Oxygen Containing Reactant Patents (Class 530/410)
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Patent number: 5320840Abstract: Pharmaceutical compositions for continuous release of a physiologically active substance in which the physiologically active substance comprises a polypeptide covalently conjugated to a water soluble polymer show particularly desirable release characteristics. Polypeptides for use in the pharmaceutical compositions include G-CSF and solution stable derivatives thereof, human calcitonin and interleukin-2. The material of the composition may be a polylactide or biodegradable hydrogel derived from an amphipathic block copolymer.The compositions enable a therapeutically effective polypeptide to be continuously released over a prolonged period of time following a single administration of the pharmaceutical composition to a patient.Type: GrantFiled: July 22, 1991Date of Patent: June 14, 1994Assignee: Imperial Chemical Industries PLCInventors: Roger Camble, David Timms, Anthony J. Wilkinson
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Patent number: 5310883Abstract: The present invention relates to novel chimeric fibroblast growth factors (FGF) wherein the alanine at amino acid 3 and serine 5 of native human recombinant basic fibroblast growth factor are replaced with glutamic acid. The N-terminus sequence of the present chimeric FGFs identify homology with that of human acidic fibroblast growth factor. The mitogenic properties of the native human recombinant basic FGF are exhibited by the present chimeric FGFs, and they are efficiently expressed in E. coli at significantly greater yields that previously reported. Novel variants of this new glu.sup.3,5 basic fibroblast growth factor, such as those in which cysteine 78 and cysteine 96 are replaced, e.g., with serine or other amino acids, to produce stabilized versions of the glu.sup.3,5 basic FGF and eliminate disulfide scrambled forms, are also described.Type: GrantFiled: November 4, 1991Date of Patent: May 10, 1994Assignee: American Cyanamid CompanyInventors: Andrew P. Seddon, Peter Bohlen, Yakov Gluzman
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Patent number: 5302703Abstract: The present invention is directed to novel THC derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to the THC metabolites. The resulting novel antigens may be used for the production of antibodies or receptors using standard methods. Once generated, the antibodies or receptors and the novel derivatives which are covalently attached to proteins, polypeptides or labels may be used in the immunoassay process.Type: GrantFiled: March 17, 1993Date of Patent: April 12, 1994Assignee: Biosite Diagnostics IncorporatedInventors: Kenneth F. Buechler, Si S. Moi
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Patent number: 5302700Abstract: Compounds of the formulae, ##STR1## are provided where L is a linking group of the formula, ##STR2## is --Sn(n--C.sub.4 H.sub.9).sub.3 or --Sn(CH.sub.3).sub.3, HgCl or --N.sub.2.sup.+ ; R is hydrogen, methyl, mono-, di- or oligosaccharide; and R' is methyl. The compounds are site-specifically halogenated or radiohalogenated at the A group and coupled with macromolecules such as monoclonal antibodies, peptides or other proteins.Type: GrantFiled: May 23, 1988Date of Patent: April 12, 1994Assignee: Duke UniversityInventors: Michael R. Zalutsky, Acharan S. Narula
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Patent number: 5298410Abstract: Disclosed are lyophilized biologically active proteinaceous compositions containing low diol polyalkylene oxide, such as polyethylene glycol, covalently attached to a biologically active proteinaceous substance and combined with the cryoprotectant cyclodextrin.Type: GrantFiled: February 25, 1993Date of Patent: March 29, 1994Assignee: Sterling Winthrop Inc.Inventors: Christopher P. Phillips, Robert A. Snow
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Patent number: 5290919Abstract: Stroma-free hemoglobin cross-linked with reagents that mimic 2,3-diphosphoglycerate and transform stroma-free hemoglobin into a physiologically competent oxygen carrier which is retained in vivo for adequate periods of time, and thus can be used in fluids for transporting oxygen is described.Type: GrantFiled: August 28, 1992Date of Patent: March 1, 1994Assignee: The University of Maryland BaltimoreInventors: Enrico Bucci, Clara Fronticelli
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Patent number: 5284832Abstract: Iron complexes with conalbumin and its derivatives, such as acetylconalbumin and succinylconalbumin, with an iron content ranging from 2 to 30% by weight, useful for the treatment of sideropenic and hypochromic anaemia, preparation process and pharmaceutical compositions containing them as active ingredients.Type: GrantFiled: October 14, 1992Date of Patent: February 8, 1994Assignee: Mediolanum Farmaceutici S.p.A.Inventors: Gianni Ferrari, Pier G. Pagella, Oscar Baiardo
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Patent number: 5284934Abstract: 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: GrantFiled: September 4, 1992Date of Patent: February 8, 1994Assignee: Health Research Inc.Inventor: Howard J. Allen, Jr.
