Carrier Is A Synthetic Polymer Patents (Class 530/815)
  • Patent number: 5928916
    Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule having a negatively charged moiety is combined with a medical device surface having a positively charged guanidino moiety to form an ionic bond immobilizing a coating of the biomolecule on the surface. In another method, the medical device surface contains an amine moiety that is combined with a guanidino forming agent to form a positively charged guanidino moiety that is combined with the negatively charged moiety to form the ionic bond. In a further embodiment, the medical device surface contains a negatively charged moiety, and a biomolecule containing an amine moiety is combined with a guanidino forming agent to form a positively charged guanidino moiety that is combined with the negatively charged moiety to form the ionic bond.
    Type: Grant
    Filed: January 22, 1998
    Date of Patent: July 27, 1999
    Assignee: Medtronic, Inc.
    Inventor: James R. Keogh
  • Patent number: 5925552
    Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety.
    Type: Grant
    Filed: April 27, 1998
    Date of Patent: July 20, 1999
    Assignee: Medtronic, Inc.
    Inventors: James R. Keogh, Paul V. Trescony
  • Patent number: 5919907
    Abstract: A method of preparing a novel, sterile, receptor rich-albumin molecule which utilizes the disinfecting properties of iodine by reacting an iodine donating material or solution with a pure preparation of albumin, and preferably subsequently removing the iodine. The resulting iodine has improved binding properties because the production method strips bacterial endotoxin and other previously bound substances from the albumin. The improved binding site capacity of the albumin product is advantageously used as an adjunct in removing toxins by means of exchange transfusions. Because iodine disinfects the albumin typical pasteurization and related additives are unnecessary.
    Type: Grant
    Filed: December 22, 1997
    Date of Patent: July 6, 1999
    Assignee: Shanbrom Technologies LLC
    Inventor: Edward Shanbrom
  • Patent number: 5906828
    Abstract: Disclosed are compositions with tethered growth effector molecules, and methods of using these compositions for growing cells and tissues. Growth effector molecules, including growth factors and extracellular matrix molecules, are flexibly tethered to a solid substrate. The compositions can be used either in vitro or in vivo to grow cells and tissues. By tethering the growth factors, they will not diffuse away from the desired location. By making the attachment flexible, the growth effector molecules can more naturally bind to cell surface receptors. A significant feature of these compositions and methods is that they enhance the biological response to the growth factors. The new method also offers other advantages over the traditional methods, in which growth factors are delivered in soluble form: (1) the growth factor is localized to a desired target cell population; (2) significantly less growth factor is needed to exert a biologic response.
    Type: Grant
    Filed: October 8, 1997
    Date of Patent: May 25, 1999
    Assignee: Massachusetts Institute of Technology
    Inventors: Linda G. Cima, Edward W. Merrill, Philip R. Kuhl
  • Patent number: 5902588
    Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.
    Type: Grant
    Filed: November 19, 1997
    Date of Patent: May 11, 1999
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Anthony Martinez, Annapurna Pendri
  • Patent number: 5891341
    Abstract: The present invention is directed to compositions and devices based upon the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions and devices having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
    Type: Grant
    Filed: April 5, 1996
    Date of Patent: April 6, 1999
    Assignee: The Picower Institute for Medical Research
    Inventors: Yong Ming Li, Helen Vlassara, Anthony Cerami
  • Patent number: 5888744
    Abstract: Aminoglycosides such as aminoglycoside antibiotics are detected and separated by non-immunoaffinity binding to an immobilized binding protein which is preferably lysozyme or .alpha.-lactalbumin. Aminoglycosides are detected in a biological sample such as milk or a fermentation broth by contacting the sample with the binding protein immobilized on a solid carrier such as particles of carboxylated latex to bind the aminoglycosides to the binding protein, adding a label that binds to the aminoglycosides and measuring the label. In another embodiment, the binding protein containing bound aminoglycosides is separated from the sample, the aminoglycosides are removed from the binding protein, a label is added to the aminoglycosides and the label is measured. Aminoglycosides are removed from a sample by passing the sample through a bioreactor containing the binding protein immobilized on a solid carrier to bind the aminoglycosides to the binding protein and recovering the sample free of aminoglycosides.
