Gonadatropins Patents (Class 530/398)
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Patent number: 6600019Abstract: The present invention provides novel isolated NOVX polynucleotides and polypeptides encoded by the NOVX polynucleotides. Also provided are the antibodies that immunospecifically bind to a NOVX polypeptide or any derivative, variant, mutant or fragment of the NOVX polypeptide, polynucleotide or antibody. The invention additionally provides methods in which the NOVX polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, as well as to other uses.Type: GrantFiled: January 4, 2001Date of Patent: July 29, 2003Assignee: CuraGen CorporationInventors: Sudhirdas K. Prayaga, Kumud Majumder, Bruce Taillon, Steven Kurt Spaderna, Kimberly Spytek, John MacDougall
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Publication number: 20030113871Abstract: Provided is a fusion protein comprising, at its carboxy terminal of human erythropoietin (EPO), a mutant having one to four amino acid substitutions in the carboxy terminal peptide (CTP) fragment of a human chorionic gonadotropin (HCG) &bgr; subunit, for increasing an in vivo half-life activity of EPO. The in vivo half-life can be greatly elongated while retaining the intrinsic activity of the EPO, without increasing the sugar chain content.Type: ApplicationFiled: July 17, 2002Publication date: June 19, 2003Applicant: Cheil Jedang CorporationInventors: Dong-eok Lee, Myung-suk Oh, Ki-wan Kim, Bo-sup Chung, Ji-sook Park
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Publication number: 20030104553Abstract: A process for the purification of recombinant human Chorionic Gonadotropin (hCG) from a sample of crude recombinant hCG in the supernatant of CHO cells comprises the combined use of ion-exchange chromatography and reverse phase HPLC. The ion-exchange chromatography is performed twice and the final use of a size exclusion chromatography allows the purification from any residual traces of contaminants. The specific bioactivity of the highly purified hCG obtained form the process is particularly high, amounting to about 25,000 IU/mg.Type: ApplicationFiled: December 9, 2002Publication date: June 5, 2003Inventors: Gianfranco Paradisi, Mara Rossi, Laura Scaglia
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Patent number: 6486303Abstract: The present invention relates to a method for preparing heterodimeric analogs of cysteine knot proteins. More specifically, the invention relates to a method for forming a subunit combination of a cysteine knot protein having an &agr;-subunit and a &bgr;-subunit to prepare a heterodimeric protein analog which comprises the steps of (a) attaching a dimerization domain to the amino termini of both an &agr;-subunit and &bgr;-subunit of a cysteine knot protein; and (b) dimerizing the &agr;-subunit and &bgr;-subunit to form a heterodimeric protein analog.Type: GrantFiled: April 14, 1998Date of Patent: November 26, 2002Assignee: University of Medicine & Dentistry of New JerseyInventor: William R. Moyle
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Patent number: 6444639Abstract: The use of hCG, hCG &bgr;-subunit, as well as fragments and active derivatives thereof, or hCG &bgr;-core in the preparation of a medicament for the prophylaxis and/or the treatment of pathologies requiring inhibition of the matrix metalloprotease (MMP) enzymatic activity.Type: GrantFiled: November 24, 1999Date of Patent: September 3, 2002Assignee: Applied Research Systems ARS Holding N.V.Inventors: Adriana Albini, Giorgia Orengo
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Patent number: 6414123Abstract: The present invention provides a method for purifying follicle stimulating hormone (FSH) from biological samples, for example, from human pituitary glands or human postmenopausal urine, wherein the FSH is contaminated with other proteins, by use of dye-ligand affinity chromatography (DAC). Depending on the starting material used and the initial purity of FSH in the starting material, additional purification steps may be employed. These steps preferably involve the use of hydrophobic interaction chromatography. This process may be used to generate affinity pure FSH suitable for therapeutic applications. The methods of the invention provide high purity FSH with high overall yield. A further advantage is the ability to easily regenerate the chromatography media for re-use, thus providing added economy to the purification process.Type: GrantFiled: November 16, 1999Date of Patent: July 2, 2002Assignee: Vitro Diagnostics, Inc.Inventors: James R. Musick, Erik Van Horn
