Oxygen Containing Reactant Patents (Class 530/410)
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Patent number: 6319498Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural &bgr; amyloid peptides (&bgr;-AP). In a preferred embodiment, the &bgr; amyloid modulator compounds of the invention are comprised of an A&bgr; aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural &bgr; amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural &bgr;-AP aggregation when the natural &bgr;-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.Type: GrantFiled: March 14, 1996Date of Patent: November 20, 2001Assignee: Praecis Pharmaceuticals IncorporatedInventors: Mark A. Findeis, Howard Benjamin, Marc B. Garnick, Malcolm L. Gefter, Arvind Hundal, Laura Kasman, Gary Musso, Ethan R. Signer, James Wakefield, Michael J. Reed
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Patent number: 6310105Abstract: The present invention is a biodegradable, reversibly-swellable, polyvalent cation-binding, protein hydrogel which comprises an acylated protein matrix in which the acylated protein matrix is crosslinked with a bifunctional crosslinking reagent, and treated with a polar organic solvent, and a method of making the same.Type: GrantFiled: February 15, 2000Date of Patent: October 30, 2001Assignee: Wisconsin Alumni Research FoundationInventor: Srinivasan Damodaran
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Patent number: 6309633Abstract: The invention provides a drug-oligomer conjugate having the following general formula: wherein D is a therapeutic drug moiety; H and H′ are each a hydrophilic moiety, independently selected from the group consisting of straight or branched PEG polymers having from 2 to 130 PEG subunits, and sugars; L is a lipophilic moiety selected from the group consisting of alkyl groups having 2-26 carbon atoms, cholesterol, adamantane and fatty acids; o is a number from 1 to the maximum number of covalent bonding sites on H; m+n+p together have a value of at least one and not exceeding the total number of covalent bonding sites on D for the —H′, —L and —H—L substituents; the H—L bond(s) are hydrolyzable and the D—L′ bond(s), when present, are hydrolyzable; the conjugate being further characterized by one of the following: (i) m is 0 and p is at least 1; (ii) n is 0 and p is at least 1; (iii) m and n are each 0 and p is at least 1; (iv) p isType: GrantFiled: June 19, 1999Date of Patent: October 30, 2001Assignee: Nobex CorporationInventors: Nnochiri Ekwuribe, Muthukumar Ramaswamy, Jayanthi Sethuraman Rajagopalan
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Patent number: 6303569Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms.Type: GrantFiled: August 21, 1998Date of Patent: October 16, 2001Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Yun H. Choe, Annapurna Pendri
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Patent number: 6248334Abstract: A process for preparing a protein-polysaccharide conjugate includes reacting a protein with a polysaccharide to produce a mixture including a protein-polysaccharide conjugate and free protein. At least one unreacted reagent or low molecular weight component is removed from this mixture, without removing all of the free protein, to provide a purified mixture that contains the protein-polysaccharide conjugate and free protein. This purified mixture can be used as a conjugate vaccine, immunogen, or immunological reagent. Keeping the free protein in the purified mixture with the conjugate saves time and money in the conjugate production process. In another aspect of the invention, the purified mixture of the protein-polysaccharide conjugate and free protein is reacted with a hapten to produce a conjugate mixture including a hapten-protein conjugate and a hapten-protein-polysaccharide conjugate.Type: GrantFiled: January 6, 1998Date of Patent: June 19, 2001Assignee: Henry M. Jackson Foundation for the Advancement of Military MedicineInventors: Andrew Lees, James Mond
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Patent number: 6217873Abstract: Provided by this invention are essentially homogeneous, defined compositions of matter and hetero-polyoximes of defined structure comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.Type: GrantFiled: January 5, 1996Date of Patent: April 17, 2001Assignee: Gryphon SciencesInventors: Keith Rose, Robin E. Offord
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Patent number: 6187751Abstract: The present invention provides a protein fragment of the ob protein, being an active site of the protein. The active site is suitably provided by the ob protein when it is in the form of a four helix bundle structure, particularly that having an up-up down-down topology. In particular, the active site is formed from one or more amino acids selected from one or more of the four helices forming the secondary stucture of the ob protein, especially a protein fragment consisting of amino acid residues 26 to 39, 74 to 88, 93 to 113 or 142 to 161. The compounds of the invention arc considered to be capable of regulating the physiological activity of the ob protein and are therefor of potential use in the treatment of nutritional and metabollic disorders, particularly obesity and diabetes in the case of agonists and anorexia and cachexia in the case of antagonists.Type: GrantFiled: September 9, 1999Date of Patent: February 13, 2001Assignee: SmithKline Beecham p.l.c.Inventors: Richard Anthony Godwin Smith, Lee James Beeley
