Lutenizing Hormone Releasing Factor (lrf); Related Peptides Patents (Class 530/313)
  • Patent number: 6878689
    Abstract: Preparations for preventing or treating acute heart failure, chronic heart failure at a phase of acute exacerbation or heart failure at a phase of transition to chronic heart failure, which contain D-alanyl-3-(naphthalen-2-yl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide and/or salts thereof as an active ingredient.
    Type: Grant
    Filed: June 25, 2001
    Date of Patent: April 12, 2005
    Assignee: Kaken Pharmaceutical Co., Ltd.
    Inventors: Takahiko Murata, Haruyoshi Ueo, Tadashi Ohyama
  • Patent number: 6875843
    Abstract: A method for reducing the incidence or delaying the onset of diabetes in diabetes-susceptible mammals (e.g., mice, rats, humans) is provided wherein the mammals are treated with a gonadotropin-releasing hormone (GnRH) antagonist. Additionally, the present invention provides a method of prolonging the honeymoon phase and decreasing the rate of islet cell infiltration by lymphocytes by administration of a GnRH antagonist. Preferably, the antagonist is administered repeatedly over time by subcutaneous injection. Preferred antagonists include Acetyl-?-[2-Naphthyl]-D-Ala-D-p-Chloro-Phe-?-[3-Pyridyl]-D-Ala-Ser-N?-[Nicotinoyl]-Lys-N?-[Nicotinoyl]-D-Lys-Leu-N?-[Isopropyl]-Lys-Pro-D-Ala-NH2, Nal-Glu, Abarelix, Degarelix, and acetyl-D2Nal-D4CIPhe-D3Pal-Ser-Aph(Ac)-D-Aph(Ac)-Leu-Lys(lpr)-Pro-D-Ala-NH2.
    Type: Grant
    Filed: July 12, 2002
    Date of Patent: April 5, 2005
    Assignee: Children's Mercy Hospital
    Inventor: Jill D. Jacobson
  • Patent number: 6867191
    Abstract: A lyophilizate, method of preparation, and use of the lyophilizate for gonad protection is described. The lyophilizate comprises cetrorelix dissolved in 30% (v/v) acetic acid, transferred to water, and freeze-dried.
    Type: Grant
    Filed: May 24, 2002
    Date of Patent: March 15, 2005
    Assignee: Zentaris GmbH
    Inventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
  • Patent number: 6863891
    Abstract: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.
    Type: Grant
    Filed: January 9, 2002
    Date of Patent: March 8, 2005
    Assignee: Zentaris AG
    Inventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
  • Publication number: 20040259801
    Abstract: A composition comprising a peptide salt having a pharmaceutically acceptable anion prepared by the method comprising the steps of: contacting a first peptide salt with a diluent to form a diluent solution; contacting the diluent solution containing the first peptide salt with a mixed bed ion exchanger, wherein the mixed bed ion exchanger has strongly acidic cations and strong anion exchangers; separating the mixed bed ion exchanger from the diluent solution; contacting the diluent solution with an acid having a pharmaceutically acceptable anion, thereby forming an acid addition salt of the peptide having the pharmaceutically acceptable anion; adding an adjuvant to the diluent solution; and separating the diluent from the diluent solution. The invention also relates to a method for treatment of benign prostate hyperplasia, myoma, or endometriosis with the composition.
    Type: Application
    Filed: July 13, 2004
    Publication date: December 23, 2004
    Inventors: Michael Damm, Waldemar Salonek, Jurgen Engel, Horst Bauer, Gabriele Stach
  • Patent number: 6828415
    Abstract: A novel lyophilizate and method of preparation as well as the use of the lyophilizate to treat female infertility and for gonad protection. Cetrorelix is dissolved in acetic acid 30% v/v, the solution is transferred to water and freeze dried.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: December 7, 2004
    Assignee: Zentaris GmbH
    Inventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
  • Patent number: 6783761
    Abstract: Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.