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Patent number: 5275814Abstract: 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: July 10, 1991Date of Patent: January 4, 1994Assignee: Allergy Immuno Technologies, Inc.Inventor: Aristo Wojdani
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Patent number: 5272257Abstract: A method for preparing phycobiliprotein/amine-reactive dye conjugates is disclosed in which the conjugates so prepared overcome the energy transfer/fluorescent quenching dilemma encountered in the use of prior art conjugates. A phycobiliprotein, for example, phycoerythrin or allophycocyanin, is conjugated with an amine-reactive dye, for example, Texas Red or carboxyfluorescein succinimidyl ester, in the presence of a selective salt which causes a hydrophobic intramolecular rearrangement of the phycobiliprotein thereby exposing more hydrophobic sites for binding to the amine-reactive dye. The conjugates prepared according to the invention are useful in multiple color fluorescence assays without requiring the use of multiple exciting sources.Type: GrantFiled: September 3, 1992Date of Patent: December 21, 1993Assignee: Coulter CorporationInventor: Ravinder K. Gupta
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Patent number: 5264209Abstract: Provided are PEGylated "interleukin-6" derivatives (PEG IL-6) having an extended plasma half-life, as well as enhanced in-vivo IL-6 biological activities.Methods for producing the modified glycosylated and unglycosylated IL-6 proteins or polypeptides, as well as, for their use in treating hematopoietic disorders and difficiencies, particularly acute thrombocytopenia, are also provided.Type: GrantFiled: December 21, 1990Date of Patent: November 23, 1993Assignee: Kirin-Amgen, Inc.Inventors: Toshihumi Mikayama, Toshihiko Kadoya, Makoto Kakitani, Hideo Inoue
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Patent number: 5262525Abstract: Method for the chemical modification of proteins using a reagent of general formula ##STR1## obtained from the diene ##STR2## and maleic anhydride by Diels-Alder addition.Type: GrantFiled: March 19, 1992Date of Patent: November 16, 1993Assignee: Societe Nationale Elf AquitaineInventors: David Bonnaffe, Andre Lubineau, Jean-Louis Seris, Michel Therisod
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Patent number: 5258499Abstract: Delivery vehicle formulations comprise active agents encapsulated within liposomal vesicles to which are attached protein hormones (ligands) such as interleukin-2. The ligands are capable of showing affinity for specific cell receptors resulting in delivery of the encapsulated active agent to target cells, enabling delivery of active agents to particular cell populations in the treatment of conditions such as immune system disorders.Type: GrantFiled: March 10, 1992Date of Patent: November 2, 1993Assignee: Vestar, Inc.Inventors: Paula J. Konigsberg, Leroy L. Richer, Paul G. Schmidt, Joseph A. Uliana
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Patent number: 5252719Abstract: 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: GrantFiled: August 27, 1990Date of Patent: October 12, 1993Assignee: Hitachi, Ltd.Inventors: Kazuo Takeda, Yoshinori Harada, Hiromichi Shimizu, Chusuke Munakata
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Patent number: 5252707Abstract: There are disclosed a novel inositol-1,4,5-triphosphoric acid derivative, inositol-1,3,4-triphosphoric acid derivative, inositol-1,3,4,5-tetraphosphoric acid derivative, and a bonded substance of the same and a protein. They control the metabolic process of an organism concerned with calcium ions to thereby exert a medicinal virtue.Type: GrantFiled: May 15, 1991Date of Patent: October 12, 1993Assignee: Mitsui Toatsu Chemicals IncorporatedInventors: Shoichiro Ozaki, Yutaka Watanabe, Masato Hirata, Akira Awaya