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Patent number: 6372711Abstract: The present invention embraces essentially pure human FSH receptor, or a fragment or mutant thereof which binds FSH, DNA encoding said receptor, fragment or mutant, expression vectors comprising said DNA, cells transfected with said expression vectors, and methods of producing said receptor, fragment or mutant by culturing said transfected cells. The present invention also includes pharmaceutical compositions comprising said receptor, fragment or mutant, as well as methods of treating patients with such compositions to reduce endogenous FSH bioactivity. An improved assay for human FSH using the receptor, fragment or mutant of the present invention is also disclosed.Type: GrantFiled: June 7, 1995Date of Patent: April 16, 2002Assignee: Applied Research Systems ARS Holding N.V.Inventors: Christie Ann Kelton, Shirley Vui Yen Cheng, Noreen Patrice Nugent, Rene Lynn Schweickhardt
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Patent number: 6251402Abstract: The use of hCG Beta-core or hCG fragments, deglycosylated hCG in the treatment of Kaposi's sarcoma is described. Inhibition of tumor production or regression on a variety of KS cell lines is shown. Purified hCG preparations do not inhibit the growth of KS cell lines.Type: GrantFiled: April 29, 1999Date of Patent: June 26, 2001Assignee: Applied Research Systems ARS Holding N.V.Inventor: Siegfried Schwarz
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Patent number: 6242580Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The &agr; and &bgr; subunits of the wild-type heterodimers or their variants or their fragments are covalently linked, optionally through a linker moiety. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity.Type: GrantFiled: March 31, 1999Date of Patent: June 5, 2001Assignee: Washington UniversityInventors: Irving Boime, William R. Moyle
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Patent number: 6238890Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The &agr; and &bgr; subunits of the wild-type heterodimers or their variants or their fragments are covalently linked, optionally through a linker moiety. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity.Type: GrantFiled: August 25, 1997Date of Patent: May 29, 2001Assignee: Washington UniversityInventors: Irving Boime, William R. Moyle
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Patent number: 6193972Abstract: A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-&bgr; and TPO, linked to a subunit of a heterodimeric proteinaceous hormone, such as hCG. Each coexpressed sequence contains a corresponding hormone subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.Type: GrantFiled: February 20, 1997Date of Patent: February 27, 2001Assignee: Applied Research Systems ARS Holding N.V.Inventors: Robert K. Campbell, Bradford A. Jameson, Scott C. Chappel
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Patent number: 6194177Abstract: A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-&bgr;and TPO, linked to a subunit of a heterodimeric proteinaceous hormone, such as hCG. Each coexpressed sequence contains a corresponding hormone subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.Type: GrantFiled: August 14, 1997Date of Patent: February 27, 2001Assignee: Applied Research Systems ARS Holding N.V.Inventors: Robert K. Campbell, Bradford A. Jameson, Scott C. Chappel
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Patent number: 6140066Abstract: The present invention relates to methods for cancer diagnosis using a chimeric toxin. In particular, the invention relates to the use of a chimeric toxin composed of gonadotropin releasing hormone (GnRH) and Pseudomonas exotoxin A (PE) to detect a tumor-associated epitope expressed by human adenocarcinomas. Mutated GnRH-PE molecules that bind but do not kill tumor cells are exemplified.Type: GrantFiled: March 24, 1998Date of Patent: October 31, 2000Inventors: Haya Lorberboum-Galski, Shai Yarkoni, Ahmi Ben-Yehudah, Irina Marianovsky, Amotz Nechushtan
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Patent number: 6103501Abstract: Single-chain agonists and/or antagonists of the glycoprotein hormones are disclosed. These proteins are of the formula.beta..sup.1 -(linker.sup.1).sub.m -.alpha.-(linker.sup.2).sub.n -.beta..sup.2 (1);or.beta..sup.1 -(linker.sup.1).sub.m -.beta..sup.2 -(linker.sup.2).sub.n -.alpha. (2);or.alpha.-(linker.sup.1).sub.m -.beta..sup.1 -(linker.sup.2).sub.n - .beta..sup.2 (3)wherein each of .beta..sup.1 and .beta..sup.2 has the amino acid sequence of the .beta. subunit of a vertabrate glycoprotein hormone or a variant thereof; ".alpha." designates the .alpha. subunit of a vertabrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that spaces the .beta..sup.1 and .beta..sup.2 subunits at distances from the .alpha. subunit and from each other effective to retain said activity, and each of m and n is independently 0 or 1.Type: GrantFiled: November 17, 1997Date of Patent: August 15, 2000Assignee: Washington UniversityInventors: Irving Boime, David Ben Menahem
