Patents Represented by Attorney James A. Giblin
  • Patent number: 5763401
    Abstract: 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 5 mM CaCl.sub.2 and 50 to 1500 IU/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 IU/ml of rFVIII. The residual water content of the lyophilized preparation is about 1 to 3% by weight, preferably about 1% by weight.
    Type: Grant
    Filed: July 12, 1996
    Date of Patent: June 9, 1998
    Assignee: Bayer Corporation
    Inventor: Rajiv Nayar
  • Patent number: 5723579
    Abstract: Peptides which bind to fibrinogen are disclosed. These peptides have available fibrinogen binding domains having a Phe-Leu-Leu-Val or Leu-Leu-Val-Pro sequence. The preferred peptide is a 6-mer having the sequence Phe-Leu-Leu-Val-Pro-Leu (SEQ ID NO:1). A method of using these peptides in an affinity chromatography process to purify fibrinogen is described.
    Type: Grant
    Filed: February 2, 1996
    Date of Patent: March 3, 1998
    Assignee: Bayer Corporation
    Inventors: Joseph A. Buettner, Christopher A. Dadd, George A. Baumbach, David J. Hammond
  • Patent number: 5688912
    Abstract: Peptide ligands which bind to von Willebrand Factor (vWF) are disclosed. These peptides are selected from the group consisting of RLHSFY, RLKSFY, RLNSFY, RLQSFY, RFRSFY, RIRSFY, RVRSFY, RYRSFY, RLRSFY, HLRSFY, and KLRSFY. The preferred peptide ligand has the sequence RVRSFY. A method of using the disclosed peptides to purify vWF comprises binding the peptides to a support, then passing a solution containing vWF over the supports under condition such that the vWF will selectively bind to the peptides, and then eluting the vWF.
    Type: Grant
    Filed: September 22, 1995
    Date of Patent: November 18, 1997
    Assignee: Bayer Corporation
    Inventors: Christopher A. Dadd, George A. Baumbach, David J. Hammond
  • Patent number: 5679549
    Abstract: 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: Grant
    Filed: May 4, 1995
    Date of Patent: October 21, 1997
    Assignee: Bayer Corporation
    Inventor: Sham-Yuen Chan
  • Patent number: 5658746
    Abstract: A method of controlling the amount of a biologically active substance binding to a cell surface having both receptors to the substance and receptors for the Fc domain of an antibody that can complex with the substance or other antibodies that can complex with the substance. By exploiting the generally more numerous Fc receptor sites, substance binding can be increased and/or controlled. Method contemplates controlling amounts of substances such as cytokines, hormones, and growth factors that are associated with cells such as monocytes, macrophages, granulocytes, B cells, T cells, and platelets. Method is illustrated using conjugated antibodies to tissue necrosis factor (TNF) to increase the binding of TNF to monocytes.
    Type: Grant
    Filed: November 3, 1995
    Date of Patent: August 19, 1997
    Assignee: Bayer Corporation
    Inventors: Michael H. Coan, Cynthia J. Galloway, Vivian W. Lee
  • Patent number: 5654407
    Abstract: Human monoclonal antibodies (mAbs) which bind to human TNF.alpha. are disclosed. Autoantibodies of both the IgM and IgG isotypes are disclosed. A preferred human monoclonal antibody is known as B5 (F78-1A10-B5 mAb) and it binds to recombinant human TNF.alpha. (rhTNF.alpha.) in ELISA format with a titer comparable to three high affinity neutralizing mouse mAbs. It also binds to cell surface TNF.alpha. and prevents TNF.alpha. secretion by human monocyte cell lines.
    Type: Grant
    Filed: May 5, 1995
    Date of Patent: August 5, 1997
    Assignee: Bayer Corporation
    Inventors: Petra Boyle, Gayle D. Wetzel, Kenneth J. Lembach
  • Patent number: 5616321
    Abstract: Bacterial meningitis infection in a mammal is treated by intravenous infusion of a therapeutically effective amount of a monoclonal antibody which binds to tumor necrosis factor alpha and an antibiotic. Treatment can be initiated up to five hours after bacterial challenge and the antibiotic is preferably selected from cephalosporins and aminoglycosides.
