Oxygen Containing Reactant Patents (Class 530/410)
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Patent number: 5736512Abstract: The invention relates to serine protease variants derived from precursor serine proteases via recombinant and/or chemical methods to form protease variants having improved peptide ligase activity. The invention also includes novel ligation substrates which in combination with the serine protease variants and a second ligation substrate are capable of forming a ligation product. The invention also relates to methods for forming such ligation products and the products formed thereby.Type: GrantFiled: June 7, 1995Date of Patent: April 7, 1998Assignee: Genentech, Inc.Inventors: Lars Abrahmsen, John Burnier, James A. Wells, David T. Jackson
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Patent number: 5700904Abstract: A method for recovering an acylated protein as a powder, especially in cases where said acylated protein is one that resists isolation by isoelectric precipitation from aqueous solutions of the protein, said method comprising in combination adjusting said aqueous solution to near the isoelectric pH of the protein and providing a suitable alcohol concentration to cause precipitation of the protein in the form of filterable particles at said pH.Type: GrantFiled: June 7, 1995Date of Patent: December 23, 1997Assignee: Eli Lilly and CompanyInventors: Jeffrey Clayton Baker, Brian A. Moser, Warren E. Shrader
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Patent number: 5681567Abstract: The present invention is directed to methods of preparing high purity polyalkylene oxide carboxylic acids. The methods include reacting a polyalkylene oxide such as polyethylene glycol with a t-butyl haloacetate in the presence of a base followed by treatment with an acid such as trifluoroacetic acid. The resultant polymer carboxylic acids are of sufficient purity so that expensive and time containing purification steps required for pharmaceutical grade polymers are avoided.Type: GrantFiled: August 13, 1996Date of Patent: October 28, 1997Assignee: Enzon, Inc.Inventors: Anthony J. Martinez, Richard B. Greenwald
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Patent number: 5672662Abstract: Active esters of PEG acids and related polymers are provided that have a single propionic or butanoic acid moiety and no other ester linkages. These polymer acids have a half life in water of from about 10 to 25 minutes. For example, alpha-methoxy, omega-propionic acid succinimidyl ester of PEG ("methoxy-PEG-SPA") has a nearly ideal reactivity with amino groups on proteins and other biologically active substances. The half life of methoxy-PEG-SPA is about 16.5 minutes in water. The invention also provides conjugates with proteins, enzymes, polypeptides, drugs, dyes, nucleosides, oligonucleotides, lipids, phospholipids, liposomes, and surfaces of solid materials that are compatible with living organisms, tissue, or fluid.Type: GrantFiled: October 2, 1995Date of Patent: September 30, 1997Assignee: Shearwater Polymers, Inc.Inventors: J. Milton Harris, Antoni Kozlowski
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Patent number: 5663074Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.Type: GrantFiled: March 17, 1993Date of Patent: September 2, 1997Assignee: Chiron Diagnostics CorporationInventor: Say-Jong Law
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Patent number: 5659015Abstract: This invention relates to a method of producing peracetyloxazolines from peracetyl saccharides. The method involves reacting the starting material, a peracetyl saccharide, with a reagent combination, to directly produce the peracetyl oxazoline. This method may be used for the activation of oligosaccharides, wherein an oligosaccharide containing a reducing GlcNAc terminus is activated by the formation of an oxazolide at the terminal GlcNAc, and then coupled with a bifunctional spacer to provide an oligosaccharide-spacer conjugate. The activated oligosaccharide-spacer conjugate is then coupled to a protein, such as granulocyte colony stimulating factor or .gamma.-interferon, providing a neoglycoprotein conjugate. The invention provides a method for forming neoglycoprotein conjugates which may improve biological and physiochemical properties of the protein. For example, serum lifetime or efficiency of drug delivery of the peptide to a target organ or cell may be improved.Type: GrantFiled: October 13, 1992Date of Patent: August 19, 1997Inventors: Marcelo Colon, Jeffrey T. Davis, James R. Rasmussen, Marianne Borowski, Barbara Y. Wan, Shirish Hirani
