Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
Type:
Grant
Filed:
February 26, 1997
Date of Patent:
January 25, 2000
Assignees:
Zymogenetics, Inc., Osteoscreen, Inc.
Inventors:
Charles Petrie, Mark W. Orme, Nand Baindur, Kirk G. Robbins, Gregory R. Mundy
Abstract: Methods for producing secreted receptor analogs and biologically active peptide dimers are disclosed. The methods for producing secreted receptor analogs and biologically active peptide dimers utilize a DNA sequence encoding a receptor analog or a peptide requiring dimerization for biological activity joined to a dimerizing protein. The receptor analog includes a ligand-binding domain. Polypeptides comprising essentially the extracellular domain of a human PDGF receptor fused to dimerizing proteins, the portion being capable of binding human PDGF or an isoform thereof, are also disclosed. The polypeptides may be used within methods for determining the presence of and for purifying human PDGF or isoforms thereof.
Type:
Grant
Filed:
November 26, 1997
Date of Patent:
January 25, 2000
Assignee:
ZymoGenetics, Inc.
Inventors:
Andrzej Z. Sledziewski, Lillian Anne Bell, Wayne R. Kindsvogel
Abstract: Methods for increasing hematopoietic cells, including platelets and erythrocytes, in patients receiving bone marrow or peripheral blood stem cell transplants are disclosed. The methods comprise administering to a donor an amount of thrombopoietin sufficient to stimulate proliferation of cells of the myeloid lineage, collecting cells from the donor, and administering the collected cells to a recipient patient. The recipient patient may be treated with additional thrombopoietin. The methods are useful within allogeneic and autologous transplantation procedures.
Abstract: The present invention provides polynucleotide and polypeptide molecules for a novel human prohormone convertase 4. The polynucleotides encoding human prohormone convertase 4, are located on chromosome 19, and may, for example, be used to identify a region of the genome associated with human disease states. The present invention also includes methods for producing the protein and antibodies thereto.
Abstract: The present invention relates to polynucleotide and polypeptide molecules for stanniocalcin-2, a novel member of the stanniocalcin family. The polypeptides, and polynucleotides encoding them, modulate electrolyte homeostasis. The present invention also includes antibodies to the stanniocalcin-2 polypeptides.
Type:
Grant
Filed:
April 1, 1997
Date of Patent:
December 28, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Rolf E. Kuestner, Darrell C. Conklin, Si Lok, Michele Buddle, William Downey
Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
Abstract: Dimeric proteins having substantially the same biological activity as PDGF are disclosed. More specifically, the protein may have two substantially identical polypeptide chains, each of the chains being substantially homologous to the A-chain of PDGF. Alternatively, the protein may have two polypeptide chains that are substantially identical to the A-chain of PDGF. In addition, proteins comprising polypeptides that are variants or derivatives of the A-chain of PDGF are also disclosed. Therapeutic compositions containing these proteins and methods for enhancing the wound-healing process in warm-blooded animals are also disclosed.
Abstract: Pichia methanolica cells in which an alcohol oxidase gene has been disrupted are disclosed. The cells may also be deficient in vacuolar protease activity. The cells are useful as hosts in recombinant protein production methods.
Abstract: The catalytic active site of Factor VII is modified to produce a compound which effectively interrupts the blood coagulation cascade. The modifications render Factor VIIa substantially unable to activate plasma Factors X or IX. The invention relates to novel methods of treatment and uses of modified Factor VII for preventing or treating myocardial injury associated with post-ischemic reperfusion, for improving regional myocardial blood flow during reperfusion, and maintaining or improving vascular patency in a patient, as well as topical application of modified Factor VII at vascular sites susceptible to thrombus formation.
Type:
Grant
Filed:
June 6, 1997
Date of Patent:
December 7, 1999
Assignees:
Novo Nordisk A/S, ZymoGenetics, Inc.
Inventors:
Charles E. Hart, Lars C. Petersen, Ulla Hedner, Mirella E. Rasmussen
Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
Type:
Grant
Filed:
February 28, 1997
Date of Patent:
November 30, 1999
Assignees:
ZymoGenetics, Inc., Osteoscreen, Inc.
Inventors:
Charles Petrie, Mark W. Orme, Nand Baindur, Kirk G. Robbins, Maria Kontoyianni, Gregory R. Mundy
Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
Type:
Grant
Filed:
February 26, 1997
Date of Patent:
November 23, 1999
Assignees:
ZymoGenetics, Inc., Osteoscreen, Inc.
Inventors:
Charles Petrie, Mark W. Orme, Nand Baindur, Kirk G. Robbins, Scott M. Harris, Gregory R. Mundy
Abstract: The present invention relates to polynucleotide and polypeptide molecules for zFGF-5 a novel member of the FGF family. The polypeptides, and polynucleotides encoding them, are proliferative for muscle cells and may be used for remodelling cardiac tissue and improving cardiac function. The present invention also includes antibodies to the zFGF-5 polypeptides.
