Patents Assigned to Bionebraska, Inc.
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Patent number: 6461834Abstract: The invention provides a method of producing a polypeptide having a C-terminal &agr;-carboxamide group. It particularly concerns an enzymatic modification of selected substrate polypeptides which result in cleavage of the substrate polypeptide to form a product peptide with a C-terminal arginine residue having an &agr;-carboxamide group (C-terminal “Arg-NH2”). The method includes contacting an aqueous-based solution including (i) ammonia reagent and (ii) the substrate polypeptide with (iii) clostripain.Type: GrantFiled: December 16, 1998Date of Patent: October 8, 2002Assignee: Bionebraska, Inc.Inventors: Dan Dormady, Jay S. Stout, Daniel J. Strydom, Barton Holmquist, Fred W. Wagner
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Patent number: 6429197Abstract: It has now been discovered that GLP-1 treatment after acute stroke or hemorrhage, preferably intravenous administration, can be an ideal treatment because it provides a means for optimizing insulin secretion, increasing brain anabolism, enhancing insulin effectiveness by suppressing glucagon, and maintaining euglycemia or mild hypoglycemia with no risk of severe hypoglycemia.Type: GrantFiled: April 30, 1999Date of Patent: August 6, 2002Assignee: Bionebraska, Inc.Inventors: Thomas R. Coolidge, Mario R. W. Ehlers
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Publication number: 20020081735Abstract: The present invention provides novel promoter sequences obtained from Chlorella virus. The invention includes gene constructs comprising a promoter sequence of the invention operably linked to a DNA sequence encoding a structural gene. The invention also provides vectors and host cells for expressing product encoded by the structural gene of a gene construct of the invention amd cells transformed with the heterologous gene operably linked to the promoter.Type: ApplicationFiled: July 9, 2001Publication date: June 27, 2002Applicant: BioNebraska, Inc.Inventor: Yuannan Xia
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Patent number: 6410707Abstract: A process for the recombinant preparation of a calcitonin fragment and the use of the fragment in the preparation of calcitonin and related analogs is provided. The process includes recombinantly forming a fusion protein which includes the calcitonin fragment linked to a carbonic anhydrase. The recombinantly formed fusion protein is subsequently cleaved to produce a polypeptide which includes the calcitonin fragment. A method for producing a calcitonin carba analog which includes condensing a desaminononapeptide with the recombinantly formed calcitonin fragment is also provided.Type: GrantFiled: January 2, 2001Date of Patent: June 25, 2002Assignee: BioNebraska, Inc.Inventors: Fred W. Wagner, Jay S. Stout, Dennis B. Henriksen, Bruce E. Partridge, Bart Holmquist, Julie A. Frank
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Patent number: 6344180Abstract: Since glucagon-like peptide-1 (GLP-1) is the most potent insulinotropic hormone known and has been shown to stimulate insulin secretion strongly in patients with type II diabetes, this invention uses GLP-1 or its biologically active analogues in &bgr;-cell stimulatory tests in order to test &bgr;-cell function in a simple way. The test provides information about insulin secretory capacity, is easy and reproducible and has insignificant side effects.Type: GrantFiled: June 15, 1999Date of Patent: February 5, 2002Assignee: BioNebraska, Inc.Inventors: J. J. Holst, Tina Vilsboll
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Patent number: 6316224Abstract: The present invention provides novel promoter sequences obtained from Chlorella virus. The invention includes gene constructs comprising a promoter sequence of the invention operably linked to a DNA sequence encoding a structural gene. The invention also provides vectors and host cells for expressing product encoded by the structural gene of a gene construct of the invention amd cells transformed with the heterologous gene operably linked to the promoter.Type: GrantFiled: September 21, 1999Date of Patent: November 13, 2001Assignee: Bionebraska, Inc.Inventor: Yuannan Xia
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Patent number: 6284725Abstract: Individuals in need of treatment of ischemia-related reperfusion are treated, preferably intravenously, with a composition which includes a compound which binds to a receptor for the glucagon-like peptide-1. The invention relates to both the method and compositions for such treatment.Type: GrantFiled: April 30, 1999Date of Patent: September 4, 2001Assignee: BioNebraska, Inc.Inventors: Thomas R. Coolidge, Mario R. W. Ehlers
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Patent number: 6251635Abstract: A process for the recombinant preparation of a calcitonin fragment and the use of the fragment in the preparation of calcitonin and related analogs is provided. The process includes recombinantly forming a fusion protein which includes the calcitonin fragment linked to a carbonic anhydrase. The recombinantly formed fusion protein is subsequently cleaved to produce a polypeptide which includes the calcitonin fragment. A method for producing a calcitonin carba analog which includes condensing a desaminononapeptide with the recombinantly formed calcitonin fragment is also provided.Type: GrantFiled: August 25, 1998Date of Patent: June 26, 2001Assignee: Bionebraska, Inc.Inventors: Fred W. Wagner, Jay S. Stout, Dennis B. Henriksen, Bruce E. Partridge, Bart Holmquist, Julie A. Frank