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Patent number: 5653974Abstract: A tumor necrosis factor (TNF) preparation with high cytolytic activity is described. The TNF preparation includes modified forms of TNF associated with or encapsulated within liposomes. The TNF molecule is modified at up to 3 amino acid residues per trimer with nearly complete retention (80-95%) of biological activity. Amino acid residues of the TNF are modified to include long chain fatty acids via TNF lysyl side chains and/or N-terminal amino acid groups. The disclosed modified TNF molecules provide a highly efficient method for preparing liposome-associated or encapsulated TNF complexes in either standard multilamellar vesicles (MLVs) or small unilamellar vesicles (SUVs) having enhanced in vivo stability. The liposomes of the present invention feature particularly small diameters in the range of 0.02-0.05 um in diameter. The binding of the modified TNF molecules to the surface of SUVs is up to 100% efficiency.Type: GrantFiled: November 30, 1994Date of Patent: August 5, 1997Assignee: Board of Regents,The University of Texas SystemInventors: Mien-Chie Hung, Toshihiko Utsumi, Jim Klostergaard
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Patent number: 5635180Abstract: There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.Type: GrantFiled: September 26, 1995Date of Patent: June 3, 1997Assignee: NeoRx CorporationInventors: Alton C. Morgan, Jr., Gowsala P. Sivam, Paul G. Abrams
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Patent number: 5631221Abstract: A polypeptide having a molecular weight of 40,000.+-.5,000 daltons and an isoelectric point of 9.5.+-.0.5 is prepared from a cedar pollen. The polypeptide which induces pollenosis can be suitably used as desensitization agent because it induces immunoglobulin antibody which is effective for desensitization, but does not substantially induce immunoglobulin E antibody, a major factor causative of side effects including anaphylaxis shock. Therefore, the polypeptide can be advantageously used in the treatment, prevention and/or diagnosis of pollenosis.Type: GrantFiled: December 14, 1994Date of Patent: May 20, 1997Assignee: Kabushiki Kaisha Hayashibara Sibutsu Kagaku KenkyujoInventors: Keizo Kohno, Manami Sawatani, Masashi Kurimoto
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Patent number: 5631347Abstract: A method for processing a fatty acid-acylated protein, especially N-palmitoyl Lys.sup.B29 human insulin, to reduce the incidence of gelation by conducting such processing in the presence of a citrate buffering agent as the primary buffer which method allows such processing to be conducted at higher protein concentrations and with less temperature control than would otherwise be possible in the absence of the citrate buffer.Type: GrantFiled: June 7, 1995Date of Patent: May 20, 1997Assignee: Eli Lilly and CompanyInventors: Jeffrey C. Baker, Jose M. Hanquier, Warren E. Shrader
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Patent number: 5624896Abstract: Novel clearing agents are provided which comprise biotin analog containing clearance-directing moieties. Preferably such clearance-directing moieties endogenously contain or a rederivatized to expose galactose and/or mannose residues.Type: GrantFiled: June 5, 1995Date of Patent: April 29, 1997Assignee: NeoRx CorporationInventors: Donald B. Axworthy, John M. Reno
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Patent number: 5623057Abstract: A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.Type: GrantFiled: May 20, 1994Date of Patent: April 22, 1997Assignee: Merck & Co., Inc.Inventors: Stephen Marburg, Richard L. Tolman, Peter J. Kniskern, William J. Miller, Arpi Hagopian, Charlotte C. Ip, John P. Hennessey, Jr., Dennis J. Kubek, Pamela D. Burke
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Patent number: 5618927Abstract: The invention concerns a process for the reactivation of denatured protein, in which the protein is incubated with a solution of Tris base or/and a salt of Tris at a concentration of at least 400 mmol/l and at a pH at which the protein to be treated can take up its native conformation.Type: GrantFiled: July 2, 1992Date of Patent: April 8, 1997Assignee: Boehringer Mannheim GmbHInventors: Dorothea Ambrosius, Rainer Rudolph
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Patent number: 5616689Abstract: In accordance with the present invention, stabilized dispersions of collagen fibers that have been treated in order to inactivate infectious agents and methods of stabilizing such collagen fibers are provided.Type: GrantFiled: July 13, 1994Date of Patent: April 1, 1997Assignee: Collagen CorporationInventors: Vivek N. Shenoy, Timothy T. Revak, George H. Chu, Hugh R. McMullin, Joel S. Rosenblatt, George R. Martin
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Patent number: 5612460Abstract: Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.Type: GrantFiled: February 17, 1994Date of Patent: March 18, 1997Assignee: Enzon, Inc.Inventor: Shmuel Zalipsky