    Type: Grant
    Filed: August 24, 1995
    Date of Patent: March 30, 1999
    Assignee: The United States of America, as represented by the Secretary of Agriculture
    Inventors: Naomi F. Campbell, Marjorie B. Medina
  • Patent number: 5872094
    Abstract: Link protein and cartilage matrix protein, which are two major components of the extracellular cartilage matrix, have been found to bind to each other. Cartilaginous tissue is attached to a surface by anchoring on the surface a fragment of cartilage matrix protein capable of binding to link protein or to collagen and link protein, or a fragment of link protein capable of binding to cartilage matrix protein or to cartilage matrix protein and a complex or proteoglycan and hyaluronic acid, and contacting the surface with cartilaginous tissue. Cartilage matrix protein is attached to a surface by anchoring on the surface a fragment of link protein capable of binding to cartilage matrix protein, and contacting the surface with cartilage matrix protein. Link protein is attached to a surface by anchoring on the surface a fragment of cartilage matrix protein capable of binding to link protein, and contacting the surface with link protein.
    Type: Grant
    Filed: January 6, 1993
    Date of Patent: February 16, 1999
    Assignee: The General Hospital Corporation
    Inventors: Paul F. Goetinck, M. Mehrdad Tondravi, Francois Binette
  • Patent number: 5871747
    Abstract: The invention concerns the use, in the induction of an immune response, of a synthetic microparticle polymer carrying on the surface one or more covalently bonded proteins capable of carrying one or more epitopes, the densities of the protein(s) on the surface of the microparticles, and their molecular weights, being adjusted so as to direct the immune response to the induction of a humoral and cellular response or to the induction of a largely cellular response. Said microparticles have an average diameter of approximately 0.25 to 1.5 .mu.m.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: February 16, 1999
    Assignee: Institut Pasteur
    Inventors: Christine Gengoux-Sedlik, Claude LeClerc
  • Patent number: 5866113
    Abstract: A medical device having a surface graft matrix comprising carboxyl-functional groups located on the device, the surface graft matrix comprising an outer portion; and one or more biomolecules covalently coupled to the surface graft matrix, wherein a majority of the biomolecules are located in the outer portion of the surface graft matrix. The surface graft matrix can also be loaded with a pharmaceutical agent.
    Type: Grant
    Filed: March 7, 1997
    Date of Patent: February 2, 1999
    Assignee: Medtronic, Inc.
    Inventors: Marc Hendriks, Michel Verhoeven, Linda L. Cahalan, Patrick T. Cahalan, Benedicte Fouache
  • Patent number: 5866387
    Abstract: There is provided a method for immobilizing a ligand by reacting a solvent-insoluble carrier having aldehyde group with a compound shown by the general formula: ##STR1## wherein X is --S-- or --O--, R.sup.1, R.sup.2 and R.sup.6 are the same or different, each of which is hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R.sup.3 is hydrogen atom or a substituent wherein an atom adjacent to nitrogen atom shown in the above-mentioned general formula has no unsaturated bond, R.sup.4, R.sup.5 and R.sup.7 are arbitrary substituents; provided that only one partial chemical structure of HX--C--C--NHR.sup.3 wherein X and R.sup.3 are the same as defined above or HX--C--C--C--NHR.sup.3 wherein X and R.sup.3 are the same as defined above is contained in one compound described above by which, a ligand or a compound to which a ligand is bonded can react specifically and effectively with aldehyde group in a solvent-insoluble carrier at a prescribed position to form a stable bond.
    Type: Grant
    Filed: August 28, 1997
    Date of Patent: February 2, 1999
    Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
    Inventors: Eiji Ogino, Kazuo Suzuki, Nobutaka Tani
  • Patent number: 5853744
    Abstract: A method for making a medical device having a biomolecule immobilized on a substrate surface is provided. The method includes: providing an immobilized biomolecule comprising a biomolecule covalently attached to a support material; attaching a photoreactive crosslinking agent to the immobilized biomolecule to form a photoreactive analog of the biomolecule; and removing the photoreactive analog of the biomolecule from the support material. The photoreactive analog of the biomolecule can then be attached to a substrate surface, such as a biomaterial that forms part of a medical device. The immobilized biomolecule may contain a peptide having an N.sup..alpha. -terminus. The photoreactive crosslinking agent is attached to the peptide at the N.sup..alpha. -terminus to form the photoreactive analog of the biomolecule. The peptide can be an adhesion peptide containing the sequence Trp-Gln-Pro-Pro-Arg-Ala-Arg-Ile. Attachment of the peptide to a substrate surface promotes cell adhesion to the surface.
    Type: Grant
    Filed: August 20, 1996
    Date of Patent: December 29, 1998
    Assignee: Regents of the University of Minnesota
    Inventors: Daniel L. Mooradian, Gregg B. Fields
  • Patent number: 5843900
    Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: December 1, 1998
    Assignee: Cortech, Inc.
