Patents Represented by Attorney, Agent or Law Firm Douglas K. Norman
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Patent number: 5858704Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: June 2, 1995Date of Patent: January 12, 1999Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5770397Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: June 2, 1995Date of Patent: June 23, 1998Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5681932Abstract: The present invention is a method of using the BK enhances in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: June 2, 1995Date of Patent: October 28, 1997Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5661002Abstract: The present invention is a modified transcription control unit which contains the P2 enhancer of BK virus spaced closely to the upstream regulatory element of the major late promoter of adenovirus, the adenovirus-2 major late promoter, a poly-GT element positioned to stimulate said promoter and a DNA sequence containing the spliced tripartite leader sequence of adenovirus. The invention further comprises methods of using this modified transcription unit in cells expressing the adenovirus E1A gene product to produce useful substances. The invention further comprises methods to increase the levels of expression in stably transformed cells by performing a second transformation with a vector containing the modified transcription unit.Type: GrantFiled: May 19, 1995Date of Patent: August 26, 1997Assignee: Eli Lilly and CompanyInventors: David T. Berg, Brian W. Grinnell
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Patent number: 5618714Abstract: The present invention relates to a method for producing high levels of functional recombinant proteins in adenovirus-transformed mammalian cells by incubating cells capable of producing recombinant proteins at a temperature range between about 38 degrees centigrade and about 39 degrees centigrade. The method allows for higher levels of expression of total protein in some cell lines and higher levels of functional protein in other cell lines.Type: GrantFiled: December 15, 1993Date of Patent: April 8, 1997Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5597726Abstract: The present invention relates to a naturally occurring, minimally modified LDL antigen which is present in human atherosclerotic lesions as well as in the serum of a high percentage of patients with coronary artery disease. The invention also comprises antibodies reactive with the antigen, hybridoma cell lines that produce the antibodies of the invention, and methods for using the antibodies in the diagnosis and treatment of atherosclerotic disease.Type: GrantFiled: March 30, 1995Date of Patent: January 28, 1997Assignee: Eli Lilly and CompanyInventors: Thomas F. Bumol, Leslie M. McEvoy
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Patent number: 5580774Abstract: The present invention discloses novel chimeric monoclonal antibodies, directed against proteoglycans of human melanoma cells, having antigen-specific variable regions of defined amino acid sequences. DNA constructs for the light and heavy chain variable regions comprising the novel antibodies of the invention are provided. Eukaryotic host cells capable of expression of the chimeric antibodies and comprising the novel chimeric antibody-encoding DNA constructs are also provided.Type: GrantFiled: July 31, 1989Date of Patent: December 3, 1996Assignee: Eli Lilly and CompanyInventors: Lisa S. Beavers, Thomas F. Bumol, Robert A. Gadski
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Patent number: 5578465Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: June 2, 1995Date of Patent: November 26, 1996Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5573938Abstract: The present invention is a modified transcription control unit which contains the P2 enhancer of BK virus spaced closely to the upstream regulatory element of the major late promoter of adenovirus, the adenovirus-2 major late promoter, a poly-GT element positioned to stimulate said promoter and a DNA sequence containing the spliced tripartite leader sequence of adenovirus. The invention further comprises methods of using this modified transcription unit in cells expressing the adenovirus E1A gene product to produce useful substances. The invention further comprises methods to increase the levels of expression in stably transformed cells by performing a second transformation with a vector containing the modified transcription unit.Type: GrantFiled: December 1, 1993Date of Patent: November 12, 1996Assignee: Eli Lilly and CompanyInventors: David T. Berg, Brian W. Grinnell
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Patent number: 5565349Abstract: A dipeptidylaminopeptidase (dDAP enzyme) and a method for isolating it from the culture medium of the cellular slime mold, Dictyostelium discoideum have been presented. The isolated dDAP enzyme has a pH optimum of about 3.5 and a mass of about 225 kDA. The dDAP enzyme has an activity which is somewhat similar to both DAP-I and DAP-III from this organism. Methods for using the dDAP enzyme to remove dipeptides from the N-terminus of recombinantly produced precursor proteins or peptides are also presented.Type: GrantFiled: September 7, 1994Date of Patent: October 15, 1996Assignee: Eli Lilly and CompanyInventors: Paul R. Atkinson, Matthew D. Hilton, Peter K. Lambooy