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Patent number: 5591710Abstract: Compositions and processes to alleviate oxygen toxicity are disclosed based on the addition of nitroxides to physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. The formulations described herein interact with free radicals, act as antioxidant enzyme-mimics, and alleviate oxidative stress and oxygen-related toxicity.Type: GrantFiled: August 15, 1994Date of Patent: January 7, 1997Inventor: Jen-Chang Hsia
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Patent number: 5580853Abstract: Modified polypeptides with increased biological activity exhibited as either increased potency or prolonged circulating half-life are disclosed with methods of preparing the modified polypeptides and methods of use.Type: GrantFiled: March 22, 1994Date of Patent: December 3, 1996Assignee: New England Deaconess HospitalInventor: Arthur J. Sytkowski
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Patent number: 5578709Abstract: A macromolecular microparticle composition formed by dehydrating an aqueous macromolecule solution and crosslinking the dehydrated macromolecules with a crosslinking agent while in a liquid phase or with heat. Preferably, the dehydrating agent is a polymer mixture of polyvinylpyrrolidone and polyethylene glycol, the crosslinking reagent is glutaraldehyde, and the macromolecule is a protein, most preferably an immunoglobulin. Methods of use for research, diagnostics and therapeutics are also provided.Type: GrantFiled: March 4, 1994Date of Patent: November 26, 1996Assignee: Middlesex Sciences, Inc.Inventor: James E. Woiszwillo
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Patent number: 5578308Abstract: A detoxified B. pertussis toxin or antigenic preparation is described, which is characterized by stability to reversion to toxicity upon storage at 4.degree.-8.degree. C. and at temperatures above 23.degree. C. Also provided are methods for producing detoxified pertussis toxin and vaccines containing same.Type: GrantFiled: November 14, 1994Date of Patent: November 26, 1996Inventors: Carine Capiau, Jean Petre
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Patent number: 5554730Abstract: A method and kit for making a polysaccharide-protein Schiff base conjugate. A polysaccharide is oxidized with an oxidizing agent and combined with a protein in the presence of a macromolecular crowding agent to form a Schiff base. Preferably, the macromolecular crowding agent is a soluble linear polymer selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, dextran, nonylphenol-ethoxylates, polyvinyl alcohol, and mixtures thereof. Most preferably, the macromolecular crowding agent is a mixture of polyvinylpyrrolidone and polyethylene glycol. The microparticles or substantially dissolved microparticles are immunogenic and are useful for inducing an immune response when administered to humans or animals.Type: GrantFiled: December 23, 1994Date of Patent: September 10, 1996Assignee: Middlesex Sciences, Inc.Inventors: James E. Woiszwillo, Jie Di
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Patent number: 5529915Abstract: Disclosed are lyophilized biologically active proteinaceous compositions containing low diol polyalkylene oxide, such as polyethylene glycol, covalently attached to a biologically active proteinaceous substance and combined with the cryoprotectant cyclodextrin.Type: GrantFiled: January 12, 1995Date of Patent: June 25, 1996Assignee: Sterling Winthrop Inc.Inventors: Christopher P. Phillips, Robert A. Snow
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Patent number: 5530100Abstract: Recovery of the 52/48 kDa tryptic fragment of vWF or peptide subfragments thereof produced in the form of inclusion bodies from recombinant host cells is carried out by providing a washed recombinant host cell suspension, adding a detergent and subjecting the cells to mechanical disruption. A second detergent is added, followed by another mechanical disruption and centrifugation to a pellet. The pellet is resuspended in a buffer and subjected to another mechanical disruption. Inclusion bodies are washed, resuspended and then recovered. In addition, endotoxins and DNA are removed from inclusion bodies containing the 52/48 kDa tryptic fragment of vWF or peptide subfragments thereof by mechanically disrupting the inclusion bodies in an aqueous buffer containing a detergent. A washed pellet is formed from these mechanically disrupted inclusion bodies and dissolved in a denaturant.Type: GrantFiled: May 7, 1990Date of Patent: June 25, 1996Assignee: Rhone-Poulenc Rorer Pharmaceuticals Inc.Inventors: Thomas L. J. Darling, Lida Y. Akhnana, Jonathan J. Mitschelen, Michael E. Hrinda
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Process for the preparation of spherules of active principles and emulsions containing the spherules
