Oxygen Containing Reactant Patents (Class 530/410)
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Patent number: 5087616Abstract: A therapeutic composition comprising a chemical conjugatge including a first moiety, other than an immunoglobulin or fragment thereof, such as epidermal growth factor, which preferentially binds to a tumor cell, and is internalized by the cell, and a second moiety linked to the first moiety, and comprising a biodegradable polymeric carrier, such as polyglutamic acid, to which one or more cytotoxic molecules, for instance, daunomycin, are attached. The degradation of the carrier by intracellular enzymes releases a cytotoxic agent, resulting in selective destruction of the tumor cells.Type: GrantFiled: August 6, 1987Date of Patent: February 11, 1992Assignee: Battelle Memorial InstituteInventors: Andre E. Myers, Daniel Bichon
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Patent number: 5073628Abstract: A novel hyposensitization agent was prepared by covalently attaching a saccharide to a cedar pollen allergen having a partial amino acid sequence of Ala-Ile-Asn-Ile-Phe-Asn- beginning at its N-terminal. The hyposensitization agent, when compared with an intact cedar pollen allergen, extremely accelerates the production of immunoglobulin G and M antibodies which are specific to intact cedar pollen allergen, but extremely reduces the production of immunoglobulin E antibody which is specific to the allergen. Thus, the hyposensitization agent is administrable to cedar pollinosis patients with no anaphylaxis and allergy, and cuts hyposensitization period to about 1/3 to 1/200.Type: GrantFiled: August 29, 1990Date of Patent: December 17, 1991Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku KenkyujoInventors: Tyoku Matsuhashi, Mitsuko Usui, Masakazu Mitsuhashi, Shunsaku Ando
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Use of intermediate length alcohols as virucidal agents in solutions of biologically active proteins
Patent number: 5071650Abstract: Soluble, intermediate length alcohols (C.sub.4 -C.sub.10) in aqueous solutions at low pH (4.0-7.0) can be used as virucidal agents for therapeutic biologically active protein preparations. Treatment with the alcohols is especially useful for proteins having activity not adversely affected by low pH.Type: GrantFiled: June 4, 1990Date of Patent: December 10, 1991Assignee: Miles Inc.Inventors: George B. Dove, Milton B. Dobkin, Michael A. Shearer -
Patent number: 5066490Abstract: Crosslinking reagents for amino group-containing compounds are provided, which crosslinkers can be cleaved under mildly acidic conditions. The crosslinkers can be used to crosslink biologically active substances to be delivered to the cells, wherein the crosslinker will be cleaved in the mildly acidic conditions within the cell.Type: GrantFiled: June 1, 1988Date of Patent: November 19, 1991Assignee: The United States of America as represented by the Secretary of the Department of Health & Human ServicesInventors: David M. Neville, Jr., Kasturi Srinivasachar
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Patent number: 5064767Abstract: Polypeptides are sequenced from the carboxyl terminus by treating the peptide with an iodoxybenzene, followed by removal of the excess reagent and reaction with 2-aminothiophenol at an elevated temperature. The resulting benzthiazolidine is then analyzed to determine the C-terminal amino acid which has been cleaved. A kit which contains the iodoxybenzene and 2-aminothiophenol reagents is separate containers is also disclosed.Type: GrantFiled: June 21, 1990Date of Patent: November 12, 1991Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Dean A. Le, Kazuhiko Tatemoto
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Patent number: 5061790Abstract: A method for conferring or increasing the antigenicity of a disulfide-crosslinked protein by treating the protein with an oxidizing agent, such as periodate, having an oxidation potential sufficient to cleave disulfide linkages. Excess oxidizing agent is then inactivated by addition of a reducing agent. The resulting protein exhibits an increase in its ability to be bound by select antibodies, particularly monoclonal antibodies directed to linear peptide epitopes in the protein.Type: GrantFiled: July 10, 1989Date of Patent: October 29, 1991Assignee: Molecular Diagnostics, Inc.Inventors: James J. Elting, Heinz Kolbl