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Patent number: 6180095Abstract: The present invention is directed to double prodrugs containing polymeric-based transport forms.Type: GrantFiled: October 30, 1998Date of Patent: January 30, 2001Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Annapurna Pendri, Yun H. Choe
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Patent number: 6177059Abstract: A complex comprising a lipid and a conjugate of GPIb and lipid having a functional group, and use thereof. The GPIb-lipid complex of the present invention is extremely useful as a platelet substitute, a pharmaceutical agent for the prophylaxis and treatment of angiopathy, vascular damages and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb-lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent therefor, since it accumulates at vascular lesions.Type: GrantFiled: December 3, 1998Date of Patent: January 23, 2001Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Hiroshi Matsuda, Kaeko Kamide, Yasuo Amatsuji, Takashi Imagawa, Yasuo Ikeda, Mitsuru Murata
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Patent number: 6174530Abstract: Provided by this invention are essentially homogeneous, defined compositions of matter comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.Type: GrantFiled: August 31, 1993Date of Patent: January 16, 2001Assignee: Gryphon SciencesInventors: Keith Rose, Robin Ewart Offord
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Patent number: 6165458Abstract: A composition for transdermal administration of a cytokine is described. The composition includes a conjugate composed of a cytokine, such as an interferon, and at least one fatty acid moiety covalently attached to the cytokine. The conjugate has enhanced cutaneous delivery relative to the cytokine alone.Type: GrantFiled: December 18, 1998Date of Patent: December 26, 2000Assignee: PharmaDerm Laboratories Ltd.Inventors: Marianna Foldvari, Sam Kwadwo Attah-Poku
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Patent number: 6133229Abstract: A protein stabilizer additive comprises two or more of a tris compound of the formula (1): (HOCH.sub.2).sub.3 --C--R, wherein R is: C.sub.1 -C.sub.4 alkyl, substituted C.sub.1 -C.sub.4 alkyl, NH.sub.2 ; NR.sup.1 R.sup.2 wherein R.sup.1 and R.sup.2 may be independently: H, C.sub.1 -C.sub.4 alkyl sulphonate, C.sub.1 -C.sub.4 hydroxyalkyl sulphonate; C.sub.1 -C.sub.4 alkyl NHC(CH.sub.2 OH).sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 hydroxyalkyl; C.sub.1 -C.sub.4 alkyl carboxylate; a polyelectrolyte; a buffer; and one or more additional components for example divalent metal salts.Type: GrantFiled: July 1, 1996Date of Patent: October 17, 2000Assignee: The University of Leeds Innovations, Ltd.Inventors: Timothy David Gibson, Barry L. Pierce, Jeanette Irene Webster
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Patent number: 6107272Abstract: The invention relates to novel modified polypeptides, with or without variations in noncoding regions, with altered biological activity. The invention discloses methods of preparing the modified polypeptides and methods of use.Type: GrantFiled: May 18, 1999Date of Patent: August 22, 2000Assignee: Beth Israel Deaconess Medical CenterInventor: Arthur J. Sytkowski
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Patent number: 6090925Abstract: Microparticles formed by mixing a macromolecule with a polymer at a pH near the isoelectric point of the macromolecule and incubating the mixture in the presence of an energy source for a predetermined length of time. The microparticles are composed of homogeneously distributed, intertwined macromolecule and polymer. Each microparticle allows aqueous fluids to enter and allows solubilized macromolecule and polymer to exit the microparticle and may be formulated to provide a sustained release of macromolecule and polymer from the interior of the microparticle when placed in an appropriate aqueous medium, such as under physiological conditions. Methods of production and methods of use for research, diagnostics and therapeutics are provided.Type: GrantFiled: August 19, 1996Date of Patent: July 18, 2000Assignee: Epic Therapeutics, Inc.Inventors: James E. Woiszwillo, Larry R. Brown, Terrence L. Scott, Jie Di, Judith Sudhalter, Charles D. Blizzard