Patent number: 5500415Abstract: A process for the preparation of spherules and emulsions containing such spherules. A primary oil-in-water emulsion is formed containing particles comprising one or more active principles in oily form suspended in water, the water optionally containing at least one protein. Controlled division of the primary emulsion is achieved by combining the primary emulsion with a water-immiscible solvent to create a second emulsion containing spherules of the primary emulsion. Preferably, the particles of the primary emulsion have mean diameters of about 1 .mu.m, and preferably, the spherules contained in the second emulsion have a diameter ranging from 100 .mu.m to 500 .mu.m. If protein is contained in the primary emulsion, the protein can be cross-linked. Further, the spherules can be separated from the water-immiscible solvent.Type: GrantFiled: March 31, 1994Date of Patent: March 19, 1996Assignee: Rhone-Poulenc Nutrition AnimaleInventors: Jean-Marie Dollat, Marc Molin, Pascal Theallier -
Patent number: 5484894Abstract: A macromolecular microparticle composition formed by dehydrating an aqueous macromolecule solution and crosslinking the dehydrated macromolecules with a crosslinking agent while in a liquid phase or with heat. Preferably, the dehydrating agent is a polymer mixture of polyvinylpyrrolidone and polyethylene glycol, the crosslinking reagent is glutaraldehyde, and the macromolecule is a protein, most preferably an immunoglobulin. Methods of use for research, diagnostics and therapeutics are also provided.Type: GrantFiled: March 4, 1994Date of Patent: January 16, 1996Assignee: Middlesex Sciences, Inc.Inventor: James E. Woiszwillo
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Patent number: 5480790Abstract: A water-soluble protein conjugate modified by saccharides is covalently bound to a carbohydrate backbone via a saccharide group. Such protein conjugates modified by saccharides can be produced in a simple way by polymerizing a vinylsaccharide and conjugating in a known way the poly(vinylsaccharide) obtained in this way with the protein, which is preferably an enzyme. The protein conjugates according to the present invention are stable over long time periods at a high enzymatic activity and also in aqueous solution and are thus particularly suitable for use in test kits.Type: GrantFiled: April 4, 1991Date of Patent: January 2, 1996Assignees: Boehringer Mannheim GmbH, Gesellschaft fur Biotechnologische Forschung mbHInventors: Wilhelm Tischer, Joachim Klein, Rolf-Joachim Muller, Stephan Engelke
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Patent number: 5474885Abstract: A modified gelatin is disclosed wherein part of the free carboxyl groups is replaced by modifiers having more acid end-standing groups chosen from --SO.sub.3 M, --OSO.sub.3 M, --SSO.sub.3 M, --OPO(OH).sub.2, --OPO(OH)(OR.sup.2), --PO(OH).sub.2, --PO(OH)(OR.sup.2).In a preferred embodiment such a modified gelatin is incorporated in a DTR photographic material which after processing can serve as a lithographic printing plate. Thanks to the more hydrophilic character of the modified gelatin the differentiation between printing and non-printing areas is improved and toning at printing start-up is reduced.Type: GrantFiled: May 26, 1994Date of Patent: December 12, 1995Assignee: Agfa-Gevaert, N.V.Inventors: Eddy Michiels, Piet Kok, Johan Loccufier, Frank Michiels, Ludo Van Rompuy
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Patent number: 5468486Abstract: A method for the treatment of the symptoms of fescue toxicosis in mammals comprising injecting a subject mammal with a vaccine which includes from about 5 .mu.g to about 1 mg of a protein-alkaloid conjugate per mL of a physiologically acceptable carrier. There is also provided a vaccine for the treatment of the symptoms of fescue toxicosis and a compound for preparing that vaccine.Type: GrantFiled: March 3, 1994Date of Patent: November 21, 1995Assignee: The University of Tennessee Research CorporationInventors: Bradford B. Reddick, Kimberly D. Gwinn, Jack W. Oliver
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Patent number: 5462593Abstract: A modified vegetable protein binder produced by and a method of producing a modified vegetable protein binder for paper coatings by bleaching a vegetable protein extract with an oxidizing agent and a magnesium compound to provide a bleached vegetable protein material and then modifying the bleached vegetable protein. The modification is generally hydrolyzing the bleached vegetable protein and when desired, also carboxylating the bleached vegetable protein.Type: GrantFiled: June 7, 1994Date of Patent: October 31, 1995Assignee: Archer Daniels Midland CompanyInventors: George Poppe, Denise Ciesielski, Mark Matlock
