Patents Represented by Attorney James A. Giblin
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Patent number: 6214975Abstract: A chemiluminescence-based gel assay may be used as an indicator of fermenter health. The assay is performed using a sample of fermentation medium essentially directly from the fermenter (with no need for complicated purification of the sample before performing the assay). Results from the assay may be correlated with the final product purification yield of a given protein/purification protocol system. This may then be used as a predictor of purification yield before actually performing the purification.Type: GrantFiled: December 17, 1999Date of Patent: April 10, 2001Assignee: Bayer CorporationInventors: Michael Zachariou, Jonathan Mazer, Hyun J. Park, Charles Olson
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Patent number: 6191256Abstract: Peptides that have domains that bind to recombinant factor VIII (rFVIII) are disclosed. A method of rFVIII binding assay using the peptides deduced from a combinatorial library in a filtration plate process is described. A method of using peptides having these available binding domains in an affinity chromatography process to purify factor VIII is also taught.Type: GrantFiled: November 20, 1998Date of Patent: February 20, 2001Assignee: Bayer CorporationInventors: Li Ang Chen, Joseph A. Buettner, Ruben G. Carbonell
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Patent number: 6171825Abstract: Recombinant Factor VIII can be produced in relatively large quantities on a continuous basis from mammalian cells in the absence of any animal-derived proteins such as albumin by culturing the cells in a protein free medium supplemented with polyol copolymers, preferably in the presence of trace metals such as copper. In very preferred embodiments, the medium includes a polyglycol known as Pluronic F-68, copper sulfate, ferrous sulfate/EDTA complex, and salts of trace metals such as manganese, molybdenum, silicon, lithium and chromium. With an alternative medium which included trace copper ions alone (without polyol copolymers) we were also able to enhance the productivity of Factor VIII in recombinant cells such as BHK cells that are genetically engineered to express Factor VIII.Type: GrantFiled: September 4, 1998Date of Patent: January 9, 2001Assignee: Bayer CorporationInventors: Sham-Yuen Chan, Kathleen Harris
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Patent number: 6136599Abstract: Human/human hybrid cells were made via fusion of human embryonic kidney cells (293S) and modified Burkitt's lymphoma cells (2B8). The fusion cells are useful as host cells for the recombinant expression of mammalian genes. The advantages of using these hybrid clones of human kidney- and B-cells, called HKBs, for mammalian gene expression, include (i) the cells are negative for immunoglobulin expression, (ii) the cells grow easily in plasma protein-free medium (with or without the addition of recombinant insulin) as suspension cultures in a shake flask or in a fermenter (iii) the cells are very susceptible for transfection of DNA, and (iv) the cells secrete high levels of heterologous recombinant proteins, such as recombinant monoclonal antibodies, soluble ICAM-1, rIL-4, and rFVIII.Type: GrantFiled: December 10, 1998Date of Patent: October 24, 2000Assignee: Bayer CorporationInventor: Myung-Sam Cho
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Patent number: 6121422Abstract: A method and device for activating and applying a solution of fibrinogen to form fibrin glue at a desired site. The method includes contacting the solution of fibrinogen with immobilized thrombin under conditions that result in a solution of polymerizable fibrin and delivering the activated solution to the desired site. The device includes a housing having a compartment for a solution of fibrinogen, a container for immobilized thrombin, a structure following the solution of fibrinogen to be brought into contact with the immobilized thrombin under conditions which permit the activation of the fibrinogen to polymerizable fibrin, and a structure allowing for delivery of the activated solution to the desired site.Type: GrantFiled: November 25, 1998Date of Patent: September 19, 2000Assignee: Bayer CorporationInventors: Thomas P. Zimmerman, Christopher A. Dadd, George A. Baumbach