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Patent number: 6127150Abstract: The present invention is directed to a protein purification construct having three tandem, coupled segments composed of a binding protein, an interconnecting linker and a variable fused polypeptide which incorporates the one or more copies of a product peptide. The binding protein is a mammalian or human carbonic anhydrase, or a modified version of the carbonic anhydrase. The protein purification construct may be employed in methods for expression of the product peptide in microbial and higher organism and for ligand immobilized affinity purification of the product peptide.Type: GrantFiled: September 5, 1997Date of Patent: October 3, 2000Assignee: BioNebraska, Inc.Inventors: Thomas R. Coolidge, Fred Wagner, Gino van Heeke, Sheldon M. Schuster, Jay Stout, Dwane E. Wylie
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Patent number: 6111079Abstract: Metal binding polypeptides which include an amino acid sequence coding for a light chain variable region of a monoclonal antibody capable of immunoreacting with a lead cation and nucleotides which include a nucleic acid sequence coding for the variable region are provided. The invention is also directed to fusion proteins and Fab fragments which include the light chain variable region.Type: GrantFiled: December 4, 1996Date of Patent: August 29, 2000Assignee: Bionebraska, Inc.Inventors: Dwane E. Wylie, Osvaldo Lopez, Peter Joseph Murray, Peter Goebel
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Patent number: 6051399Abstract: A method for the production of C-terminal amidated recombinant peptides is provided. The method employs a recombinant protein construct having multiple copies of a target peptide linked by intraconnecting peptides. The intraconnecting peptides permit the multicopy construct to be selectively reacted to produce product peptides having a C-terminal .alpha.-carboxamide. A recombinant gene containing a DNA sequence coding for the recombinant protein construct and an expression cassette, an expression vector and a transformed cell including the recombinant gene are also provided.Type: GrantFiled: September 19, 1997Date of Patent: April 18, 2000Assignee: BioNebraska, Inc.Inventors: Jay S. Stout, Bruce E. Partridge, Dennis B. Henriksen, Barton Holmquist, Fred W. Wagner
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Patent number: 6037143Abstract: The method of the invention provides for the formation of a recombinant polypeptide which has been modified at the C-terminal end through the use of a transpeptidation process. The method is suitable for modifying recombinant polypeptides of any source including those which may be commercially available, those derived from recombinant single copy or multicopy polypeptide constructs, or those derived from single or multicopy recombinant fusion protein constructs. The transpeptidation reaction involves contacting an endopeptidase enzyme with a recombinant polypeptide to substitute an addition unit, of one or more amino acids, for a leaving unit, linked to a core polypeptide through a cleavage site recognized by the endopeptidase enzyme. Recombinant polypeptides derived from multicopy polypeptide constructs may be cleaved from the multicopy polypeptide at the N-terminal and C-terminal ends and simultaneously under go substitution of the leaving unit by the desired addition unit.Type: GrantFiled: November 7, 1997Date of Patent: March 14, 2000Assignee: BioNebraska, Inc.Inventors: Fred W. Wagner, Jay Stout, Dennis Henriksen, Bruce Partridge, Shane Manning
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Patent number: 5972656Abstract: Metal binding polypeptides which include an amino acid sequence coding for a variable region of a monoclonal antibody which immunoreacts with a mercury cation and nucleotides which include a nucleic acid sequence coding for the variable region are provided. The invention is also directed to fusion proteins which include a phage coat protein or portion thereof and the monoclonal antibody heavy chain variable region. The invention also provides bacteriophages which include the fusion protein in their coat. In addition, methods for detecting, removing, adding, or neutralizing mercuric cations in biological or inanimate systems through the use of the mercury binding polypeptides are provided.Type: GrantFiled: July 3, 1997Date of Patent: October 26, 1999Assignee: BioNebraska, Inc.Inventors: Osvaldo Lopez, Dwane E. Wylie, Fred W. Wagner
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Patent number: 5962270Abstract: A process for the recombinant preparation of a calcitonin fragment and the use of the fragment in the preparation of calcitonin and related analogs is provided. The process includes recombinantly forming a fusion protein which includes the calcitonin fragment linked to a carbonic anhydrase. The recombinantly formed fusion protein is subsequently cleaved to produce a polypeptide which includes the calcitonin fragment. A method for producing a calcitonin carba analog which includes condensing a desaminononapeptide with the recombinantly formed calcitonin fragment is also provided.Type: GrantFiled: February 6, 1996Date of Patent: October 5, 1999Assignee: Bionebraska, Inc.Inventors: Fred W. Wagner, Jay S. Stout, Dennis B. Henriksen, Bruce E. Partridge, Bart Holmquist, Julie A. Frank