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Patent number: 5252708Abstract: Preparation process for a protein comprising at least one intramolecular disulphide bridge, and optionally one or more additional cysteines, comprising the oxidation of the corresponding reduced recombinant protein using an oxidizing agent and characterized in that an aqueous solution of the reduced protein is reacted at a pH of less than 5.0.Type: GrantFiled: May 6, 1992Date of Patent: October 12, 1993Assignee: Roussel UclafInventors: Pierre Y. Abecassis, Jacques Leclaire, Philippe Riberon
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Patent number: 5252714Abstract: A new polyethylene glycol derivative (PEG) having the property of not being destroyed by water and also being able to retain reactivity in water and selectively react with amine groups. Also provided is a process for modifying organic or polymer surfaces in water by connecting PEG derivatives to exposed amine groups which provides a process whereby there is efficient linking to organic or polymer surfaces in water by use of the PEG derivatives.Type: GrantFiled: November 28, 1990Date of Patent: October 12, 1993Assignee: The University of Alabama in HuntsvilleInventors: J. Milton Harris, M. R. Sedaghat-Herati
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Patent number: 5250665Abstract: A modified hemoglobin comprising hemoglobin which is cross-linked with a cross-linking reagent. The cross-linking reagent is selected such that the .beta.-chains are cross-linked within the 2,3-diphosphoglycerate binding site and the linkage distance between the .beta.-chains is between about 5 to 9 angstroms. A method of preparing the modified hemoglobin and its use as a blood substitute or a plasma expander are also described.Type: GrantFiled: August 16, 1991Date of Patent: October 5, 1993Assignee: The University of Toronto Innovations FoundationInventors: Ronald Kluger, Jolanta Wodzinska
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Patent number: 5246865Abstract: A protein microsequencing method for use in conjunction with the thiobenzoylation degradation of polypeptides and proteins is disclosed. The process involves reaction of the N-terminal amino acid of a polypeptide with an excess of a thiobenzoylating reagent. The derivatized polypeptide is subjected to cleavage by acid which forms a 4-substituted 2-phenyl-5(4H) thiazolone. The thiazolone is acylated to form a 5-acyloxy-2-phenylthiazole and subjected to detection by both gas chromatography and chemical ionization mass spectroscopy.Type: GrantFiled: July 24, 1992Date of Patent: September 21, 1993Assignee: California Institute of TechnologyInventor: Mark L. Stolowitz
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Patent number: 5243028Abstract: The present invention relates to a series of novel silicone proteins which are high substantive to fiber and hair. They are cationic materials which contain an ester linkage. A chloroester of a dimethicone copolyol is reacted with the amino group of a protein or amino acid. The compounds contain both a silicone portion and protein portion in a covalent bone one molecule. Since the compounds of the present invention are high molecular weight silicone polymers, they have a high degree of oxidative stability, even at elevated temperatures and are nonirritating to skin and eyes. The proteins of the present invention plate out on and form a film on the surface of hair skin and textile fibers. In addition, these compounds are non volatile and exhibit a inverse cloud point. These combination of properties makes these polymers ideally suited for use in personal care applications.Type: GrantFiled: March 16, 1992Date of Patent: September 7, 1993Assignee: Siltech CorporationInventor: Anthony J. O'Lenick, Jr.
