Patents Represented by Attorney John W. Mahoney
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Patent number: 7105653Abstract: The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.Type: GrantFiled: April 17, 2004Date of Patent: September 12, 2006Inventors: Armen B. Shanafelt, Jeffrey M. Greve, Gary Jesmok, Kenneth Lembach, Gayle D. Wetzel
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Patent number: 6955807Abstract: The invention is directed to a polypeptide comprising a human IL-2 mutein numbered in accordance with wild-type IL-2 wherein said human IL-2 is substituted at at least one of positions 20, 88 or 126, whereby said mutein preferentially activates T cells over NK cells. D20H and I, N88G, I, and R, in particular have a relative T cell-differential activity much greater than native IL-2, with predicted associated reduced in vivo toxicity. The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.Type: GrantFiled: May 13, 1999Date of Patent: October 18, 2005Assignee: Bayer Pharmaceuticals CorporationInventors: Armen B. Shanafelt, Jeffrey M. Greve, Gary Jesmok, Kenneth J. Lembach, Gayle D. Wetzel
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Patent number: 6953692Abstract: A device and method for seed-train expansion of a source of mammalian cells and their use in production of proteins expressed by the cells comprising the use of a dedicated inoculation bioreactor for expanding the cells prior to the transfer to a production bioreactor is disclosed. The novel inoculation bioreactor is designed to facilitate an improved method of mammalian cell seed-train expansion, and is distinguished by the presence of an “inoculation well” which communicates with the interior of the bioreactor and which facilitates the growth of mammalian cells for commercial seed-train expansion. The method comprises adding the cryopreserved cells to media within the inoculation well of the inoculation bioreactor, enabling the cells to grow to a predetermined concentration within the inoculation well by monitoring and adjusting the condition of the media and environment, and thereafter incrementally increasing the volume of the media within the reactor so that optimal cell growth is maintained.Type: GrantFiled: December 18, 2001Date of Patent: October 11, 2005Assignee: Bayer Pharmaceuticals CorporationInventors: Rudiger Heidemann, Mokhtar Mered, James D. Michaels, Konstantin Konstantinov
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Patent number: 6927043Abstract: Glycosylated interleukin-2 muteins are described. A method of producing the muteins using mammalian cells is included. The muteins may be incorporated into pharmaceutical preparations useful for, e.g., cancer therapy.Type: GrantFiled: January 22, 2002Date of Patent: August 9, 2005Assignee: Bayer CorporationInventors: Sham-Yuen Chan, Ruth Kelly
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Patent number: 6844000Abstract: A purified Parapoxvirus ovis envelope protein termed “B2L” can be used as a monotherapeutic agent. B2L protein also can be used in screening methods to identify potential therapeutic agents for modulating a subject's immune response to the B2L protein.Type: GrantFiled: December 6, 2002Date of Patent: January 18, 2005Assignee: Bayer Pharmaceuticals CorporationInventors: Delanie Cassell, Jeffrey S. Tepper, Isa Samuels, Nathalie Dubois-Stringfellow
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Patent number: 6835381Abstract: The present invention provides methods for modulating angiogenesis by administering anti-angiogenic Ang-7 polypeptides to a subject. Methods of modulating angiogenesis by administering an anti-angiogenic ANG-7 nucleic acid are also provided.Type: GrantFiled: May 17, 2002Date of Patent: December 28, 2004Assignee: Bayer AGInventors: Gabi Friedrich, Gustav Hagen, Maresa Wick, Dmitry Zubov, Nathalie Dubois-Stringfellow
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Patent number: 6689582Abstract: BTL.010 is a novel human serine proteinase inhibitor of the Kunitz family that exhibits greater potency towards neutral serine proteinases, particularly leukocyte elastase and proteinase 3 than towards trypsin-like proteinases. BTL.010, or variants thereof, may be employed as therapeutics in diseases such as emphysema, idiopathic pulmonary fibrosis, adult respiratory distress syndrome, cystic fibrosis, rheumatoid arthritis, organ failure, and glomerulonephritis in which uncontrolled proteolysis due to neutral serine proteinase activity results in tissue damage.Type: GrantFiled: May 12, 2000Date of Patent: February 10, 2004Assignee: Bayer Pharmaceuticals CorporationInventors: Christopher Davies, Dadong Chen, Steve Roczniak
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Patent number: 6689353Abstract: A stable pharmaceutical preparation comprising Human interleukin-2 or a variant thereof and a stabilizing amount of histidine. A preferred formulation includes glycine and sucrose and a variant of IL-2 having a single mutation, N88R. The preferred formulation is in lyophilized form which, on reconstitution with an aqueous diluent, results in a solution having a pH ranging from about 5.0 to 6.5.Type: GrantFiled: June 28, 2000Date of Patent: February 10, 2004Assignee: Bayer Pharmaceuticals CorporationInventors: Wei Wang, Rajiv Nayar, Michael A. Shearer
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Patent number: 6670175Abstract: The invention is a novel cell freezing and storage bag assembly and method for using the assembly in the seed train expansion of mammalian cells. The bag is constructed principally of polytetrafluoroethylene fabric. The bag is designed to hold enough cells that a bioreactor can be inoculated directly. The bag is designed to be filled to a fraction of its maximum capacity so that the cell suspension has a very thin cross-section (less than about 10 millimeters). The bag design includes a transfer set that can be sterilely welded to the source of the mammalian cells. This sterile-weldable transfer set allows the bags to be filled quickly with minimal risk of contamination. In the method, once each bag is filled, it is sealed below the connection with the transfer set and the bag is cut “above” the new seal (on the same side of the seal as the transfer set). When a bioreactor is to be inoculated, the contents of the bag are drained via a sterile-weldable inoculation line.Type: GrantFiled: May 9, 2002Date of Patent: December 30, 2003Assignee: Bayer Pharmaceuticals CorporationInventors: De Qian Wang, Bruce Gardner, Rudiger Heidemann, Mokhtar Mered, William H. Kelsey