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Patent number: 6057426Abstract: The present invention relates to the discovery of novel genes and proteins, which function in pathways involved in brain pathogenesis. In particular, the novel genes and proteins relate to inflammatory tissue responses caused by brain injuries such trauma, ischemia or autoimmune-inflammation or other diseases or processes related to neuroinflammation. The compounds disclosed in the present invention are useful as therapeutics, diagnostics and in screening assays.Type: GrantFiled: April 30, 1998Date of Patent: May 2, 2000Assignee: Hoffmann-La Roche Inc.Inventors: Werner Lesslauer, Ulrike Utans-Schneitz
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Patent number: 6042822Abstract: Compositions containing alpha interferon conjugated to a substantially non-antigenic polymer are disclosed in which at least about 30% of the conjugates include covalent attachment of the alpha interferon to the substantially non-antigenic polymer at a histidine. Also disclosed is a process for preparing the conjugates. The process includes contacting an alpha interferon with a succinimidyl carbonate-activated substantially non-antigenic polymer at a pH which is sufficient to facilitate covalent attachment of the polymer on a histidine of the alpha interferon.Type: GrantFiled: April 6, 1999Date of Patent: March 28, 2000Assignee: Enzon, Inc.Inventors: Carl W. Gilbert, Myung-ok Park-Cho
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Patent number: 6037452Abstract: Factor VIIIC:vWF, Factor VIII C, Factor IX or Factor IX or the activated co-factors thereof are covalently linked to a poly(alkylene oxide).Type: GrantFiled: April 10, 1992Date of Patent: March 14, 2000Assignee: Alpha Therapeutic CorporationInventors: Hitoshi Minamino, Edward H. Mealey
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Patent number: 6034220Abstract: Highly repetitive proteins which are relatively insoluble in water are chemically modified to increase solubility. The protein is reacted with a functionalizing agent to introduce additional polar functionalities and disrupt the order of the protein. The solubility of the protein in water is increased by the chemical modification, while adhesive and surfactant properties are retained.Type: GrantFiled: February 23, 1998Date of Patent: March 7, 2000Assignee: Protein Polymer TechnologiesInventor: Erwin R. Stedronsky
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Patent number: 6022955Abstract: This invention discloses a method for chemically modifying a pulmonary surfactant protein or polypeptides with various fatty acids. These conjugates are useful in preparing formulations for the treatment of respiratory disease.Type: GrantFiled: December 10, 1991Date of Patent: February 8, 2000Assignee: Abbott LaboratoriesInventors: Virender Kumar Sarin, Darryl Robin Absolom, Shanker Lal Gupta
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Patent number: 6001364Abstract: Provided by this invention are defined compositions of hetero-polyoximes of defined structure comprising a baseplate structure having a plurality of oxime bonds, wherein each oxime bond links a specifically active molecule to the baseplate. Also provided are novel baseplates having a plurality of oxime forming complementary reactive groups and novel specifically reactive molecules having an oxime forming complementary reactive group. Also provided by this invention are methods of preparing these novel compositions of matter by chemoselectively ligating via oxime bond formation a complementary orthogonal reactive group on the baseplate to a complementary reactive orthogonal group on a specifically active molecule. Methods of using these defined compositions of matter as well as pharmaceutical compositions comprising these defined compositions of matter and methods of their use are also provided by this invention.Type: GrantFiled: August 31, 1993Date of Patent: December 14, 1999Assignee: Gryphon SciencesInventors: Keith Rose, Robin E. Offord
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Patent number: 5985263Abstract: Substantially pure histidine-linked protein-polymer conjugates and processes for their preparation are disclosed. The processes include contacting a protein with an activated polymer under conditions sufficient to facilitate covalent attachment of at least a portion of the polymer strands on histidine residues of the protein and thereafter substantially separating the histidine-linked conjugates from the remaining reactants.Type: GrantFiled: December 19, 1997Date of Patent: November 16, 1999Assignee: Enzon, Inc.Inventors: Seoju Lee, Charles McNemar