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Patent number: 5219895Abstract: Collagen-based compositions as adhesives and sealants for medical use and preparation thereof are described. Prior to polymerization, soluble or partially fibrillar collagen monomers in solution are chemically modified with an acylating agent, sulfonating agent or a combination of the foregoing. The collagen compositions prepared accordingly can be used as medical adhesives for bonding soft tissues or be made in to a sealant film for a variety of medical uses such as wound closures and tendon wraps for preventing adhesion formation following surgery.Type: GrantFiled: January 29, 1991Date of Patent: June 15, 1993Assignee: Autogenesis Technologies, Inc.Inventors: Charles D. Kelman, Dale P. DeVore
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Patent number: 5217705Abstract: A fibrin-binding protein such as t-PA is labeled with a detectable substance, such as a radionuclide, and administered to a patient for diagnosis of blood clots and for monitoring the dissolution thereof during therapy. The detectable substance preferably is attached to t-PA through linkers which specifically bind to the portion of the t-PA protein responsible for enzymatic activity, thereby diminishing this activity while leaving the fibrin-binding property of the protein intact.Type: GrantFiled: September 22, 1988Date of Patent: June 8, 1993Assignee: Neorx CorporationInventors: John M. Reno, Stephen W. Hadley, Marjorie A. Mohler
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Patent number: 5208323Abstract: The present invention relates to antitumor compounds of the formula I: ##STR1## wherein M is selected from the group consisting of an hydrogen atom, a peptide residue, and a protein residue linked to the carbon atom via the amino residue of .epsilon.-lysine present therein which can be an antibody used to target the anti-tumor agent to the malignant cells, and R can be an antitumor agent such as daunorubicin, doxorubicin, or an epirublicin derivative.Type: GrantFiled: January 13, 1992Date of Patent: May 4, 1993Assignee: Universite LavalInventors: Michel Page, Denis Thibeault
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Patent number: 5204448Abstract: A new series of bifunctional chelating agents useful for attaching metal ions to proteins, polypeptides and other polymers and methods for their preparation are described. These reagents are unique in their ability to bind a variety of metal ions and to yield a high metal ion concentration per protein molecule. Using these methods polymeric analogs of these bifunctional chelating agents called Starburst ligands can also be obtained. Protein metal chelates thus obtained will have useful radiophysical, chemical, fluorescent, photochemical and magnetic properties suitable for biomedical applications.Type: GrantFiled: May 26, 1989Date of Patent: April 20, 1993Assignee: Akzo N.V.Inventor: Ramaswamy Subramanian
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Patent number: 5202423Abstract: The invention pertains to terpyridine compounds having structure (I). These compounds form fluorescent lanthanide chelates with the appropriate metal ions. The fluorescent metal chelates are useful as probes in time-resolved fluorescence spectroscopy.Type: GrantFiled: April 19, 1991Date of Patent: April 13, 1993Assignee: Wallac OyInventors: Jouko Kankare, Harri Takalo, Elina Hanninen, Matti Helenius, Veli-Matti Mukkala
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Patent number: 5183660Abstract: Polyethylene glycol derivatives of the formula ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents a lower alkyl, m and n are the same or different and each represents a positive integer and p is 0 or a positive integer, peptides modified by the polyethylene glycol derivatives, methods for producing them and use of the modified peptides. The peptides modified by the polyethylene glycol derivatives (I) of the invention, as compared with the corresponding non-modified peptides, show decreased antigenicity, are considerably delayed in biological clearance, and exhibit their physiological activities effectively over a long period, rendering them very effective as pharmaceuticals as well as drugs for animals.Type: GrantFiled: August 15, 1991Date of Patent: February 2, 1993Assignee: Sumitomo Pharmaceuticals Company, LimitedInventors: Yoshiharu Ikeda, Yoshiyuki Kai, Keiichi Ono
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Patent number: 5171846Abstract: A method for preparing a phycobiliprotein-Texas Red conjugate which overcomes the energy transfer/fluorescent quenching dilemma is disclosed. A phycobiliprotein, such as phycoerythrin, is conjugated with dye, such as Texas Red, in the presence of a selective salt which causes a hydrophobic intramolecular rearrangement of the phycobiliprotein thereby exposing more hydrophobic sites for binding to Texas Red. The conjugate is useful in multiple color fluorescence assays without requiring the use of multiple exciting sources.Type: GrantFiled: May 21, 1990Date of Patent: December 15, 1992Assignee: Coulter CorporationInventor: Ravinder K. Gupta
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Patent number: 5169627Abstract: Polyethylene glycol serum immunoglobulin conjugates exhibit substantial rstance to degradation by intestinal enzyme while retaining their immuno-activity. Thus, PEG-IgG or PEG-IgA conjugates can be used as orally administered therapeutics to treat patients with gastrointestinal immunodeficiency to reconstitute secretory immunity. Preferred conjugates are made by reacting activated PEG and IgG in ratios of from 1:5 to 1:1000 such that less than about 27% of the IgG lysine residues are bonded to the PEG. The conjugates are advantageously formulated into a pharmaceutical composition comprising the conjugate and a pharmaceutically acceptable oral carrier. Particularly for administration to infants, a preferred oral carrier is milk.Type: GrantFiled: October 28, 1991Date of Patent: December 8, 1992Assignee: Mount Sinai School of Medicine of the City University of New YorkInventor: Charlotte Cunningham-Rundles