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Patent number: 5461142Abstract: Described are derivatives of the precursor peptide of the cardiodilatin/atrial sodiuretic factor (CDD-ANF) or fragments thereof which comprise at least the amino acid sequence of alpha-hANaP. The derivatives according to the present invention are compounds of the formula (I) ##STR1## X is a phosphate or thiophosphate group. R is NH.sub.2 or a peptide fragment from the amino acid sequence of gamma-hANaP. Radio-labelled derivatives are also possible. A method for the qualitative and/or quantitative determination of peptides containing the sequence of alpha-hANaP and a use of the compounds having the formula (I) as medicaments for various vaso- and renal related disorders are further described.Type: GrantFiled: July 22, 1993Date of Patent: October 24, 1995Assignees: Pharma Bissendorf Peptide GmbH, Wolf-Georg ForssmannInventors: Wolf-Georg Forssmann, Michael Gagelmann, Dieter Hock
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Patent number: 5451661Abstract: A process is described for generating conjugates of lipids and biologically active agents to produce compositions having therapeutic utility, such as drug delivery vehicles. The process involves mixing the reactive lipid with an appropriate amount of diketene to form an acetoacetylated lipid which is then isolated, dissolved in a suitable medium, and mixed with a nucleophilic-containing biologically active agent to form a biologically active agent-lipid conjugate. Alternatively, the acetoacetylated lipid can be mixed with a polyamine to form a cationic lipid.Type: GrantFiled: November 5, 1993Date of Patent: September 19, 1995Assignee: Genzyme CorporationInventor: Barbara Y. Wan
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Patent number: 5444154Abstract: The present invention relates to a series of novel crosslinked polymers. The compounds of the present invention are prepared by the reaction of chloracetic acid with a pendant hydroxyl group which is present on a polyoxyalkylene polymer, followed by the reaction of the halo-ester with a protein or amino acid to give a crosslinked protein compound. In a preferred embodiment the polyoxyalkylene glycol has been prepared by the reaction of both ethylene oxide and propylene oxide. In a more preferred embodiment, the ethylene oxide is at the terminal portion of the molecule and the propylene oxide is in the center. The proteins of the present invention plate out on the surface of hair skin and once dry act as humectants, trapping moisture to the hair. This results in hair which is fuller, has less static and is cosmetically more appealing. This combination of properties makes these polymers ideally suited for use in personal care applications.Type: GrantFiled: June 15, 1994Date of Patent: August 22, 1995Assignee: Siltech Inc.Inventor: Anthony J. O'Lenick, Jr.
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Patent number: 5438040Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may, for example, be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.Type: GrantFiled: July 19, 1994Date of Patent: August 1, 1995Assignee: Protein Delivery, Inc.Inventor: Nnochiri N. Ekwuribe
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Patent number: 5412074Abstract: Organofunctional silicone chains having an organic moiety on at least one end of the chains, are covalently linked to free amino groups of proteins by the organic moieties to provide a useful ingredient for cosmetic formulations.Type: GrantFiled: November 2, 1992Date of Patent: May 2, 1995Assignee: Croda International PLC.Inventors: Roger T. Jones, Mark A. Humphreys
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Patent number: 5399671Abstract: Hemoglobin is site-specifically crosslinked into its tetrameric form by reaction with a trifunctional reagent which combines electrostatic effects, steric effects and the presence of functional groups so that two of the functional groups react with specific sites on the hemoglobin whilst the third site is left free for reaction with endogenous nucleophilic compounds. A specific example of such a crosslinking reagent is trimesoyl tris(3,5-dibromosalicylate), TTDS, which effects specific crosslinking between the amino groups of lysine-82 on each respective .beta. sub-unit. While the crosslinking reagent TTDS has three available carboxyl groups for the crosslinking reaction, only two so react, leaving one free carboxyl for reaction with exogenous nucleophiles, e.g. to render the hemoglobin product useful as a carrier for nucleophilic compounds through the body's circulatory system.Type: GrantFiled: November 18, 1992Date of Patent: March 21, 1995Inventors: Ronald Kluger, Yonghong Song
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Patent number: 5389381Abstract: Disclosed are lyophilized biologically active proteinaceous compositions containing low diol polyalkylene oxide, such as polyethylene glycol, covalently attached to a biologically active proteinaceous substance and combined with the cryoprotectant cyclodextrin.Type: GrantFiled: January 5, 1994Date of Patent: February 14, 1995Assignee: Sterling Winthrop Inc.Inventors: Christopher P. Phillips, Robert A. Snow