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Patent number: 5061626Abstract: The invention concerns antigens for the production of antibodies to Platelet Activating Factor (PAF). The antigens are PAF analogues of formula (I) ##STR1## wherein X comprises a high molecular weight group, R.sup.1 is a linking group and R.sup.2 to R.sup.5 are selected from C.sub.1 to C.sub.6 alkyl.Other aspects of the invention include PAF-antibodies produced using said antigens, labelled PAF analogues, intermediates for the preparation of PAF analogues and methods and a kit for the immunoassay of PAF.Type: GrantFiled: November 24, 1987Date of Patent: October 29, 1991Assignee: University of SydneyInventors: Brian A. Baldo, John W. Redmond
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Patent number: 5057302Abstract: The present invention provides bifunctional chelating agents comprising a unique substrate reactive moiety incorporated into a carboxymethyl arm of a polyaminopolycarboxylate chelating framework capable of forming stable complexes with metal ions.Type: GrantFiled: January 4, 1988Date of Patent: October 15, 1991Assignee: Abbott LaboratoriesInventors: David K. Johnson, Steven J. Kline
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Patent number: 5055562Abstract: Fluorocarbon chain-containing linking arms can be used to conjugate haptens to protein carriers such as BSA, HSA, or antibodies without recourse to harsh chemistry. In addition, .sup.19 F atoms serve as markers for quantitative estimation of bound haptens.Type: GrantFiled: February 1, 1988Date of Patent: October 8, 1991Assignee: Biomira, Inc.Inventor: R. Rao Koganty
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Patent number: 5043424Abstract: A peptide or protein is modified by reacting a phosphoric acid ester represented by the following general formula (I) with a peptide or protein: ##STR1## wherein R.sub.1 means a linear or branched, C.sub.1-36 alkyl or C.sub.2-36 alkenyl group whose hydrogen atom or atoms may be substituted by the corresponding number of fluorine atom(s) or a phenyl group substituted by at least one linear or branched C.sub.1-15 alkyl group, R.sub.2 denotes a C.sub.2-3 alkylene group, m stands for a number of 0-30, and M is a hydrogen atom, an alkali metal ion, an alkaline earth metal ion, an ammonium ion, an alkylamine residue or an alkanolamine residue.Type: GrantFiled: October 21, 1988Date of Patent: August 27, 1991Assignee: Kao CorporationInventors: Akira Matsunaga, Nobutaka Horinishi, Junya Wakatsuki, Takashi Imamura, Tomihiro Kurosaki
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Patent number: 5030719Abstract: Cytotoxic antibody conjugates in which a folic acid-antagonistic folic acid analogue is bound to an antibody or its fragment through an oligopeptide. The conjugates can be used as a chemotherapeutic agent against malignant tumors.Type: GrantFiled: April 27, 1988Date of Patent: July 9, 1991Assignee: Teijin LimitedInventors: Naoji Umemoto, Yoshinori Kato, Takeshi Hara
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Patent number: 5023323Abstract: A method for the solubilization and naturation of somatotropin from refractile bodies produced by r-DNA technology wherein the refractile bodies are dissolved in an aqueous solution comprising a chaotropic agent such as urea or guanidine hydrochloride and a soluble surfactant such as sodium dodecylsulfate. The solubilized protein is exposed to mild oxidation for a time sufficient to allow the protein to form disulfide bonds and refold to its native conformation. The presence of the surfactant suppresses the formation of somatotropin dimers and aggregates and results in higher yields of the desirable monomeric form of the protein.Type: GrantFiled: September 12, 1990Date of Patent: June 11, 1991Assignee: Monsanto CompanyInventor: Sa V. Ho
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Patent number: 5017693Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier.Type: GrantFiled: December 19, 1989Date of Patent: May 21, 1991Assignee: NeoRx CorporationInventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
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Patent number: 5013547Abstract: A drug-protein conjugate of the general formula (I): ##STR1## where the moiety A--NH-- is the condensation product of an anticancer antibiotic having a free amino group, n is 0, 1 or 2, m is 0, 1, 2 or 3, the moiety --NHAB is the condensation product of a protein having a free amino group and the moiety ##STR2## is the condensation product of an amino acid of the formula HOOC--AA--NH.sub.2.Type: GrantFiled: February 7, 1989Date of Patent: May 7, 1991Assignee: Erbamont, Inc.Inventors: Frederick Sweet, Leonard O. Rosik