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Patent number: 5169933Abstract: Covalently-linked complexes (CLCs) for targeting a defined population of cells, comprising a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety is capable of promoting CLC-target cell interaction are disclosed. Methods for using the claimed CLCs to obtain enhanced in vivo cytotoxicity and enhanced in vivo imaging are also described.Type: GrantFiled: August 7, 1989Date of Patent: December 8, 1992Assignee: NeoRx CorporationInventors: David C. Anderson, A. Charles Morgan, Jr., Paul G. Abrams, Alan R. Fritzberg, Everett J. Nichols
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Patent number: 5166319Abstract: This invention provides a method of preparing conjugates of bioactive compounds and site-specific compounds in which covalent bonding between the compounds is effected by interfacial condensation while protecting the active binding sites from the condensation reaction. This provides very high yields of the bioactive, site-specific conjugate, the products are homogeneous and it provides novel conjugate products. It is of particular advantage for monoclonal antibodies conjugated with cytotoxic agents.Type: GrantFiled: October 10, 1989Date of Patent: November 24, 1992Assignee: Brunswick CorporationInventor: Wolfgang J. Wrasidlo
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Patent number: 5164486Abstract: The invention relates to an anti-HIV agent comprising as an effective component a plasma protein of which the polarity of the amino group of the amino acid residue constituting the plasma protein is chemically modified into a negative moiety by a carboxylic acid, for example, by maleic anhydride or succinic anhydride.Plasma proteins modified with dicarboxylic anhydride, which are the effective components of the anti-HIV agent of this invention, inhibit the formation of large cells in mixed culturing of HIV infected cells and non-infected cells as well as the direct infection of helper T cells with HIV. They are very safe compounds and are expected to be applicable to the treatment of HIV infected patients.Type: GrantFiled: September 10, 1990Date of Patent: November 17, 1992Assignee: Meiji Milk Products Co., Ltd.Inventors: Hajime Tsunoo, Masao Takami, Kenji Mizumoto
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Patent number: 5162503Abstract: Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.Type: GrantFiled: May 19, 1987Date of Patent: November 10, 1992Assignee: Hoffmann-La Roche, Inc.Inventors: Pascal Bailon, John E. Smart, David V. Weber
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Patent number: 5162218Abstract: Polypeptide compositions are provided having a binding site specific for a particular target ligand and further having an active functionality proximate the binding site. The active functionality may be a reporter molecule, in which case the polypeptide compositions are useful in performing assays for the target ligand. Alternatively, the active functionality may be a chemotherapeutic agent, in which case the polypeptide compositions are useful for therapeutic treatment of various diseased states. A novel method for preparing such polypeptides having active functionalities proximate their binding site comprises combining the polypeptide specific for the target ligand with an affinity label including ligand having a reactive group attached thereto. The reactive group is then covalently attached to an amino acid side chain proximate the binding site and cleaved from the substrate. The substrate is eluted, leaving a moiety of the reactive group covalently attached to the polypeptide.Type: GrantFiled: June 10, 1991Date of Patent: November 10, 1992Assignee: The Regents of the University of CaliforniaInventor: Peter Schultz
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Patent number: 5162502Abstract: The present invention relates to a novel glycoprotein, extracted from the seeds of Trichosanthes kirilowii, called: trichokirin, as well as to its modified derivatives containing a free or blocked SH group. It relates to a process for its preparation, to its use and to pharmaceutical compositions in which it is present.Type: GrantFiled: June 13, 1991Date of Patent: November 10, 1992Assignee: SanofiInventors: Luigi Barbieri, Pierre Casellas, Fiorenzo Stirpe
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Patent number: 5153177Abstract: A method of crosslinking protein comprises making a composition which comprises a protein, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is to be encapsulated or entrapped within the crosslinked protein matrix. The composition is thereafter heated while maintaining the moisture content at a level of at least about 3 weight percent, based on the weight of the composition.A product comprises a protein which is crosslinked to degree at which it is substantially insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a water-soluble salt of a carboxylic acid, water, and an additional ingredient which is encapsulated or entrapped within the crosslinked protein matrix.Type: GrantFiled: January 10, 1991Date of Patent: October 6, 1992Assignee: BASF CorporationInventors: Frederick K. Chaundy, David K. Bower, Terence K. Kilbride, Jr.