    Inventors: John C. Cheronis, Albert Gyorkos, Lyle W. Spruce, Eric T. Whalley
  • Patent number: 5817528
    Abstract: A method is provided for producing a sterile and pyrogen-free column containing coupled protein for use in removing a predetermined substance from the blood of a human subject. The method abrogates sterilization of the finished protein-containing product by providing sterile and pyrogen-free raw materials at each production step. The method provides a pathogen-free, purified solution of protein which binds to a predetermined substance in human blood such as LDL or immunoglobulin. Typically, the protein is anti-human LDL immunoglobulin or anti-human Ig immunoglobulin. The method also provides a sterile and pyrogen-free column matrix material such as an agarose which is chemically activated, either using CNBr and triethylamine or using 1,1'-carbonyldiimidazole.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: October 6, 1998
    Assignee: Therasorb Medizinische Systeme GmbH
    Inventors: Wolfgang Bohm, Franz A. Bieber, Jutta Muller-Derlich, Alan Barclay, Reiner Spaethe, Michael Bernhard, Christine Kraus
  • Patent number: 5817527
    Abstract: A new method for immobilization of small molecules on solid supports via a macromolecular spacer has been developed. A protein or another macromolecule is first immobilized in an aqueous medium, and the solid support is than washed with an organic solvent. The small molecule is coupled in an organic medium, followed by organic medium washes. The new solid phases are useful for affinity purifications, immunoassays and other binding assays, and for selection of binders by panning procedures.
    Type: Grant
    Filed: November 6, 1995
    Date of Patent: October 6, 1998
    Assignee: Chiron Diagnostics Corporation
    Inventors: Uri Piran, Steve C. S. Chang, William J. Riordan, James W. Peterson, Edward M. Sunshine
  • Patent number: 5808012
    Abstract: Thermoplastics interdispersed with a variety of functional thermostable proteins and methods for their production are provided. To prepare the subject thermoplastics, a plastic material is contacted with a thermostable polypeptide and then subjected to the heating and molding/extrusion/casting process. The resultant thermoplastics comprise the thermostable polypeptide on the formed plastic surface and at a depth below the plastic surface. The thermostable polypeptides contained in the disclosed compositions retain functional properties or binding specificities through the heating and molding/extrusion/casting processes. Preferred thermostable polypeptides used in the disclosed compositions include silk-like protein polymers, particularly ProNectin.RTM.F. The disclosed methods and compositions find use in many applications where plastics containing finctional thermostable proteins are desired, in particular, cell cultureware.
    Type: Grant
    Filed: January 16, 1996
    Date of Patent: September 15, 1998
    Assignee: Protein Polymer Technologies, Inc.
    Inventors: David M. Donofrio, Erwin R. Stedronsky
  • Patent number: 5773587
    Abstract: Perfluorocarbon polymer-based matrices are coated with a hydrophilic polymer for use in bioaffinity separations. Coating is carried out by dispersing porous particles of inert perfluorocarbon polymer in a water-miscible organic solvent such as acetone or tetrafydrofuran to wet surfaces of the particles, forming a dispersion of the wetted particles in an aqueous solution of hydrophilic polymer such as poly(vinyl alcohol) containing a plurality of hydroxyl groups, at least one being at an end of a polymer chain, to adsorb the hydrophilic polymer onto the wetted surfaces of the particles, admixing a homobifunctional cross-linking agent such as glutaraldehyde with the particles to cross-link the hydrophilic polymer, activating hydroxyl groups on the surface of the cross-linked hydrophilic polymer and covalently bonding a ligand or ligand binder to the activated hydroxyl groups.
    Type: Grant
    Filed: August 6, 1996
    Date of Patent: June 30, 1998
    Assignee: DVC, Inc.
    Inventors: Christopher Robin Lowe, Norman A Parris, Ian Pitfield, Duncan Ross Purvis
  • Patent number: 5753611
    Abstract: Use of .alpha.-hydroxy acids and poly-.alpha.-hydroxy acids as spacer between a therapeutically and/or diagnostically active compound and a soluble macromolecular carrier in pharmaceutical compositions having site-specific delivery. In one embodiment glycolic acid, L-lactic acid or tetra-L-lactic acid is used as spacer between a non-steroidal anti-inflammatory substance and a carrier of low molecular protein (LMWP).