    Type: Grant
    Filed: May 4, 2001
    Date of Patent: August 31, 2004
    Assignee: Aphton Corporation
    Inventors: Stephen Grimes, Dov Michaeli, Vernon C. Stevens
  • Patent number: 6780969
    Abstract: The invention provides a peptide immunogen comprising a FAFSD target peptide or an anlogue thereof, covalently linked to a helper T cell epitope and optionally to an invasin immunostimulatory domain. The present invention also provides for the use of such peptide immunogens to elicit the production in mammals of high titer polyclonal antibodies, which are specific to the FAFSD target peptide. The peptide immunogens are expected to be useful in evoking antibodies that prevent the adherence of E. coli and other enterobacteria to the bladder mucosa for protection against urinary tract infection.
    Type: Grant
    Filed: December 22, 2000
    Date of Patent: August 24, 2004
    Assignee: United Biomedical, Inc.
    Inventor: Chang Yi Wang
  • Patent number: 6747125
    Abstract: Peptides which include unnatural amino acids and which either promote or inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions.
    Type: Grant
    Filed: October 7, 1996
    Date of Patent: June 8, 2004
    Assignee: The Salk Institute for Biological Studies
    Inventors: Carl A. Hoeger, Jean E. F. Rivier, Paula Guess Theobald, John S. Porter
  • Patent number: 6740634
    Abstract: A sustained-release composition containing a hydroxynaphthoic acid salt of a biologically active substance and a biodegradable polymer, a method of its production, and a pharmaceutical composition containing said sustained-release composition.
    Type: Grant
    Filed: July 6, 2000
    Date of Patent: May 25, 2004
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Akira Saikawa, Yasutaka Igari, Yoshio Hata, Kazumichi Yamamoto
  • Patent number: 6737039
    Abstract: Improved methods for detecting lesions in dense breast tissue are disclosed. The methods of the invention generally feature administration to a subject of an LHRH antagonist in an amount and for a period of time sufficient to reduce the density of breast tissue prior to generating an image of the breast tissue, for example by mammography, to detect a lesion in the breast tissue. Packaged formulations for reducing breast density in a subject prior to generating an image of the subject's breast tissue, comprising an LHRH antagonist packaged with instructions for using the LHRH antagonist to reduce breast density in a subject prior to imaging the breast tissue, are also disclosed.
    Type: Grant
    Filed: December 12, 2002
    Date of Patent: May 18, 2004
    Assignee: Praecis Pharmaceutics, Inc.
    Inventor: Marc B. Garnick
  • Patent number: 6716817
    Abstract: A method of treating female infertility using a novel cetrorelix acetate lyophilizate is disclosed.
    Type: Grant
    Filed: January 20, 1999
    Date of Patent: April 6, 2004
    Assignee: Zentaris AG
    Inventors: Jürgen Engel, Burkhard Wichert, Dieter Eauerbiar, Thomas Reissman
  • Patent number: 6703367
    Abstract: Methods to inhibit hot flashes or gynaecomastia in a subject are provided. In the methods of the invention, an LHRH antagonist is administered to a subject in need of treatment for hot flashes or gynaecomastia such that hot flashes or gynaecomastia are inhibited in the subject. In a particularly preferred embodiment, the invention provides a method for inhibiting menopause-related hot flashes in which an LHRH antagonist is administered to a subject in need of treatment for menopause-related hot flashes such that the hot flashes are inhibited in the subject.
    Type: Grant
    Filed: February 16, 2001
    Date of Patent: March 9, 2004
    Assignee: Praecis Pharmaceuticals Inc.
    Inventor: Marc B. Garnick
  • Patent number: 6699833
    Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptide and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptide in a small volume and for delivery of a pharmaceutically active peptide for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptide of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.
    Type: Grant
    Filed: July 8, 1999
    Date of Patent: March 2, 2004
    Assignee: Praecis Pharmaceuticals, Inc.
    Inventors: Malcolm L. Gefter, Nicholas Barker, Gary Musso, Christopher J. Molineaux
  • Publication number: 20030211127
    Abstract: The present invention relates to crosslinked protein crystals characterized by the ability to change from insoluble and stable form to soluble and active form upon a change in the environment of said crystals, said change being selected from the group consisting of change in temperature, change in pH, change in chemical composition, change from concentrate to dilute form, change in oxidation-reduction potential of the solution, change in the incident radiation, change in transition metal concentration, change in flouride concentration, change in free radical concentration, change in metal chelater concentration, change in shear force acting upon the crystals and combinations thereof. According to one embodiment of this invention, such crosslinked protein crystals are capable of releasing their protein activity at a controlled rate.