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Patent number: 5153312Abstract: The present invention relates to an improved method for producing oligosaccharide conjugate vaccines. In an additional aspect of the invention, oligosaccharide vaccines are produced which elicit a monospecific and homogeneous immune response to capsular polysaccharide. A specific embodiment of the invention provides for vaccines which induce immunity to prevalent serotypes of Streptococcus pneumoniae.Type: GrantFiled: September 28, 1990Date of Patent: October 6, 1992Assignee: American Cyanamid CompanyInventor: Massimo Porro
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Patent number: 5153265Abstract: A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.Type: GrantFiled: August 30, 1990Date of Patent: October 6, 1992Assignee: Cetus CorporationInventors: Paula J. Shadle, Kirston E. Koths, Margaret Moreland, Nandini Katre, Walter J. Laird, Lois Aldwin, Danute E. Nitecki, John D. Young
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Patent number: 5151501Abstract: The present invention relates to a process for solubilization and naturation of somatotropins utilizing a combination of sulfolane and an aqueous alkaline solution. By utilizing the process of the present invention, enhanced yields of end product result.Type: GrantFiled: December 20, 1991Date of Patent: September 29, 1992Assignee: American Cyanamid CompanyInventor: Kevin M. McCoy
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Patent number: 5149788Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.Type: GrantFiled: October 24, 1988Date of Patent: September 22, 1992Assignee: Hoffmann-La Roche, Inc.Inventors: Pascal Bailon, John E. Smart, David V. Weber
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Patent number: 5149782Abstract: Molecular conjugates which facilitate the attachment of macromolecular drugs onto cellular surfaces and their entry into cells are described. The molecular conjugates comprise a macromolecular drug linked to an "inactivated" membrane blending agent which inserts into the cellular plasma membrane. The membrane blending agent is inactivated by cleavable linkage to a blocking agent which, until released from the conjugate under appropriate conditions, blocks and ability of the membrane blending agent to insert into the cellular membrane. Upon release of the blocking agent, the membrane blending agent is "activated" and the conjugate can be inserted into a cellular plasma membrane. The membrane blending agents can be peptides such as fusogenic or ion channel forming peptides or long chain fatty acids. The blocking agents can be bulky or charged moieties which mask and prevent insertion of the membrane blending agent.Type: GrantFiled: August 19, 1988Date of Patent: September 22, 1992Assignee: Tanox Biosystems, Inc.Inventors: Tse-wen Chang, Jean deVilliers, Wayne Gordon
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Patent number: 5144012Abstract: Conjugates of antibodies and cytotoxic methotrexate drugs make use of liners between the drug and antibody which are simple organic groups, wherein the link to the antibody is an acyl group and the link to the drug is an alkylidene hydrazide.Type: GrantFiled: February 15, 1991Date of Patent: September 1, 1992Assignee: Eli Lilly and CompanyInventors: David A. Johnson, Bennett C. Laguzza, William L. Scott
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Patent number: 5144009Abstract: 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, proteins such as peptide hormones or human proteins, and peptide ligands. It also relates to the activated inophores.These conjugates are suitable as immunotoxin potentiators.Type: GrantFiled: December 28, 1989Date of Patent: September 1, 1992Assignee: SanofiInventors: Franz Jansen, Pierre Gros
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Patent number: 5144011Abstract: A method for controlling the release of durgs or other passenger molecules form carrier conjugates, and a class of conjugates that releases drugs when ingested by a cell or subjected to acidic conditions, are disclosed. These conjugates contain a passenger molecule which is attached to a spacer molecule through an acidic bonding group, such as carboxyl, that is in a "cis" configuration with another acidic group, and a carrier molecule that is bonded to the spacer molecule at another site. When subjected to a mild increase in acidity, such as occurs within a lysosome of a cell, the drug or other passenger molecule is hydrolyzed from the the conjugate and released in unmodified, active form.Type: GrantFiled: February 6, 1989Date of Patent: September 1, 1992Assignee: Boston UniversityInventors: Wei C. Shen, Hugues J.-P. Ryser
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Patent number: 5126328Abstract: A method for crosslinking protein comprises making an aqueous compositiion of a protein, sugar, a salt, and water, followed by heating the composition while maintaining the moisture content of the composition at a level of at least about 3 weight percent. The composition is made, and the heating carried out, so that the protein is crosslinked to a degree at which it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes. A crosslinked protein product comprises a protein crosslinked to a degree that it is substantially water insoluble upon being placed in water at 100.degree. C. for at least 3 minutes, a sugar, a salt, and water.Type: GrantFiled: January 10, 1991Date of Patent: June 30, 1992Inventors: David K. Bower, Frederick K. Chaundy, Terence K. Kilbride, Jr.
