Carrier - Bound Or Immobilized Peptides Or Proteins And The Preparation Thereof, E.g., Biological Cell Or Cell Fragment As Carrier, Etc. Patents (Class 530/810)
  • 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: 5750335
    Abstract: Disclosed is a method of genetic screening for a nucleotide variation, the method including the steps of (A) providing a mixture of nucleic acids comprising heteroduplex nucleic acids and excess homoduplex nucleic acids, wherein each said heteroduplex comprises a test nucleic acid strand isolated from an organism and a reference nucleic acid strand, each said heteroduplex also comprising a mismatched nucleotide pair, wherein said excess homoduplex nucleic acids are generated by reannealing of a first test or reference nucleic acid strand with a fully complementary second test or reference nucleic acid strand; (B) subjecting said mixture to a mismatch binding protein under conditions which promote binding to form a heteroduplex/binding protein complex; and C) detecting the presence of said mismatched nucleotide pair as an indication of the presence of genetic variation between said test and reference nucleic acids.
    Type: Grant
    Filed: April 22, 1993
    Date of Patent: May 12, 1998
    Assignee: Massachusetts Institute of Technology
    Inventor: David K. Gifford
  • Patent number: 5747337
    Abstract: Polypeptides have been discovered which exhibit high specific VIII:C coagulant activity. Monoclonal antibodies to the polypeptides are also disclosed.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: May 5, 1998
    Assignee: The Scripps Research Institute
    Inventors: Theodore S. Zimmerman, Carol A. Fulcher
  • Patent number: 5726243
    Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.
    Type: Grant
    Filed: July 3, 1996
    Date of Patent: March 10, 1998
    Assignee: Regents of the University of Minnesota
    Inventor: Gregg B. Fields
  • Patent number: 5719031
    Abstract: This invention relates to polymers labeled with fluorescent dye to the point that significant fluorescence quenching occurs, such that degradation of the polymer results in fluorescence enhancement. The resulting fluorescence enhancement is useful for measuring the degradation of such polymers, for example as a result of enzymatic hydrolyis of a protein, carbohydrate, nucleic acid, or other natural or synthetic polymer.
    Type: Grant
    Filed: August 14, 1996
    Date of Patent: February 17, 1998
    Assignee: Molecular Probes, Inc.
    Inventors: Richard P. Haugland, Mingjie Zhou
  • Patent number: 5714360
    Abstract: A chemical linking agent is formed of a di- or higher functional photoactivatable compound having at least one group that is charged under the conditions of use in order to provide improved water solubility. The linking agent contains two or more photoreactive groups in order to allow the agent to be used as a cross-linking agent in aqueous systems. The charged group can be provided by a radical that includes one or more salts of organic acids, onium compounds, or protonated amines, (and optionally one or more additional photoreactive groups) and the photoreactive groups can be provided by two or more radicals that include an aryl ketone. The onium compound can provide a quaternary ammonium, sulfonium or phosphonium group.
    Type: Grant
    Filed: November 3, 1995
    Date of Patent: February 3, 1998
    Assignee: BSI Corporation
    Inventors: Dale G. Swan, Richard A. Amos, Terrence P. Everson
  • Patent number: 5691447
    Abstract: Disclosed are immunogens and peptides based on the binding site of gC1q-R for HIV-1 gp120, and immunogens and peptides based on the binding site of HIV-1 gp120 for gC1q-R. The sequence of the gC1q-R binding site for gp120 is shown in SEQ ID NO.: 2. The sequence of the HIV-1 gp120 binding site for gC1q-R is shown in SEQ ID NO.: 3. Also disclosed are antibodies and binding molecules to all such immunogens and peptides, and inducing the endogenous production of such antibodies.
    Type: Grant
    Filed: March 24, 1995
    Date of Patent: November 25, 1997
    Assignee: Tanox Biosystems, Inc.
    Inventors: Michael S. C. Fung, Bill N. C. Sun, Cecily R. Y. Sun, Young Woo Kim, Liming Yu
  • Patent number: 5688506
    Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.