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Patent number: 6033903Abstract: The extracellular domain, or fragment thereof, of a gonadotropin glycoprotein hormone receptor is expressed and secreted in a soluble and functionally hormone-binding form. A recombinant baculovirus transfer vector is constructed to include a gene segment encoding the extracellular domain, or fragment thereof, of the glycoprotein hormone receptor joined in frame with a gene segment encoding a baculovirus signal peptide and operably linked to a baculovirus promoter. Recombinant baculovirus generated by transfection or co-transfection of insect cells are then used to infect insect host cells for the expression and secretion of soluble receptor.Type: GrantFiled: June 2, 1995Date of Patent: March 7, 2000Assignee: Applied Research Systems, Ars Holding N.V.Inventors: William P. Sisk, Shirley Vui Yen Cheng, David Rogers Buckler, Holly Lynn Prentice
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Patent number: 5990288Abstract: The present invention provides a method for purifying follicle stimulating hormone (FSH) from biological samples, for example, from human pituitary glands or human postmenopausal urine, wherein the FSH is contaminated with other proteins, by use of dye-ligand affinity chromatography (DAC). This process may be used to generate affinity pure FSH suitable for therapeutic applications.Type: GrantFiled: May 8, 1998Date of Patent: November 23, 1999Assignee: Vitro Diagnostics, Inc.Inventors: James R. Musick, Erik Van Horn
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Patent number: 5985611Abstract: Improved methods for recombinant production of human reproductive hormones are disclosed. These methods involve the use of animal-derived cells that contain regulated secretory granules as host cells for expression systems capable of expressing DNA encoding human reproductive hormones or their .beta. subunits.Type: GrantFiled: April 30, 1992Date of Patent: November 16, 1999Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5929211Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.Type: GrantFiled: September 4, 1997Date of Patent: July 27, 1999Assignee: Genentech, Inc.Inventors: Avi J. Ashkenazi, Steven M. Chamow, Timothy P. Kogan
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Patent number: 5929028Abstract: The invention concerns a liquid gonadotropin-containing formulation characterised in that the formulation comprises a gonadotropin and stabilising amounts of a polycarboxylic acid or a salt thereof and of a thioether compound. The particular proteins (e.g. LH, TSH, FSH, or HCG) are in admixture with the particular stabilizers in an aqueous solution. The preparations contain a sufficient amount of the polycarboxylic acid or a salt thereof, preferably sodium citrate, and a sufficient amount of the thioether compound, preferably methionine, to stabilize the protein. The preparations preferably also include a nonreducing disaccharide like sucrose, and a non-ionic surfactant.Type: GrantFiled: April 14, 1998Date of Patent: July 27, 1999Assignee: Akzo Nobel, N.V.Inventors: Arnold Titus Philip Skrabanja, Petrus Johannes Maria van den Oetelaar
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Patent number: 5889155Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.Type: GrantFiled: March 31, 1995Date of Patent: March 30, 1999Assignee: Genentech, Inc.Inventors: Avi J. Ashkenazi, Steven M. Chamow, Timothy P. Kogan
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Patent number: 5883073Abstract: The invention is directed to a glycosylated or nonglycosylated protein which is composed of the amino acid sequence of a first .alpha. subunit common to the glycoprotein hormones linked covalently, optionally through a linker moiety, to the amino acid sequence of a second .alpha. subunit of said hormones, wherein said first and second .alpha. subunits consist of the native amino acid sequences or variants of said amino acid sequences. These proteins are useful as agonists or antagonists of glycoprotein hormone activity.Type: GrantFiled: April 3, 1997Date of Patent: March 16, 1999Assignee: Washington UniversityInventors: Irving Boime, David Ben-Menahem
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Patent number: 5877148Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.Type: GrantFiled: June 6, 1997Date of Patent: March 2, 1999Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Yanto Lunardi-Iskandar, Robert C. Gallo, Joseph L. Bryant
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Patent number: 5851997Abstract: Prophylaxis against viral infections, as well as treatment for individuals infected with a virus, can be achieved through the administration of human chorionic gonadotropin (HCG). Exemplary of the viral infections that are amenable to the use of HCG in this regard include those caused by HIV-1, Kaposi's sarcoma herpes virus, molluscipoxvirus and cytomegalovirus. In addition, HCG can be used as a neonatal immune booster via administration to a baby at delivery and, optionally, for the first several months of life, until the infantile immune system matures, in order to prevent HIV transmission and control any low-level viremia, as well as to protect against various other viruses, such as herpes viruses and oncogenic viruses.Type: GrantFiled: July 2, 1996Date of Patent: December 22, 1998Inventor: Pamela Jo Harris
