Carrier Is A Synthetic Polymer Patents (Class 530/815)
-
Patent number: 5928916Abstract: 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: GrantFiled: January 22, 1998Date of Patent: July 27, 1999Assignee: Medtronic, Inc.Inventor: James R. Keogh
-
Patent number: 5925552Abstract: 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: GrantFiled: April 27, 1998Date of Patent: July 20, 1999Assignee: Medtronic, Inc.Inventors: James R. Keogh, Paul V. Trescony
-
Patent number: 5919907Abstract: 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: GrantFiled: December 22, 1997Date of Patent: July 6, 1999Assignee: Shanbrom Technologies LLCInventor: Edward Shanbrom
-
Patent number: 5906828Abstract: 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: GrantFiled: October 8, 1997Date of Patent: May 25, 1999Assignee: Massachusetts Institute of TechnologyInventors: Linda G. Cima, Edward W. Merrill, Philip R. Kuhl
-
Patent number: 5902588Abstract: 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: GrantFiled: November 19, 1997Date of Patent: May 11, 1999Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Anthony Martinez, Annapurna Pendri
-
Patent number: 5891341Abstract: 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: GrantFiled: April 5, 1996Date of Patent: April 6, 1999Assignee: The Picower Institute for Medical ResearchInventors: Yong Ming Li, Helen Vlassara, Anthony Cerami
-
Patent number: 5888744Abstract: 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: GrantFiled: August 24, 1995Date of Patent: March 30, 1999Assignee: The United States of America, as represented by the Secretary of AgricultureInventors: Naomi F. Campbell, Marjorie B. Medina
-
Patent number: 5871747Abstract: 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: GrantFiled: April 28, 1995Date of Patent: February 16, 1999Assignee: Institut PasteurInventors: Christine Gengoux-Sedlik, Claude LeClerc
-
Patent number: 5872094Abstract: 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: GrantFiled: January 6, 1993Date of Patent: February 16, 1999Assignee: The General Hospital CorporationInventors: Paul F. Goetinck, M. Mehrdad Tondravi, Francois Binette
-
Patent number: 5866113Abstract: 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: GrantFiled: March 7, 1997Date of Patent: February 2, 1999Assignee: Medtronic, Inc.Inventors: Marc Hendriks, Michel Verhoeven, Linda L. Cahalan, Patrick T. Cahalan, Benedicte Fouache
-
Patent number: 5866387Abstract: 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: GrantFiled: August 28, 1997Date of Patent: February 2, 1999Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Eiji Ogino, Kazuo Suzuki, Nobutaka Tani
-
Patent number: 5853744Abstract: 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: GrantFiled: August 20, 1996Date of Patent: December 29, 1998Assignee: Regents of the University of MinnesotaInventors: Daniel L. Mooradian, Gregg B. Fields
-
Patent number: 5843900Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.Type: GrantFiled: June 5, 1995Date of Patent: December 1, 1998Assignee: Cortech, Inc.Inventors: John C. Cheronis, Albert Gyorkos, Lyle W. Spruce, Eric T. Whalley
-
Patent number: 5817528Abstract: 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: GrantFiled: May 16, 1995Date of Patent: October 6, 1998Assignee: Therasorb Medizinische Systeme GmbHInventors: Wolfgang Bohm, Franz A. Bieber, Jutta Muller-Derlich, Alan Barclay, Reiner Spaethe, Michael Bernhard, Christine Kraus
-
Patent number: 5817527Abstract: 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: GrantFiled: November 6, 1995Date of Patent: October 6, 1998Assignee: Chiron Diagnostics CorporationInventors: Uri Piran, Steve C. S. Chang, William J. Riordan, James W. Peterson, Edward M. Sunshine
-
Patent number: 5808012Abstract: 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: GrantFiled: January 16, 1996Date of Patent: September 15, 1998Assignee: Protein Polymer Technologies, Inc.Inventors: David M. Donofrio, Erwin R. Stedronsky
-