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Patent number: 5011913Abstract: Diphosphonate-derivatized macromolecules, such as proteins, suitable for use as technetium-99m-based scanning agents and as anticalcification agents are disclosed. The scanning agents are prepared by combining Tc-99m in a +3, +4 and/or +5 oxidation state with the diphosphonate-derivatized macromoleules. Also disclosed are pharmaceutical compositions containing these diphosphonate-derivatized macromolecules and methods for scintigraphic imaging using these diphosphonate-derivatized macromolecules labeled with Tc-99m.Type: GrantFiled: May 11, 1989Date of Patent: April 30, 1991Assignee: The Procter & Gamble CompanyInventors: James J. Benedict, Charles R. Degenhardt, James W. Poser
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Patent number: 5008377Abstract: A method for the preparation of a protein in a physiologically active or native form, which method includesproviding a source of protein in a solubilized form,and a cationic exchange medium;contacting the source of protein and cationic exchange medium; andrecovering the protein in a physiologically active form.Type: GrantFiled: April 21, 1988Date of Patent: April 16, 1991Assignee: Bunge (Australia) Pty. Ltd.Inventors: Joseph J. Patroni, Malcolm R. Brandon
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Patent number: 5008372Abstract: Deblocking of amino terminal N-acetyl serine and N-acetyl threonine residue in proteins and peptides to allow sequencing by the Edman degradation technique is carried out by reacting blocked protein or peptide with anhydrous trifluoracetic acid for 1 to 15 minutes at 30.degree. to 60.degree. C., removing the remaining trifluoroacetic acid and maintaining reacting mixture from which trifluoroacetic acid has been removed at 30.degree. to 100.degree. C. for 60 minutes to 5 days.Type: GrantFiled: February 12, 1990Date of Patent: April 16, 1991Assignee: Cornell Research Foundation, Inc.Inventor: Daniel Wellner
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Patent number: 4996299Abstract: Disclosed is a method for preparing pertussis toxin toxoid by a treatment pertussis toxin with formaldehyde, which comprises carrying out said treatment in the presence of lysine or glycine in combination with N-acetyltriptophan. The resultant toxoid does not exhibit toxicity reversion, thereby making the toxoid highly suitable for use in pertussis vaccines.Type: GrantFiled: November 28, 1989Date of Patent: February 26, 1991Assignee: Juridical Foundation The Chemo-Sero-Therapeutic Research InstituteInventors: Akihiro Ginnaga, Kazunori Morokuma, Katsutoshi Aihara, Mitsuo Sakoh
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Patent number: 4985544Abstract: Reactivation of cysteine-containing protein in a process, in which a reduced and denatured cysteine-containing protein such as salmon growth hormone I or eel growth hormone I can be efficiently reactivated.Type: GrantFiled: August 2, 1988Date of Patent: January 15, 1991Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Yoshiharu Yokoo, Seiji Sugimoto
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Patent number: 4977248Abstract: A method for the renaturation of unfolded proteins comprises reversibly immobilizing the denatured protein on a solid phase and inducing folding of the immobilized protein by progressively reducing with time the concentration of a denaturing agent in the solvent in contact with the solid phase. The refolded protein is recovered from the solid phase in native form. The proteins can be folded and recovered in high yield in a small volume of buffer.Type: GrantFiled: August 10, 1989Date of Patent: December 11, 1990Inventor: Thomas E. Creighton
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Patent number: 4962189Abstract: The invention herein is directed to methods using Procion dyes to perform separations of interest in manipulating the NAD.sup.+ -independent ribotoxins. The methods are useful for preparing therapeutic agents containing these ribotoxins or their A polypeptide components. This separation method has been applied in particular to preparing hybrid toxins containing ricin toxins, both for purifying the resulting products and also for separating the components intended to be used in the preparation of these end products. In addition, a novel ricin isotoxin prepared using the method of the invention is disclosed.Type: GrantFiled: December 11, 1987Date of Patent: October 9, 1990Assignee: Cetus CorportionInventor: Will Bloch