    Type: Grant
    Filed: January 27, 1994
    Date of Patent: November 18, 1997
    Assignee: Aphton Corp.
    Inventors: Stephen Grimes, Robert Scibienski
  • Patent number: 5686252
    Abstract: An immunochemical method is provided for the detection and determination of an analyte. The zeta potential of a latex-particle loaded with an immunologically active substance is measured before and after bringing the loaded latex-particle into contact with an analyte. The difference in zeta potential is correlated with changes of zeta potential for known concentrations of the analyte in order to determine the presence and amount of the analyte.
    Type: Grant
    Filed: October 23, 1995
    Date of Patent: November 11, 1997
    Assignee: Hoechst Japan Limited
    Inventor: Hiroshi Nishizaki
  • Patent number: 5674689
    Abstract: Human calcitonin receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereto may be used in screening systems to identify agonists and antagonists of human calcitonin receptors, thereby providing means for treating and preventing abnormal bone resorption, as well as in methods of diagnosis.
    Type: Grant
    Filed: May 30, 1995
    Date of Patent: October 7, 1997
    Assignee: ZymoGenetics, Inc.
    Inventors: Emma E. Moore, Paul O. Sheppard, Rolf E. Kuestner
  • Patent number: 5670624
    Abstract: Protein is two-dimensionally aggregated and fixed to produce a functional thin film. A denatured film of a first protein is formed on the surface of a substrate solution such as an aqueous sugar or salt solution. A solution of a second protein which may be the same as or different from the first protein is then injected below the surface of the substrate solution at a distance sufficient not to disturb the surface. The substrate solution has a higher surface tension and specific gravity than the second protein solution causing the second protein to float between the denatured protein film and the substrate solution surface to form the two-dimensionally aggregated and fixed protein. The denatured film of first protein may be formed by injection of a solution of the first protein below the surface of the substrate solution. The aggregated and fixed protein can be heated and then transferred onto a solid surface such as in the formation of a biosensor.
    Type: Grant
    Filed: September 20, 1995
    Date of Patent: September 23, 1997
    Assignee: Research Development Corporation of Japan
    Inventors: Hideyuki Yoshimura, Kuniaki Nagayama
  • Patent number: 5663306
    Abstract: A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials.
    Type: Grant
    Filed: September 10, 1987
    Date of Patent: September 2, 1997
    Assignee: Chiron Corporation
    Inventors: Lois Aldwin, Danute E. Nitecki
  • Patent number: 5661019
    Abstract: A trifunctional conjugate is providing having three chemical moieties attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moieties. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second tridentate member to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.
    Type: Grant
    Filed: March 22, 1995
    Date of Patent: August 26, 1997
    Assignee: Beckman Instruments, Inc.
    Inventors: Chan S. Oh, James C. Sternberg
  • Patent number: 5658734
    Abstract: The present invention relates to a process for synthesizing on a single substrate a plurality of chemical compounds having diverse structures. The process involves the use of a bilayer photoresist to build up selected regions of the array in a step wise fashion.
    Type: Grant
    Filed: October 17, 1995
    Date of Patent: August 19, 1997
    Assignee: International Business Machines Corporation
    Inventors: Phillip Joe Brock, William Dinan Hinsberg, Jeffrey William Labadie, Glenn McGall, Gregory Michael Wallraff
  • Patent number: 5658894
    Abstract: Polyionic derivatives of cyclodextrins and methods for preparing these derivatives are provided in which a polyionic derivative of cyclodextrin is combined with a growth factor, preferably a heparin binding growth factor. These compositions are of low solubility and are applied directly to the location of a wound. By virtue of the low solubility, the compositions remain in place at the site of application and slowly release growth factor. In an alternative embodiment, the cyclodextrin derivatives are administered in the absence of growth factor and are used to absorb growth factor present in the body at the location of the wound in order to prevent overstimulation of the wound response.