Patent number: 5773587Abstract: 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: GrantFiled: August 6, 1996Date of Patent: June 30, 1998Assignee: DVC, Inc.Inventors: Christopher Robin Lowe, Norman A Parris, Ian Pitfield, Duncan Ross Purvis
-
Patent number: 5753611Abstract: 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: GrantFiled: November 4, 1994Date of Patent: May 19, 1998Assignee: Rijksuniversiteit GroningenInventors: Erik J. F. Franssen, Frits Moolenaar, Dirk K. F. Meijer, Dick De Zeeuw
-
Patent number: 5741686Abstract: 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: GrantFiled: October 3, 1994Date of Patent: April 21, 1998Assignee: Board of Regents of the University of NebraskaInventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
-
Patent number: 5730968Abstract: 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: GrantFiled: March 31, 1994Date of Patent: March 24, 1998Assignee: Sterling Winthrop Inc.Inventors: Dennis E. Butterfield, Dennis K. Fujii, David L. Ladd, Robert A. Snow, Julia S. Tan, John L. Toner
-
Patent number: 5723588Abstract: 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: GrantFiled: July 9, 1993Date of Patent: March 3, 1998Assignee: Protein Polymer Technologies, Inc.Inventors: David A. Donofrio, Erwin R. Stedronsky
-
Patent number: 5717075Abstract: 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: GrantFiled: March 28, 1996Date of Patent: February 10, 1998Assignee: The Perkin-Elmer CorporationInventors: Victoria Lee Boyd, Pau-Miau Yuan
-
Patent number: 5679539Abstract: 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: GrantFiled: January 24, 1995Date of Patent: October 21, 1997Inventors: Derek Hudson, Ronald M. Cook
-
Patent number: 5679779Abstract: 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: GrantFiled: May 23, 1995Date of Patent: October 21, 1997Assignee: Minnesota Mining and ManufacturingInventors: Steven M. Heilmann, Gary J. Drtina, Louis C. Haddad, Frederick W. Hyde, Dean M. Moren, Robert A. Pranis
-
Patent number: 5656450Abstract: 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: GrantFiled: May 27, 1994Date of Patent: August 12, 1997Assignee: Board of Regents, the University of Texas SystemInventors: Barbara D. Boyan, Zvi Schwartz, Lynda F. Bonewald
-
Patent number: 5656506Abstract: 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: GrantFiled: June 1, 1995Date of Patent: August 12, 1997Assignee: Canon Kabushiki KaishaInventors: Haruma Kawaguchi, Takeshi Miyazaki
-
Patent number: 5637455Abstract: 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: GrantFiled: December 14, 1994Date of Patent: June 10, 1997Assignees: Qiagen GmbH, Chemotherapeutisches Forschunginstitut Georg-Speyer-HausInventors: Karsten Henco, Hagen von Briesen, Andreas Immelmann, Herbert Kuhnel, Ursula Dietrich, Helga Rubsamen-Waigmann, Michalina Adamski
-
Patent number: 5635593Abstract: 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: GrantFiled: May 12, 1995Date of Patent: June 3, 1997Assignee: Cortech, Inc.Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
-
Patent number: 5620958Abstract: 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: GrantFiled: April 13, 1994Date of Patent: April 15, 1997Assignee: Coretech, Inc.Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
-
Patent number: 5610140Abstract: 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: GrantFiled: August 1, 1994Date of Patent: March 11, 1997Assignee: Cortech, Inc.Inventors: Val S. Goodfellow, Eric T. Whalley, Francine E. Wincott
-
Patent number: 5567422Abstract: 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: GrantFiled: March 30, 1994Date of Patent: October 22, 1996Assignee: Enzon, Inc.Inventor: Richard B. Greenwald
-
Patent number: 5563056Abstract: 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: GrantFiled: February 27, 1995Date of Patent: October 8, 1996Assignee: BSI CorporationInventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
-