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Patent number: 5981719Abstract: Microparticles formed by mixing a macromolecule with a polymer at a pH near the isoelectric point of the macromolecule and incubating the mixture in the presence of an energy source for a predetermined length of time. The microparticles are composed of homogeneously distributed, intertwined macromolecule and polymer. Each microparticle allows aqueous fluids to enter and allows solubilized macromolecule and polymer to exit the microparticle and may be formulated to provide a sustained release of macromolecule and polymer from the interior of the microparticle when placed in an appropriate aqueous medium, such as under physiological conditions. Methods of production and methods of use for research, diagnostics and therapeutics are provided.Type: GrantFiled: December 14, 1998Date of Patent: November 9, 1999Assignee: Epic Therapeutics, Inc.Inventors: James E. Woiszwillo, Larry R. Brown, Terrence L. Scott, Jie Di, Judith Sudhalter, Charles D. Blizzard, Frank J. Riske
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Patent number: 5981709Abstract: A process for preparing .alpha.-interferon-polymer conjugates having high levels of retained interferon activity and relatively long circulating lives in vivo is disclosed. The process includes forming substantially non-antigenic .alpha.-interferon-polymer conjugates, combining the .alpha.-interferon-polymer conjugates with a sufficient amount of an acid to reduce the pH of the conjugates to a level which is sufficient to cleave the polymer linkages in an active site area of the interferon and thereafter adjusting the .alpha.-interferon-polymer conjugates to a physiologically-acceptable pH. Methods of treating interferon-susceptible conditions with the compositions of the present invention are also disclosed.Type: GrantFiled: December 19, 1997Date of Patent: November 9, 1999Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Carl W. Gilbert
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Patent number: 5977310Abstract: This invention relates to a PEG-modified HGF (Hepatocyte Growth Factor), namely HGF modified by polyethylene glycol. The PEG-modified HGF of the invention has a prolonged clearance in vivo, effectively exhibits its physiological activity for a long period of time, and has the same physiological activity as HGF, which makes it possible to reduce the dose and relieve the side effects of the same.Type: GrantFiled: November 4, 1997Date of Patent: November 2, 1999Assignee: Toshikazu Nakamura and Sumitomo Pharmaceuticals Co., Ltd.Inventors: Mitsuo Namiki, Naoto Kusunose, Noriko Akimaru
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Patent number: 5972889Abstract: A conjugate of a polypeptide reactive with a fibroblast growth factor receptor and a cytotoxic agent is used for inhibiting the proliferation of epithelial lens cells, especially following extracapsular cataract surgery.Type: GrantFiled: November 26, 1997Date of Patent: October 26, 1999Assignee: Pharmacia S.p.A.Inventor: Yves Courtois
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Catalytic condensation method for the preparation of chlorophyll and bacteriochlorophyll derivatives
Patent number: 5955585Abstract: Conjugates of chlorophyll (Chl) and bacteriochlorophyll (Bchl) derivatives with amino acids, peptides and proteins are provided by the invention. The amino acid, peptide or protein residue is linked to the 17-propionic acid group of a Chl or Bchl residue directly or through a chain. The conjugates are for use as photosensitizers in photodynamic therapy and in diagnostics of tumors. Conjugation with cell-specific ligands, such as hormones, growth factors or tumor-specific antibodies, will target the Chl or Bchl moiety to the tumor site. Thus, conjugates with melanocyte stimulating hormones are suitable for photodynamic therapy of melanoma tumors.Type: GrantFiled: June 5, 1995Date of Patent: September 21, 1999Assignee: Yeda Research and Development Co., Ltd.Inventors: Avigdor Scherz, Yoram Salomon, Leszek Fiedor -
Patent number: 5951974Abstract: Compositions containing alpha interferon conjugated to a substantially non-antigenic polymer are disclosed in which at least about 30% of the conjugates include covalent attachment of the alpha interferon to the substantially non-antigenic polymer at a histidine. Also disclosed is a process for preparing the conjugates. The process includes contacting an alpha interferon with a succinimidyl carbonate-activated substantially non-antigenic polymer at a pH which is sufficient to facilitate covalent attachment of the polymer on a histidine of the alpha interferon.Type: GrantFiled: December 19, 1997Date of Patent: September 14, 1999Assignee: Enzon, Inc.Inventors: Carl W. Gilbert, Myung-ok Park-Cho
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Patent number: 5919758Abstract: The invention relates to novel modified polypeptides, with or without variations in noncoding regions, with altered biological activity. The invention discloses methods of preparing the modified polypeptides and methods of use.Type: GrantFiled: February 3, 1998Date of Patent: July 6, 1999Assignee: Beth Israel Deaconess Medical CenterInventor: Arthur J. Sytkowski
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Patent number: 5919455Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.Type: GrantFiled: March 20, 1997Date of Patent: July 6, 1999Assignee: Enzon, Inc.Inventors: Richard B. Greenwald, Anthony J. Martinez