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Patent number: 5840857Abstract: Purification of human FSH from post-menopausal urine gonadogropin using immunochromatography and reverse phase HPLC steps yelds a biologically active hormone which is free from detectable traces of LH and other urinary proteins.Type: GrantFiled: December 29, 1995Date of Patent: November 24, 1998Assignee: Istituto di Ricerca Cesare Serono S.p.A.Inventors: Guiseppe Arpaia, Serenella Serani, Antonino Sirna, Stefano Villa
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Patent number: 5811390Abstract: Described is a method for inhibiting the growth and/or replication of human immunodeficiency virus (HIV) in human patients. The invention relates to the unexpected activity of human chorionic gonadotropin (hCG) and in particular, to the beta chain of hCG (beta hCG) in controlling a human immunodeficiency virus (HIV) infection and other virus-related immunodeficiency disorders. The invention comprises administering an anti-HIV effective amount of beta hCG to an asymptomatic individual with an HIV infection, including an individual presenting the symptoms of AIDS.Type: GrantFiled: August 22, 1995Date of Patent: September 22, 1998Assignee: Metatron, Inc.Inventor: Aldar S. Bourinbaiar
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Patent number: 5792460Abstract: "Partial" and "complete" CTP units are used to modify biologically active proteins and peptides to alter their clearance patterns. "Complete" CTP units have the amino acid sequence found at positions 112-118 to position 145 of the .beta.-subunit of human chorionic gonadotropin; "partial" CTP units are missing at least one amino acid in the region of position 118-145 inclusive. Variants of these CTP units contain 1-5 conservative amino acid substitutions which do not destroy activity. Suitable peptides or proteins which may be modified in this manner include various hormones and cytokines.Type: GrantFiled: April 10, 1995Date of Patent: August 11, 1998Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5767067Abstract: Purification of human FSH from post-menopausal urine gonadogropin using immunochromatography and reverse phase HPLC steps yelds a biologically active hormone which is free from detectable traces of LH and other urinary proteins.Type: GrantFiled: March 30, 1995Date of Patent: June 16, 1998Assignee: Istituto di Ricerca Cesare Serono S.p.A.Inventors: Guiseppe Arpaia, Serenella Serani, Antonino Sirna, Stefano Villa
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Patent number: 5759818Abstract: "Partial" and "complete" CTP units are used to modify biologically active proteins and peptides at the aminoterminus to alter their clearance patterns. "Complete" CTP units have the amino acid sequence found at positions 112-118 to position 145 of the .beta.-subunit of human chorionic gonadotropin; "partial" CTP units are missing at least one amino acid in the region of position 118-145 inclusive. Variants of these CTP units contain 1-5 conservative amino acid substitutions which do not destroy activity. Suitable peptides or proteins which may be modified in this manner include various hormones and cytokines.Type: GrantFiled: June 7, 1995Date of Patent: June 2, 1998Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5716853Abstract: Herein disclosed are methods for prenatally assessing risks of a pregnancy being affected by Down syndrome by testing maternal urine samples for levels of urinary gonadotropin peptide (UGP) elevated above normal. The methods employ immunoassays that are highly specific for UGP and have molar cross-reactivities of less than about 10% with intact hCG, with .beta.-subunit hCG, and with .alpha.-subunit hCG. The immunoassay methods of this invention are useful to test first trimester maternal urine samples. Among other benefits, first trimester prenatal screening provides the opportunity to terminate the pregnancy at an early gestational age, in the case of an unfavorable outcome.Type: GrantFiled: April 30, 1996Date of Patent: February 10, 1998Assignee: Chiron Diagnostics CorporationInventors: Howard S. Cuckle, Roger P. Walker
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Patent number: 5705478Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. The single chain compounds of the invention comprise two .beta. subunits of the glycoprotein hormones, which .beta. subunits are the same or different. These "two-.beta." forms are antagonists of glycoprotein hormone activity.Type: GrantFiled: November 4, 1994Date of Patent: January 6, 1998Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5700781Abstract: Prophylaxis against HIV, treatment for individuals infected with HIV, and treatment Kaposi's sarcoma can be effected, respectively, through the administration of human chorionic gonadotropin.Type: GrantFiled: November 10, 1994Date of Patent: December 23, 1997Inventor: Pamela Jo Harris