    Type: Grant
    Filed: November 23, 1994
    Date of Patent: August 19, 1997
    Assignee: The Trustees of the University of Pennsylvania
    Inventor: Paul B. Weisz
  • Patent number: 5652333
    Abstract: Disclosed are immunogens and peptides based on the binding site of gC1q-R for HIV-1 gp120 and immunogens and peptides based on the binding site of HIV-1 gp120 for gC1q-R. The sequence of the gC1q-R binding site for gp120 is shown in SEQ ID NO.: 2. The sequence of the HIV-1 gp120 binding site for gC1q-R is shown in SEQ ID NO.: 3. Also disclosed are antibodies and binding molecules to all such immunogens and peptides, and inducing the endogenous production of such antibodies.
    Type: Grant
    Filed: September 6, 1996
    Date of Patent: July 29, 1997
    Assignee: Tanox Biosystems, Inc.
    Inventors: Michael S. C. Fung, Bill N. C. Sun, Cecily R. Y. Sun, Young Woo Kim, Liming Yu
  • 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: 5618710
    Abstract: A protein such as an enzyme of antibody is immobilized by crosslinking crystals of the protein with a multifunctional crosslinking agent. The crosslinked protein crystals may be lyophilized for storage. A preferred protein is an enzyme such as thermolysin, elastase, asparaginase, lysozyme, lipase or urease. Crosslinked enzyme crystals preferably retain at least 91% activity after incubation for three hours in the presence of a concentration of Pronase.TM. that causes the soluble uncrosslinked form of the enzyme to lose at least 94% of its initial activity under the same conditions. A preferred enzyme:Pronase.TM. ratio is 1:40. Enzyme crystals that are crosslinked may be microcrystals having a cross-section of 10.sup.-1 mm or less.
    Type: Grant
    Filed: February 12, 1993
    Date of Patent: April 8, 1997
    Assignee: Vertex Pharmaceuticals, Inc.
    Inventors: Manuel A. Navia, Nancy L. St. Clair
  • Patent number: 5565548
    Abstract: A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals.
    Type: Grant
    Filed: March 15, 1993
    Date of Patent: October 15, 1996
    Assignees: New York Blood Center, Inc., California Institute of Technology
    Inventors: Alexander R. Neurath, Stephen B. H. Kent
  • Patent number: 5541097
    Abstract: A method for preparing an immobilized enzyme conjugate, whereby the enzyme is treated with a polyfunctional amine reactive material for forming a treated enzyme-containing adduct before being immobilized on a solid support which has been contacted with a solution of a polyamine compound. The method is especially preferred for use with glucoamylase, fungal .alpha.-amylase and .beta.-amylase. Immobilized enzyme conjugates formed by use of this method include treated enzyme-containing adducts. The immobilized enzyme conjugates disclosed herein are more stable and the enzymes immobilized therein are more tightly-held than those otherwise obtained and provided.
    Type: Grant
    Filed: February 9, 1995
    Date of Patent: July 30, 1996
    Assignee: Solvay Enzymes, Inc.
    Inventors: Oreste J. Lantero, Jack W. Brewer, Sharon M. Sarber
  • Patent number: 5516766
    Abstract: Polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are disclosed. Compositions and methods for separating a molecular species, including but not limited to a biologically active protein, from a mixture, for the storage of protein factors and for the therapeutic biodelivery of protein factors which employ the polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are also disclosed.
    Type: Grant
    Filed: November 12, 1993
    Date of Patent: May 14, 1996
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Paul B. Weisz, Yuen W. Shing, Judah Folkman
  • 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: 5510466
    Abstract: A substantially pure receptor protein capable of binding acetylated low density lipoprotein and oxidized low density lipoprotein is disclosed herein. This protein is characterized by having a molecular weight of about 220,000 daltons, and an affinity for oxidized low density lipoprotein and acetylated low density lipoprotein. Further, it is an integral membrane protein which includes a collagen domain. Proteins having an affinity for the receptor protein as well as DNA sequences encoding at least a portion of the receptor protein are also disclosed herein. In addition, devices for purification purposes and methods for detecting atherosclerotic plaques are described, both of which utilize the receptor protein or binding proteins thereto.