    Type: Application
    Filed: January 2, 2003
    Publication date: November 13, 2003
    Inventors: Alexey L. Margolin, Rose A. Persichetti, Nancy L. St. Clair, Nazer K. Khalaf, Bhami C. Shenoy
  • Patent number: 6635739
    Abstract: Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of chicken II GnRH or salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine, D-Trp or other active D amino acids at position 6 and ethylamide, aza-Gly-amide or other Gly amide at position 10. The D-Arg (6)-chicken II GnRH-ethylamide, D-Arg (6)-chicken II GnRH-aza-Gly(10)-amide, the D-Arg (6)-salmon GnRH ethylamide, and D-Arg (6)-salmon GnRH-aza-Gly(10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH, ovarian, endometrial, tubal, uterine, prostate and testicular receptors. Biopotency is greater at the ovary and endometrium than at the pituitary. These non-mammalian GnRH analogs may be used in pharmaceutical preparation, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent.
    Type: Grant
    Filed: August 28, 2001
    Date of Patent: October 21, 2003
    Inventor: Theresa Siler-Khodr
  • Patent number: 6627609
    Abstract: The invention relates to peptides which contain N-methylated amino acid units and have improved water solubility. Medicaments in which the peptides according to the invention are contained can be used for the treatment of hormone-dependent tumours and hormone-influenced non-malignant disorders.
    Type: Grant
    Filed: March 14, 2000
    Date of Patent: September 30, 2003
    Assignee: Zentaris AG
    Inventors: Michael Bernd, Bernhard Kutscher, Eckhard Günther, Peter Romeis, Thomas Reissmann, Thomas Beckers
  • Patent number: 6610497
    Abstract: The present invention relates to the discovery of novel genes encoding an angiotensin converting enzyme, Angiotensin Converting Enzyme-2 (ACE-2). The invention provides therapeutics, prognostic and diagnostics methods for treating blood pressure related disorders as well as various types of allergic conditions, among others. Also disclosed are screening assays for identifying compounds for treating and preventing these conditions.
    Type: Grant
    Filed: September 29, 1999
    Date of Patent: August 26, 2003
    Assignee: Millennium Pharmaceuticals, Inc.
    Inventors: Susan L. Acton, Keith Earl Robison, Frank Y. Hsieh
  • Publication number: 20030059898
    Abstract: Biologically active heteropolymeric protein composed of a plurality of subunits, both subunits being synthesized in a single cell having an expression vector comprising heterologous DNA encoding the subunits. Preferably the protein is similar to the human or ungulate fertility hormones, LH and FSH.
    Type: Application
    Filed: August 26, 2002
    Publication date: March 27, 2003
    Applicant: Genzyme Corporation
    Inventors: Anton Beck, Edward Bernstine, Nancy Hsiung, Vermuni B. Reddy
  • Patent number: 6528093
    Abstract: A sustained-release preparation which comprises a physiologically active peptide of general formula: wherein X represents an acyl group; R1, R2 and R4 each represents an aromatic cyclic group; R3 represents a D-amino acid residue or a group of the formula: wherein R3′ is a heterocyclic group; R5 represents a group of the formula —(CH2)n—R5′ wherein n is 2 or 3, and R5′ is an amino group which may optionally be substituted, an aromatic cyclic group or an O-glycosyl group; R6 represents a group of the formula —(CH2)n—R6′ wherein n is 2 or 3, and R6′ is an amino group which may optionally be substituted; R7 represents a D-amino acid residue or an azaglycyl residue; and Q represents hydrogen or a lower alkyl group, or a salt thereof and a biodegradable polymer having a terminal carboxyl group.