    Type: Grant
    Filed: November 4, 1994
    Date of Patent: May 19, 1998
    Assignee: Rijksuniversiteit Groningen
    Inventors: Erik J. F. Franssen, Frits Moolenaar, Dirk K. F. Meijer, Dick De Zeeuw
  • Patent number: 5741686
    Abstract: A method is provided for preparing a labeled protein, immobilized protein or protein-bioactive agent composition by attaching a label, support or bioactive agent to a protein by exopeptidase catalysis at a site that is remote from the active site of the protein. More specifically, an amine or alcohol group of an amino acid, amine or alcohol nucleophile is reacted by exopeptidase catalysis with a C-terminus carboxylic acid group of a protein such as an antibody, enzyme or hormone to couple the nucleophile to the protein to form an adduct, and the adduct is bound to an auxiliary substance such as a support, label or bioactive agent or its combination with a linker arm by reacting a reactive substituent of the nucleophile with a reactive group of the auxiliary substance. Alternatively, the nucleophile is bound to the auxiliary substance or its combination with a linker arm to form an intermediate, and the intermediate is coupled by exopeptidase catalysis to the protein.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: April 21, 1998
    Assignee: Board of Regents of the University of Nebraska
    Inventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
  • Patent number: 5730968
    Abstract: A composition suitable for use in diagnostic imaging or as a cell killing agent comprising a chelating residue linked via an amide linkage to a poly(alkylene oxide) moiety, said composition having a molecular weight of at least 4,500; ##STR1## wherein: Z is a chelating residue;Q is a divalent poly(alkylene oxidylene) moiety having a carbon terminus at R and at L;L represents an amide linkage;E.sup.(b) is one or more counterions each having a charge of b;b is an integer from 1, 2 and 3;n is an integer selected from the group 1, 2, 3 and 4;w is zero or an integer from 1 to 5;M.sup.(+a) is a cation, having a charge of +a;a is an integer from 1 to 4;r is 0 or an integer from 1 to 3, provided that when r is 2-3, each M.sup.(+a) can be the same or different cation;d is the total charge on the chelating residue and is an integer from 0 to 10;d+.SIGMA.(b.multidot.w)+.SIGMA.(a.multidot.r)=O; andR is a capping moiety chosen from the group consisting of hydrogen, hydroxyl, C.sub.1 -C.sub.
    Type: Grant
    Filed: March 31, 1994
    Date of Patent: March 24, 1998
    Assignee: Sterling Winthrop Inc.
    Inventors: Dennis E. Butterfield, Dennis K. Fujii, David L. Ladd, Robert A. Snow, Julia S. Tan, John L. Toner
  • Patent number: 5723588
    Abstract: Thermoplastics interdispersed with a variety of functional thermostable polypeptides, including proteins, and methods of making such thermoplastics are provided. The disclosure demonstrates that certain polypeptides can retain functional activity through exposure to plastic thermomolding. The polypeptides are exposed to the heating and molding/extrusion/casting process and are hence present on the formed plastic surface and at a depth below the plastic surface. The polypeptides contained in the disclosed compositions retain functional properties or binding specificities through the heating and molding/extrusion/casting processes. Preferred thermostable polypeptides used in the disclosed compositions include silk-like protein polymers, particularly ProNectin.RTM.F. The disclosed methods and compositions find use in many applications where plastics containing functional thermostable polypeptides are desired, in particular, cell cultureware.
    Type: Grant
    Filed: July 9, 1993
    Date of Patent: March 3, 1998
    Assignee: Protein Polymer Technologies, Inc.
    Inventors: David A. Donofrio, Erwin R. Stedronsky
  • Patent number: 5717075
    Abstract: A solid support having surface-attached carboxylic acid groups is reacted with an isoxazolium salt to form an activated support having enol ester and sulfonate groups. After washing to remove residual isoxazolium salt and base, the activated support is dried. A polypeptide is covalently or non-covalently bound to the support. The resultant immobilized polypeptide can be conveniently sequenced by N- and C-terminal sequencing methods. The support can be a polyvinylidene difluoride membrane or a glass fiber membrane having surface attached carboxylic acid groups, and the enol and sulfonate groups are provided by reacting the support with 2-ethyl-5'-phenylisoxazolium sulfonate. The dry support can be stored for at least about 3 months to achieve a peptide immobilization yield that is substantially the same as the yield obtained in the absence of drying.
    Type: Grant
    Filed: March 28, 1996
    Date of Patent: February 10, 1998
    Assignee: The Perkin-Elmer Corporation
    Inventors: Victoria Lee Boyd, Pau-Miau Yuan
  • Patent number: 5679539
    Abstract: Polyolefin particles are chemically modified by oxidation to provide a large surface area and high loading. The particles result in low back pressure in column systems, and are economical to manufacture. The particles are useful as supports in a wide range of applications including general organic as well as biopolymer synthesis, library methods, purification processes and enzyme mediated processes. In a preferred embodiment, polyethylene or polypropylene particles are oxidized in a solution containing trifluoroacetic acid or trifluoromethane sulfonic acid, chromium trioxide and sulfuric acid to provide the particles with a chemically reactive irregular surface and open channels that extend below the surface and up to essentially the length of the radius of the particles resulting in increased surface area and decreased density. The particles have pendant functional groups produced by the oxidation and/or by subsequent chemical reaction.