    Type: Grant
    Filed: September 16, 1994
    Date of Patent: April 23, 1996
    Assignee: Massachusetts Institute of Technology
    Inventors: Monty Krieger, Tatsuhiko Kodama
  • Patent number: 5476653
    Abstract: Biological factors with enhanced biological activity are prepared by covalently linking a biomolecule to one or more chains of a synthetic polymer wherein the synthetic polymer is derived from the oxymethylene-oxyethylene part structure.
    Type: Grant
    Filed: March 22, 1995
    Date of Patent: December 19, 1995
    Assignee: Amgen Inc.
    Inventors: Colin G. Pitt, Wayne Hendren
  • Patent number: 5472861
    Abstract: A method for preparing an immobilized enzyme conjugate, whereby the enzyme is treated with a polyfunctional amine reactive material for forming a treated enzyme-containing adduct before being immobilized on a solid support which has been contacted with a solution of a polyamine compound. The method is especially preferred for use with glucoamylase, fungal .alpha.-amylase and .beta.-amylase. Immobilized enzyme conjugates formed by use of this method include treated enzyme-containing adducts. The immobilized enzyme conjugates disclosed herein are more stable and the enzymes immobilized therein are more tightly-held than those otherwise obtained and provided.
    Type: Grant
    Filed: January 9, 1995
    Date of Patent: December 5, 1995
    Assignee: Solvay Enzymes, Inc.
    Inventors: Oreste J. Lantero, Jack W. Brewer, Sharon M. Sarber
  • Patent number: 5470712
    Abstract: The present invention relates to antigenic proteins specific to Borrelia burgdorferi which have a molecular weight of 28 kDa or 39 kDa as determined by SDS-PAGE and are reactivity with Lyme borreliosis serum or fragments thereof and to the corresponding DNA. The proteins, especially the 39 kDa proteins (.alpha. and .beta.) can be used to diagnosis mammals previously or currently infected with the Lyme borreliosis causing agent.
    Type: Grant
    Filed: February 19, 1993
    Date of Patent: November 28, 1995
    Inventors: Warren Simpson, T. G. Schwan
  • Patent number: 5466609
    Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.
    Type: Grant
    Filed: October 29, 1992
    Date of Patent: November 14, 1995
    Assignee: Coulter Corporation
    Inventors: Olavi Siiman, Alexander Burshteyn, Ravinder K. Gupta
  • Patent number: 5466589
    Abstract: The present invention is directed to coated substrates having a coating of biological macromolecules, preferably proteins, which are capable of being immobilized on a substrate surface and have a marker. These proteins usually are mutant proteins obtained by mutagenesis of the gene encoding a random positioning protein. When a mutant protein molecule is immobilized on the substrate, the marker of the mutant protein molecule is in a select spatial relationship with both the substrate and the markers of adjacent protein molecules. A substrate coated with an oriented layer of the mutant proteins exhibits improved or different properties when compared to a substrate having a randomly positioned layer of proteins thereon.
    Type: Grant
    Filed: September 11, 1992
    Date of Patent: November 14, 1995
    Assignee: Biotechnology Research & Development Corporation
    Inventors: Jill M. Olinger, Stephen G. Sligar, Mark A. McLean, Paul W. Bohn, Patrick Stayton
  • Patent number: 5459041
    Abstract: Antigenic compositions are disclosed for use in diagnostic kits and the like for detecting the presence of antibodies specific for Campylobacter pylori, bacteria often associated with the occurrence of Type B gastritis and peptic ulcer disease. Samples of bodily fluids, for instance, may be contacted with immobilized antigen which is then washed and tested for the occurrence of significant levels of antigen/antibody complex. Levels exceeding a predetermined positive threshold are indicative of antibodies to Campylobacter pylori in the sample tested. Kits employing the antigenic compositions of the invention preferably include means for detecting the antigen/antibody complex such as materials and reagents for conducting an enzyme-linked immunosorbent assay, Western blot technique, liposome-based assay or other known detection tests.