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Patent number: 5387672Abstract: Stroma-free hemoglobin cross-linked with reagents that mimic 2,3-diphosphoglycerate and transform stroma-free hemoglobin into a physiologically competent oxygen carrier which is retained in vivo for adequate periods of time, and thus can be used in fluids for transporting oxygen is described.Type: GrantFiled: March 2, 1993Date of Patent: February 7, 1995Assignee: The University of Maryland at BaltimoreInventors: Enrico Bucci, Clara Fronticelli
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Patent number: 5382657Abstract: Substituted PEG-interferon conjugates of formulae IA and IB where PEG is linked by means of activated linking reagents of formulae IIA, IIB, or IIB-1 to an amino group in the interferon, and activated linking reagents of formulae IIA, IIB, or IIB-1. The conjugates are not readily susceptible to in vivo hydrolytic cleavage, have enhanced in vivo half life, and reduce the immunogenicity of the interferon while maintaining biological activity.Type: GrantFiled: August 26, 1992Date of Patent: January 17, 1995Assignee: Hoffmann-La Roche Inc.Inventors: Robert Karasiewicz, Carlo Nalin, Perry Rosen
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Patent number: 5374539Abstract: A process is described to purify collagen fibers while allowing the individual constituent molecules to retain their native configuration and 3-dimensional arrangement characteristic of the tissues from which they are derived. Collagenous tissues used as sources of purified collagen and for manufacturing bioprosthesis contain significant amounts of other substances (elastin, glycoproteins, polysaccharides, cell derived materials, etc.). This process becomes therefore useful to selectively preserve the collagen in its native conformation and to eliminate contaminants. The method described allows for enzymatic removal of all extraneous materials while preserving the native collagen molecules in their original fiber configuration.Type: GrantFiled: June 17, 1991Date of Patent: December 20, 1994Inventors: Marcel E. Nimni, David T. Cheung
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Patent number: 5364465Abstract: A method of producing a modified vegetable protein binder for paper coatings having improved whiteness, brightness and strength wherein a vegetable protein material is oxidized with an oxidizing agent and a low level of magnesium compound.Type: GrantFiled: December 7, 1992Date of Patent: November 15, 1994Assignee: Archer Daniels Midland CompanyInventors: George Poppe, Denise Ciesielski, Mark Matlock
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Patent number: 5362491Abstract: A composition which comprises a modified biologically active protein consisting essentially of a biologically active protein bonded to lecithin via a covalent linkage and a protein inhibitor which does not inhibit the modified biologically active protein.Type: GrantFiled: February 2, 1994Date of Patent: November 8, 1994Assignees: Yutaka Mizushima, Asahi Glass Company Ltd., Seikagaku Kogyo Co., Ltd.Inventor: Yutaka Mizushima
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Patent number: 5362852Abstract: A process is disclosed for site-directed chemical modification of peptides and proteins that consists of two steps; (a) selective oxidation of a 2-hydroxyethylamine moiety, --CH(NH.sub.2)--CH(OH)--, in the peptide or protein to generate an aidehyde, and (b) reaction of the new aldehyde with a second reagent to form a product in which the native biological properties of the peptide are augmented by new and useful properties conferred by the second reagent. Additionally, the invention pertains to certain specified types of product formed by the above process.Type: GrantFiled: September 27, 1991Date of Patent: November 8, 1994Assignee: Pfizer Inc.Inventor: Kieran F. Geoghegan
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Patent number: 5362858Abstract: The present invention relates to a process for preparing a polyethylene glycol (or derivatives)-hirudin conjugate. It also relates to the polyethylene glycol (or derivatives)-hirudin conjugate obtained and its use as medicinal product for the treatment of thromboses.Type: GrantFiled: February 17, 1993Date of Patent: November 8, 1994Assignee: Transgene S.A.Inventor: Rainer Bischoff
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Patent number: 5359030Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.Type: GrantFiled: May 10, 1993Date of Patent: October 25, 1994Assignee: Protein Delivery, Inc.Inventor: Nnochiri N. Ekwuribe