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Patent number: 5691455Abstract: The present invention relates to gonadotropins consisting of an .alpha. and .beta. subunit, said gonadotropins comprising non-native disulfide bridges, preferably non-native intersubunit disulfide bridges. The gonadotropins according to the invention have improved stability. The present invention furthermore provides for pharmaceutical compositions comprising said gonadotropins.Type: GrantFiled: November 9, 1995Date of Patent: November 25, 1997Assignee: Akzo Nobel N.V.Inventors: Pieter Diederik Jan Grootenhuis, Judith Christina Heikoop
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Patent number: 5677275Abstract: Methods useful for treating cancers are disclosed. The methods involve administering human chorionic gonadotropin (hCG) or human luteinizing hormone (hLH) to patients having cancers. Articles of manufacture that are useful for carrying out the described methods are also described. The claimed methods are effective against breast, prostate, ovary, and stomach carcinomas, as well as neuroblastomas, and Kaposi's sarcoma, among others.Type: GrantFiled: August 5, 1994Date of Patent: October 14, 1997Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Yanto Lunardi-Iskandar, Robert C. Gallo, Joseph L. Bryant
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Patent number: 5674983Abstract: The present invention relates to the purification of the human chorionic gonadotropin .beta.-core molecule which can then be used as the antigen in the preparation of antibodies to the .beta.-core molecule. The combination of the purified .beta.-core molecule and the antibodies can be used in an immunoassay kit to measure .beta.-core molecules in the presence of structurally similar molecules, i.e., hCG, LH, hCG.beta.-subunit and LH.beta.-subunit. Measurement of the .beta.-core molecule is particularly useful in testing for pregnancy and many malignancies.Type: GrantFiled: May 23, 1995Date of Patent: October 7, 1997Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Diana L. Blithe, Robert E. Wehmann, Bruce C. Nisula
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Patent number: 5674711Abstract: Cultured mammalian cells transfected with new vectors comprising full-length or partial .alpha. and .beta. subunit genomic DNA sequences produce significantly higher levels of dimeric glycoprotein hormone than do cells transfected with .alpha. and .beta. subunit cDNA sequences. In cases where only the cDNA clones are available, the cDNA sequences can be used in new expression vectors comprising introns or other important genomic regions from a homologous or heterologous source.Type: GrantFiled: July 23, 1993Date of Patent: October 7, 1997Assignee: Genzyme CorporationInventors: Christie A. Kelton, Noreen P. Nugent, Scott C. Chappel
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Patent number: 5656597Abstract: The invention relates to lyospheres comprising gonadotropin, the preparation thereof, as well as pharmaceutical preparations containing the same.Type: GrantFiled: June 5, 1995Date of Patent: August 12, 1997Assignee: Akzo Nobel N.V.Inventors: Arnold Titus Philip Skrabanja, Herman Vromans
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Patent number: 5585345Abstract: Extended forms of beta subunits of human glycoproteins wherein the amino acid sequence of a carboxy terminal peptide (CTP) representing positions from about 112-118 to 145 of the human CG-beta subunit or a variant form thereof is appended to the C-terminus are disclosed. Recombinant materials for the production of these extended human glycoprotein beta subunits and production of the modified hormones containing the extended beta subunits are also described. Pharmaceutical compositions containing the modified forms of these hormones are useful in pharmacological applications analogous to those of the unmodified forms.Type: GrantFiled: May 6, 1994Date of Patent: December 17, 1996Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5565198Abstract: Zona pellucida is useful for growth stimulation in animals and especially in female ruminants such as heifers. Immunization of heifers with Zona pellucida obtained from young pig ovaries leads to increased weight gains that are comparable to, or exceed the weight gain achieved with by other growth stimulants given to cattle, such as steroids, antibiotics or ionophores. Zona pellucida treatment results in longer-lasting weight gain response than that achieved with conventional growth stimulants and results in less frequent cattle handling and decreased production costs.Type: GrantFiled: January 9, 1995Date of Patent: October 15, 1996Inventors: John F. Edwards, David P. Hutcheson, Ronald D. Randel, Francis M. Rouquette, Jr.