    Type: Grant
    Filed: February 18, 1988
    Date of Patent: October 17, 1995
    Assignee: Enteric Research Laboratories, Inc.
    Inventors: Martin J. Blaser, Guillermo I. Perez-Perez
  • Patent number: 5443976
    Abstract: Antivenoms to snake, spider, scorpion and jelly fish venoms are produced for the treatment of humans and animals, and for analytical use. The antivenom is purified with an antigen matrix containing a single whole venom or a plurality of whole venoms covalently attached to an insoluble support such as aldehyde-activated agarose. Preferably, the whole venoms forming the plurality of whole venoms are selected from the four whole venoms from C. atrox, B. atrox, C. adamanteus and C. durissus terrificus. A combination of immobilized C. atrox and C. durissus terrificus whole venoms can substantially purify antivenom reactive with all four venoms. The antivenom can be horse or avian such as chicken antivenom.
    Type: Grant
    Filed: July 14, 1994
    Date of Patent: August 22, 1995
    Inventor: Sean B. Carroll
  • Patent number: 5439829
    Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.
    Type: Grant
    Filed: January 24, 1992
    Date of Patent: August 8, 1995
    Assignees: Eli Lilly and Company, Hybritech Incorporated
    Inventors: Leslie D. Anderson, James A. Cook, Gary S. David, Susan M. Hochschwender, Mary S. Kasher, Michele C. Smith, Willem P. C. Stemmer
  • Patent number: 5411865
    Abstract: A method for detecting anti-Leishmania parasite antibodies to a 230 kDa antigen present in Leishmania chagasi and Leishmania donovani is disclosed which comprises obtaining a sample from an individual, contacting the sample with a recombinant K39 repeat unit antigen comprising the amino acid sequence as shown in SEQ ID NO:3, and detecting the presence of anti-Leishmania parasite antibodies in the sample which bind to the recombinant K39 repeat unit antigen.
    Type: Grant
    Filed: January 15, 1993
    Date of Patent: May 2, 1995
    Assignee: Iasys Corporation
    Inventor: Steven Reed
  • Patent number: 5405766
    Abstract: Enzymes and certain other bioactive substances are immobilized on solid substrates which have sufficient functional groups such as hydroxyl or carboxyl. The bioactive substances are linked to the substrates through spacer compounds having a long open alkyl chain with 7-18 carbon atoms and also through phospholipid intermediates. The spacer compound is chemically linked to the substrate. The phospholipid is covalently linked to the spacer compound. Immobilized bioactive substances of the invention exhibit a marked increase in activity and stability. In a preferred embodiment, immobilized enzymes having a high degree of resistance to thermal inactivation are prepared.
    Type: Grant
    Filed: March 25, 1993
    Date of Patent: April 11, 1995
    Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National Defence
    Inventors: Krishna M. R. Kallury, Michael Thompson, William E. Lee
  • Patent number: 5401828
    Abstract: The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis.
    Type: Grant
    Filed: December 15, 1992
    Date of Patent: March 28, 1995
    Assignees: The Johns Hopkins University, Duke University
    Inventors: Bert Vogelstein, Darell Bigner
  • Patent number: 5399481
    Abstract: The present invention discloses polypeptides consisting essentially of an amino acid residue sequence corresponding to a formula selected from the group consisting of: Tyr-His-Asp-Arg-Lys-Glu-Phe-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Tr p-Asp-Thr-Ala-Asn-Asn (SEQ ID NO 1); Ala-Asn-Asn-Pro-Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-Thr-Tyr-Ar g-Gly-Thr (SEQ ID NO 2); Ile-His-Asp-Arg-Lys-Glu-Phe-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Tr p-Asp-Thr-Ala-Asn-Asn-Pro-Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-T hr-Tyr-Arg-Gly-Thr (SEQ ID NO 4); and Gly-Pro-Asp-Ile-Leu-Val-Val-Leu-Leu-Ser-Val-Met-Gly-Ala-Ile-Leu-Leu-Thr-Gl y-Leu-Ala-Ala-Leu-Leu-Ile-Trp-Lys-Leu-Leu-Ile-Thr-Ile-His-Asp-Arg-Lys-Glu-P he-Ala-Lys-Phe-Glu-Glu-Glu-Arg-Ala-Arg-Ala-Lys-Trp-Asp-Thr-Ala-Asn-Asn-Pro- Leu-Tyr-Lys-Glu-Ala-Thr-Ser-Thr-Phe-Thr-Asn-Ile-Thr-Tyr-Arg-Gly-Thr (SEQ ID NO 5), as well as diagnostic kits including same.