    Type: Grant
    Filed: January 24, 1995
    Date of Patent: October 21, 1997
    Inventors: Derek Hudson, Ronald M. Cook
  • Patent number: 5679779
    Abstract: Insoluble supports are prepared which possess high surface areas and efficiently dispersed isocyanate groups. These reactive supports are useful for covalently binding proteins which preferably are enzymes and provide catalysts for conducting organic reactions.
    Type: Grant
    Filed: May 23, 1995
    Date of Patent: October 21, 1997
    Assignee: Minnesota Mining and Manufacturing
    Inventors: Steven M. Heilmann, Gary J. Drtina, Louis C. Haddad, Frederick W. Hyde, Dean M. Moren, Robert A. Pranis
  • Patent number: 5656506
    Abstract: A dry detection reagent for detecting an immunologically active substance is prepared containing solid fine polymer particles immobilizing a substance immunologically active for the substance detected. The polymer particles are prepared by one of the following methods: a) ternary copolymerization of a monomer having carboxyl groups, a monomer having amino groups and styrene or its derivatives; b) binary copolymerization of a monomer having carboxyl groups and styrene or its derivatives, and reacting part of the carboxyl groups with a bifunctional amine such as ethylene diamine to provide amino groups; or c) copolymerizing styrene or its derivatives with a monomer having amide groups, and converting part of the amide groups to amino groups and carboxyl groups with the Hofmann reaction, or hydrolyzing part of the amide groups to form carboxyl groups.
    Type: Grant
    Filed: June 1, 1995
    Date of Patent: August 12, 1997
    Assignee: Canon Kabushiki Kaisha
    Inventors: Haruma Kawaguchi, Takeshi Miyazaki
  • Patent number: 5656450
    Abstract: A latent growth factor such as transforming growth factor beta (TGF.beta.) is converted to active form by matrix vesicles or an extract from matrix vesicles. The matrix vesicles may be stimulated with a Regulator of Enhancing Factor (REF) such as 1,25-dihydroxy vitamin D (1,25-(OH).sub.2 D.sub.3) or steroid hormones which may be intercalated into the vesicle membrane. The latent growth factor may be activated in culturing cells such as chondrocytes that have been pretreated with 24,25-(OH).sub.2 D.sub.3 to activate cell differentiation, or in healing of bone or cartilage defects, and activation can be carried out in vivo or in vitro. Biodegradable polymeric implants may be prepared containing latent growth factor, REF, matrix vesicle or matrix vesicle extract.
    Type: Grant
    Filed: May 27, 1994
    Date of Patent: August 12, 1997
    Assignee: Board of Regents, the University of Texas System
    Inventors: Barbara D. Boyan, Zvi Schwartz, Lynda F. Bonewald
  • Patent number: 5637455
    Abstract: HIV-2 virus variants, namely virus HIV D194 and virus HIV D205, which can be cloned from the corresponding virus isolate HIV D194 (ECACC V 87122303) or from the infected cell line HUT 194 (ECACC V 87122306) or from the virus isolate HIV D205 (ECACC V 87122304), respectively, and their RNA or RNA-fragments and DNA and DNA-fragments derived therefrom and/or proteins and the use thereof for diagnostics and therapy.
    Type: Grant
    Filed: December 14, 1994
    Date of Patent: June 10, 1997
    Assignees: Qiagen GmbH, Chemotherapeutisches Forschunginstitut Georg-Speyer-Haus
    Inventors: Karsten Henco, Hagen von Briesen, Andreas Immelmann, Herbert Kuhnel, Ursula Dietrich, Helga Rubsamen-Waigmann, Michalina Adamski
  • Patent number: 5635593
    Abstract: A brandykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.
    Type: Grant
    Filed: May 12, 1995
    Date of Patent: June 3, 1997
    Assignee: Cortech, Inc.
    Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
  • Patent number: 5620958
    Abstract: A bradykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.
    Type: Grant
    Filed: April 13, 1994
    Date of Patent: April 15, 1997
    Assignee: Coretech, Inc.
    Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
  • Patent number: 5610140
    Abstract: The present invention provides a heterodimeric compound possessing bradykinin and neurokinin receptor antagonist activities useful in the treatment of asthma and other inflammatory diseases especially those involving the airway or pulmonary system. The present invention is also useful in the treatment of pain and inflammation.
    Type: Grant
    Filed: August 1, 1994
    Date of Patent: March 11, 1997
    Assignee: Cortech, Inc.
