Sulfur Containing Reactant Patents (Class 530/408)
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Patent number: 6037455Abstract: The present invention is directed to novel propoxyphene derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to propoxyphene and propoxyphene 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: November 9, 1992Date of Patent: March 14, 2000Assignee: Biosite Diagnostics IncorporatedInventor: Kenneth F. Buechler
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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: 6010999Abstract: The present invention relates to physiologically-active derivatized natural and recombinant mammalian and human proteins and polypeptides. The invention provides chemical methods for derivatizing natural and recombinantly-derived proteins or polypeptides containing cysteine residues, either naturally or through site specific mutageneses. The pharmaceutical compositions containing said derivatized proteins and/or polypeptides are formulated to provide stable, long-acting compositions of such proteins and/or polypeptides, previously difficult to achieve.Type: GrantFiled: June 2, 1995Date of Patent: January 4, 2000Assignee: American Cyanamid CompanyInventors: Michael Joseph Daley, Brian Lee Buckwalter, Susan Mancini Cady, Hong-Ming Shieh, Peter Bohlen, Andrew P. Seddon
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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: 5986071Abstract: A method for C-Terminal degradation of peptides and proteins involves forming a thiohydantoin derivative of the C-Terminal amino acid and then cleaving the derivatized amino acid by reaction with methoxide or methiolate ions.Type: GrantFiled: June 16, 1997Date of Patent: November 16, 1999Assignee: City of HopeInventors: Kenneth S. Graham, John E. Shively
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Patent number: 5976492Abstract: .sup.32 P- and .sup.33 P-labeled proteins which are useful for radiotherapy are prepared by stably linking .sup.32 P- or .sup.33 P-containing molecules to targeting proteins in such a way that the targeting protein retains the ability to bind to a cellular target. Methods for preparing the labeled proteins and their use in methods of radiotherapy are described.Type: GrantFiled: November 26, 1997Date of Patent: November 2, 1999Assignee: Immunomedics, Inc.Inventors: Gary L. Griffiths, Hans J. Hansen, Habibe Karacay
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Patent number: 5968778Abstract: The invention relates to a process for the preparation of PDGF-A and to biologically active PDGF-AA and PDGF-AB.Type: GrantFiled: February 24, 1997Date of Patent: October 19, 1999Assignee: Jurgen HoppeInventors: Jurgen Hoppe, Herbert Weich
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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: 5955578Abstract: A conjugate of a synthetic polypeptide containing RGD or (dR) GD and a biodegradable polymer, such as hyaluronic acid or chondroitin sulfate is disclosed. Methods of making the conjugate and using it to aid wound healing by providing a temporary matrix are disclosed.Type: GrantFiled: June 5, 1995Date of Patent: September 21, 1999Assignee: La Jolla Cancer Research FoundationInventors: Michael D. Pierschbacher, James W. Polarek, Marianne P. Petrica, Erkki I. Ruoslahti
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Patent number: 5952185Abstract: The invention addresses new photo-activatable biotin derivatives having the formula I ##STR1## wherein R=?(CH.sub.2).sub.n --O.sub.m !.sub.q --?(CH.sub.2).sub.r --O.sub.s !.sub.t --(CH.sub.2).sub.pwith n,r=2,3; m,s=0,1; q+t=1-4; p=1-4,wherein the sum of all CH.sub.2 groups does not exceed 10and wherein R1 as a single or multiple substituent is hydrogen, C.sub.1 -C.sub.5 alkyl, NH.sub.2, COOH, F, Cl, or Br.and their preparation, their use to inactivate streptavidin, the use of the inactivated streptavidin to reduce interference in immunoassays.Type: GrantFiled: October 27, 1997Date of Patent: September 14, 1999Assignee: Boehringer Mannheim GmbHInventors: Erasmus Huber, Michael Wiedmann, Frederic Donie
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Patent number: 5932433Abstract: Biotinylation peptides can be fused to other peptides or proteins of interest using recombinant DNA techniques to provide efficient methods for biotinylating the resulting fusion proteins in vivo or in vitro.Type: GrantFiled: October 28, 1997Date of Patent: August 3, 1999Assignee: Affymax Technologies N.V.Inventor: Peter J. Schatz