    Type: Grant
    Filed: December 29, 1992
    Date of Patent: March 21, 1995
    Assignee: The Scripps Research Institute
    Inventors: Robert McMillan, Mark H. Ginsberg, Edward F. Plow
  • Patent number: 5399501
    Abstract: A specific binding member such as an antigen or antibody is immobilized by covalent attachment to a solid phase such as a latex microparticle. The solid phase is reacted with a heterobifunctional or homobifunctional coupling agent to form a complex that is then reacted with a dithiol compound to form a thiolated solid phase. A specific binding member is reacted with the coupling agent to form a complex which is then reacted with the thiolated solid phase to link the specific binding member to the solid phase through thioethers. Alternatively, the dithiol compound may be reacted with the specific binding member/coupling agent complex to form a thiolated complex that is reacted with the solid phase/coupling agent complex. The coupling agent may contain a spacer. In another embodiment, the solid phase is reacted with a disulfide compound to form a complex and the complex is reacted with a reductant to form a thiolated solid phase which is reacted with a specific binding member/coupling agent complex.
    Type: Grant
    Filed: March 16, 1992
    Date of Patent: March 21, 1995
    Assignee: Abbott Laboratories
    Inventors: Mark R. Pope, Kevin M. Knigge
  • Patent number: 5372809
    Abstract: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity.
    Type: Grant
    Filed: January 31, 1992
    Date of Patent: December 13, 1994
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Lance A. Liotta, William Stetler-Stevenson, Henry Krutzsch
  • Patent number: 5366958
    Abstract: This invention encompasses new and substantially improved methods and compositions for delivery of therapeutic agents to specifically chosen body sites. Conjugation of fibronectin to bioactive agents or to lipids or to liposomes which entrap the bioactive agents permits immobilization of the bioactive agent when administered at collagen-, heparin-, hyaluronic acid-, fibrin/fibrinogen-, or ganglioside-rich sites. Covalent conjugation is achieved by two methods: (1) the enzymatically catalyzed cross-linkage of fibronectin to an amine containing compound, and (2) by a modified NHS method which permits formation of peptide bonds between fibronectin and lipid compounds.
    Type: Grant
    Filed: August 20, 1993
    Date of Patent: November 22, 1994
    Assignee: The Liposome Company, Inc.
    Inventors: Alan L. Weiner, Robert P. Lenk, Sharon S. Carpenter-Green, Michael W. Fountain
  • Patent number: 5362859
    Abstract: An affinity support having an improved capacity for binding target compounds. The support includes an immobilized modified ligand of increased molecular weight. The molecular weight of the ligand is increased via the action of condensation reagents or crosslinkers prior to immobilization. The affinity support is useful in affinity separations of proteins and other biomolecules from complex, biologically-derived fluids.
    Type: Grant
    Filed: July 27, 1992
    Date of Patent: November 8, 1994
    Assignee: Sepracor, Inc.