    Type: Grant
    Filed: August 31, 1999
    Date of Patent: March 4, 2003
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Shigeru Kamei, Yasutaka Igari, Yasuaki Ogawa
  • Patent number: 6506730
    Abstract: The present invention relates to a pharmaceutical composition for the nasal transmucosal delivery of a biocompatible polymer-biologically active peptide conjugate. The pharmaceutical composition of the present invention increases the water solubility of peptide, which is sparingly soluble in water, improves its stability by protecting it from being degraded by proteases. As a result, the number of administrations of the drug and the side-effects induced by drug abuse are decreased. In addition, since the pharmaceutical composition of the present invention is delivered through the nasal cavity, it allows drug activity to be expressed in a short period of time and improves a bioavailability.
    Type: Grant
    Filed: August 15, 2000
    Date of Patent: January 14, 2003
    Inventors: Kang Choon Lee, Myung-Ok Park
  • Patent number: 6492177
    Abstract: Agents which increase the levels of human insulin-like growth factor-1 binding protein (h-ICFBP-1), such as an estrogen, are used in conjunction with a gonadotropin releasing hormone (GnRH) analogue in the treatment of PCOD and associated infertility.
    Type: Grant
    Filed: May 5, 1995
    Date of Patent: December 10, 2002
    Assignee: Applied Research Systems ARS Holding NV
    Inventor: Bruno Lunenfeld
  • Patent number: 6479063
    Abstract: A method of decreasing atherosclerosis and its complications involving administering to a human or animal various combinations of medications with Finasteride, Bicalutamide, Flutamide and Nilutamide.
    Type: Grant
    Filed: December 26, 2000
    Date of Patent: November 12, 2002
    Inventors: Kenneth Weisman, Michael E. Goldberg
  • Patent number: 6433135
    Abstract: PEG-LHRH analog conjugates, where a PEG moiety is covalently bound to a serine residue of a LHRH analog either directly or via a bifunctional linker molecule, such as an amino acid, and methods for producing these conjugates are provided in the present invention. Also provided are a pharmaceutical composition and a method for treating pathologies in which LHRH analog administration is beneficial.
    Type: Grant
    Filed: October 30, 2000
    Date of Patent: August 13, 2002
    Assignee: Applied Research Systems ARS Holding N.V.
    Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
  • Publication number: 20020028914
    Abstract: The present invention relates particularly to neoplastic cells targeted chimeric toxins comprising of cell targeting moieties and cell killing moieties for recognizing and for destroying the neoplastic cells, wherein the cell targeting moieties consist of gonadotropin releasing hormone homologues and the cell killing moieties consist of Pseudomonas Exotoxin A. The present invention further relates to pharmaceutical compositions containing as an active ingredient these neoplastic cells targeted chimeric toxins and to a method for the production of these chimeric toxins. The said invention also relates to a method for cancer therapy, treating malignant carcinoma cells and benign hyperplasia including uterine lyomyoma cells, extra uterian endometrial island cells, benign hyperplasia of prostate and breast and pituitary tumor adenoma cells, by the use of the above-mentioned chimeric toxins.
    Type: Application
    Filed: March 1, 1999
    Publication date: March 7, 2002
    Inventors: SHAI YARKONI, AMOTZ NECHUSHTAN, HAYA LORBERBOUM-GALSKI, IRINA MARIANOVSKY
  • Patent number: 6323179
    Abstract: Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of Chicken II GnRH or Salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp at position 6 and ethylamide or aza-Gly-amide at position 10. The D-Arg (6)-Chicken II GnRH-ethylamide, D-Arg (6)-Chicken II GnRH-aza-Gly (10)-amide, the D-Arg (6)-Salmon GnRH ethylamide, and D-Arg (6)-Salmon GnRH-aza-Gly (10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH receptor that is greater relative to the biding of these analogs to pituitary GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparation, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent.
    Type: Grant
    Filed: October 15, 1999
    Date of Patent: November 27, 2001
    Inventor: Theresa Siler-Khodr
  • Patent number: 6303123
    Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: October 16, 2001
    Assignee: Aphton Corporation
    Inventors: Stephen Grimes, Robert Scibienski
  • Patent number: 6297354
    Abstract: The present invention relates to a class of pentapeptide analogs of LHRH. These compounds are useful in the treatment of disease conditions which are mediated by reproductive hormones, including benign prostate hyperplasia, prostate tumors, breast and ovaries tumors, cryptorchidism, hirsuitism, gastric motility disorders, dysmenorrhea, and endometriosis.