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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: 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: 5910427Abstract: Antigen non-specific human glycosylation inhibiting factor derivatives having the inmunosuppressive activity in which a mutation was introduced for replacement, deletion and/or insertion of a part of the amino acid sequence of SEQ ID NO:21, and/or which has received a chemical modification of one or more amino acid residue(s) in the amino acid sequence of SEQ ID NO:21, wherein the mutation and the chemical modification attenuate the strength of an intermolecular association in the region, which participates in trimerization, of an antigen non-specific human glycosylation inhibiting factor having the amino acid sequence of SEQ ID NO:21; DNAs containing a base sequence encoding the amino acid sequence of the antigen non-specific human glycosylation inhibiting factor derivative; recombinant vectors containing the DNAs; prokaryotic or eukaryotic cells transformed with the DNAs; methods of producing the antigen non-specific human glycosylation inhibiting factor derivatives; pharmaceutical compositions comprising tType: GrantFiled: March 4, 1996Date of Patent: June 8, 1999Assignee: La Jolla Institute for Allergy and ImmunologyInventors: Toshifumi Mikayama, Takafumi Tomura, Hiroshi Watarai, Ryota Kuroki, Yoichi Kato, Kimishige Ishizaka, Tatsumi Nakano
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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: 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: 5843900Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.Type: GrantFiled: June 5, 1995Date of Patent: December 1, 1998Assignee: Cortech, Inc.Inventors: John C. Cheronis, Albert Gyorkos, Lyle W. Spruce, Eric T. Whalley
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Patent number: 5837499Abstract: Disclosed are polypeptide analogues of human C5a which are C5a receptor antagonists that exhibit substantially no analphylatoxin or agonist activity, and derivatives of the analogues, and dimeric forms of the analogues or derivatives. DNA molecules encoding the polypeptides and methods of making the analogues are also provided. Pharmaceutical formulations containing a C5a analogue, are used therapeutically in the treatment of C5a-mediated diseases and inflammatory conditions in mammals, and prophylactically to prevent or reduce inflammation caused by an event which causes inflammation or aggravates an existing inflammatory condition, respectively. Further disclosed are antibodies specific to the C5a analogues, derivatives thereof, and dimers of the analogues and derivatives which exhibit substantially no cross-reactivity with human C5a. The antibodies are used to detect or quantify circulating C5a analogue or derivative, as well as to modify, e.g.Type: GrantFiled: June 5, 1995Date of Patent: November 17, 1998Assignee: Ciba-Geigy CorporationInventors: Jan van Oostrum, William C. Boyar, Nicholas G. Galakatos, Albert Schmitz, Gino Van Heeke
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Patent number: 5807997Abstract: A method for the immobilization of an organic thiol compound, HS--R, in which R is an organic residue, to a water-insoluble polymer of non-polypeptide structure exhibiting a disulfide (--S--S--) group directly bound to a saturated carbon atom at each of its sulphur atoms, which comprising contacting the polymer with an oxidation agent in such an amount and of such a kind that it is capable of transforming the disulfide group (--S--S--) to an oxidized disulfide group capable of reacting with thiol groups, whereupon the polymer obtained exhibiting one or more oxidized disulfide groups is contacted with the organic thiol compound HS--R under conditions allowing reaction to the formation of one --S--S--R group and one --SO.sub.n (H) group per disulfide oxide group that undergoes the reaction, where n is 1 or 2.Type: GrantFiled: December 20, 1991Date of Patent: September 15, 1998Inventor: Francisco Batista
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Patent number: 5789547Abstract: The present invention provides a novel method for refolding insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3(IGFBP-3). The method involves mixing of IGF-I and IGFBP-3 together in a cofolding reaction. The inventive cofolding method results in substantially higher yields of correctly folded protein for both molecules and alters the kinetics of refolding. The method includes the production of correctly folded IGF-I, IGFBP-3, and/or IGF-I/IGFBP-3 complex.Type: GrantFiled: June 7, 1995Date of Patent: August 4, 1998Assignee: Celtrix Pharmaceuticals, Inc.Inventors: Andreas Sommer, Yasushi Ogawa, Peggy Tao