    Inventor: Stephen E. Zale
  • Patent number: 5352772
    Abstract: A new cellular protein produced by activated T cells and involved in the high affinity binding of interleukin-2 has been discovered. This protein has a molecular weight of about 75,000 (Mr) and is further characterized as having an affinity for IL-2 (in the absence of other receptor proteins) of about 10.sup.-9 molar and is substantially unreactive with anti-Tac antibodies. This new cellular protein, referred to herein as the ".alpha. chain," is believed to interact with the previously isolated 55,000 dalton receptor protein (referred to herein as the ".beta. chain") to form the high affinity interleukin-2 receptor which triggers the growth and mitosis of T cells during an immune response. Methods for isolating and purifying the .alpha. chain protein are disclosed herein as well as techniques for cloning and expressing the protein and related materials. Techniques for raising monoclonal antibodies to such proteins are also disclosed.
    Type: Grant
    Filed: December 19, 1986
    Date of Patent: October 4, 1994
    Assignees: The Trustees of Dartmouth College, United States of America
    Inventor: Kendall A. Smith
  • Patent number: 5284934
    Abstract: The present invention provides a process for preparing a carbohydrate-binding lectin derivative for use as immune modulators or immunoconjugates. The polymer-lectin conjugate produced in accordance with the process is polyethylene glycol Ricinus communis agglutinin I (PEG-RCAI). The lectin is coupled to the polymer by activating the polymer with a coupling agent such as 1,1-carbonyldiimidazole. The polymer-lectin conjugate is biologically active, biocompatible and is expected to be substantially non-immunogenic.
    Type: Grant
    Filed: September 4, 1992
    Date of Patent: February 8, 1994
    Assignee: Health Research Inc.
    Inventor: Howard J. Allen, Jr.
  • Patent number: 5277589
    Abstract: For the determination of antibodies based on an immunoassay technique by incubation with at least three receptors R.sub.1, R.sub.2 and R.sub.3 which are present dissolved in a liquid phase and of which R.sub.1 is an antigen which is capable of being specifically bound to the antibody to be determined, R.sub.2 mediates the binding to the solid phase and R.sub.3 carries a label, separation of the complex which forms from the solution by binding to a solid phase and measurement of the label in one of the phases, a conjugate is used as the receptor R.sub.2 composed of a receptor capable of specific binding to R.sub.1 and a substance S.sub.1, which can be specifically bound, and a conjugate of a receptor which can specifically bind to R.sub.1 and a label is used as R.sub.3, wherein the immobilization of the complex which forms is mediated by binding to a component of the solid phase which can specifically bind S.sub.1.
    Type: Grant
    Filed: March 1, 1991
    Date of Patent: January 11, 1994
    Assignee: Boehringer Mannheim GmbH
    Inventors: Urban Schmitt, Wolfgang Rudinger, Gertraud Ehrlich-Weinreich
  • Patent number: 5258492
    Abstract: The present invention deals with LHRH analogues which contain cytotoxic moieties and have influence on the release of gonadotropins from the pituitary gland of mammals, including humans. The compounds of this invention are represented by the formula:X--R.sup.1 --R.sup.2 --R.sup.3 -Ser-R.sup.5 --R.sup.6 (Q)-Leu-Arg-Pro-R.sup.10 --NH.sub.2whereinR.sup.1 is pGlu, Pro, D-Nal(2), or D-Phe(4Cl),R.sup.2 is His or D-Phe(4Cl),R.sup.3 is Trp, D-Trp or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Phe or R*.sup.6, where R*.sup.6 is D-Orn, D-Lys or D-Phe(NH.sub.2),R.sup.10 is Gly or D-Ala,X is hydrogen, a lower alkanoyl group of 2-5 carbon atoms or carbamyl,Q is bis-(2-chloroethyl)amino group provided that R.sup.6 is D-Phe,where R.sup.6 is R*.sup.6,Q is a complexed metal-containing acyl group having the formula: ##STR1## wherein Q' is Pt(Y).sub.
    Type: Grant
    Filed: June 3, 1991
    Date of Patent: November 2, 1993
    Assignee: The Administrators of the Tulane Educational Fund
    Inventors: Andrew V. Schally, Sandor Bajusz
  • Patent number: 5254672
    Abstract: The invention relates to synthetic peptides which contain certain partial sequences from factor VIIa, the synthesis thereof and the use of these peptides for immunizing an animal and for purifying specific antibodies against the said peptides, to antibodies against these peptides and the use of these antibodies and peptides in therapy and diagnosis.