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Patent number: 4952495Abstract: Hydrolyzable substrates comprise blocked moieties which, when cleaved from the substrate during hydrolysis, provide electron transfer agents. The released electron transfer agents can be recycled between a reductant and a reducible compound that upon reduction provides a detectable species. Alternatively, they can be recycled between an oxidant and an oxidizable compound that upon oxidation provides a detectable species. These substrates are useful in analytical compositions, elements and methods for the determination of hydrolytic analytes, such as hydrolytic enzymes or biological cells containing such enzymes.Type: GrantFiled: June 8, 1987Date of Patent: August 28, 1990Assignee: Eastman Kodak CompanyInventors: Robert T. Belly, Patricia M. Scensny, Annie L. Wu, Chung-yuan Chen
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Patent number: 4946945Abstract: A protein conjugate or mixture useful in immunotherapy composed of a biological response modifier (BRM) and an allergen is disclosed. In use the protein conjugate or mixture is combined with a pharmaceutically acceptable carrier. Cytokines, bacterial, fungal and viral immunopotentiators and thymus hormones are disclosed as suitable BRM's for use in the invention.Type: GrantFiled: June 23, 1987Date of Patent: August 7, 1990Assignee: Allergy Immuno Technologies, Inc.Inventor: Aristo Wojdani
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Patent number: 4933434Abstract: The present invention provides a process for the renaturation of denatured proteins in solution in a renaturation buffer, wherein a solution is prepared of the protein to be renatured in the critical concentration in a selected buffer and, after formation of the folding intermediate, further protein to be renatured is added in the amount necessary for the achievement of the critical concentration.Type: GrantFiled: January 13, 1989Date of Patent: June 12, 1990Assignee: Boehringer Mannheim GmbHInventors: Rainer Rudolph, Stephan Fischer
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Patent number: 4931544Abstract: A pharmaceutical composition is prepared wherein biologically active conjugated interleukin-2 is dissolved in an aqueous carrier medium without the presence of a solubilizing agent. The unconjugated IL-2, which is not water soluble or not readily soluble in water at pH 6-8 without such solubilizing agent, is selectively conjugated to one or more succinyl groups by reaction with succinic anhydride.Type: GrantFiled: January 27, 1988Date of Patent: June 5, 1990Assignee: Cetus CorporationInventors: Nandini Katre, Michael J. Knauf
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Patent number: 4931543Abstract: A process for recovering substantially pure rIL-2 from transformed microorganisms in which the cells are disrupted, impure insoluble rIL-2 is separated from the bulk of the cellular components, the separated impure rIL-2 is solubilized and partially purified in a reduced form, the solubilized rIL-2 is oxidized, the oxidized rIL-2 is purified to clinically acceptable levels, and the oxidized, purified IL-2 is denatured by placing it into a solution of a chaotropic agent, solids are removed from the solution and rIL-2 is renatured from the solution.Type: GrantFiled: March 25, 1988Date of Patent: June 5, 1990Assignee: Cetus CorporationInventors: Robert Halenbeck, Flint Smith, Michael Kunitani
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Patent number: 4925921Abstract: This process involves the use of benzoquinone as cross-linking agent in large excess compared with the substance to be activated. The activation reaction is realized in a homogeneous liquid medium. Said process making it possible for example to couple antibodies to enzymes for determining or detecting said antibodies.The process can be used for the determination of antitetanic antibodies in human serum.Type: GrantFiled: March 24, 1986Date of Patent: May 15, 1990Assignee: Etablissement Declare d'Utilite Publique Dit. Institut PasteurInventors: Stratis Avrameas, Therese M. F. Ternynck
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Patent number: 4919928Abstract: The present invention relates to conjugates in which a monovalent carboxylic ionophore is associated by means of a covalent bond with a macromolecule chosen from antibodies, fragments of antibodies, and peptide ligands. It also relates to the activated ionophores.These conjugates are suitable as immunotoxin potentiators.Type: GrantFiled: April 6, 1987Date of Patent: April 24, 1990Assignee: SanofiInventors: Franz Jansen, Pierre Gros
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Patent number: 4911912Abstract: Glycoprotein (GPIR) having the ribosome-inhibiting activity of the native GPIR and having a prolonged-action in vivo which is obtained by oxidation of its osidic units by the action of periodate ions, and simultaneous reduction with cyanoborohydride ions. Said modified glycoprotein may be coupled to an antibody or a fragment thereof in order to form an immunotoxin having a prolonged-action in vivo.Type: GrantFiled: December 15, 1986Date of Patent: March 27, 1990Assignee: SanofiInventors: Pierre Casellas, Bernard Bourrie, Xavier Canat