    Type: Grant
    Filed: August 12, 1999
    Date of Patent: October 2, 2001
    Assignee: Abbott Laboratories
    Inventors: Fortuna Haviv, Wesley Dwight, Jonathan Greer
  • Patent number: 6284733
    Abstract: The invention relates to a modified tandem LHRH-peptide vaccine preparation in which the amino acid glycine at position (6) of one or both LHRH decapeptides that constitute the tandem unit is substituted by a dextrorotatory amino acid that contains a side chain to which a carrier compound can be coupled. In addition, the tandem LHRH-peptide can be brought into a tandem-dimer form which is also suitable for producing a vaccine that is effective against LHRH (luteinizing hormone releasing hormone) also referred to as GnRH (gonadotropin-releasing hormone), for immunological castration, to inhibit or affect reproductive functions or to affect behaviour in vertebrates in general and in domesticated animals and man in particular.
    Type: Grant
    Filed: March 22, 1999
    Date of Patent: September 4, 2001
    Assignee: DLO Instituut Voor Dierhouderij en Diergezondheid
    Inventors: Robert Hans Meloen, Hendrica Berendina Oonk
  • Patent number: 6258782
    Abstract: The present invention relates to enhancer peptide sequences originally derived from various retroviral envelope (gp41) protein sequences that enhance the pharmacokinetic properties of any core polypeptide to which they are linked. The invention is based on the discovery that hybrid polypeptides comprising the enhancer peptide sequences linked to a core polypeptide possess enhanced pharmacokinetic properties such as increased half life. The invention further relates to methods for enhancing the pharmacokinetic properties of any core polypeptide through linkage of the enhancer peptide sequences to the core polypeptide. The core polypeptides to be used in the practice of the invention can include any pharmacologically useful peptide that can be used, for example, as a therapeutic or prophylactic reagent.
    Type: Grant
    Filed: May 20, 1998
    Date of Patent: July 10, 2001
    Assignee: Trimeris, Inc.
    Inventors: Shawn Barney, Kelly I. Guthrie, Gene Merutka, Mohmed K. Anwer, Dennis M. Lambert
  • Patent number: 6235712
    Abstract: This invention relates to stable non-aqueous polar aprotic formulations of peptide compounds. These stable formulations comprise peptide in non-aqueous polar aprotic solvent. They may be stored at elevated temperatures for long periods of time and are especially useful in implantable delivery devices for long term delivery of drug.
    Type: Grant
    Filed: February 28, 2000
    Date of Patent: May 22, 2001
    Assignee: ALZA Corporation
    Inventors: Cynthia L. Stevenson, Steven J. Prestrelski
  • Patent number: 6228987
    Abstract: The present invention is directed to novel peptide immunogens for eliciting antibodies to LHRH comprising artificial T helper cell epitopes (Th epitopes) designed to provide optimum immunogenicity. The artificial Th epitopes are covalently linked to LHRH and optionally an immunostimulatory sequence.
    Type: Grant
    Filed: April 30, 1999
    Date of Patent: May 8, 2001
    Assignee: United BIomedical, Inc.
    Inventor: Chang Yi Wang
  • Patent number: 6217844
    Abstract: Improved methods for detecting lesions in dense breast tissue are disclosed. The methods of the invention generally feature administration to a subject of an LHRH antagonist in an amount and for a period of time sufficient to reduce the density of breast tissue prior to generating an image of the breast tissue, for example by mammography, to detect a lesion in the breast tissue. Packaged formulations for reducing breast density in a subject prior to generating an image of the subject's breast tissue, comprising an LHRH antagonist packaged with instructions for using the LHRH antagonist to reduce breast density in a subject prior to imaging the breast tissue, are also disclosed.
    Type: Grant
    Filed: April 27, 1998
    Date of Patent: April 17, 2001
    Assignee: Praecis Pharmaceuticals, Inc.
