, such as a TNF? mutein, capable of specifically binding to a targeted immune system inhibitor such as soluble TNF receptor.Type: GrantFiled: February 11, 2009Date of Patent: August 6, 2013Assignee: Cytologic, Inc.Inventor: Mark Douglas Howell
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Patent number: 8372799Abstract: A protein which is composed N-terminally of one or several C-terminal parts of the amino acid sequence of the mature tumor necrosis factor and C-terminally of one or several N-terminal parts of the amino acid sequence of the mature tumor necrosis factor, which activates epithelial ion channels and improves the lung function and which can be used for the manufacture of medicaments for the treatment of diseases associated with the lung function, such as oedemas.Type: GrantFiled: December 12, 2008Date of Patent: February 12, 2013Assignee: Apeptico Forschung und Entwicklung GmbHInventors: Bernhard Fischer, Rudolf Lucas
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Patent number: 8093363Abstract: Human TNF-gamma-alpha and TNF-gamma-beta polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides to inhibit cellular growth, for example in a tumor or cancer, for facilitating wound-healing, to provide resistance against infection, induce inflammatory activities, and stimulating the growth of certain cell types to treat diseases, for example restenosis. Also disclosed are diagnostic methods for detecting a mutation in the TNF-gamma-alpha and TNF-gamma-beta nucleic acid sequences or overexpression of the TNF-gamma-alpha and/or TNF-gamma-beta polypeptides. Antagonists against such polypeptides and their use as a therapeutic to treat cachexia, septic shock, cerebral malaria, inflammation, arthritis and graft-rejection are also disclosed.Type: GrantFiled: September 10, 2010Date of Patent: January 10, 2012Assignee: Human Genome Sciences, Inc.Inventors: Guo-Liang Yu, Jian Ni, Craig A. Rosen, Jun Zhang
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Patent number: 8063182Abstract: The present invention is concerned with non-soluble proteins and soluble or insoluble fragments thereof, which bind TNF, in homogeneous form, as well as their physiologically compatible salts, especially those proteins having a molecular weight of about 55 or 75 kD (non-reducing SDS-PAGE conditions), a process for the isolation of such proteins, antibodies against such proteins, DNA sequences which code for non-soluble proteins and soluble or non-soluble fragments thereof, which bind TNF, as well as those which code for proteins comprising partly of a soluble fragment, which binds TNF, and partly of all domains except the first of the constant region of the heavy chain of human immunoglobulins and the recombinant proteins coded thereby as well as a process for their manufacture using transformed pro- and eukaryotic host cells.Type: GrantFiled: May 19, 1995Date of Patent: November 22, 2011Assignee: Hoffman-LaRoche Inc.Inventors: Manfred Brockhaus, Reiner Gentz, Dembic Zlatko, Werner Lesslauer, Hansruedi Lotscher, Ernst-Jurgen Schlaeger
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Patent number: 7785579Abstract: Modifying TNF with polyethyleneglycol (PEG) having an approximate weight average molecular weight in the range of about 10,000 to about 40,000, preferably in the range of about 20,000 to 30,000, significantly increases the circulating half-life of the TNF while not increasing its toxicity. As a result, lower doses of the TNF may be administered to effectively treat tumors with fewer, accompanying adverse side effects to the patient.Type: GrantFiled: February 27, 2006Date of Patent: August 31, 2010Assignee: Polaris GroupInventor: Mike A. Clark
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Patent number: 7597886Abstract: Human TNF-gamma-alpha and TNF-gamma-beta polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing such polypeptides to inhibit cellular growth, for example in a tumor or cancer, for facilitating wound-healing, to provide resistance against infection, induce inflammatory activities, and stimulating the growth of certain cell types to treat diseases, for example restenosis. Also disclosed are diagnostic methods for detecting a mutation in the TNF-gamma-alpha and TNF-gamma-beta nucleic acid sequences or overexpression of the TNF-gamma-alpha and/or TNF-gamma-beta polypeptides. Antagonists against such polypeptides and their use as a therapeutic to treat cachexia, septic shock, cerebral malaria, inflammation, arthritis and graft-rejection are also disclosed.Type: GrantFiled: July 6, 2001Date of Patent: October 6, 2009Assignee: Human Genome Sciences, Inc.Inventors: Guo-Liang Yu, Jian Ni, Craig A. Rosen, Jun Zhang