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Patent number: 5917020Abstract: Crosslinking reagents for protein modification are provided, which comprise four functional, leaving groups capable of reacting with amino acid residues on the protein chains, one pair at each end of a relatively rigid chemical spacer group comprising aromatic residues joined by amide linkages. Such crosslinking reagents react with hemoglobin to effect intramolecular crosslinking of two dimeric hemoglobin units to stabilize the tetramers, by use of the respective pairs of functional groups, and to produce dimers of such tetrameric units, i.e. bis-tetrameric, intramolecularly crosslinked and stabilized hemoglobin, to the exclusion of higher molecular weight hemoglobin species.Type: GrantFiled: January 15, 1997Date of Patent: June 29, 1999Inventors: Ronald H. Kluger, Jodi J.L. Lock-O'Brien
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Patent number: 5880255Abstract: The invention relates to fractionating a mixture of polyethylene glycol (PEG)-protein adducts having different degrees of PEG substitution by partitioning the PEG-protein adducts in a PEG-containing aqueous biphasic system according to the degree of PEG substitution. A new PEG-gm-CSF obtained by the process is useful in pharmaceutical compositions for use in therapeutic or diagnostic methods.Type: GrantFiled: April 14, 1995Date of Patent: March 9, 1999Assignee: PolyMASC Pharmaceuticals plcInventors: Cristina Delgado, Gillian Elizabeth Francis, Derek Fisher
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Patent number: 5874537Abstract: 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: March 5, 1996Date of Patent: February 23, 1999Assignee: C. R. Bard, Inc.Inventors: Charles D. Kelman, Dale P. DeVore
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Patent number: 5869457Abstract: The invention relates to pharmaceutical preparations which are suitable for treating viral infections, including influenza and immunodeficiency diseases and which can also be used in vitro, to inhibit fusion of virus-infected cells with non-infected cells, which preparations contain modified proteins or polypeptides as active substance or substance contributing to the action or as carrier for other substances, which are also active, which modified proteins or polypeptides have acquired an additional net negative charge by derivatisation of their amino groups and/or other basic functional groups with aconitic acid which prevents protonation of basic amino acids and/or other basic functional groups or replaces basic amino acids and/or other basic functional groups by one or more functional groups having a negative charge, and to modified proteins and polypeptides themselves and their preparation and use.Type: GrantFiled: September 4, 1997Date of Patent: February 9, 1999Assignee: Rijksuniversiteit Te GroningenInventors: Robert Walter Jansen, Dirk Klaas Fokke Meijer, Grietje Molema, Erik Desire Alice De Clercq, Rudi Wilfried Jan Pauwels, Dominique Schols
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Patent number: 5849884Abstract: Microparticles formed by mixing a macromolecule with a polymer at a pH near the isoelectric point of the macromolecule and incubating the mixture in the presence of an energy source for a predetermined length of time. The microparticles are composed of homogeneously distributed, intertwined macromolecule and polymer. Each microparticle allows aqueous fluids to enter and allows solubilized macromolecule and polymer to exit the microparticle and may be formulated to provide a sustained release of macromolecule and polymer from the interior of the microparticle when placed in an appropriate aqueous medium, such as under physiological conditions. Methods of production and methods of use for research, diagnostics and therapeutics are provided.Type: GrantFiled: August 19, 1996Date of Patent: December 15, 1998Assignee: Epic Therapeutics, Inc.Inventors: James E. Woiszwillo, Larry R. Brown, Terrence L. Scott, Jie Di, Judith Sudhalter, Charles D. Blizzard
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Patent number: 5849599Abstract: A method for making a preconjugate which includes immunogenic species of a polymorphic analyte. The method is carried out by reacting an activated binding moiety, and a polymorphic analyte at room temperature for between about 10 hours and about 60 hours. The attaching reaction results in an excess of the preconjugate which includes the immunogenic species of the polymorphic analyte. The preconjugate can be used to make an immunoreactive conjugate useful as a developer antigen in a competitive inhibition immunoassay for the polymorphic analyte.Type: GrantFiled: February 7, 1997Date of Patent: December 15, 1998Assignee: Beckman Instruments, Inc.Inventors: Chan S. Oh, Anthony K. Cheng, Josephine M. Michael, Thomas S. Dobashi