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Patent number: 5508261Abstract: The present invention pertains to an alpha, beta-heterodimeric polypeptide having binding affinity to vertebrate luteinizing hormone (LH) receptors and vertebrate follicle stimulating hormone (FSH) receptors comprising a glycoprotein hormone alpha-subunit polypeptide and a non-naturally occurring beta-subunit polypeptide, wherein the beta-subunit polypeptide is a chain of amino acids comprising the following four joined subsequences:(a) a first subsequence homologous to the amino acid sequence of residues 1-93 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG), vertebrate luteinizing hormone (LH), vertebrate follicle stimulating hormone (FSH), and vertebrate thyroid stimulating hormone (TSH);(b) a second subsequence homo logous to the amino acid sequence of residues 94-97 of the beta-subunit selected from the group consisting of human chorionic gonadotrophin (hCG) and vertebrate luteinizing hormone (LH);(c) a third subsequence homologous to the amino acid sequence ofType: GrantFiled: April 18, 1995Date of Patent: April 16, 1996Assignee: University of Medicine & Dentistry of New JerseyInventors: William R. Moyle, Robert K. Campbell, Gordon J. Macdonald, Yi Han, Yanhong Wang
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Patent number: 5492893Abstract: Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, .alpha.-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.Type: GrantFiled: July 20, 1993Date of Patent: February 20, 1996Assignee: Colorado State University Research FoundationInventors: Torrance M. Nett, Leonard M. Glode
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Patent number: 5488036Abstract: Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, .alpha.-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.Type: GrantFiled: July 20, 1993Date of Patent: January 30, 1996Assignee: Colorado State University Research FoundationInventors: Torrance M. Nett, Leonard M. Glode
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Patent number: 5461034Abstract: A biochemically pure polypeptide(s), termed osteogenic growth polypeptide (OGP), which exhibits stimulatory effects on osteoblastic cells, in vivo bone formation and hemopoietic reconstruction. OGP, identified from regenerating bone marrow, has an amino acid sequence ofAla-Leu-Lys-Arg-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-Gly-Gly.Type: GrantFiled: June 18, 1993Date of Patent: October 24, 1995Assignee: Yissum Research Development Company of the Hebrew University of JerusalemInventors: Gideon A. Rodan, John W. Jacobs, Mohinder K. Sardana, Dan Gazit, Michael Chorev, Andras Muhlrad, Arye Shteyer, Nura Mansur, Zvi Greenberg, Shimon Slavin, Olga Gurevitch, Itai A. Bab
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Patent number: 5428023Abstract: An orally administered complex of a drug, hormone, bio-active peptide, or immunogen with the carrier molecule, such as vitamin B12 or analogue thereof, and a method for delivering said complex to the intestine of a host vertebrate in order to deliver the complex to the circulation of the host and thereby elicit a pharmacological response to the drug, hormone, or bio-active molecule or to elicit a systemic immune response to the immunogen. The invention also provides a method for the production of the complex. Further the invention provides medicaments containing the complex.Type: GrantFiled: May 17, 1993Date of Patent: June 27, 1995Assignee: Biotechnology Australia Pty. Ltd.Inventors: Gregory J. Russell-Jones, Peter Howe, Henry J. de Aizpurua, Geoffery L. Burge
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Patent number: 5384132Abstract: Disclosed are lyophilized gonadotropin containing preparations containing a dicarboxylic acid salt stabilizer. The particular proteins (e.g. LH, TSH, FSH, or HCG) are in admixture with, and at least partially capable of stabilization by, the particular stabilizer in lyophilized form. The preparations contain a sufficient amount of dicarboxylic acid salt to stabilize the protein in freeze-dried form for a desired time at a desired temperature. Typical dicarboxylic acid salts disclosed are the salts of citric, tartaric, and aspartic acids. The preparations preferably include a non-reducing disaccharide to increase the collapse temperature of the solution to be lyophilized. Methods of making the preparations in lyophilized form and the resulting injectable preparations are also disclosed.Type: GrantFiled: September 3, 1993Date of Patent: January 24, 1995Assignee: Akzo N.V.Inventors: Andreas L. J. De Meere, Marinus A. De Ruiter