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Patent number: 5846774Abstract: The present invention provides novel promoter sequences obtained from Chlorella virus. The invention includes gene constructs comprising a promoter sequence of the invention operably linked to a DNA sequence encoding a structural gene. The invention also provides vectors and host cells for expressing a product encoded by the structural gene of a gene construct of the invention and cells transformed with the heterologous gene operably linked to the promoter.Type: GrantFiled: March 21, 1997Date of Patent: December 8, 1998Assignee: BioNebraska, Inc.Inventor: Yuannan Xia
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Patent number: 5656456Abstract: The invention provides for a chemical method for preparing a recombinant single copy polypeptide or a portion thereof with a modified terminal amino acid .alpha.-carbon reactive group selected from the group consisting of N-terminal .alpha.-amine, C-terminal .alpha.-carboxyl, and a combination thereof. The steps of the method involve forming the recombinant single copy polypeptide or a portion thereof so that the single copy polypeptide is protected with one or more biologically added protecting groups at the N-terminal .alpha.-amine, C-terminal .alpha.-carboxyl. The recombinant single copy polypeptide can then be reacted with up to three chemical protecting agents to selectively protect reactive side chain groups and thereby prevent side chain groups from being modified. The recombinant single copy polypeptide can be cleaved with at least one cleavage reagent specific for the biological protecting group to form an unprotected terminal amino acid .alpha.-carbon reactive group.Type: GrantFiled: June 1, 1995Date of Patent: August 12, 1997Assignee: BioNebraska, Inc.Inventors: Jay Stout, Fred W. Wagner, Thomas R. Coolidge, Bart Holmquist
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Patent number: 5639624Abstract: The invention is directed to monoclonal antibodies, their fragments, single chains and polypeptide mimics of their hypervariable regions which immunoreact with bare small moieties such as metallic cations the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.Type: GrantFiled: June 27, 1994Date of Patent: June 17, 1997Assignees: Board of Regents of the University of Nebraska, BioNebraska, Inc.Inventors: Fred W. Wagner, Dwane E. Wylie, Sheldon M. Schuster
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Patent number: 5635371Abstract: The invention provides for a chemical method for preparing a recombinant single copy polypeptide or a portion thereof with a modified terminal amino acid .alpha.-carbon reactive group selected from the group consisting of N-terminal .alpha.-amine, C-terminal .alpha.-carboxyl, and a combination thereof. The steps of the method involve forming the recombinant single copy polypeptide or a portion thereof so that the single copy polypeptide is protected with one or more biologically added protecting groups at the N-terminal .alpha.-amine, C-terminal .alpha.-carboxyl. The recombinant single copy polypeptide can then be reacted with up to three chemical protecting agents to selectively protect reactive side chain groups and thereby prevent side chain groups from being modified. The recombinant single copy polypeptide can be cleaved with at least one cleavage reagent specific for the biological protecting group to form an unprotected terminal amino acid .alpha.-carbon reactive group.Type: GrantFiled: August 23, 1994Date of Patent: June 3, 1997Assignee: BioNebraska, Inc.Inventors: Jay Stout, Fred W. Wagner, Thomas R. Coolidge, Bart Holmquist
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Patent number: 5620856Abstract: The invention provides method and kits for detecting a metallic cation in a sample of a body fluid. The preferred method and kits include the use of at least two different types of antibodies having different specificities. In the preferred method, the sample of body fluid can be contacted with an effective amount of a capture antibody specific for a naturally occurring polypeptide that can bind the metallic cation to form a first antigen-antibody complex. An effective amount of an antibody specific for an epitope on a metallic cation-naturally occurring polypeptide complex or an antibody specific for a metallic cation is added to the first antigen-antibody complex to form a second antigen-antibody complex. The amount of the metallic cation in the sample of body fluid is determined by detecting the amount of the second antigen-antibody complex.Type: GrantFiled: June 6, 1995Date of Patent: April 15, 1997Assignee: BioNebraska, Inc.Inventors: Randall R. Carlson, Jay S. Stout, Dwane E. Wylie, Fred W. Wagner, Malcolm Riddell
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Patent number: 5595887Abstract: Methods are presented for producing and purifying a variable fusion polypeptide which can be purified by affinity chromatography with the binding protein partner. The variable fusion polypeptide construct has tandem coupled segments containing one or more copies of a desired peptide linked to carbonic anhydrase as the purification binding protein. In the methods, the fusion protein is expressed in a recombinant host using a recombinant vector containing a gene encoding the fusion polypeptide. Then the expressed fusion polypeptide is purified by immobilized reversible inhibitor affinity chromatography. Finally, the purified fusion polypeptide is cleaved from the desired peptides by chemical or enzymatic means and the desired peptides purified with affinity chromatography.Type: GrantFiled: July 16, 1990Date of Patent: January 21, 1997Assignee: BioNebraska, Inc.Inventors: Thomas R. Coolidge, Fred Wagner, Gino van Heeke, Sheldon M. Schuster, Jay Stout, Dwane E. Wylie