Type:
Grant
Filed:
October 16, 1997
Date of Patent:
November 23, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Theresa A. Deisher, Darrell C. Conklin, Fenella Raymond, Thomas R. Bukowski, Susan D. Holderman, Birgit Hansen, Paul O. Sheppard
Abstract: Methods for stimulating granulocyte/macrophage lineage cells using thrombopoiet in are provided. The methods provided may be used to stimulate granulocyte/macrophage progenitors and neutrophils in bone marrow and peripheral blood cells and in vitro and in vivo. In addition, methods for treatment of neutropenia in patients are disclosed.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
November 23, 1999
Assignees:
ZymoGenetics, Inc., University of Washington
Inventors:
Richard D. Holly, Si Lok, Donald C. Foster, Frederick S. Hagen, Kenneth Kaushansky, Joseph L. Kuijper, Catherine E. Lofton-Day, Pieter J. Oort
Abstract: Purified mammalian thrombopoietin proteins and methods of making them are disclosed. The proteins are characterized by a M.sub.r =70,000.+-.10,000 daltons as determined by SDS-polyacrylamide gel electrophoresis under denaturing conditions and are at least 90% pure with respect to contaminating proteins. The proteins can be prepared by a method in which thrombopoietin is adsorbed to and eluted from a polypeptide comprising a ligand-binding domain of an MPL receptor, then the eluted thrombopoietin is fractionated by anion exchange chromatography.
Type:
Grant
Filed:
June 1, 1995
Date of Patent:
November 16, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
John W. Forstrom, Catherine E. Lofton-Day, Si Lok
Abstract: Methods for inhibiting intimal hyperplasia in the vasculature of mammals, including primates, are disclosed. The methods comprise administering to the mammal an anti-PDGF receptor antibody, such as an anti-PDGF-alpha receptor antibody or an anti-PDGF-beta receptor antibody. The methods are useful in reducing intimal hyperplasia due to, for example, vascular injuries resulting from angioplasty, endarterectomy, reduction atherectomy or anastomosis of a vascular graft. The anti-PDGF receptor antibodies may optionally be administered coordinately with heparin, whereby the coordinately administered antibody and heparin are combinatorially effective in inhibiting intimal hyperplasia.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
November 2, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Charles E. Hart, Richard D. Kenagy, Alexander W. Clowes
Abstract: Novel class II cytokine receptor polypeptides, polynucleotides encoding the polypeptides, an related compositions and methods are disclosed. Th polypeptides comprise an extracellular domain of a cell-surface receptor that is expressed in pancreas, small intestine, colon and thymus. The polypeptides may be used within methods for detecting ligands that promote the proliferation and/or differentiation of these organs.
Type:
Grant
Filed:
August 5, 1997
Date of Patent:
October 12, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Si Lok, Robyn L Adams, Anna C. Jelmberg, Theodore E. Whitmore, Theresa M. Farrah
Abstract: Methylotrophic yeast are used for high-level expression of GAD65 that makes the production of GAD65 feasible on an industrial scale. A methanol-inducible promoter from, for example, an alcohol oxidase gene, such as Pichia pastoris AOX1, can be used to regulate GAD65 expression. The recombinant GAD65 has high specific activity and retains antigenic characteristics of the native molecule that are essential to immunological assays and therapeutic protocols.
Type:
Grant
Filed:
November 8, 1996
Date of Patent:
October 12, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Christopher K. Raymond, Thomas R. Bukowski, Paul D. Bishop
Abstract: Compounds containing two aromatic systems covalently linked through a linker containing one or more atoms, or "linker" defined as including a covalent bond per se so as to space the aromatic systems at a distance 1.5-15 .ANG., are effective in treating conditions associated with bone deficits. The compounds can be administered to vertebrate subjects alone or in combination with additional agents that promote bone growth or that inhibit bone resorption. They can be screened for activity prior to administration by assessing their ability to effect the transcription of a reporter gene coupled to a promoter associated with a bone morphogenetic protein and/or their ability to stimulate calvarial growth in model animal systems.
Type:
Grant
Filed:
March 6, 1997
Date of Patent:
October 12, 1999
Assignees:
Zymogenetics, Inc., Osteoscreen, Inc.
Inventors:
Charles Petrie, Mark W. Orme, Nand Baindur, Kirk G. Robbins, Maria Kontoyianni, Gregory R. Mundy
Abstract: The present invention provides testis-specific insulin homolog polypeptides and polynucleotides encoding the polypeptides, as well as related compositions and methods are disclosed. The polypeptides and polynucleotides may be used within methods for enhancing viability of cryopreserved sperm, for enhancing sperm motility, to enhance fertilization in methods of assisted reproduction, as contraceptives and other related uses.
Type:
Grant
Filed:
August 1, 1997
Date of Patent:
September 28, 1999
Assignee:
ZymoGenetics, Inc.
Inventors:
Si Lok, Darrell C. Conklin, Robyn L Adams, Anna C. Jelmberg, Catherine E. Lofton-Day, Stephen R. Jaspers
Abstract: DNA constructs, Pichia methanolica cells, and methods for producing polypeptides using the DNA constructs and cells are disclosed. The DNA constructs comprise a transcription promoter of a Pichia methanolica gene, a DNA segment encoding a polypeptide heterologous to P. methanolica, a transcription terminator of a P. methanolica gene, and a selectable marker. P. methanolica cells containing the DNA constructs are used within methods for producing polypeptides heterologous to P. methanolica. DNA molecules comprising transcription promoters of P. methanolica genes are also disclosed.