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Patent number: 5783673Abstract: 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: October 10, 1996Date of Patent: July 21, 1998Assignee: Coulter CorporationInventor: Ravinder K. Gupta
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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: 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: 5728369Abstract: .sup.32 P- and .sup.33 P-labeled proteins which are useful for radiotherapy are prepared by stably linking .sup.32 P- or .sup.33 P- containing molecules to targeting proteins in such a way that the targeting protein retains the ability to bind to a cellular target. Methods for preparing the labeled proteins and their use in methods of radiotherapy are described.Type: GrantFiled: October 5, 1994Date of Patent: March 17, 1998Assignee: Immunomedics, Inc.Inventors: Gary L. Griffiths, Hans J. Hansen, Habibe Karacay
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Patent number: 5723584Abstract: Biotinylation peptides can be fused to other peptides or proteins of interest using recombinant DNA techniques to provide efficient methods for biotinylating the resulting fusion proteins in vivo or in vitro.Type: GrantFiled: February 3, 1995Date of Patent: March 3, 1998Assignee: Affymax Technologies N.V.Inventor: Peter J. Schatz
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Patent number: 5714386Abstract: Novel tandem dyes comprising a conjugate of a Cy7 dye and allophycocyanin are provided. Also provided are probes comprising the subject dyes conjugated to a member of a specific binding pair. Probes comprising the subject tandem dyes find use as labels in variety of fluorescence detection assays.Type: GrantFiled: January 11, 1996Date of Patent: February 3, 1998Assignee: Board of Trustees of the Leland Stanford Junior UniversityInventor: Mario Roederer
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Patent number: 5710253Abstract: A method for decoloring a recombinant human serum albumin by treating the albumin with a reducing agent is disclosed. Also, a method for decoloring a recombinant human serum albumin by treating the albumin with a method removing free polysaccharides with a cation exchanger followed by heat treatment is disclosed. The present invention provides a recombinant human serum albumin, coloring of which is fully suppressed by preventing binding of certain coloring components, which are contained in the raw materials or contaminants secreted by a microorganism, to human serum albumin so as not to cause coloring of the human serum albumin.Type: GrantFiled: December 19, 1994Date of Patent: January 20, 1998Assignee: The Green Cross CorporationInventors: Wataru Ohtani, Naoto Furuhata, Akinori Sumi, Munehiro Noda, Takao Ohmura
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Patent number: 5681927Abstract: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.Type: GrantFiled: June 11, 1993Date of Patent: October 28, 1997Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Tripuraneni N. Rao, Jean-Luc VanderHeyden, Ananthachari Srinivasan
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Patent number: 5672687Abstract: The invention relates to magnetic protein conjugates of the formula I ##STR1## in which M represents a dispersible magnetically reacting material or particle which carries aminogroups, Ig represents a protein which carries one or more mercapto groups, and X represents an organic chemical structure which links the two ligands by chemical means, to a process for the preparation of protein conjugates of the formula I, and to the use of conjugates of this type for removing cells or soluble bioorganic molecules or components from aqueous salt solutions or body fluids, and to the use thereof within the framework of a diagnostic method or as a diagnostic aid.Type: GrantFiled: January 19, 1995Date of Patent: September 30, 1997Assignee: Behringwerke AktiengesellschaftInventors: Peter Hermentin, Reiner Donges, Karlheinz Enssle, Roland Kurrle, Friedrich Robert Seiler