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Patent number: 4911911Abstract: Glycoprotein (GPIR) the ribosome-inhibiting activity of the native GPIR and having a prolongedaction in vivo which is obtained by oxidation of its osidic units by the action of periodate ions, and simultaneous blocking of the oxidation product by formation of a Schiff's base with a suitable primary amine. Said modified glycoprotein may be coupled to an antibody or a fragment thereof in order to form an immunotoxin.Type: GrantFiled: December 15, 1986Date of Patent: March 27, 1990Assignee: SanofiInventors: Pierre Casellas, Bernard Bourrie, Xavier Canat
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Patent number: 4904584Abstract: A homogeneously modified protein is provided having one or more selected naturally occurring lysine residues replaced by a suitable amino acid, or having one or more lysine residues substituted for other amino acids or inserted into a polypeptide sequence, leaving selected lysine residues having .epsilon.-amino groups in the protein and coupling amine reactive compounds to selected lysine residues. Methods for producing the selected homogeneously modified proteins and pharmaceutical compositions containing such proteins are provided.Type: GrantFiled: December 23, 1987Date of Patent: February 27, 1990Assignee: Genetics Institute, Inc.Inventor: Gray Shaw
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Patent number: 4886780Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumor agents. Such conjugates are useful in the treatment of tumors. Suitable anti-tumor agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin is preferably coupled to the anti-tumor agent by means of glutaraldehyde.Type: GrantFiled: July 12, 1988Date of Patent: December 12, 1989Inventor: Ward P. Faulk
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Patent number: 4841023Abstract: There is disclosed a process for rendering a labile protein-containing composition, substantially free of lipid-containing viruses without incurring substantial protein denaturation comprising contacting said composition with an effective amount of a fatty acid or a soluble ester, alcohol or a salt thereof for a sufficient period of time to inactivate virus contained therein.Type: GrantFiled: June 25, 1986Date of Patent: June 20, 1989Assignee: New York Blood Center, Inc.Inventor: Bernard Horowitz
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Patent number: 4820805Abstract: A mammalian blood protein-containing composition such as whole blood, plasma, serum, plasma concentrate, cryoprecipitate, cryosupernatant, plasma fractionation precipitate or plasma fractionation supernatant substantially free of hepatitis and other lipid coated viruses with the yield of protein activity to total protein being at least 80% is disclosed. The protein-containing composition is contacted with di- or trialkylphosphate, preferably a mixture of trialkylphosphate and detergent, usually followed by removal of the di- or trialkylphosphate.Type: GrantFiled: April 22, 1985Date of Patent: April 11, 1989Assignee: New York Blood Center, Inc.Inventors: Alexander R. Neurath, Bernard Horowitz
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Patent number: 4791192Abstract: The chemically modified protein of the present invention has a strong islet-activating activity and is lower in various side effects than non-modified IAP, so that it may be employed as a prevention and therapeutic drug for diabetes.Type: GrantFiled: June 18, 1987Date of Patent: December 13, 1988Assignee: Takeda Chemical Industries, Ltd.Inventors: Yasushi Nakagawa, Takashi Ito
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Patent number: 4782138Abstract: This invention relates to a process for selectively separating the alpha-lactalbumin from the proteins of whey; the process comprises a heat treatment of the whey previously concentrated to a dry matter content of 10 to 40% by weight, and acidified to a pH of less than 4, preferably from 3 to 3.5, said heat treatment being carried out at a temperature not exceeding 75.degree. C., preferably from 45.degree. to 75.degree. C., for a duration of 15 seconds to 1 hour so as selectively to precipitate the alpha-lactalbumin; this heat treatment is followed by the recovery of the alpha-lactalbumin in the form of a precipitate and possibly of the other lacto-proteins remaining in solution in the residual whey. The process presents the advantage of being simple to carry out and being of low cost.Type: GrantFiled: June 17, 1986Date of Patent: November 1, 1988Assignee: Laiteries E. Bridel, s.a.Inventors: Jean-Paul Rialland, Jean-Pierre Barbier
