Abstract: Glucagon antagonists and methods relating thereto are disclosed. The glucagon antagonists include skyrin and skyrin analogs, and serve to inhibit the stimulation of a glucagon-induced response pathway, such as the adenylate cyclase response pathway or the inositol phosphate response pathway. The glucagon antagonists may be used within therapeutic compositions to treat disease states associate with elevated glucose levels, including diabetes and hyperglycemia. The present invention also discloses a biologically pure culture of ATCC accession number 74200, as well as methods relating to the production of glucagon antagonists by cultivating the same in a nutrient medium and recovering the glucagon antagonist therefrom.
Type:
Grant
Filed:
September 11, 1995
Date of Patent:
October 14, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Robert R. West, Virender Labroo, James R. Piggott, Robert A. Smith, Patricia A. McKernan
Abstract: The present invention provides isolated DNA molecules comprising a DNA segment encoding a novel human amyloid protein precursor homologue and novel Kunitz-type inhibitors. Also provided are DNA constructs comprising a first DNA segment encoding a novel human amyloid protein precursor homologue or a novel Kunitz-type inhibitor wherein said first DNA segment is operably linked to additional DNA segments required for the expression for the first DNA segment, as well as host cells containing such DNA constructs and methods for producing proteins from the host cells.
Type:
Grant
Filed:
April 18, 1995
Date of Patent:
October 14, 1997
Assignee:
Zymogenetics, Inc.
Inventors:
Cindy A. Sprecher, Donald C. Foster, Kjeld E. Norris
Abstract: Human calcitonin receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereto may be used in screening systems to identify agonists and antagonists of human calcitonin receptors, thereby providing means for treating and preventing abnormal bone resorption, as well as in methods of diagnosis.
Type:
Grant
Filed:
May 30, 1995
Date of Patent:
October 7, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Emma E. Moore, Paul O. Sheppard, Rolf E. Kuestner
Abstract: Human calcitonin receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereto may be used in screening systems to identify agonists and antagonists of human calcitonin receptors, thereby providing means for treating and preventing abnormal bone resorption, as well as in methods of diagnosis.
Type:
Grant
Filed:
May 30, 1995
Date of Patent:
October 7, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Emma E. Moore, Paul O. Sheppard, Rolf E. Kuestner
Abstract: A method of producing proteins of interest is disclosed. The method includes the introduction of a first DNA sequence encoding the protein of interest and at least one additional DNA sequence encoding a protein which processes or stabilizes the protein of interest into a eukaryotic host cell. The host cell is subsequently cultured under conditions which allow the DNA sequences to be expressed. Suitable eukaryotic hosts include mammalian cells and yeast cells.
Abstract: The present invention provides an immature dendritic cell line derived from p53 growth suppressor gene deficient animals. The immature dendritic cell line may be induced to become an activated dendritic cell line that will stimulate T-cells to proliferate. The cell line is useful for presentation of antigens involved in autoimmune disease and analysis of peptides that produce a T-cell response.
Abstract: The present invention relates to an orthogonally-protected compound of the formula: ##STR1## wherein PG.sub.1 is a first protecting group that is unreactive to a chemistry used at another position within the compound, and that is capable of selective removal without affecting PG.sub.2 or linkage to a solid support; PG.sub.2 is a second protecting group that is unreactive to a chemistry used at another position within the compound, and that is capable of selective removal without affecting PG.sub.1 or linkage to a solid support; Y is CH.sub.2 COOH, CH.sub.2 SO.sub.2 OH, CH.sub.2 PO.sub.2 ROH, CH.sub.2 Ph--COOH, CH.sub.2 Ph--SO.sub.2 OH, or CH.sub.2 Ph--PO.sub.2 ROH; R is H or a substituted or unsubstituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, or heteroarylalkyl; and n is 1 or 2. PG.sub.1 is preferably a carbamate group, a trityl group, or a trifluoroacetyl group; and PG.sub.2 is preferably an ester.
Abstract: DNA constructs useful in the production of thrombopoietin are disclosed. In general, the DNA constructs comprise a first DNA segment encoding a fusion of an amino-terminal secretory peptide joined to a thrombopoietin polypeptide and one or more additional DNA segments that provide for the transcription of the first segment. The secretory peptide is a native mammalian t-PA secretory peptide or may be modified to enhance proteolytic cleavage of the fusion. Also disclosed are cultured eukaryotic cells containing these DNA constructs and methods for producing thrombopoietin polypeptides through the use of the DNA constructs and cultured eukaryotic cells.
Type:
Grant
Filed:
November 30, 1994
Date of Patent:
June 24, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Donald C. Foster, Mark D. Heipel, Richard D. Holly
Abstract: Materials and methods for producing fibrinogen in transgenic non-human mammals are disclosed. DNA segments encoding A.alpha., B.beta. and .gamma. chains of fibrinogen are introduced into the germ line of a non-human mammal, and the mammal or its female progeny produces milk containing fibrinogen expressed from the introduced DNA segments. Non-human mammalian embryos and transgenic non-human mammals carrying DNA segments encoding heterologous fibrinogen polypeptide chains are also disclosed.
Type:
Grant
Filed:
March 3, 1994
Date of Patent:
June 17, 1997
Assignees:
Pharmaceutical Proteins Ltd., ZymoGenetics, Inc.