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Patent number: 5124438Abstract: Chemically modified proteins obtainable by reacting casein, collagen, gelatin, albumin or mixtures thereof(a) with 0.5 to 15% by weight of chlorine or of a compound which liberates chlorine under the reaction conditions, in an aqueous medium at a pH of from 0 to 7 or(b) with 0.5 to 50% by weight of a non-aromatic mono- or disulfonic acid which contains in its organic radical one or more groups or structural features which react with nucleophiles, in an aqueous medium at a pH of from 6 to 14,are used as dispersants in colorant formulations.Type: GrantFiled: January 12, 1990Date of Patent: June 23, 1992Assignee: BASF AktiengesellschaftInventors: Ralf Brueckmann, Johannes P. Dix, Manfred Herrmann, Herbert Leiter, Norbert Zimmermann
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Patent number: 5116612Abstract: 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 7, 1990Date of Patent: May 26, 1992Assignee: Allergy Immuno Technologies, Inc.Inventor: Aristo Wojdani
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Patent number: 5109119Abstract: This invention provides a crystalline form of recombinant human granulocyte-macrophage colony-stimulating factor (r-h-GM-CSF) and methods for making such crystals.Type: GrantFiled: June 6, 1989Date of Patent: April 28, 1992Assignee: Schering CorporationInventors: Paul Reichert, Gerald S. Hammond, Hung V. Le, Tattanahalli L. Nagabhushan, Paul P. Trotta
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Patent number: 5108987Abstract: Conjugates of transferrin or ceruloplasmin with anti-tumour agents. Such conjugates are useful in the treatment of tumours. Suitable anti-tumour agents include adriamycin, daunomycin, methotrexate, vincristin, 6-mercaptopurine, cytosine arabinoside and cyclophosphamide. Transferrin or ceruloplasmin in preferably coupled to the anti-tumour agent by means of glutaraldehyde.Type: GrantFiled: July 31, 1989Date of Patent: April 28, 1992Inventor: Ward P. Faulk
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Patent number: 5106955Abstract: A process for production of antibody conjugates which comprises modification of a part of the amino groups in an antibody or its fragment whose antigen-binding activity is lowered by the modification of its amino groups, with a reversible modifier for protein amino groups, reaction of the antibody or its fragment with a substance bearing a group reactive with the amino group and removal of the residues of the reversible modifier from the amino groups and, when necessary, the residues of the substance bearing a group reactive with the amino group in case they are introduced onto groups other than amino groups. The process according to the present invention gives antibody conjugates with retention of antigen-binding activity and these conjugates have a possibility of being used in affinity chromatography or as a diagnostic agent or a drug for cancer therapy.Type: GrantFiled: November 23, 1988Date of Patent: April 21, 1992Assignee: Teijin LimitedInventors: Noriaki Endo, Yumiko Takeda, Yoshinori Kato, Takeshi Hara
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Patent number: RE34271Abstract: 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: May 24, 1990Date of Patent: June 1, 1993Assignee: University of Iowa Research FoundationInventor: Joseph A. Walder