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Patent number: 5985836Abstract: Peptides which bind to alpha-1 Proteinase inhibitor (AlPI) are disclosed. The peptides have an available AlPI binding domain which may be any of the following preferred sequences: Val Ile Trp Leu Val Arg, Ile Ile Trp Leu Tyr Lys, Arg Tyr Arg Ile Phe Ile, Arg Ala Phe Trp Tyr Ile, Arg Phe Ile Tyr Tyr Thr, Tyr Lys Phe Arg Phe Trp, Leu Ile Val His Arg Trp, Pro Tyr Trp Ile Val Arg, Ala Arg Trp Tyr Ile His, Gln Tyr His Phe Trp Tyr, Arg Leu Trp Arg Tyr Gly, Val Ile Tyr Leu Val Arg, Val Ile Phe Leu Val Arg, Lys Ile Phe Leu Val Arg, Arg Ile Phe Leu Val Arg, His Ile Phe Leu Val Arg, Arg Val Leu Phe Ile Val, or Arg Val Leu Phe Ile His (SEQ ID NOS: 1-8, 10, 11, 15, 36, 37, 45, 46, 47, 61, and 62 respectively). A method of using peptides having these available binding domains in an affinity chromatography process to purify AlPI is described.Type: GrantFiled: July 31, 1998Date of Patent: November 16, 1999Assignee: Bayer CorporationInventors: Patrick D. Bastek, John M. Lang, George A. Baumbach, Ruben G. Carbonell
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Patent number: 5972632Abstract: Immunoassays for complement components, complement activation products or, preferably both, can be used to determine an acceptable level of anticomplement activity (AC) in plasma derived biologically active products intended for infusion into a mammal. In one application an ELISA for complement components (CC) such as C1q, C1r or C1s can be used to determine AC in an IgM-enriched immune serum globulin (ISG). In another application, an immunoassay for complement activation products (CAP) is used for a similar determination. In yet a preferred third application, assays for both a CC (such as measuring a decreasing amount of C1r) and a CAP (such as measuring an increasing amount of C4a) are used to assess the relative AC (and safety) of a biologically active, therapeutic preparation.Type: GrantFiled: April 22, 1991Date of Patent: October 26, 1999Assignee: Bayer CorporationInventors: Grace C. Tsay, Neal Cheung
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Patent number: 5952198Abstract: Recombinant Factor VIII expression in a mammalian cell culture can be increased by including a novel liposome-like substance in the culture medium. The liposome-like substance comprises at least two (preferably at least three) different lipids in defined molar ratios. In a preferred embodiment, the addition of a liposome-like substance comprised of dioleoyl phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine in a molar ratio of 4:1:1 to the culture medium of GS-MDR cells resulted in an increase in FVIII production by a factor greater than five.Type: GrantFiled: April 17, 1996Date of Patent: September 14, 1999Assignee: Bayer CorporationInventor: Sham-Yuen Chan
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Patent number: 5911165Abstract: An improved method and device for measuring the mechanical properties of fibrin clots. A mixture of fibrinogen and thrombin is formed between two synthetic polymeric substrate materials and allowed to form a fibrin clot. The force required to separate the substrate materials is then measured and indicates the strength of the clot.Type: GrantFiled: May 29, 1997Date of Patent: June 8, 1999Assignee: Bayer CorporationInventors: John W. Guo, Rajiv Nayar
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Patent number: 5886154Abstract: An improved process for the purification of antibodies from human plasma or other sources is disclosed. The process involves suspension of the antibodies at pH 3.8 to 4.5 followed by addition of caprylic acid and a pH shift to pH 5.0 to 5.2. A precipitate of contaminating proteins, lipids and caprylate forms and is removed, while the majority of the antibodies remain in solution. Sodium caprylate is again added to a final concentration of not less than about 15 mM. This solution is incubated for 1 hour at 25.degree. C. to effect viral inactivation. A precipitate (mainly caprylate) is removed and the clear solution is diluted with purified water to reduce ionic strength. Anion exchange chromatography using two different resins is utilized to obtain an exceptionally pure IgG with subclass distribution similar to the starting distribution. The method maximizes yield and produces a gamma globulin with greater than 99% purity.Type: GrantFiled: June 20, 1997Date of Patent: March 23, 1999Inventors: Wytold R. Lebing, Patricia Alred, Doug C. Lee, Hanns-Ingolf Paul