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Patent number: 4777244Abstract: Crosslinked hemoglobin preparations of extended shelf life and high oxygen transport capacity can be made by reducing a hemoglobin solution with an oxygen consuming reducing agent down to an oxygen partial pressure of 0 mbar, then adding an effector, crosslinking with a dialdehyde, reducing with a carbonyl-group-specific reducing agent, circulating through an ultrafilter, and stabilizing the product by adding a reducing agent thereto.Type: GrantFiled: May 8, 1987Date of Patent: October 11, 1988Assignee: Biotest-Serum-Institut GmbHInventors: Klaus Bonhard, Norbert Kothe
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Patent number: 4762710Abstract: A method of preparing toxoid by treating a toxin with an oxidizing agent is described. Preparation of a vaccine against pertussis in accordance with the method is illustrated.Type: GrantFiled: June 16, 1986Date of Patent: August 9, 1988Assignee: The United States of America as represented by the Department of Health and Human ServicesInventor: Ronald D. Sekura
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Patent number: 4749567Abstract: A product and method for increasing fertility in sheep. By "increasing felity" is meant increasing the potential of a flock of sheep to multiply by increasing ovulation in ewes. The product is an immunogenic conjugate of 4-androstene-3, 17-dione and a soluble milk protein (SMP): 6-hydroxyandrost-4-ene-3, 17-dione 6-hemisuccinyl: SMP. The method comprises immunizing the ewes in a flock of sheep against 4-androstene-3, 17-dione by administering 6-hydroxyandrost-4-ene-3, 17-dione 6-hemisuccinyl SMP at the rate of 3 to 5 mg per ewe. In previously untreated ewes, two administrations are required at between 8 to 9 and 4 to 5 weeks before the planned commencement of mating. Subsequent administrations are annually and are recommended at 5 weeks before the commencement of mating.Type: GrantFiled: October 24, 1986Date of Patent: June 7, 1988Assignee: The Director General of the Ministry of Agriculture and FisheriesInventors: Kenneth P. McNatty, Anton F. Erasmuson, Douglas R. Crump
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Patent number: 4746730Abstract: Bio-available iron-protein derivatives having an iron content of from 2% to 20% by weight and a nitrogen content of from 12% to 16% by weight obtained by reacting acetylated globin with an iron compound selected from the group consisting of ferric chloride, iron fructate and iron saccharate, and pharmaceutical compositions for treating and preventing iron deficiency in animals and humans.Type: GrantFiled: July 17, 1987Date of Patent: May 24, 1988Assignee: Mediolanum FarmaceuticiInventors: Luigi De Ambrosi, Piergiuseppe Pagella
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Patent number: 4745178Abstract: This application describes a process for selectively cleaving a peptide or protein at one or more of its tryptophan residues. The process comprises treating in trifluoroacetic acid said peptide or protein at a concentration of from about 0.05 mM to about 50 mM with an organic sulfoxide at a concentration of from about 0.01M to about 1M, chloride ion at a concentration of from about 0.01M to about 2M, and water at a concentration not in excess of about 10M.Type: GrantFiled: April 22, 1987Date of Patent: May 17, 1988Assignee: Eli Lilly and CompanyInventors: Richard D. DiMarchi, Harlan B. Long
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Patent number: 4720385Abstract: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.Type: GrantFiled: May 20, 1985Date of Patent: January 19, 1988Assignee: Miles Laboratories, Inc.Inventor: Kenneth J. Lembach
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Patent number: 4705845Abstract: A process for sulphation and phosphorylation of a protein or peptide comprising contacting said protein or peptide with sulphuric or phosphoric acid in the presence of a non-aqeuous apolar organic solvent and contacting the resultant solution with a dehydrating agent is disclosed. Non-aggregating insulin products with bioactivity may be prepared by this process.Type: GrantFiled: September 5, 1986Date of Patent: November 10, 1987Assignee: Rockefeller UniversityInventors: Anthony Cerami, Sandor Pongor, Michael Brownlee