    Type: Grant
    Filed: March 11, 1991
    Date of Patent: October 19, 1993
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hermann Pelzer, Werner Stuber
  • Patent number: 5252719
    Abstract: A process for producing a protein-oriented membrane which is enhanced physically and chemically by orienting protein and cross linking the oriented protein together, is described. The proteinaceous membrane which is subjected to orientation treatment alone is weak physically and chemically, and its processing and handling are therefore difficult. However, according to the present invention, the protein after the process of orientation is cross linked together to produce a protein-oriented membrane remarkably enhanced physically and chemically.
    Type: Grant
    Filed: August 27, 1990
    Date of Patent: October 12, 1993
    Assignee: Hitachi, Ltd.
    Inventors: Kazuo Takeda, Yoshinori Harada, Hiromichi Shimizu, Chusuke Munakata
  • Patent number: 5227309
    Abstract: A method for the C-terminal sequencing of a peptide in which an alkyl or aryl tin isothiocyanate coupling reagent is used to form a thiohydantoin derivative. Free halogen producing activating agents, such as 2-halo-1-methyl pyridinium salts, may be used as an activating agent for the coupling reagent.
    Type: Grant
    Filed: October 18, 1991
    Date of Patent: July 13, 1993
    Assignee: City of Hope
    Inventors: Jerome Bailey, John E. Shively, Narmada R. Shenoy
  • Patent number: 5223435
    Abstract: Sequential degradation of peptides for sequencing purposes by successive cleavage of amino acids from one end of the peptide chain is performed in an adsorption column with flows of the degradation reagents and wash liquids passing through the column in both directions. Migration of the peptide in one direction is thereby compensated by a subsequent migration in the other, and loss of peptide from the column over repeated cleavages is avoided. In preferred embodiments, the column contains two serially arranged adsorbent zones with differing adsorption characteristics, and the directions of flow of the various system components through the column are selected with a view toward a difference in peptide partitioning between the stationary and mobile phases in one zone vs. the other. The result is that any migration of the peptide occurring at any stage of a given cycle of the procedure occurs at a greater rate toward the zone interface than away from it.
    Type: Grant
    Filed: October 25, 1991
    Date of Patent: June 29, 1993
    Assignee: Genetech, Inc.
    Inventor: William J. Kohr
  • Patent number: 5219564
    Abstract: Copolymers of poly(alkylene oxides) and amino acids or peptide sequences are disclosed, which amino acids or peptide sequences have pendant functional groups that are capable of being conjugated with pharmaceutically active compounds for drug delivery systems and cross-linked to form polymer matrices functional as hydrogel membranes. The copolymers can also be formed into conductive materials. Methods are also disclosed for preparing the polymers and forming the drug conjugates, hydrogel membranes and conductive materials.
    Type: Grant
    Filed: July 5, 1991
    Date of Patent: June 15, 1993
    Assignee: Enzon, Inc.
    Inventors: Samuel Zalipsky, Durgadas Bolikal, Aruna Nathan, Joachim B. Kohn
  • Patent number: 5217881
    Abstract: Ligand reagents are disclosed which consist essentially of recombinant hyperglycosylated cytokines, expressed in yeast, which are purified and conjugated to various functional moieties, for example, biotin groups, via oligosaccharide residues.
    Type: Grant
    Filed: January 24, 1992
    Date of Patent: June 8, 1993
    Assignee: Immunex Corporation
    Inventor: Linda S. Park
  • Patent number: 5196478
    Abstract: This invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligands of organic or inorganic nature to immobilize such ligands.
    Type: Grant
    Filed: April 9, 1990
    Date of Patent: March 23, 1993
    Assignee: Epipharm Allergie-Service Gesellschaft m.b.H.
    Inventors: Janos M. Varga, Peter Fritsch