    Type: Grant
    Filed: March 23, 1995
    Date of Patent: April 1, 1997
    Assignee: Bayer Corporation
    Inventors: Richard F. Hector, Michael S. Collins
  • Patent number: 5612033
    Abstract: Mild heat-treatment of IgM antibody concentrates diminishes the potential to induce non-specific complement activation without significant loss of normal immunologic effector functions. These IgM immunoglobulin concentrates retain specific antigen binding properties and activate complement when bound to antigen. Preferred product includes at least 20% by weight IgM in an IgM/IgG antibody mixture. Heating is done at a temperature within the range of about 40.degree. C. to 62.degree. C., preferably about 45.degree. to 55.degree. C., in a solution having an acid pH (preferably 4.0 to 5.0) for at least about 10 minutes.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: March 18, 1997
    Assignee: Bayer Corporation
    Inventors: Grace C. Tsay, Gary Jesmok
  • Patent number: 5612213
    Abstract: A method of selecting transfected cell lines for heterologous protein expression from a population of cells some of which include an endogenous sequence for an amplificable marker and some of which do not include the sequence. The method is based on a minimum amplifiability index which, contrary to current practice, focuses cell lines having relatively low productivity prior to amplification. Transfected cell lines selected with the instant invention produce greater amounts of heterologous protein than cells selected according to the prior art. In one embodiment, the amplifiability index is used to select for further amplification a cell line transfected with a vector containing the coding sequence for human Factor VIII.
    Type: Grant
    Filed: November 3, 1994
    Date of Patent: March 18, 1997
    Assignee: Bayer Corporation
    Inventor: Sham Y. Chan
  • Patent number: 5610285
    Abstract: Cation chromatography with solutions at pH less than 6.0 and low ionic strength can be utilized to purify human .alpha.-1 proteinase inhibitor (.alpha.-1 PI) from biological fluids including plasma and plasma fractions. The cation chromatography takes advantage of the fact that active .alpha.-1 PI does not bind to the cation column under these conditions but other proteins, including denatured .alpha.-1 PI and albumin, do. The effect is that active .alpha.-1 PI flows through the chromatography column leaving the contaminating proteins behind. Recovery of .alpha.-1 PI is high and improvement of purity is dramatic.
    Type: Grant
    Filed: August 24, 1994
    Date of Patent: March 11, 1997
    Assignee: Bayer Corporation
    Inventors: Wytold R. Lebing, Sharon X. Chen
  • Patent number: 5561108
    Abstract: Human .alpha..sub.1 -antichymotrypsin (ACT) can be purified from solutions containing human .alpha..sub.1 -proteinase inhibitor (PI) and antithrombin III (AT-III) using chromatography adsorption steps at carefully controlled pH and conductivity. The separated ACT retains in vitro inhibitory capacity and has potential therapeutic use.
    Type: Grant
    Filed: July 29, 1994
    Date of Patent: October 1, 1996
    Assignee: Bayer Corporation
    Inventors: Grace C. Tsay, Neal K. H. Cheung, Jeffrey D. Bettencourt
  • Patent number: 5561115
    Abstract: Highly stable plasma-derived therapeutic albumin solutions, having a turbidity level of 5 NTU or less can be made by adding sodium caprylate to Cohn fraction II+III or IV-1 effluent at relatively low temperatures. The sodium caprylate acts as a partitioning agent to separate albumin from unwanted proteins. In preferred embodiments, the albumin source solution temperature is elevated, increased in pH and reacted for approximately six hours under conditions sufficient to disrupt the initial solution colloid, and partition albumin-containing supernatant from a colloidal disperse phase, which retains unwanted globulins and manufacturing debris. Since it tends to be a scavenger molecule, albumin is selectively stabilized by diafiltration against a buffer containing sodium caprylate, thereby assuring a high albumin monomer content and low turbidity level. The amount of sodium caprylate required for selective stabilization is determined by the amount of available binding sites on the albumin molecule.
    Type: Grant
    Filed: August 10, 1994
    Date of Patent: October 1, 1996
    Assignee: Bayer Corporation
    Inventor: Robert A. Tenold
  • Patent number: 5527546
    Abstract: A previously undescribed Interleukin-6 inhibitor activity has been successfully isolated from the supernatant of the human promyelocytic leukemia cell line HL-60. Treatment of the HL-60 cell line with cycloheximide prevents the appearance of the inhibitory activity in the cellular supernatant. Incubation of the HL-60 supernatant with trypsin destroys the activity. The above observations indicate the inhibitor is a protein. Membrane and gel filtration studies indicate the protein has a molecular weight between 10,000 and 30,000 daltons. The inhibitor was partially isolated from other proteins by dye-ligand and reverse phase chromatography.
    Type: Grant
    Filed: August 10, 1994
    Date of Patent: June 18, 1996
    Assignee: Bayer Corporation
    Inventors: Delia E. Penza, Susan K. Faris, Kenneth J. Lembach
  • Patent number: 5514781
    Abstract: Soluble azoles in aqueous solutions can be used as virucidal agents for biologically active protein preparations.