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Patent number: 5847089Abstract: The present invention is a biodegradable, reversibly-swellable, polyvalent cation-binding, protein-based hydrogel which comprises an acyl-modified protein matrix in which the acyl-modified protein matrix is crosslinked with a bifunctional crosslinking reagent, and a method of making the same.Type: GrantFiled: June 7, 1995Date of Patent: December 8, 1998Assignee: Wisconsin Alumni Research FoundationInventors: Srinivasan Damodaran, Der-Chyan Hwang
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Patent number: 5843893Abstract: A conjugate of a polypeptide reactive with a fibroblast growth factor receptor and a cytotoxic agent is used for inhibiting the proliferation of epithelial lens cells, especially following extracapsular cataract surgery.Type: GrantFiled: October 12, 1994Date of Patent: December 1, 1998Assignee: Pharmacia S.p.A.Inventor: Yves Courtois
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Patent number: 5824784Abstract: Provided herein are methods and compositions relating to the attachment of water soluble polymers to proteins. Provided are novel methods for N-terminally modifying proteins or analogs thereof, and resultant compositions, including novel N-terminally chemically modified G-CSF compositions and related methods of preparation. Also provided is chemically modified consensus interferon.Type: GrantFiled: October 12, 1994Date of Patent: October 20, 1998Assignee: Amgen Inc.Inventors: Olaf B. Kinstler, Nancy E. Gabriel, Christine E. Farrar, Randolph B. DePrince
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Patent number: 5811521Abstract: Multifunctional chemical reagents useful in cross-linking hemoglobin and having the capability of leaving two or more reaction sites available for further chemical reactions, after completion of the cross-linking process. These reagents are broadly defied as aromatic compounds comprising an aromatic nucleus including but not limited phenyl, biphenyl, naphthyl and binaphthyl, with at least four independently selected electronegative substituent groups bonded directly or indirectly to the aromatic nucleus.Type: GrantFiled: April 11, 1997Date of Patent: September 22, 1998Inventors: Ronald H. Kluger, Krisztina Paal
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Patent number: 5807981Abstract: The present invention is directed to the isolation and identification of the nucleic acid sequence encoding C-proteinase, the recognition of such protein's activity and applications, and tools, processes, and methods of use thereof. The invention is further directed to the identification of molecules modulating C-proteinase's activity, and methods, processes and tools therefor. In a more specific aspect, the invention is directed to peptides resembling the C-proteinase recognition site of procollagen. Such peptides may be employed as modulators of C-proteinase activity, by, for example, acting as competitive inhibitor, and may be employed for the treatment of disorders which involve unregulated production of collagen. Furthermore, such peptides may be employed as C-proteinase substrates for screening of molecules to identify compounds which modulate C-proteinase's activity.Type: GrantFiled: December 13, 1995Date of Patent: September 15, 1998Assignee: FibroGen Inc.Inventor: Mitch Brenner
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Patent number: 5807748Abstract: Novel alkoxythiocarbonylimidazoles provide new reagents for the N-terminal sequencing of small polypeptide samples. These reagents form an alkoxy thiourea derivative which is cleaved with acid to remove the N-terminal amino acid as a stable thiazolinone which does not rearrange to a thiohydantoin. This thiazolinone may be derivatized to provide a detectable group such as a fluorescent group or ionizable group detectable by mass spectrometry.Type: GrantFiled: April 11, 1997Date of Patent: September 15, 1998Assignee: City of HopeInventor: Jerome Bailey
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Patent number: 5789376Abstract: Compositions and processes to alleviate oxygen toxicity are disclosed based on the addition of nitroxides to physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. The formulations described herein interact with free radicals, act as antioxidant enzyme-mimics, and alleviate oxidative stress and oxygen-related toxicity.Type: GrantFiled: January 6, 1997Date of Patent: August 4, 1998Inventor: Jen-Chang Hsia
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Patent number: 5783627Abstract: An enzymatic reaction system including a modified enzyme, and a dense gas system; modified enzymes; and methods of reacting modified enzymes in a dense gas system or liquid carbon dioxide.Type: GrantFiled: September 9, 1996Date of Patent: July 21, 1998Assignee: University of MassachusettsInventors: Fu-jung Kao, Kenneth E. Laintz, Samuel P. Sawan, L. Dale Sivils, W. Dale Spall