    Inventor: Marc B. Garnick
  • Patent number: 6214798
    Abstract: Peptides are provided which have improved duration of GnRH antagonistic properties. These antagonists may be used to regulate fertility and to treat steroid-dependent tumors and for other short-term and long-term treatment indications. These antagonists have a derivative of aminoPhe or its equivalent in the 5- or the 5- and 6-positions. This derivative is modified so as to contain a carbamoyl group or heterocycle, including a urea moiety, in its side chain. Decapeptides having the formula: Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(L-hydroorotyl)-D-4Amf(Q2)-Leu-Lys(isopropyl)-Pro-Xaa10, wherein Q2 is Cbm or MeCbm and Xaa10 is D-Ala-ol or Ala-ol are particularly effective and continue to exhibit very substantial suppression of LH secretion at 96 hours following injection.
    Type: Grant
    Filed: January 3, 2000
    Date of Patent: April 10, 2001
    Assignee: Ferring BV
    Inventors: Graeme Semple, Guangcheng Jiang
  • Patent number: 6214969
    Abstract: The present invention deals with LHRH analogs which contain cytotoxic moieties, have influence on the release of gonadotropins from the pituitary in mammals (possess high agonistic or antagonistic activity) and have antineoplastic effect.
    Type: Grant
    Filed: January 25, 1993
    Date of Patent: April 10, 2001
    Assignee: The Administrators of the Tulane Educational Fund
    Inventors: Tamas Janaky, Attila Juhasz, Sandor Bajusz, Andrew V. Schally
  • Patent number: 6211333
    Abstract: A peptide of the formula: 5-oxo—Pro—R1—Trp—Ser—R2—R3—R4—Arg—Pro—R6  (I) wherein R1 represents His, Tyr, Trp or p—NH2—Phe, R2 represents Tyr or Phe, R3 represents an optionally substituted Gly or an optionally substituted &agr;-D-amino acid residue, R4 represents Leu, Ile or Nle, R6 represents (1) Gly—NH—R7, wherein R7 represents a hydrogen atom or an alkyl group which may optionally be substituted with a hydroxyl group, or (2) NH—R8, wherein R8 represents a hydrogen atom, an alkyl group which may optionally be substituted with a hydroxyl group or an ureido group (—NH—CO—NH2), is produced advantageously in an industrial scale by reacting a peptide of the formula: 5-oxo—Pro—R1—Trp—Ser—R2—R3—OH  (II) wherein R1, R2 and R3 have the same meanings as defined above or its salts, with a peptide of the formula: H—R4—R5—Pro&mda
    Type: Grant
    Filed: December 18, 1998
    Date of Patent: April 3, 2001
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Chitoshi Hatanaka, Yasuaki Abe, Mitsuhisa Yamano
  • Patent number: 6210927
    Abstract: Novel peptide hormones which influence the release of gonadotropins by the pituitary gland in fish are disclosed. Methods in which such peptides may be administered to fish to control their reproduction are also described. Furthermore, novel isolated cDNA encoding the precursor of the novel gonadotropin-releasing hormone is disclosed. The use of such cDNA in controlling the gonadal development and spawning of fish is also described.
    Type: Grant
    Filed: June 30, 1997
    Date of Patent: April 3, 2001
    Assignee: University of Maryland Biotechnology Institute
    Inventors: Yonathan Zohar, Yoav Gothilf
  • Patent number: 6191115
    Abstract: The present invention relates to a class of heptapeptide analogs of LHRH. These compounds are useful in the treatment of disease conditions which are mediated by reproductive hormones, including benign prostate hyperplasia, prostate tumors, breast and ovaries tumors, cryptorchidism, hirsuitism, gastric motility disorders, dysmenorrhea, and endometriosis.
    Type: Grant
    Filed: January 15, 1999
    Date of Patent: February 20, 2001
    Assignee: Abbott Laboratories
    Inventors: Fortuna Haviv, Wesley J. Dwight, Charles J. Nichols, Jonathan Greer
  • Patent number: 6184374
    Abstract: This invention is in the field of the chemistry of targeting anticancer anthracycline derivatives. More particularly, it concerns doxorubicin (DOX) or its daunosamine modified derivatives (DM-DOX) linked covalently to analogs of peptide hormones such as LH-RH, bombesin and somatostatin. These covalent conjugates are targeted to various tumors bearing receptors for the peptide hormone analogs. The compounds of this invention are represented by General Formula Q14—O—R—P wherein Q has the general formula wherein: Q14 signifies a Q moiety with a side chain at the 14 position, R— is H or —C(O)—(CH2)n—C(O)— and n=0-7, R′ is NH2 or an aromatic, saturated or partially saturated 5 or 6 membered heterocyclic compounds having at least one ring nitrogen and optionally having a butadiene moiety bonded to adjacent carbon atoms of said ring to form a bicyclic system; P is H or a peptide moiety, suitably an LHRH, somatostatin or bombesin analogs.