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Patent number: 6472155Abstract: PCR (polymerase chain reaction) primers for the detection of certain Bacillus species, such as Bacillus anthracis. The primers specifically amplify only DNA found in the target species and can distinguish closely related species. Species-specific PCR primers for Bacillus anthracis, Bacillus globigii and Clostridium perfringens are disclosed. The primers are directed to unique sequences within sasp (small acid soluble protein) genes.Type: GrantFiled: June 8, 2000Date of Patent: October 29, 2002Assignee: The Regents of the University of CaliforniaInventor: Nancy McKinney
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Patent number: 6433157Abstract: The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1).Type: GrantFiled: September 30, 1999Date of Patent: August 13, 2002Assignee: Bayer CorporationInventors: Armen B. Shanafelt, Jeffrey Greve, Robert Gundel
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Patent number: 6358703Abstract: This invention describes a protein-free production process for proteins having factor VIII procoagulant activity. The process includes the derivation of stable human cell clones with high productivity for B-domain deleted Factor VIII, and (2) the adaptation of cells to grow in a medium free of plasma-derived proteins.Type: GrantFiled: December 10, 1998Date of Patent: March 19, 2002Assignee: Bayer CorporationInventors: Myung-Sam Cho, Sham-Yuen Chan, William Kelsey, Helena Yee
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Patent number: 6338964Abstract: A cell culture medium which is low in dissolved carbon dioxide is disclosed. The medium contains less than about 1 g/L added sodium bicarbonate and includes an organic buffer and a metal complexing agent. The medium is preferably essentially free of added sodium bicarbonate. Methods of use of the medium in culturing mammalian cells, particularly cells engineered to produce recombinant factor VIII, are also disclosed.Type: GrantFiled: May 7, 1999Date of Patent: January 15, 2002Assignee: Bayer CorporationInventors: Ricaredo Matanguihan, Eva Sajan, Konstantin Konstantinov, Michael Zachariou, Charles Olson
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Patent number: 6335426Abstract: This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.Type: GrantFiled: April 23, 1999Date of Patent: January 1, 2002Assignee: Bayer CorporationInventors: Armen B. Shanafelt, Jeffrey M. Greve, Robert Gundel
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Patent number: 6313272Abstract: A recombinant human IL-4 mutein numbered in accordance with wild-type IL-4 wherein the mutein comprises at least one amino acid substitution in the binding surface of either the A- or C-alpha helices of the wild-type IL-4 whereby the mutein binds to the IL-4R&agr; receptor with at least greater affinity than native IL-4. The substitution is more preferably selected from the group of positions consisting of, in the A-helix, positions 13 and 16, and in the C-helix, positions 81 and 89. A most preferred embodiment is the recombinant human IL-4 mutein wherein the substitution at position 13 is Thr to Asp. Pharmaceutical compositions, amino acid and polynucleotide sequences encoding the muteins, transformed host cells, antibodies to the muteins, and methods of treatment are also described.Type: GrantFiled: July 9, 1999Date of Patent: November 6, 2001Assignee: Bayer CorporationInventors: Jeffrey M. Greve, Armen B. Shanafelt, Steven Roczniak
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Patent number: 6299897Abstract: This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 106 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.Type: GrantFiled: November 15, 1999Date of Patent: October 9, 2001Assignee: The Regents of the University of CaliforniaInventors: Jon O. Nagy, Wayne R. Spevak, Falguni Dasgupta, Caroline Bertozzi
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Patent number: 6123941Abstract: A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.Type: GrantFiled: April 28, 1998Date of Patent: September 26, 2000Assignee: The Regents of the University of CaliforniaInventors: Mina J. Bissell, Valerie M. Weaver
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Patent number: 6100033Abstract: A a diagnostic test useful for prenatal identification of Down syndrome and mental retardation. A method for gene therapy for correction and treatment of Down syndrome. DYRK gene involved in the ability to learn. A method for diagnosing Down's syndrome and mental retardation and an assay therefor. A pharmaceutical composition for treatment of Down's syndrome mental retardation.Type: GrantFiled: April 30, 1998Date of Patent: August 8, 2000Assignee: The Regents of the University of CaliforniaInventors: Desmond J. Smith, Edward M. Rubin
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Patent number: 5985852Abstract: This invention provides compositions for inhibiting the binding between two cells, one expressing P- or L-selectin on the surface and the other expressing the corresponding ligand. A covalently crosslinked lipid composition is prepared having saccharides and acidic group on separate lipids. The composition is then interposed between the cells so as to inhibit binding. Inhibition can be achieved at an effective oligosaccharide concentration as low as 10.sup.6 fold below that of the free saccharide. Since selectins are involved in recruiting cells to sites of injury, these composition scan be used to palliate certain inflammatory and immunological conditions.Type: GrantFiled: February 16, 1999Date of Patent: November 16, 1999Assignee: The Regents of the University of CaliforniaInventors: Jon O. Nagy, Wayne R. Spevak, Falguni Dasgupta, Caroline Bertozzi