Patent number: 5532137Abstract: 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: GrantFiled: June 6, 1996Date of Patent: July 2, 1996Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Mineo Niwa, Kouichi Tamura, Tsutomu Kaizu, Masakazu Kobayashi
-
Patent number: 5516673Abstract: 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: GrantFiled: February 10, 1994Date of Patent: May 14, 1996Assignee: Bar Ilan UniversityInventors: Shlomo Margel, Sophia Sturchak
-
Patent number: 5514600Abstract: 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: GrantFiled: September 27, 1994Date of Patent: May 7, 1996Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Joel Moss, Koichi Mishima, Maria S. Nightingale, Mikako Tsuchiya
-
Patent number: 5512474Abstract: 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: GrantFiled: March 9, 1994Date of Patent: April 30, 1996Assignee: BSI CorporationInventors: David L. Clapper, Wei-Shou Hu
-
Patent number: 5466749Abstract: 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: GrantFiled: September 14, 1994Date of Patent: November 14, 1995Assignee: Minnesota Mining and Manufacturing CompanyInventors: Richard J. Rolando, Patrick L. Coleman, Steven L. Kangas, Thomas A. Kotnour
-
Patent number: 5462867Abstract: 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: GrantFiled: February 2, 1994Date of Patent: October 31, 1995Assignee: Hemasure, Inc.Inventors: A. R. M. Azad, Randal A. Goffe
-
Patent number: 5449720Abstract: 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: GrantFiled: May 24, 1993Date of Patent: September 12, 1995Assignee: Biotech Australia PTY LimitedInventors: Gregory J. Russell-Jones, Steven W. Westwood, Alison R. Gould, Bernard V. McInerney
-
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.
-
Patent number: 5439972Abstract: 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: GrantFiled: October 12, 1994Date of Patent: August 8, 1995Assignee: Bio MerieuxInventors: Marie-Helene Charles, Thierry Delair, Monique Jaubert, Bernard F. Mandrand
-
Patent number: 5427779Abstract: 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: GrantFiled: July 10, 1990Date of Patent: June 27, 1995Assignee: Nunc A/SInventors: Henrik Elsner, Soren Mouritsen
-
Patent number: 5418284Abstract: 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: GrantFiled: September 3, 1993Date of Patent: May 23, 1995Assignee: Cytec Technology Corp.Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
-
Patent number: 5403706Abstract: 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: GrantFiled: July 20, 1989Date of Patent: April 4, 1995Assignee: Boehringer Mannheim GmbHInventors: Hans-Erich Wilk, Dieter Mangold, Rolf Lerch, Joachim Steinbiss
-
Patent number: 5399665Abstract: 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: GrantFiled: November 5, 1992Date of Patent: March 21, 1995Assignees: Massachusetts Institute of Technology, Children's HospitalInventors: Denise Barrera, Robert S. Langer, Peter T. Lansbury, Jr., Joseph P. Vacanti
-
Patent number: 5389534Abstract: 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: GrantFiled: March 22, 1993Date of Patent: February 14, 1995Assignee: Siemens AktiengesellschaftInventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
-
Patent number: 5389533Abstract: 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: GrantFiled: March 22, 1993Date of Patent: February 14, 1995Assignee: Siemens AktiengesellschaftInventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
-
Patent number: 5386014Abstract: 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: GrantFiled: May 22, 1992Date of Patent: January 31, 1995Assignee: Enzon, Inc.Inventors: Kwang Nho, Shmuel Zalipsky, Frank Davis
-
Patent number: 5380658Abstract: 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: GrantFiled: September 16, 1993Date of Patent: January 10, 1995Assignee: Teijin LimitedInventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
-
Patent number: 5376369Abstract: 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: GrantFiled: February 8, 1990Date of Patent: December 27, 1994Assignee: 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