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Patent number: 5672662Abstract: Active esters of PEG acids and related polymers are provided that have a single propionic or butanoic acid moiety and no other ester linkages. These polymer acids have a half life in water of from about 10 to 25 minutes. For example, alpha-methoxy, omega-propionic acid succinimidyl ester of PEG ("methoxy-PEG-SPA") has a nearly ideal reactivity with amino groups on proteins and other biologically active substances. The half life of methoxy-PEG-SPA is about 16.5 minutes in water. The invention also provides conjugates with proteins, enzymes, polypeptides, drugs, dyes, nucleosides, oligonucleotides, lipids, phospholipids, liposomes, and surfaces of solid materials that are compatible with living organisms, tissue, or fluid.Type: GrantFiled: October 2, 1995Date of Patent: September 30, 1997Assignee: Shearwater Polymers, Inc.Inventors: J. Milton Harris, Antoni Kozlowski
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Patent number: 5663074Abstract: This invention is directed to novel nucleophilic polysubstituted aryl acridinium conjugates and the methods for preparation thereof. The novel nucleophilic polysubstituted aryl acridinium conjugates are useful in biological assays, including novel assays for the determination of Vitamin B.sub.12, folate, cortisol, estradiol, and thromboxane B.sub.2.Type: GrantFiled: March 17, 1993Date of Patent: September 2, 1997Assignee: Chiron Diagnostics CorporationInventor: Say-Jong Law
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Patent number: 5659015Abstract: This invention relates to a method of producing peracetyloxazolines from peracetyl saccharides. The method involves reacting the starting material, a peracetyl saccharide, with a reagent combination, to directly produce the peracetyl oxazoline. This method may be used for the activation of oligosaccharides, wherein an oligosaccharide containing a reducing GlcNAc terminus is activated by the formation of an oxazolide at the terminal GlcNAc, and then coupled with a bifunctional spacer to provide an oligosaccharide-spacer conjugate. The activated oligosaccharide-spacer conjugate is then coupled to a protein, such as granulocyte colony stimulating factor or .gamma.-interferon, providing a neoglycoprotein conjugate. The invention provides a method for forming neoglycoprotein conjugates which may improve biological and physiochemical properties of the protein. For example, serum lifetime or efficiency of drug delivery of the peptide to a target organ or cell may be improved.Type: GrantFiled: October 13, 1992Date of Patent: August 19, 1997Inventors: Marcelo Colon, Jeffrey T. Davis, James R. Rasmussen, Marianne Borowski, Barbara Y. Wan, Shirish Hirani
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Patent number: 5650496Abstract: Disclosed is an improved process for obtaining purified, monomeric, intact, correctly-folded insulin-like growth factor-I (also known as somatomedin-C). The improvements, consisting primarily of the addition of an IGF-I unfolding/refolding step and the substitution of a reverse phase chromatography step for a gel filtration chromatography step result in a three-fold increase in final yield. The process includes the following steps, in order: first cation exchange, unfolding/refolding, hydrophobic interaction chromatography, second cation exchange, and reverse phase chromatography.Type: GrantFiled: April 14, 1995Date of Patent: July 22, 1997Assignee: Cephalon, Inc.Inventors: Russell A. Brierley, Joan N. Abrams, John M. Hanson, Francis C. Maslanka
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Patent number: 5650492Abstract: Analysis of the culture media of p40-transfected COS cells indicated the presence of 40 kDa monomers and 80 kDa disulfide-linked homodimers. Examination of partially purified p40 recombinant proteins demonstrated that only the homodimer but not the monomer binds to the IL-12 receptor. Partially purified 80 kDa homodimer inhibited [.sup.125 I]IL-12 binding to PHA-activated human lymphoblasts with an IC.sub.50 of 80 ng/ml, which is similar to the IC.sub.50 value (20 ng/ml) for the human IL-12 heterodimer. Although neither the 40 kDa monomer nor the 80 kDa dimer could stimulate human PHA-blast proliferation, the 80 kDa dimer inhibited IL-12-induced proliferation in a dose-dependent manner with an IC.sub.50 of 1 .mu.g/ml. The IL-12 p40 subunit contains the essential epitopes for receptor binding, but they are only active when p40 is covalently associated with a second protein such as p35 or p40. When p40 is associated with the p35 subunit, the heterodimer acts as an agonist mediating biologic activity.Type: GrantFiled: April 18, 1995Date of Patent: July 22, 1997Assignee: Hoffmann-La Roche Inc.Inventors: Maurice Kent Gately, John Hakimi, Ping Ling
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Patent number: 5643575Abstract: 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: October 27, 1993Date of Patent: July 1, 1997Assignee: Enzon, Inc.Inventors: Anthony Martinez, Richard B. Greenwald