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Patent number: 7258997Abstract: The present invention relates to methods of increasing protein expression levels whereby at least one amino acid in a protein amino acid sequence is substituted for the amino acid, proline. Preferably, the substitution occurs within 15 amino acids, more preferably within 10 amino acids and most preferably within 5 amino acids of a cysteine amino acid residue. The present invention not only includes methods for polypeptides with proline substitutions, but also polynucleotides with codon substitutions for which a codon for any amino acid, except proline, is substituted for a codon encoding for proline.Type: GrantFiled: November 21, 2002Date of Patent: August 21, 2007Assignee: Applied Research Systems Ars Holding N.V.Inventors: William Brondyk, Xuliang Jiang, Rene Lynn Schweickhardt
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Patent number: 7118750Abstract: A modified human TNF? molecule is capable of raising neutralizing antibodies towards unmodified human TNF? following administration of the modified TNF? to a human host, wherein one or more peptide fragments of the human TNF? molecule has been substituted by one or more peptides containing immunodominant T cell epitopes or a truncated form of the molecule containing the immunodominant epitope and one or both flanking regions of the human TNF?-molecule containing at least one TNF? B cell epitope, wherein the substitution introduces a substantial change in the amino acid sequence of any one of the strands of the front ?-sheet, in any one of the connecting loops, or in any one of the B?, I, or D strands of the back ?-sheet.Type: GrantFiled: April 15, 1998Date of Patent: October 10, 2006Assignee: Pharmexa A/SInventors: Martin Roland Jensen, Søren Mouritsen, Henrik Elsner, Iben Dalum
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Patent number: 6930097Abstract: A compound of formula 1-[3,4-dihydroxy-5-(2-hydroxyethyl)tetrahydrofuran-2-yl]pryimidine-2,4(1H,3H)-dione has inhibitory effects of matrix metalloproteinase-2 (gelatinase A) enzyme and binding of TNF? to TNF?-RI.Type: GrantFiled: April 21, 2003Date of Patent: August 16, 2005Assignee: Advanced Gene Technology Corp.Inventors: Li-Wei Hsu, Su-Chen Chang, Jeng-Woei Lee, Pang-Hsi Liu, Hui-Ping Lee, Yi-Ching Chen, Chun-Tsun Chen
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Patent number: 6683060Abstract: The invention discloses methods of treatment and prevention for TNF&agr;-related disorders and MMP-related disorders and compounds useful in such treatments. In particular, the invention dislcoses pharmaceutical compositions comprising a compound of the general formula: wherein X is a Zn(II) chelating group and selected from the group consisting of (CH2)nOH, (CH2)nNH2, (CH2)nSH, (CH2)mCOOH, (CH2)mCOOR, (CH2)mCONH2, (CH2)m″CONH—OH, (CH2)m″CONH—R, and (CH2)n′O(PO3)m″(m″+1), wherein n=2, 3, 4, or 5, n′=2 or 3, m=1, 2, 3, or 4, m′=1, 2, 3, 4, 5, or 6, m″=1, 2, 3, and R=—Cm′, H2m′+1 or aryl groups, especially 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione, which has an inhibitory effect on matrix metalloproteinase-2 (gelatinase A) and on the binding of TNF&agr; to TNF&agr;-RI.Type: GrantFiled: February 25, 2002Date of Patent: January 27, 2004Assignee: Advanced Gene Technology Corp.Inventors: Li-Wei Hsu, Su-Chen Chang, Jeng-Woei Lee, Pang-Hsi Liu, Hui-Ping Lee, Yi-Ching Chen, Chun-Tsun Chen
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Patent number: 6635743Abstract: The present invention relates to a novel member of the TNF-Ligand superfamily. More specifically, isolated nucleic acid molecules are provided encoding a human Apoptosis Inducing Molecule II (AIM II). AIM II polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of AIM II activity. Also provided are therapeutic methods for treating lymphadenopathy, aberrant bone development, autoimmune and other immune system diseases, graft versus host disease, rheumatoid arthritis, osteoarthritis and to inhibit neoplasia, such as tumor cell growth.Type: GrantFiled: March 10, 2000Date of Patent: October 21, 2003Assignee: Human Genome Sciences, Inc.Inventors: Reinhard Ebner, Guo-Liang Yu, Steven M. Ruben, Stephen Ullrich, Yifan Zhai