    Type: Grant
    Filed: July 15, 1998
    Date of Patent: February 6, 2001
    Assignee: The Administrators of the Tulane Educational Fund
    Inventors: Andrew V. Schally, Attila A. Nagy, Ren-Zhi Cai
  • Patent number: 6180608
    Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.
    Type: Grant
    Filed: December 11, 1997
    Date of Patent: January 30, 2001
    Assignee: Praecis Pharmaceuticals, Inc.
    Inventors: Malcolm L. Gefter, Nicholas Barker, Gary Musso, Christopher J. Molineaux
  • Patent number: 6156731
    Abstract: There is disclosed a composition containing a biologically active polypeptide selected from LHRH, an LHRH analog, somatostatin and a somatostatin analog, in a therapeutically effective amount, a membrane permeability enhancing agent, and a protease enzyme inhibitor enveloped within an enteric coating. The composition possesses enhanced bioavailability upon oral administration.
    Type: Grant
    Filed: December 5, 1995
    Date of Patent: December 5, 2000
    Assignee: G. D. Searle & Co.
    Inventors: George M. Grass, Stephanie A. Sweetana
  • Patent number: 6153587
    Abstract: LH-RH analogues with excellent affinity for LH-RH receptors, of the formula A.sub.1 -A.sub.2 -W-A.sub.3 -A.sub.4 -SPL-A.sub.5 -A.sub.6 -Pro-Z(I) in which:-A.sub.1 is pGlu, AcSar or an aromatic D-amino acid;-A.sub.2 is a direct bond, His, DPhe, DpFPhe or DpClPhe;*W is an aromatic L- or D-amino acid;-A.sub.3 is Ala, Thr, Ser, DSer, Ser(OBzl) or MeSer;-A.sub.4 is Tyr, Phe, cPzACAla, L- or D-PicLys, L- or D-NicLys or L- or D-IprLys;*SPL is the spirolactam of formula: ##STR1## -A.sub.5 is an amino acid with a (C.sub.1 -C.sub.8)alkyl or (C.sub.3-C.sub.6)cycloalkyl side chain;-A.sub.6 is L- or D-(Arg, HArg, Lys, HLys, Orn, Cit, HCit or Aph), where L- or D-(Arg and HArg) can be substituted by one or two (C.sub.1 -C.sub.4)alkyl groups and L- or D-(Lys, HLys, Orn and Aph) can be substituted by an isopropyl, nicotinoyl or picolinoyl group; and*Z is GlyNH.sub.2, DAlaNH.sub.2, AzaGlyNH.sub.2 or --NHR.sub.1 where R.sub.1 is a (C.sub.1 -C.sub.
    Type: Grant
    Filed: May 24, 1999
    Date of Patent: November 28, 2000
    Assignee: Laboratoire THERAMEX
    Inventors: Remi Delansorne, Jacques Paris
  • Patent number: 6132720
    Abstract: Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.
    Type: Grant
    Filed: November 17, 1997
    Date of Patent: October 17, 2000
    Assignee: Aphton Corp.
    Inventors: Stephen Grimes, Robert Scibienski
  • Patent number: 6124261
    Abstract: This invention relates to stable non-aqueous polar aprotic formulations of peptide compounds. These stable formulations comprise peptide in non-aqueous polar aprotic solvent. They may be stored at elevated temperatures for long periods of time and are especially useful in implantable delivery devices for long term delivery of drug.