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Patent number: 5874408Abstract: A stable albumin-free Recombinant Factor VIII (rFVIII) formulation in lyophilized form having both crystalline and amorphous components and comprising, when reconstituted with water, about 65 to 400 mM glycine, up to 50 mM histidine, 15 to 60 mM sucrose, up to 50 mM NaCl (up to 100 mM NaCl if cake appearance not critical), up to 5 mM CaCl.sub.2 and 50 to 1500 lU/ml of rFVIII. A very preferred formulation comprises upon reconstitution with water about 290 mM glycine, 20 mM histidine, 30 mM sucrose, 30 mM NaCl, 2.5 mM CaCl.sub.2 and 50 to 1500 lU/ml of rFVIII. The residual water content of the lyophilized preparation is about 1 to 3% by weight, preferably about 1% by weight.Type: GrantFiled: May 28, 1998Date of Patent: February 23, 1999Assignee: Bayer CorporationInventor: Rajiv Nayar
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Patent number: 5854021Abstract: An expression vector comprising a promoter, a coding sequence of a heterologous protein, the coding sequence being operably linked to the promoter, and an intronic sequence downstream of the promoter and upstream of the coding sequence, the intronic sequence comprising two identical donor sites and one acceptor site.Type: GrantFiled: February 28, 1997Date of Patent: December 29, 1998Assignee: Bayer CorporationInventors: Myung-Sam Cho, Van-Mai Tran
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Patent number: 5844087Abstract: A method and device for activating and applying a solution of fibrinogen to a desired site. The method includes contacting the solution of fibrinogen with immobilized thrombin resulting in an activated solution of polymerizable fibrin, and delivering the activated solution to the desired site. The device includes a housing having a compartment for a solution of fibrinogen, immobilized thrombin, a structure for bringing the solution of fibrinogen in contact with the immobilized thrombin under conditions which permit the activation of the fibrinogen resulting in polymerizable fibrin, and a structure for delivery of the activated solution to the desired site.Type: GrantFiled: November 5, 1996Date of Patent: December 1, 1998Assignee: Bayer CorporationInventors: Thomas P. Zimmerman, Christopher A. Dadd, George A. Baumbach
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Patent number: 5837519Abstract: A method of rendering a biologically active protein composition substantially free of viruses is disclosed. The method includes the steps of preparing lyophilized samples of the protein composition having a given moisture content, determining a minimum or threshold moisture content which, when the composition is heated to pasteurizing conditions will result in at least a 3.2 log.sub.10 reduction in virus titer, and then heating the sample under pasteurizing conditions that will result in at least a 3.2 log.sub.10 reduction in virus titer while maintaining biological activity of the protein.Type: GrantFiled: November 21, 1996Date of Patent: November 17, 1998Assignee: Bayer CorporationInventors: Margaret Savage, Juan Torres
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Patent number: 5834318Abstract: Ligands that interact with a target can be more easily identified if false positive interactions (either specific or non-specific) from the detecting system are differentiated from the target-specific interaction. An improved method of identifying peptides which bind with a target protein is presented. The steps are: binding a random library of peptides to a support material, allowing detection reagents to contact the peptides and the support material then identifying these interactions, then allowing the target protein to selectively bind to the peptides, allowing detection reagents to contact the bound target protein, and characterizing the peptide bound to the identified support material. Interaction of a ligand or the support material with the detection reagents will cause a distinct color change which distinguishes those ligands which selectively bind to target protein. The characterized peptide can then be used in affinity purification of the target protein.Type: GrantFiled: May 10, 1995Date of Patent: November 10, 1998Assignee: Bayer CorporationInventor: Joseph A. Buettner