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Patent number: 5565330Abstract: A method for removing dipeptides from the amino terminus of precursor polypeptides to produce a polypeptide product is presented which comprises contacting the precursor polypeptide for sufficient time to remove the dipeptide with a dipeptidylaminopeptidase (dDAP) from the slime mold, Dictyostelium descoideum, which has a mass of about 225 kilodaltons and a pH optimum of about 3.5. The precursor polypeptides may be made recombinantly and may be analogs of naturally occurring polypeptides.Type: GrantFiled: May 19, 1995Date of Patent: October 15, 1996Assignee: Eli Lilly and CompanyInventors: Paul R. Atkinson, Matthew D. Hilton, Peter K. Lambooy
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Patent number: 5559094Abstract: Analogs of human insulin containing an aspartic acid at position 1 of the B chain (Asp.sup.B1), and optionally, having a gln modification at position 13 (Gln.sup.B13), display modified physico-chemical and pharmacokinetic properties which enable them to be long acting. These analogs are useful in the treatment of hyperglycemia because they are soluble and display an increased tendency to self-associate.Type: GrantFiled: August 2, 1994Date of Patent: September 24, 1996Assignee: Eli Lilly and CompanyInventors: David N. Brems, Diane L. Bakaysa
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Patent number: 5550036Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: March 9, 1994Date of Patent: August 27, 1996Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: 5534488Abstract: The present invention is directed to an insulin formulation comprising a suspension of Ultralente crystals and a total formulation zinc concentration of between about 0.5 milligrams to about 20 milligrams per 100 units of insulin. Greater than fifty percent of the total zinc in the formulation resides in the soluble fraction, rather than in complex with the insulin. This insulin formulation generally has a pH from between about 6.0 to about 7.4. In addition, the insulin formulation of the present invention does not contain other proteins like protamine. This zinc-modified formulation displays characteristics of a very long lasting human insulin product.Type: GrantFiled: August 13, 1993Date of Patent: July 9, 1996Assignee: Eli Lilly and CompanyInventor: James A. Hoffmann
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Patent number: 5506118Abstract: The present invention is a method of using a poly-GT element with a eukaryotic promoter in the presence of an immediate-early gene product of a large DNA virus to increase transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. A novel enhancer system is described comprising a cis-acting poly-GT element and a trans-acting E1A gene product, whereby the poly-GT element does not itself possess enhancer activity with certain eukaryotic promoters but rather requires the E1A gene product for enhancer activity. The present invention further comprises a number of useful expression vectors that comprise a poly-GT element with a BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, tissue plasminogen activator, a modified tissue plasminogen activator, or an interferon.Type: GrantFiled: August 23, 1993Date of Patent: April 9, 1996Assignee: Eli Lilly and CompanyInventors: David T. Berg, Brian W. Grinnell
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Patent number: 5460953Abstract: A method for the recombinant production of forms of human protein C with higher activity is described. These forms differ from native protein C in their increased amidolytic and functional activities and novel carbohydrate structures. DNA compounds, vectors, and transformants useful in the method are also disclosed.Type: GrantFiled: September 9, 1993Date of Patent: October 24, 1995Assignee: Eli Lilly and CompanyInventors: Bruce E. Gerlitz, Brian W. Grinnell
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Patent number: 5453373Abstract: Human protein C derivatives with high activity and reduced dependence on thrombin activation are described. These derivatives differ from the native forms of human protein C in their increased activation rates, functional activities and carbohydrate structures. DNA compounds, transfer vectors, expression vectors and transformants useful in producing these derivatives are also described.Type: GrantFiled: July 9, 1993Date of Patent: September 26, 1995Assignee: Eli Lilly and CompanyInventors: Bruce E. Gerlitz, Brian W. Grinnell
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Patent number: 5382527Abstract: A novel method for isolating transposable elements was used to isolate an approximately 1.6 kb insertion sequence from Streptomyces. The method entails transforming a cell with a plasmid containing a repressor gene, so that the introduction of a transposable element into the gene allows the expression of a selectable marker in a second host cell. The novel insertion sequence isolated from Streptomyces lividans CT2 has been designated IS493.Type: GrantFiled: October 18, 1993Date of Patent: January 17, 1995Assignee: Eli Lilly and CompanyInventor: Patricia J. Solenberg
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Patent number: RE37720Abstract: The present invention is a method of using the BK enhancer in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: August 26, 1999Date of Patent: May 28, 2002Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell
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Patent number: RE37806Abstract: The present invention is a method of using the BK enhances in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene produce for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.Type: GrantFiled: August 26, 1999Date of Patent: July 23, 2002Assignee: Eli Lilly and CompanyInventor: Brian W. Grinnell