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Patent number: 5635593Abstract: A brandykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.Type: GrantFiled: May 12, 1995Date of Patent: June 3, 1997Assignee: Cortech, Inc.Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
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Patent number: 5629291Abstract: The present invention provides fibronectin self-assembly sites. The invention provides a set of polypeptides derived from the first type III repeat of fibronectin which contain a fibronectin-fibronectin binding site. These polypeptides have been used to obtain a second set of polypeptides derived from the C-terminal type I repeats which contain a second fibronectin-fibronectin binding site which interacts with the first type III repeat of fibronectin. These polypeptides are capable of inhibiting fibronectin matrix assembly by interfering with fibronectin-fibronectin binding. These polypeptides are also capable of enhancing fibronectin matrix assembly and inducing disulfide cross-linking of fibronectin molecules in vitro. In addition, these polypeptides are capable of inhibiting migration of tumor cells. The polypeptides of the present invention have a number of related uses as well.Type: GrantFiled: November 17, 1994Date of Patent: May 13, 1997Assignee: La Jolla Cancer Research FoundationInventors: Erkki I. Ruoslahti, Alex Morla
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Patent number: 5623057Abstract: A novel conjugate vaccine comprising partially hydrolyzed, highly purified, capsular polysaccharide (Ps) from Streptococcus pneumoniae bacteria (pneumococci, Pn) linked to an immunogenic carrier protein, is produced by a new process. The conjugate is useful in the prevention of pneumococcal infections. Vaccines comprising a mixture of from one to ten different pneumococcal polysaccharide-immunogenic protein (Pn-Ps-PRO) conjugates induce broadly protective recipient immune responses against the cognate pathogens from which the polysaccharide components are derived. Young children and infants younger than 2 years old, normally unable to mount a protective immune response to the Pn-Ps alone, exhibit protective immune responses upon vaccination with these Pn-Ps-PRO conjugates.Type: GrantFiled: May 20, 1994Date of Patent: April 22, 1997Assignee: Merck & Co., Inc.Inventors: Stephen Marburg, Richard L. Tolman, Peter J. Kniskern, William J. Miller, Arpi Hagopian, Charlotte C. Ip, John P. Hennessey, Jr., Dennis J. Kubek, Pamela D. Burke
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Patent number: 5620958Abstract: A bradykinin antagonist of the formula:X(BKA).sub.nwherein BKA is the peptide chain of a bradykinin antagonist peptide, X is a linking group and n is a whole number greater than 1. The BKA substituents may be the same or different. Monomeric antagonists of the formula X(BKA) are also disclosed. Also disclosed are bradykinin antagonists of the formula:(Y)(X)(BKA)where X and BKA have the meanings indicated above and Y is the peptide chain of an antagonist or agonist for a non-bradykinin receptor.Type: GrantFiled: April 13, 1994Date of Patent: April 15, 1997Assignee: Coretech, Inc.Inventors: John C. Cheronis, James K. Blodgett, Eric T. Whalley, Shadrach R. Eubanks, Lisa G. Allen, Khe T. Nguyen
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Patent number: 5618927Abstract: The invention concerns a process for the reactivation of denatured protein, in which the protein is incubated with a solution of Tris base or/and a salt of Tris at a concentration of at least 400 mmol/l and at a pH at which the protein to be treated can take up its native conformation.Type: GrantFiled: July 2, 1992Date of Patent: April 8, 1997Assignee: Boehringer Mannheim GmbHInventors: Dorothea Ambrosius, Rainer Rudolph
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Patent number: 5616692Abstract: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.Type: GrantFiled: May 8, 1995Date of Patent: April 1, 1997Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Tripuraneni N. Rao, Jean-Luc VanderHeyden, Ananthachari Srinivasan
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Patent number: 5616327Abstract: Peptides substantially corresponding to the 148-162 region of type A influenza M protein and additionally containing at least one amino acid in the 163-166 region are disclosed to have high activity as influenza transcription inhibitors and thus as antiviral agents against influenza virus and other RNA viruses. The modification of these peptides by incorporation into liposomes or by addition of long-chain alkylamino acids is also shown as in the use of all such materials in antiviral drug formulations.Type: GrantFiled: November 7, 1994Date of Patent: April 1, 1997Assignees: SRI International, New York Medical CollegeInventors: Amrit K. Judd, Doris J. Bucher