    Type: Grant
    Filed: April 19, 1999
    Date of Patent: September 26, 2000
    Assignee: ALZA Corporation
    Inventors: Cynthia L. Stevenson, Steven J. Prestrelski
  • Patent number: 6106805
    Abstract: The invention relates to a diagnostic composition for improving the effectiveness of hysteroscopy, characterized in that it contains an LH-RH antagonist, in particular cetrorelix. The composition is envisaged for use prior to hysteroscopy and/or for preparation for surgery, specifically in a single dose of between 0.1 and 2 mg/kg.However, the composition can also be administered, for use prior to hysteroscopy and/or for preparation for surgery, in a multiple dose of between 0.01 and 0.5 mg/kg, preferably spread over 1-14 days. The composition is furthermore suitable for use in hysteroscopy in combination with the subsequent treatment of pathological conditions of the uterus such as myoma and endometrial hyperplasia.
    Type: Grant
    Filed: October 30, 1997
    Date of Patent: August 22, 2000
    Assignee: Asta Medica Aktiengesellschaft
    Inventors: Jurgen Engel, Klaus Diedrich, Ricardo Felberbaum
  • Patent number: 6103881
    Abstract: 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: Grant
    Filed: April 7, 1998
    Date of Patent: August 15, 2000
    Assignee: Colorado State University Research Foundation
    Inventors: Torrance M. Nett, Leonard Michael Glode, Marat Karpeisky
  • Patent number: 6066619
    Abstract: This invention relates to stable non-aqueous protic formulations of peptide compounds. These stable formulations comprise peptide in non-aqueous protic solvent. They may be stored at elevated temperatures for long periods of time and are especially useful in implantable delivery devices for long term delivery of drug.
    Type: Grant
    Filed: April 16, 1999
    Date of Patent: May 23, 2000
    Assignee: Alza Corporation
    Inventors: Cynthia L. Stevenson, Sally A. Tao, Steven J. Prestrelski, James B. Eckenhoff, Jeremy C. Wright, John J. Leonard, Jr.
  • Patent number: 6054555
    Abstract: In this invention, a release-delaying system is to be developed for LHRH antagonists, in particular for cetrorelix, which allows the active compound to be released in a controlled manner over several weeks by complexation with suitable biophilic carriers. The acidic polyamino acids polyglutamic acid and polyaspartic acid were selected for complexation with cetrorelix. The cetrorelix polyamino acid complexes are prepared from aqueous solutions by combination of the solutions and precipitation of the complexes, which are subsequently centrifuged off and dried over P.sub.2 O.sub.5 in vacuo. If complexes having a defined composition are to be obtained, lyophilization proves to be a suitable method. The cetrorelix-carboxylic acid complexes were also prepared from the aqueous solutions. In the random liberation system, the acidic polyamino acids poly-Glu and poly-Asp showed good release-delaying properties as a function of the hydrophobicity and the molecular mass of the polyamino acid.
    Type: Grant
    Filed: October 22, 1999
    Date of Patent: April 25, 2000
    Assignee: Asta Medica Aktiengesellschaft
    Inventors: Jurgen Engel, Wolfgang Deger, Thomas Reissmann, Gunter Losse, Wolfgang Naumann, Sandra Murgas
  • Patent number: 6025468
    Abstract: The present invention is directed to novel peptide immunogens for eliciting antibodies to LHRH comprising artificial T helper cell epitopes (Th epitopes) designed to provide optimum immunogenicity. The artificial Th epitopes are covalently linked to LHRH and optionally an immunostimulatory seqence.
    Type: Grant
    Filed: June 20, 1998
    Date of Patent: February 15, 2000
    Assignee: United Biomedical, Inc.
    Inventor: Chang Yi Wang
  • Patent number: RE37710
    Abstract: Peptide, derivatives of leutenizing hormone releasing hormone that are capable of binding radionuclides are provided. The peptide derivatives are readily labeled with isotopes of rhenium or technetium, while retaining their ability to tightly bind LHRH receptors. Methods for preparing the labeled peptides and their use in methods of radiodiagnosis and radiotherapy are described.
    Type: Grant
    Filed: May 18, 2000
    Date of Patent: May 21, 2002
    Assignee: Immunomedics, Inc.
    Inventors: William J. McBride, Habibe Karacay, Gary L. Griffiths