    Inventors: Val S. Goodfellow, Eric T. Whalley, Francine E. Wincott
  • Patent number: 5567422
    Abstract: Water-soluble azlactone activated polyalkylene oxides having improved hydrolytic stability and conjugates of the azlactone activated polyalkylene oxides with biologically active nucleophiles are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.
    Type: Grant
    Filed: March 30, 1994
    Date of Patent: October 22, 1996
    Assignee: Enzon, Inc.
    Inventor: Richard B. Greenwald
  • Patent number: 5563056
    Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.
    Type: Grant
    Filed: February 27, 1995
    Date of Patent: October 8, 1996
    Assignee: BSI Corporation
    Inventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
  • Patent number: 5532137
    Abstract: Monoclonal or polyclonal antibodies capable of recognizing at least one antigenic determinant located on the FR-900506 compound, are disclosed. FR-900506 isa compound having pharmacological activities such as immunosuppressive activity and antimicrobial activity, and has the following structure: ##STR1## Also disclosed are enzyme immunoassays for FR-900506 based on the antibodies of the invention and test kits for detection of FR-900506. A process for preparing a monoclonal antibody which selectively binds to FR-900506 is also disclosed.
    Type: Grant
    Filed: June 6, 1996
    Date of Patent: July 2, 1996
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Mineo Niwa, Kouichi Tamura, Tsutomu Kaizu, Masakazu Kobayashi
  • Patent number: 5516673
    Abstract: Polymers containing a plurality of free hydroxy groups, such as cellulose, agarose or polyvinyl alcohol, are contacted in absence of reactants for hydroxy groups, with at least one N-heterocyclic compound, e.g. pyridine, pyrrole, pyridazine, their partially or fully hydrogenated analogs and any of these which may be substituted, in a pre-activation step prior to reaction with reactant for free hydroxy groups in the polymer, the polymer-bound residue of which reactant may be thereafter reacted in turn with amino compounds containing at least one unsubstituted N-attached hydrogen atom, e.g. proteins, thereby to form amine-polymer conjugates. The invention further relates to a powder, bandage, patch or like cover for application to wounds which has been manufactured from polymer containing a plurality of hydroxy groups by a process which includes the step of providing an amine conjugated to the polymer; the amine may be, e.g., trypsin, chymotrypsin, lysozyme, collagenase, albumin and hyaluronidase.
    Type: Grant
    Filed: February 10, 1994
    Date of Patent: May 14, 1996
    Assignee: Bar Ilan University
    Inventors: Shlomo Margel, Sophia Sturchak
  • Patent number: 5514600
    Abstract: The invention provides a method for detecting the presence of ARD 1 protein in a sample. The method includes the steps of providing labeled or immobilized anti-ARD 1 antibody in a reaction zone, introducing sample into the reaction zone such that ARD 1 protein in the sample, if present, will react with said antibody to form an immunological complex, and detecting the formation of said immunological complex. Cells, nucleotide and amino acid sequences and vectors associated with ARD 1 are also described.
    Type: Grant
    Filed: September 27, 1994
    Date of Patent: May 7, 1996
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Joel Moss, Koichi Mishima, Maria S. Nightingale, Mikako Tsuchiya
  • Patent number: 5512474
    Abstract: A combination of a cell adhesion factor and a positively-charged molecule are bound to the surface of a cell culture support of a bioreactor to improve cell attachment and stabilize cell growth. The positively charged molecule is preferably polylysine, chitosan, poly(ethyleneimine) or acrylics polymerized from acrylamide or methacrylamide and incorporating positively-charged groups in the form of primary, secondary or tertiary amines, or quaternary salts. The cell adhesion factor is preferably fibronectin, laminin, collagen, vitronectin or tenascin, or fragments or analogs having a cell binding domain thereof. The positively-charged molecule and the cell adhesion factor can be covalently bound to the supporting surface. In another embodiment, the positively-charged molecule and the cell adhesion factor are covalently bound to one another and either the positively-charged molecule or the cell adhesion factor is covalently bound to the supporting surface.
    Type: Grant
    Filed: March 9, 1994
    Date of Patent: April 30, 1996
    Assignee: BSI Corporation
    Inventors: David L. Clapper, Wei-Shou Hu
  • Patent number: 5466749
    Abstract: Graft copolymers comprising a poly-alpha-olefin base polymer selected from the group consisting of polyethylene, polypropylene, polystyrene, and compatible mixtures thereof, having grafted thereto an olefinic monomer. The grafted monomer is present in an amount effective to increase the amount of protein that will bind to the graft copolymer as compared with the base polymer.Also disclosed are polymer/protein compositions comprising a graft copolymer having a protein immobilized on the surface thereof, processes for the preparation of the above-described graft copolymers and compositions, methods of immobilizing proteins, and methods of immunoassay based on such immobilization.