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Patent number: 6479254Abstract: The present invention relates to a novel member of the TNF-Ligand superfamily, Apoptosis Inducing Molecule II (AIM II). In particular, isolated nucleic acid molecules are provided encoding the human AIM II protein. AIM II polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of AIM II activity. Also provided are therapeutic methods for treating lymphadenopathy, autoimmune disease, graft versus host disease, and to inhibit neoplasia, such as tumor cell growth.Type: GrantFiled: February 20, 1998Date of Patent: November 12, 2002Assignee: Human Genome Sciences, Inc.Inventors: Reinhard Ebner, Guo-Liang Yu, Steven M. Ruben
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Patent number: 6271346Abstract: DNA sequences coding for a TNF-binding protein and for the TNF receptor of which this protein constitutes the soluble domain. The DNA sequences can be used for preparing recombinant DNA molecules in order to produce TNF-binding protein and TNF receptor. Recombinant TNF-binding protein is used in pharmaceutical preparations for treating indications in which TNF has a harmful effect. With the aid of the TNF receptor or fragments thereof or with the aid of suitable host organisms transformed with recombinant DNA molecules containing the DNA which codes for the TNF receptor or fragments or modifications thereof, it is possible to investigate substances for their interaction with the TNF receptor and/or for their effect on the biological activity of TNF.Type: GrantFiled: June 7, 1995Date of Patent: August 7, 2001Assignee: Amgen Inc.Inventors: Rudolf Hauptmann, Adolf Himmler, Ingrid Maurer-Fogy, Christian Stratowa
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Patent number: 6127528Abstract: The present invention relates to an adsorbent being capable of efficiently removing tumor necrosis factor-.alpha. (TNF-.alpha.) in a body fluid, an adsorber using the adsorbent and a process for adsorbing and removing TNF-.alpha., namely an adsorbent of TNF-.alpha., wherein onto a water-insoluble carrier a compound having a functional group represented by the formula (I): ##STR1## wherein X.sup.- is an anionic functional group, A is a substituent group except for the anionic functional group, n is an integer of 0 to 4 and in case n is at least 2, groups A, the number of which is n, may be the same or different from each other; a process for adsorbing and removing TNF-.alpha., which comprises coming the adsorbent into contact with a body fluid; and an adsorber for adsorbing TNF-.alpha. wherein a vessel having an inlet and an outlet for a body fluid and being equipped with a means for preventing the adsorbent from flowing to the outside of the vessel, is charged with the adsorbent.Type: GrantFiled: April 2, 1999Date of Patent: October 3, 2000Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Fumiyasu Hirai, Nobutaka Tani, Takashi Asahi
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Patent number: 6030945Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.Type: GrantFiled: January 9, 1996Date of Patent: February 29, 2000Assignee: Genentech, Inc.Inventor: Avi J. Ashkenazi
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Patent number: 5889156Abstract: A virion expression system for a desired protein packaged in an envelope derived from a retrovirus useful in administering proteins which cross cell membranes in order to serve their function. Preferred virions are those that carry an RNA sequence that encodes cytokines or lymphokines, and includes IL-2, multiple drug resistance protein, and TNF.Type: GrantFiled: May 24, 1995Date of Patent: March 30, 1999Assignee: Chiron CorporationInventors: Michael Kriegler, Carl F. Perez
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Patent number: 5698518Abstract: A method of treating patients to inhibit inflammation is disclosed. In the method, an effective amount of calmodulin, a calmodulin analogue or calmodulin receptor agonist is administered to a patient to inhibit production of tumor necrosis factor and/or augment elastase. In another method, an effective amount of calmodulin antagonist is administered to a patient to stimulate immune response or inhibit elastase release. In another embodiment, a diagnostic test is disclosed to be used on patient blood samples to determine individual propensity to regulate tumor necrosis factor and/or elastase by calmodulin, its analogues or receptor agonists.Type: GrantFiled: March 30, 1994Date of Patent: December 16, 1997Assignee: Oklahoma Medical Research FoundationInventors: Craig W. Carson, Charles T. Esmon, Donald S. Houston