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Patent number: 5349052Abstract: The invention relates to fractionating a mixture of polyethylene glycol (PEG)-protein adducts having different degrees of PEG substitution by partitioning the PEG-protein adducts in a PEG-containing aqueous biphasic system according to the degree of PEG substitution. A new PEG-gm-CSF obtained by the process is useful in pharmaceutical compositions for use in therapeutic or diagnostic methods.Type: GrantFiled: May 12, 1993Date of Patent: September 20, 1994Assignee: Royal Free Hospital School of MedicineInventors: Cristina Delgado, Gillian E. Francis, Derek Fisher
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Patent number: 5349054Abstract: The invention is directed to a stroma-free tetrameric mammalian hemoglobin which is crosslinked with benzenepentacarboxylate, in which the crosslinking is carried out by a method comprising the step of activating at least two carboxylate groups of the benzenepentacarboxylate with an activating agent prior to reaction with the hemoglobin as well as methods for its production. Crosslinked stroma-free hemoglobin produced by methods of the present invention may be used in applications requiring physiological oxygen carriers such as in blood substitute solutions, or as in a plasma expander.Type: GrantFiled: August 15, 1991Date of Patent: September 20, 1994Assignee: Duke UniversityInventors: Joseph Bonaventura, Marius Brouwer, Robert E. Cashon
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Patent number: 5334707Abstract: A process for the preparation of acyl phosphate esters of the formula I or salts thereof: ##STR1## wherein R and R.sup.1 are the same or different and represent a linear or branched alkyl group having up to 4 carbon atoms, phenyl or benzyl;n is an integer;when n is 1, R.sup.2 represents the group ##STR2## wherein R.sup.4 is a linear or branched alkyl, alkenyl or alkynyl, a cyclic alkyl, a cyclic alkenyl, or aryl which may be substituted by alkyl, alkenyl, alkynyl, aryl, arylalkyl, or arylalkenyl, orwhen n is at least 2, R.sup.2 represents the group ##STR3## wherein R.sup.4 is as defined above. Novel compounds of the formula I wherein n is at least 2, and modified hemoglobin obtained using the novel compounds are also provided.Type: GrantFiled: September 15, 1992Date of Patent: August 2, 1994Inventors: Ronald H. Kluger, Andrew S. Grant
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Patent number: 5334705Abstract: The invention is directed to a low oxygen affinity stroma-free tetrameric mammalian hemoglobin which is produced by crosslinkng with a derivative of benzenetricarboxylate, as well as methods for its preparation. Crosslinked stroma-free hemoglobin produced by methods of the present invention may be used in applications requiring physiological oxygen carriers such as in blood substitute solutions, or as in a plasma expander.Type: GrantFiled: August 15, 1991Date of Patent: August 2, 1994Assignee: Duke UniversityInventors: Joseph Bonaventura, Marius Brouwer, Robert E. Cashon
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Patent number: 5324844Abstract: Poly(ethylene glycol)-N-succinimide carbonate and its preparation are disclosed. Polyethylene glycol (PEG) is converted into its N-succinimide carbonate derivative. This form of the polymer reacts readily with amino groups of proteins in aqueous buffers. The modified proteins have PEG-chains grafted onto the polypeptide backbone by means of stable, hydrolysis-resistant urethane (carbamate) linkages.Type: GrantFiled: January 8, 1992Date of Patent: June 28, 1994Assignee: Enzon, Inc.Inventor: Shmuel Zalipsky
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Patent number: 5322678Abstract: There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.Type: GrantFiled: February 17, 1988Date of Patent: June 21, 1994Assignee: NeoRx CorporationInventors: Alton C. Morgan, Jr., Gowsala P. Sivam, Paul G. Abrams
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Patent number: H1662Abstract: The invention provides chemically modified lymphokines comprising a lymphokine moiety and at least one polyethylene glycol moiety of the formula: R.paren open-st.O--CH.sub.2 CH.sub.2 .paren close-st..sub.n wherein R is a protective group for the terminal oxygen and n is at least one, bonded directly to at least one primary amino group of the lymphokine moiety, and a method of producing the same.The chemically modified lymphokines according to the invention can be produced by reacting a lymphokine with an aldehyde of the formula R.paren open-st.O--CH.sub.2 CH.sub.2 .paren close-st..sub.n-1 O--CH.sub.2 CHO wherein R and n are as defined above, in the presence of a reducing agent.The chemically modified lymphokines according to the invention are useful as drugs, among others.Type: GrantFiled: April 5, 1990Date of Patent: July 1, 1997Inventors: Osamu Nishimura, Masahiko Fujino