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Patent number: 4694073Abstract: A method for solubilization and naturation of somatotropin protein from refractile bodies of host cells is disclosed. The method embraces the discovery that an aqueous solution of urea, or dimethylsulfone, or mixtures of urea and dimethylsulfone, can be effectively used to solubilize refractile bodies containing such somatotropin protein. Once solubilized, somatotropin protein can be natured in an aqueous solution of urea, or dimethylsulfone, or mixtures of urea and dimethylsulfone, by contacting the solution with a mild oxidizing agent for a time sufficient to result in the formation of the disulfide bonds. Naturation can efficiently occur even at high protein concentration, in an impure preparation and in the absence of reducing agent.Type: GrantFiled: August 25, 1986Date of Patent: September 15, 1987Assignee: Monsanto CompanyInventors: Larry A. Bentle, James W. Mitchell, Stephen B. Storrs, Grant T. Shimamoto
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Patent number: 4692509Abstract: A radioactively labeled protein comprising a protein, and a radioactive nucleoside or nucleotide, the protein being covalently linked to the nucleoside or nucleotide. Advantageously the linkage is through an NH.sub.2 group of the protein and through a carbonyl group of a ring-opened sugar moiety of the nucleoside or nucleotide. The protein can be insulin, an immunoglobulin or protein A. The radioactive moiety may be a P, C, S, H, I or Hg atom. The labels can be used to indicate the presence and amount of the protein in a biological assay.Type: GrantFiled: November 27, 1984Date of Patent: September 8, 1987Assignee: Molecular Diagnostics, Inc.Inventor: Nanibhushan Dattagupta
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Patent number: 4683135Abstract: According to the present invention there is provided an essentially pure protein found in nature in mast cells and in basophiles, which protein is involved in the transfer of calcium into such cells. Such a protein has an isoelectric point of about 3.9 and a MW about 60,000.+-.2,000, and has an amino acid composition as herein defined. There are also provided processes for the preparation of such purified protein. Such protein is of use in blocking histamine release from cells.Type: GrantFiled: March 20, 1986Date of Patent: July 28, 1987Assignee: Yeda Research and Development Co., Ltd.Inventors: Israel Pecht, Nachman Mazurek
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Patent number: 4642335Abstract: This invention relates to an antitumor composition of anthracycline compounds bonded to hydrophilic polypeptides having a molecular weight between 10,000 and 15,000.Type: GrantFiled: May 28, 1985Date of Patent: February 10, 1987Assignee: Ajinomoto Co., Inc.Inventors: Shigeyoshi Miyashiro, Takao Kida, Tsuyoshi Shiio, Hiroshiro Shibai
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Patent number: 4640893Abstract: The present invention relates to a new class of novel Rhodamine derivatives. These derivatives which are bisamide substitution products are nonfluorescent. Whereas the monoamide substitution products exhibit high fluorescence. Cleavage of a single specified amide bond by bond-specific proteinases will therefore convert the nonfluorescent bisamide derivative into a highly fluorescent monoamide derivative.Type: GrantFiled: September 27, 1985Date of Patent: February 3, 1987Assignee: University of IllinoisInventors: Walter F. Mangel, Stephen Leytus, L. Lee Melhado
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Patent number: 4600531Abstract: A high yield method of production of a cross-linked hemoglobin derivative suitable for use as a blood substitute and plasma expander which is cross-linked between Lys 99 Alpha.sub.1 and Lys 99 Alpha.sub.2 in high percentage by adding the cross-linker in the presence of an added polyanion which blocks competing reactions at other sites of the protein.Type: GrantFiled: March 18, 1985Date of Patent: July 15, 1986Assignee: University of Iowa Research FoundationInventor: Joseph A. Walder
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Patent number: 4587122Abstract: The drug such as antitumor agents or antibiotics can preferentially be carried to a morbid part, for example, injured tissue and tumor site by administering its complex with fibronectin combined through an oxidized dextran to repair the morbid part. The complex is prepared by reacting the drug, an oxidized dextran having a cleaved structure of aldohexopyranose ring, and fibronectin.Type: GrantFiled: April 23, 1985Date of Patent: May 6, 1986Assignee: The Green Cross CorporationInventors: Yoshio Kagitani, Yasuo Ueda, Kozi Munechika, Satoshi Morimoto, Shirou Komeda, Kenji Tanaka, Kazumasa Yokoyama