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Patent number: 5370870Abstract: Methods suitable for the protection inhibtion and prevention of the deleterious effects of reactive oxygen species are provided, wherein an effective amount of a protective agent(s) selected from the group of tumor necrosis factor-alpha and -beta, growth hormone, IL-1, and D-factor is administered. Treatment of tissues and organs to be transplanted is described. Perfusion solutions and the preparation of perfused, excised tissue are described.Type: GrantFiled: June 11, 1993Date of Patent: December 6, 1994Assignee: Genentech, Inc.Inventor: Grace H. W. Wong
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Patent number: 5298603Abstract: Expression of a gene coding for human granulocyte macrophage colony-stimulating factor (CSF) in bacteria results in CSF proteins which are biologically active. Modification of the natural or of a synthetic gene structure results in biologically active derivatives with a modified amino acid sequence.Type: GrantFiled: December 21, 1992Date of Patent: March 29, 1994Assignee: Hoechst AktiengesellschaftInventors: Paul Habermann, Hubert Mullner
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Patent number: 5288852Abstract: A novel cloned DNA encoding a human tumor necrosis factor (TNF), a vector having said DNA inserted thereinto, a host transformed with said vector and a novel human TNF polypeptide, and processes for producing them.Type: GrantFiled: July 1, 1993Date of Patent: February 22, 1994Assignee: Dainippon Pharmaceutical Co., Ltd.Inventors: Masaaki Yamada, Yasuji Furutani, Mitsue Notake, Juniti Yamagishi
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Patent number: 5247070Abstract: A polypeptide which is a tumor necrosis factor polypeptide having an amino acid sequence represented by from the 1st Ser to the 155th Leu as shown by SEQ ID NO:1 in the Sequence Listing, or its mutein, wherein the amino acid sequence of the 1st Ser to the 8th Asp of the SEQ ID NO:1 or the corresponding amino acid sequence of the mutein is replaced by an amino acid sequence containing at least one amino acid sequence of cell-adherent peptide of laminin and from 5 to 30 amino acids. Also disclosed are a recombinant plasmid containing a DNA encoding such a polypeptide, a recombinant microbial cell transformed by such a recombinant plasmid, a process for producing the polypeptide, a pharmaceutical composition comprising the polypeptide as an active ingredient, and a DNA for the polypeptide.Type: GrantFiled: September 20, 1991Date of Patent: September 21, 1993Assignee: Ishihara Sangyo Kaisha Ltd.Inventors: Nobutoshi Yamada, Masanari Kato, Keizo Miyata, Yoshiyuki Aoyama, Hiroshi Shikama
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Patent number: 5200176Abstract: Methods suitable for the protection, inhibition and prevention the deleterious effects of reactive oxygen species are provided, wherein an effective amount of a tumor necrosis factor is administered. Pretreatment of tissues and organs to be transplanted is described. Perfusion solutions and the preparation of perfused, excised tissue are described.Type: GrantFiled: October 6, 1989Date of Patent: April 6, 1993Assignee: Genentech, Inc.Inventors: Grace H. W. Wong, David V. Goeddel
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Patent number: 5180811Abstract: Derivatives of a tumor necrosis factor (TNF), which originate from a modification at the amino terminus of the TNF molecule are suitable for controlling diseases.Type: GrantFiled: May 13, 1988Date of Patent: January 19, 1993Assignee: BASF AktiengesellschaftInventors: Thomas Doerper, Achim Moeller, Heinz Hillen, Gerhard Keilhauer, Franz Emling, Lothar Daum
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Patent number: 5157106Abstract: Polypeptides which differ from lymphotoxin by the absence of amino acids at the N-terminal end of the lymphotoxin are described. The polypeptides can be prepared by gene manipulation and are suitable, alone or in combination with lymphokines, as pharmaceuticals.Type: GrantFiled: June 15, 1987Date of Patent: October 20, 1992Assignee: BASF AktiengesellschaftInventors: Klaus Schollmeier, Achim Moeller, Wolfgang Koerwer, Thomas Doerper, Heinz Hillen, Lothar Daum, Franz Emling, Gerhard Keilhauer