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Patent number: 5831003Abstract: Peptide ligands which bind to thrombin and prothrombin are disclosed. The sequences of these peptides are Gln-Leu-Trp-Gly-Ser-His, Arg-Gln-Leu-Trp-Gly-Ser-His, His-Gln-Leu-Trp-Gly-Ser-His, and Tyr-Phe-Pro-Gly-Pro-Tyr-Leu. The preferred peptides have the sequence Gln-Leu-Trp-Gly-Ser-His or Tyr-Phe-Pro-Gly-Pro-Tyr-Leu. A method of using these peptides in an affinity chromatography process to purify thrombin is described.Type: GrantFiled: June 28, 1996Date of Patent: November 3, 1998Assignee: Bayer CorporationInventors: George A. Baumbach, Christopher A. Dadd, Joseph A. Buettner, David J. Hammond
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Patent number: 5804420Abstract: Recombinant Factor VIII can be produced in relatively large quantities on a continuous basis from mammalian cells in the absence of any animal-derived proteins such as albumin by culturing the cells in a protein free medium supplemented with polyol copolymers, preferably in the presence of trace metals such as copper. In very preferred embodiments, the medium includes a polyglycol known as Pluronic F-68, copper sulfate, ferrous sulfate/EDTA complex, and salts of trace metals such as manganese, molybdenum, silicon, lithium and chromium.Type: GrantFiled: April 18, 1997Date of Patent: September 8, 1998Assignee: Bayer CorporationInventors: Sham-Yuen Chan, Kathleen Harris
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Patent number: 5786458Abstract: A process for viral inactivation of a solution containing a biologically active protein, wherein the process comprises the steps of 1) contacting the solution with an immobilized ligand under conditions which allow protein to bind to the ligand, 2) subjecting the bound protein to a viral inactivation method under conditions which would result in substantial denaturation of the protein if it were not bound to the ligand, and 3) recovering the protein by washing the immobilized protein under conditions which favor the release of the protein into the solution under conditions in which the recovered protein retains its biological activity.Type: GrantFiled: June 28, 1996Date of Patent: July 28, 1998Assignee: Bayer CorporationInventors: George A. Baumbach, David J. Hammond, John M. Lang, Cynthia J. Galloway
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Patent number: 5783663Abstract: Peptides which bind to fibrinogen are disclosed. These peptides have available fibrinogen binding domains having a Trp-Gln-Glu-His-Tyr-Asn, Trp-Gln-Glu-Thr-TyrGln,or Tyr-Glu-Asn-Tyr-Gly-Tyr sequence. Peptides containing at least one of these fibrinogen binding domains are immobilized upon a chromatographic substrate in a preferred embodiment of the invention. This preferred embodiment is useful in an affinity chromatography process to purify fibrinogen.Type: GrantFiled: January 23, 1998Date of Patent: July 21, 1998Assignee: Bayer CorporationInventors: Kristine Mondorf, Ruben C. Carbonell, Joseph A. Buettner
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Patent number: RE36259Abstract: A composition is disclosed which comprises a solution of human serum albumin essentially free of chemicals used in processing. The preparation is also essentially free of metals such as aluminum. The composition is 100% pure by cellulose acetate electrophoresis and is essentially monomeric when tested by high pressure liquid chromatography. The turbidity is less than 5 N.T.U. (National Turbidity Units). This preparation has a substantially longer shelf life and remains biologically active longer than products currently available. The novelty of this product is also such that it does not leach metallic substances such as aluminum from its closure. Novel applications of process methodology are taught in the preparation of this composition and a novel preparation results from essentially non hemoglobin containing albumin sources such as Source Plasma (Human).Type: GrantFiled: July 18, 1994Date of Patent: July 27, 1999Assignee: Bayer CorporationInventor: Robert A. Tenold