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Patent number: 5338835Abstract: The invention provides recombinant native and mutein forms of human reproductive hormones with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern and activity. Modified forms of LH and FSH beta subunits which enhance the rate of dimerization and secretion of the dimers or individual chains are also disclosed.Type: GrantFiled: September 24, 1992Date of Patent: August 16, 1994Assignee: Washington UniversityInventor: Irving Boime
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Patent number: 5316754Abstract: The present invention relates to a method and associated agents for measuring the presence and amount of advanced glycosylation endproducts in cells and fluids. The methods take advantage of the existence of receptors and receptor complexes for AGEs and include receptor-containing ligands comprising whole mesangial and other cells, mesangial cellular fragments and protein extracts therefrom. Competitive assays, sandwich assays and assays involving AGE antisera are disclosed. Numerous diagnostic applications are defined and test kits are also contemplated.Type: GrantFiled: January 28, 1993Date of Patent: May 31, 1994Assignee: The Rockefeller UniversityInventors: Helen Vlassara, Anthony Cerami
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Patent number: 5304603Abstract: The present invention relates to a compound which when administered to Leydig cells in the testes stimulates the production of androgen such as testosterone. This compound, when mixed with other known compounds, can produce testosterone levels in excess of those obtained by the administration of a maximal stimulatory dose of Lutenizing Hormone (LH).Type: GrantFiled: June 18, 1991Date of Patent: April 19, 1994Assignee: The Population CouncilInventors: C. Yan Cheng, C. Wayne Bardin
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Patent number: 5276141Abstract: The invention proposes a process for purifying a highly glycosylated protein from a crude preparation which comprises the action (i) of adding to said preparation a divalent metal ion in a sufficient amount in order to form a mixture which precipitates and (ii) after precipitation, of harvesting said protein from the mixture supernatant.Type: GrantFiled: February 14, 1992Date of Patent: January 4, 1994Assignee: Transgene S.A.Inventor: Hanno Kolbe
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Patent number: 5270057Abstract: Disclosed are lyophilized gonadotropin containing preparations containing a dicarboxylic acid salt stabilizer. The particular proteins (e.g. LH, TSH, FSH, or HCG) are in admixture with, and at least partially capable of stabilization by, the particular stabilizer in lyophilized form. The preparations contain a sufficient amount of dicarboxylic acid salt to stabilize the protein in freeze-dried form for a desired time at a desired temperature. Typical dicarboxylic acid salts disclosed are the salts of citric, tartaric, and aspartic acids. The preparations preferably include a non-reducing disaccharide to increase the collapse temperature of the solution to be lyophilized. Methods of making the preparations in lyophilized form and the resulting injectable preparations are also disclosed.Type: GrantFiled: July 13, 1992Date of Patent: December 14, 1993Assignee: Akzo N.V.Inventors: Andreas L. J. de Meere, Marinus A. De Ruiter
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Patent number: 5260421Abstract: Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.Type: GrantFiled: December 21, 1987Date of Patent: November 9, 1993Assignee: Applied Research Systems ARS Holding N.V.Inventors: Scott C. Chappel, Edward G. Bernstine