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Patent number: 5614419Abstract: Immunoassay methods and reagents for the specific quantification of amitriptyline or nortriptyline in a test sample are disclosed employing antibodies prepared with amitriptyline or nortriptyline derivatives of the Formula III: ##STR1## wherein for amitriptyline, R is CH.sub.3, and for nortriptyline, R is H. The present invention also describes the synthesis of unique fluorescein tracers of the structure of Formula IV and Formula V: ##STR2## wherein for a specific amitriptyline immunoassay, W.sub.1 is a heteroatom linked to the aromatic ring at the 2 or 3 position, and for a specific nortriptyline immunoassay, W.sub.2 is two heteroatoms linked together and attached to the aromatic ring at the 2 or 3 position, and wherein Q is a detectable moiety, preferably fluorescein or a fluorescein derivative.Type: GrantFiled: August 5, 1994Date of Patent: March 25, 1997Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Jeffrey R. Fishpaugh, Donald Johnson, Daryl E. Hartter
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Patent number: 5612016Abstract: Provided are conjugates useful in cancer, cardiovascular or infectious disease detection and/or therapy. The conjugate is of a ligand and protein. The ligand has a moiety capable of binding to mercapto groups and is capable of chelating a metal useful for detection or therapy. The protein reacts with a substance associated with a targeted cell, pathologic lesion or pathogen. The protein prior to conjugation has at least one mercapto group which becomes a site for conjugation to the ligand. Also provided are metal chelates of the conjugate, methods of detection and therapy, methods for producing the conjugate and pharmaceuticals compositions of the conjugates.Type: GrantFiled: March 29, 1993Date of Patent: March 18, 1997Assignee: Immunomedics, Inc.Inventors: Gary L. Griffiths, Habibe Diril, Hans J. Hansen
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Patent number: 5610140Abstract: The present invention provides a heterodimeric compound possessing bradykinin and neurokinin receptor antagonist activities useful in the treatment of asthma and other inflammatory diseases especially those involving the airway or pulmonary system. The present invention is also useful in the treatment of pain and inflammation.Type: GrantFiled: August 1, 1994Date of Patent: March 11, 1997Assignee: Cortech, Inc.Inventors: Val S. Goodfellow, Eric T. Whalley, Francine E. Wincott
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Patent number: 5610283Abstract: The present invention is directed to novel opiate derivatives which are synthesized for the covalent attachment to antigens (proteins or polypeptides) for the preparation of antibodies or receptors to the opiates and opiate 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: February 15, 1995Date of Patent: March 11, 1997Assignee: Biosite Diagnostics IncorporatedInventor: Kenneth F. Buechler
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Patent number: 5606030Abstract: A novel coconjugate comprising an immunogenic protein or protein complex having a first set of covalent linkages to low molecular weight moieties, --a.sup.--, which have an anionic or polyanionic character at physiological pH, and a second set of covalent linkages to peptides comprising Human Immunodeficiency Virus (HIV) Principal Neutralizing Determinants (PNDs), or peptides immunologically equivalent therewith, is useful for inducing anti-peptide immune responses in mammals, for inducing HIV-neutralizing antibodies in mammals, for formulating vaccines to prevent HIV infection or disease, including the Acquired Immune Deficiency Syndrome (AIDS), or for treating humans afflicted with HIV infection or disease.Type: GrantFiled: September 14, 1994Date of Patent: February 25, 1997Assignee: Merck & Co., Inc.Inventors: Emilio A. Emini, William J. Leanza, Stephen Marburg, Richard L. Tolman
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Patent number: 5606028Abstract: Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.Type: GrantFiled: September 21, 1995Date of Patent: February 25, 1997Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Ananthachari Srinivasan