    Type: Grant
    Filed: April 11, 1994
    Date of Patent: May 7, 1996
    Assignee: Bayer Corporation
    Inventors: Milton B. Dobkin, Paul Ng, George B. Dove
  • Patent number: 5510465
    Abstract: Mild heat-treatment of IgM antibody concentrates diminishes the potential to induce non-specific complement activation without significant loss of normal immunologic effector functions. These IgM immunoglobulin concentrates retain specific antigen binding properties and activate complement when bound to antigen. Preferred product includes at least 20% by weight IgM in an IgM/IgG antibody mixture. Heating is done at a temperature within the range of about 40.degree. C. to 62.degree. C., preferably about 45.degree. to 55.degree. C., in a solution having an acid pH (preferably 4.0 to 5.0) for at least about 10 minutes.
    Type: Grant
    Filed: July 26, 1993
    Date of Patent: April 23, 1996
    Assignee: Bayer Corporation
    Inventors: Grace C. Tsay, Gary Jesmok
  • Patent number: 5419906
    Abstract: The effects of Cohn-Oncley cold alcohol fractionation on infectivity of two prototype retroviruses, mouse xenotropic type C and the LAV strain of AIDS retrovirus result in a significant reduction in retrovirus titer. At least a 100,000-fold reduction of LAV was obtained when fractionating plasma to fraction II. Adjustment to pH 4.0 at filtrate III was as effective for viral inactivation as was precipitation of fraction II from filtrate III with 25% ethanol. Liquid immunoglobulin preparations spiked with LAV and incubated at 27.degree. C. for 3 days resulted in an additional 1,000-10,000-fold reduction of LAV titer. Our results support the clinical and epidemiological evidence that therapeutic immunoglobulin preparations prepared by Cohn-Oncley cold ethanol processing (at least about 18% v/v alcohol, pH.ltoreq.5.4) and then stored at a pH equal to or less than about 5.4 and a temperature of at least 27.degree. C. for at least 3 days, do not transmit retroviruses such as the LAV strain of the AIDS virus.
    Type: Grant
    Filed: October 23, 1992
    Date of Patent: May 30, 1995
    Assignee: Miles Inc.
    Inventors: Gautam Mitra, Milton M. Mozen, Robert E. Louie
  • Patent number: 5356878
    Abstract: Highly purified antihemophilic factor is produced by a process comprising a PEG precipitation step, a gel filtration step and a virus inactivation step. Al(OH).sub.3 adsorption and PEG precipitation carried out at room temperature allow processing to proceed directly to a gel filtration step.
    Type: Grant
    Filed: January 4, 1993
    Date of Patent: October 18, 1994
    Assignee: Miles Inc.
    Inventors: William J. Brockway, Richard L. Seng
  • Patent number: 5356373
    Abstract: Method and apparatus for collecting and storing umbilical blood in a system that allows for the closed aliquoting of small blood volumes for autologous transfusion in neonates. The method involves locating a venous access site on an umbilical cord of the placenta of a neonate. A vacuum pressure is applied to a blood collection bag to facilitate removal of an amount of blood from the umbilical cord. The blood may then be stored in the collection bag and used for subsequent autologous neonate blood transfusion.
    Type: Grant
    Filed: November 15, 1991
    Date of Patent: October 18, 1994
    Assignee: Miles Inc.
    Inventor: Robert A. Dracker
  • Patent number: 5330976
    Abstract: Nikkomycin compounds have been found to be orally or parenterally effective as anti-fungals in animals. They may be used alone or, preferably, in combination with azole antimycotics for a synergistic anti-fungal effect.
    Type: Grant
    Filed: February 11, 1993
    Date of Patent: July 19, 1994
    Assignee: Miles Inc.
    Inventors: Richard F. Hector, Klaus Schaller, Heinrich F. Moeschler, Manfred Plempel
  • Patent number: 5300060
    Abstract: A generally flat, elongated edge-sealed polymeric blood bag having a length to width ratio of at least 2 to 1 and one end portion in tapering communication with a connected single tubing which in turn is in closed communication via a Y-connector with both a bag access port and at least one other Y-connector. The second Y-connector is in closed communication with at least one auxiliary bag, preferably two auxiliary bags. Once the upper neocyte portion is expressed from the elongated blood bag the lower, more dense gerocytes can be saved in the original elongated bag or expressed into another connected bag via the Y-connector assembly for subsequent use or storage. The bag system is especially useful for separating and isolating both components of a neocyte/gerocyte red blood cell mixture in an open system and for providing a means for saving the otherwise discarded gerocytes for subsequent use.
    Type: Grant
    Filed: October 7, 1991
    Date of Patent: April 5, 1994
    Assignee: Miles Inc.
    Inventor: Edward J. Nelson