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Patent number: 5773581Abstract: The present invention provides a conjugate of a solution stable G-CSF derivative and a water soluble polymer which is an acid stable physiologically active substance derived from naturally occurring G-CSF.Type: GrantFiled: June 7, 1995Date of Patent: June 30, 1998Assignee: Zeneca LimitedInventors: Roger Camble, David Timms, Anthony James Wilkinson
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Patent number: 5770577Abstract: Derivatives of the neurotrophic factors BDNF and NT-3 have been prepared by attachment of these polypeptides to a water soluble polymer, for instance, polyethylene glycol.Type: GrantFiled: November 14, 1994Date of Patent: June 23, 1998Assignee: Amgen Inc.Inventors: Olaf Boris Kinstler, Qiao Yan
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Patent number: 5763579Abstract: The present invention relates to a modified collagen which is soluble in water and/or in aprotic polar organic solvents and which comprises free or substituted thiol functional groups carried by residues of cysteine or its derivatives, the residues being, at least partially, residues which are directly grafted onto the collagen chain, characterized in that it possesses a level of free or substituted thiol functional groups greater than 0.3, preferably 0.5 mM/g of collagen. The invention also relates to the production of these new collagen derivatives and to their application in the preparation of biomaterials, it being possible for the latter to be used especially in the manufacture of implants, prostheses or the like.Type: GrantFiled: June 16, 1995Date of Patent: June 9, 1998Assignee: Flamel TechnologiesInventors: Christian Gagnieu, Florence Nicolas, Gerard Soula
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Patent number: 5763583Abstract: A process for the production of a solubilized protein is disclosed, which is obtained by reducing disulfide bonds in a disulfide bond-containing water-insoluble protein material into mercapto groups and subsequently converting a part or an entire portion thereof into carboxymethyldisulfide groups. In particular, the disclosed process for the production of a solubilized protein which comprises (a) treating a disulfide bond-containing water-insoluble protein material with an aqueous alkaline solution of a reducing agent, and (b) reacting the protein treated by step (a) with thioglycolic acid in the presence of an oxidizing agent under a weakly acidic to a weakly alkaline condition. A process for the production of regenerated protein products, which comprises regenerating disulfide bonds in the solubilized protein, is also disclosed.Type: GrantFiled: October 6, 1995Date of Patent: June 9, 1998Assignee: Kao CorporationInventors: Kozo Arai, Hiroshi Nojiri, Sachio Naito
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Patent number: 5756678Abstract: It has been discovered that it is possible to treat solutions of connective tissue material for the inactivation of prions in a manner such that connective tissue molecules are not adversely affected by the inactivation treatment. For example, solubilized atelopeptide collagen can be treated with sodium hydroxide for the inactivation of prions and other infectious agents without affecting the ability of the solubilized collagen to form stable fibers.Type: GrantFiled: May 1, 1995Date of Patent: May 26, 1998Assignee: Cohesion Technologies, Inc.Inventors: Vivek N. Shenoy, Timothy T. Revak
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Patent number: 5747446Abstract: Modified polypeptides with increased biological activity exhibited as either increased potency or prolonged circulating half-life are disclosed with methods of preparing the modified polypeptides and methods of use.Type: GrantFiled: November 26, 1996Date of Patent: May 5, 1998Assignee: Beth Israel Deaconess Medical CenterInventor: Arthur J. Sytkowski
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Patent number: RE36359Abstract: Provided is a long chain carboxylic acid imide ester (I) represented by the following general formula (I) ##STR1## wherein W is a divalent long chain hydrocarbon group which may optionally be interrupted by one or more groups each independently selected from the group consisting of an oxygen, atom, a sulfur atom, and a group of --N(R.sup.1)-- (R.sup.1 being a lower alkyl group) and X represents a divalent hydrocarbon group which may optionally be substituted, or salt thereof. The above long chain carboxylic acid imide ester or its salts is useful for modifying enzymes or proteins having biological activities to give their derivatives which have, while retaining most of the original biological activities, an extremely prolonged plasma half-life as compared with the proteins and have no antigenecities and can be administered to animals.Type: GrantFiled: May 1, 1997Date of Patent: October 26, 1999Assignee: Kuraray Co., Ltd.Inventors: Iwao Ebashi, Tetsuo Takigawa, Masayasu Inoue