    Type: Grant
    Filed: September 14, 1994
    Date of Patent: November 14, 1995
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: Richard J. Rolando, Patrick L. Coleman, Steven L. Kangas, Thomas A. Kotnour
  • Patent number: 5462867
    Abstract: A hydrophobic polymer such as polysulfone or polyethersulfone is modified to contain an increased number of functionalizable chain ends such as by treating with an alkali hydroxide to provide hydroxyl groups. A linker is covalently bonded to a chain end of the polymer and a macromolecule is covalently bonded to the linker. A ligand may be covalently bonded to the macromolecule. The macromolecule can be a natural polymer, a synthetic polymer or a biologically active species. The hydrophobic polymer is preferably in the form of a microporous membrane. By the use of a four-component dope composition, substantially isotropic microporous structures in the form of flat sheets or hollow fibers are produced. An improved spinnerette assembly is provided for the production of hollow fibers.
    Type: Grant
    Filed: February 2, 1994
    Date of Patent: October 31, 1995
    Assignee: Hemasure, Inc.
    Inventors: A. R. M. Azad, Randal A. Goffe
  • Patent number: 5449720
    Abstract: The invention relates to the oral delivery of peptide and protein pharmaceuticals using the vitamin B.sub.12 (VB.sub.12) uptake system, with the delivery being amplified using polymers. More particularly, the invention concerns a complex having the general formula:(V--Q).sub.n --P--(Q'--A).sub.mwhere, V is a carrier which will bind to natural intrinsic factor (IF) selected from vitamin B.sub.12 or an analogue thereof, n is the molar substitution ratio of V in the complex, and is a number from 1.0 to about 10, P is a pharmaceutically acceptable polymer, A is a pharmaceutically active substance, m is the molar substitution ratio of A in the complex, and is a number greater than 1.0 to about 1000, Q and Q' are independently a covalent bond, or a spacer compound linking V, P and A by covalent bonds.
    Type: Grant
    Filed: May 24, 1993
    Date of Patent: September 12, 1995
    Assignee: Biotech Australia PTY Limited
    Inventors: Gregory J. Russell-Jones, Steven W. Westwood, Alison R. Gould, Bernard V. McInerney
  • Patent number: 5444154
    Abstract: 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: Grant
    Filed: June 15, 1994
    Date of Patent: August 22, 1995
    Assignee: Siltech Inc.
    Inventor: Anthony J. O'Lenick, Jr.
  • Patent number: 5439972
    Abstract: Water-soluble compounds derived from a homopolymer or copolymer of maleic anhydride, and applications of the said compounds to supporting biological moleculesWater-soluble compound derived from a homopolymer or copolymer of maleic anhydride having available anhydride functional groups and hydrolyzed anhydride functional groups, wherein the hydrolyzed anhydride functional groups consist of carboxyl functional groups and functional groups derived from carboxyl functional groups carrying a residue of a compound corresponding to the formula I:C.sub.x H.sub.y A.sub.z O.sub.tin which:- A is the nitrogen atom of a primary, secondary or tertiary amine functional group or the sulfur atom of a thiol functional group,- x, z and t, independently of each other, are non-zero integers, and- y is a non-zero integer, not less than 5 when A is a nitrogen atom and not less than 4 when A is a sulfur atom.
    Type: Grant
    Filed: October 12, 1994
    Date of Patent: August 8, 1995
    Assignee: Bio Merieux
    Inventors: Marie-Helene Charles, Thierry Delair, Monique Jaubert, Bernard F. Mandrand
  • Patent number: 5427779
    Abstract: A method for modifying the surface of a solid polymer wherein the polymer surface is exposed to an aqueous solution containing a two-ring heterocyclic compound that is described in more detail herein. The polymer and the two-ring heterocyclic compound are irradiated with electromagnetic radiation having a wavelength ranging from about 10 nm to about 400 nm to photochemically immobilize the two-ring heterocyclic compound to the polymer.
    Type: Grant
    Filed: July 10, 1990
    Date of Patent: June 27, 1995
    Assignee: Nunc A/S
    Inventors: Henrik Elsner, Soren Mouritsen
  • Patent number: 5418284
    Abstract: A bead composition is disclosed herein which comprises a core of a polyacrylonitrile homopolymer or copolymer and a surface of pendant N-haloamide groups. Also disclosed is a process for the production of said composition.
    Type: Grant
    Filed: September 3, 1993
    Date of Patent: May 23, 1995
    Assignee: Cytec Technology Corp.
    Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
  • Patent number: 5403706
    Abstract: A carrier matrix of polyvinyl alcohol-coated glass is dissolvably impregnated with reagent. The matrix is manufactured by slurrying glass fibers in an excess of water and polyvinyl alcohol and forming a layer, which is then dried and impregnated with reagent.
    Type: Grant
    Filed: July 20, 1989
    Date of Patent: April 4, 1995
    Assignee: Boehringer Mannheim GmbH
    Inventors: Hans-Erich Wilk, Dieter Mangold, Rolf Lerch, Joachim Steinbiss
  • Patent number: 5399665
    Abstract: Polymers more suitable for use in organ transplantation are formed by coupling biologically active moieties to the free amino groups of polymers formed by incorporation of .alpha. amino acids into polymers formed of alpha hydroxy acids such as lactic acids. In the preferred embodiment, the peptides are coupled to the free amino groups.
    Type: Grant
    Filed: November 5, 1992
    Date of Patent: March 21, 1995
    Assignees: Massachusetts Institute of Technology, Children's Hospital
    Inventors: Denise Barrera, Robert S. Langer, Peter T. Lansbury, Jr., Joseph P. Vacanti
  • Patent number: 5389533
    Abstract: Biochemical substances such as enzymes are immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5389534
    Abstract: A biosensor is prepared having a selective detection system containing a biochemical substance such as an enzyme immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5386014
    Abstract: The present invention relates to chemically modified hemoglobin produced by a novel and efficient method in which stroma-free hemoglobin is first effectively deoxygenated and reduced and then conjugated with a polyalkylene oxide such as polyethylene glycol (PEG) under conditions which maintain the structural integrity of the heme oxygen binding site. In specific, preferred embodiments of the invention, the deoxygenation and reduction is performed under an inert atmosphere by the amino acid cysteine. In additional specific, preferred embodiments, the structural integrity of the heme oxygen binding site is maintained by a high anionic concentration in the reaction mixture. In further preferred specific emodiments of the invention, the polyalkylene oxide is polyethylene glycol; in still further preferred specific embodiments of the invention, the polyalkylene oxide is linked to hemoglobin via a urethane (carbamate) linkage.
    Type: Grant
    Filed: May 22, 1992
    Date of Patent: January 31, 1995
    Assignee: Enzon, Inc.
    Inventors: Kwang Nho, Shmuel Zalipsky, Frank Davis
  • Patent number: 5380658
    Abstract: A phosphazene polymer carrier is prepared that has functional groups capable of binding a biologically active substance such as an enzyme or antibody and groups which are non-reactive and hydrophilic. A bifunctional aldehyde is reacted with primary amino groups of a shaped phosphazene polymer to form side chains having aldehyde groups, an amino group-containing compound is reacted with a portion of the aldehyde groups to produce the groups that are non-reactive and hydrophilic, and aldehyde groups not reacted are capable of binding a biologically active substance. The phosphazene polymer may be crosslinked prior to reacting with the bifunctional aldehyde.
    Type: Grant
    Filed: September 16, 1993
    Date of Patent: January 10, 1995
    Assignee: Teijin Limited
    Inventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
  • Patent number: 5376369
    Abstract: This invention is directed to an adjuvant composition in the form of an emulsion which is comprised of an emulsion-forming amount of a non-toxic tetra-polyol or of a POP-POE block polymer and an immunopotentiating amount of a muramyldipeptide of the formula: ##STR1## or a pharmaceutically acceptable salt thereof, where R and R.sub.1 are each independently H or acyl of 1 to 22 carbon atoms, R.sub.2 is optionally substituted alkyl or optionally substituted aryl, R.sub.3 is H, alkyl, or aryl, R.sub.4 is H or lower alkyl, X is L-alanyl, L-.alpha.-aminobutyryl, L-arginyl, L-asparginyl, L-aspartyl, L-cysteinyl, L-glutaminyl, L-glutamyl, glycyl, L-histidyl, L-hydroxyprolyl, L-isoleucyl, L-leucyl, L-lysyl, L-methionyl, L-ornithinyl, L-phenylalanyl, L-prolyl, L-seryl, L-threonyl, L-tyrosyl, L-tryptophanyl, or L-valyl, and Y is D-glutamine, D-isoglutamine or D-isoasparagine. This invention is also directed to a vaccine containing an antigen and an adjuvant composition of the invention.
    Type: Grant
    Filed: February 8, 1990
    Date of Patent: December 27, 1994
    Assignee: Syntex (U.S.A.) Inc.
    Inventors: Anthony C. Allison, Noelene E. Byars, Cherng-Chyi Fu, Deborah M. Lidgate, Philip L. Felgner, Linda C. Foster, William A. Lee