Inventors:
Ian Garner, Michael L. Dalrymple, Donna E. Prunkard, Donald C. Foster
Abstract: Human calcitonin receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereto may be used in screening systems to identify agonists and antagonists of human calcitonin receptors, thereby providing means for treating and preventing abnormal bone resorption, as well as in methods of diagnosis.
Type:
Grant
Filed:
May 30, 1995
Date of Patent:
April 22, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Emma E. Moore, Paul O. Sheppard, Rolf E. Kuestner
Abstract: Isolated polynucleotide molecules encoding mammalian phospholipid transfer proteins (PLTP) and phospholipid transfer protein polypeptides are disclosed. The DNA molecules are transformed or transfected into host cells and the cells cultured to produce recombinant PLTP and PLTP polypeptides. PLTP and PLTP polypeptides may be combined with a pharmaceutically acceptable vehicle and administered to patients to regulate phospholipid transfer activity and thereby obtain a more favorable lipoprotein profile in the blood. The proteins and polypeptides may also be used within methods to measure phospholipid transfer activity or identify inhibitors of phospholipid transfer activity.
Type:
Grant
Filed:
December 30, 1993
Date of Patent:
April 22, 1997
Assignees:
Zymogenetics, Inc., University of Washington
Inventors:
Joseph R. Day, John J. Albers, Catherine E. Lofton-Day, Janet L. Adolphson
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:
December 30, 1994
Date of Patent:
April 15, 1997
Assignees:
ZymoGenetics, Inc., University of Washington
Inventors:
Charles E. Hart, Richard D. Kenagy, Alexander W. Clowes
Abstract: Methods for inhibiting intimal hyperplasia in the vasculature of mammals, including primates, are disclosed. The methods comprise administering to the mammal an effective amount of Brefeldin A or a derivative of Brefeldin A. 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 non-peptide PDGF antagonists Brefeldin A and its derivatives may optionally be administered coordinately with heparin, whereby the coordinately administered of non-peptide PDGF antagonist and heparin are combinatorially effective in inhibiting intimal hyperplasia.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
April 8, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Charles E. Hart, Oliver J. McConnell, Robert R. West, Theresa Martinez
Abstract: Isolated DNA molecules that encode a novel PDGF receptor are disclosed. The receptor binds the AA, AB and BB isoforms of PDGF with high affinity. Cells transfected or transformed with the DNA molecules are also disclosed. The cells can be used within methods for detecting PDGF agonist or antagonist activity in a test compound.
Abstract: Highly purified factor XIII and methods of purifying factor XIII are disclosed. Factor XIII is purified from a biological fluid, such as a cell lysate. The methods provide factor XIII compositions that are greater than 99% pure with respect to contaminating proteins. The methods further provide factor XIII compositions wherein 1% or less of the factor XIII is activated factor XIII.
Type:
Grant
Filed:
November 2, 1994
Date of Patent:
March 18, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Paul D. Bishop, Gerald W. Lasser, Mads Laustsen, Jin-Jyi Chang
Abstract: Isolated polynucleotide molecules encoding mammalian phospholipid transfer proteins (PLTP) and phospholipid transfer protein polypeptides are disclosed. The DNA molecules are transformed or transfected into host cells and the cells cultured to produce recombinant PLTP and PLTP polypeptides. PLTP and PLTP polypeptides may be combined with a pharmaceutically acceptable vehicle and administered to patients to regulate phospholipid transfer activity and thereby obtain a more favorable lipoprotein profile in the blood. The proteins and polypeptides may also be used within methods to measure phospholipid transfer activity or identify inhibitors of phospholipid transfer activity.
Type:
Grant
Filed:
June 5, 1995
Date of Patent:
March 11, 1997
Assignee:
ZymoGenetics, Inc.
Inventors:
Joseph R. Day, John J. Albers, Catherine E. Lofton-Day, Janet L. Adolphson
Abstract: Blood loss in a patient undergoing surgery, particularly thoracic or abdominal surgery, is reduced by administration of factor XIII. The factor XIII may be administered in combination with aprotinin.
Abstract: Methods and pharmaceutical compositions for use in inhibiting calmodulin activity in a patient are disclosed. 2,3-diaryl-1-benzopyrans and their pharmaceutically acceptable salts are formulated into medicaments, including oral and topical medicaments, which are administered to a patient in need of treatment of a non-estrogen dependent condition.
Abstract: Cytopasmic Antiproteinase-2 and Cytoplasmic Antiproteinase-3 nucleic acids and serine protease inhibitor proteins encoded thereby are useful in the purification of proteins and in the treatment of inflammatory diseases and diseases involving apoptosis.
Abstract: Methods are disclosed for producing hybrid G protein-coupled receptors. DNA sequences encoding hybrid G protein-coupled receptors are provided, wherein the receptors comprise mammalian G protein-coupled receptors having at least one domain other than the ligand-binding domain replaced with a corresponding domain of a yeast G protein-coupled receptor. DNA constructs comprising the following operatively linked elements: a transcriptional promoter, a DNA sequence encoding a hybrid G protein-coupled receptor, wherein the receptor comprises a mammalian G protein-coupled receptor having at least one domain other than the ligand-binding domain replaced with a corresponding domain of a yeast G protein-coupled receptor, and a transcriptional terminator. Host cells transformed with the DNA constructs and methods utilizing the transformed cells are also provided.
Type:
Grant
Filed:
February 7, 1994
Date of Patent:
November 19, 1996
Assignee:
ZymoGenetics, Inc.
Inventors:
Andrzej Z. Sledziewski, Paul O. Sheppard