Lutenizing Hormone Releasing Factor (lrf); Related Peptides Patents (Class 530/313)
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Patent number: 6878689Abstract: 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: GrantFiled: June 25, 2001Date of Patent: April 12, 2005Assignee: Kaken Pharmaceutical Co., Ltd.Inventors: Takahiko Murata, Haruyoshi Ueo, Tadashi Ohyama
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Patent number: 6875843Abstract: 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: GrantFiled: July 12, 2002Date of Patent: April 5, 2005Assignee: Children's Mercy HospitalInventor: Jill D. Jacobson
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Patent number: 6867191Abstract: 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: GrantFiled: May 24, 2002Date of Patent: March 15, 2005Assignee: Zentaris GmbHInventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
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Patent number: 6863891Abstract: 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: GrantFiled: January 9, 2002Date of Patent: March 8, 2005Assignee: Zentaris AGInventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
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Publication number: 20040259801Abstract: 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: ApplicationFiled: July 13, 2004Publication date: December 23, 2004Inventors: Michael Damm, Waldemar Salonek, Jurgen Engel, Horst Bauer, Gabriele Stach
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Patent number: 6828415Abstract: 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: GrantFiled: June 6, 1995Date of Patent: December 7, 2004Assignee: Zentaris GmbHInventors: Jürgen Engel, Burkhard Wichert, Dieter Sauerbier, Thomas Reissmann
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Patent number: 6783761Abstract: 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: GrantFiled: May 4, 2001Date of Patent: August 31, 2004Assignee: Aphton CorporationInventors: Stephen Grimes, Dov Michaeli, Vernon C. Stevens
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Patent number: 6780969Abstract: 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: GrantFiled: December 22, 2000Date of Patent: August 24, 2004Assignee: United Biomedical, Inc.Inventor: Chang Yi Wang
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Patent number: 6747125Abstract: 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: GrantFiled: October 7, 1996Date of Patent: June 8, 2004Assignee: The Salk Institute for Biological StudiesInventors: Carl A. Hoeger, Jean E. F. Rivier, Paula Guess Theobald, John S. Porter
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Patent number: 6740634Abstract: 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: GrantFiled: July 6, 2000Date of Patent: May 25, 2004Assignee: Takeda Chemical Industries, Ltd.Inventors: Akira Saikawa, Yasutaka Igari, Yoshio Hata, Kazumichi Yamamoto
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Patent number: 6737039Abstract: 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: GrantFiled: December 12, 2002Date of Patent: May 18, 2004Assignee: Praecis Pharmaceutics, Inc.Inventor: Marc B. Garnick
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Patent number: 6716817Abstract: A method of treating female infertility using a novel cetrorelix acetate lyophilizate is disclosed.Type: GrantFiled: January 20, 1999Date of Patent: April 6, 2004Assignee: Zentaris AGInventors: Jürgen Engel, Burkhard Wichert, Dieter Eauerbiar, Thomas Reissman
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Patent number: 6703367Abstract: 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: GrantFiled: February 16, 2001Date of Patent: March 9, 2004Assignee: Praecis Pharmaceuticals Inc.Inventor: Marc B. Garnick
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Patent number: 6699833Abstract: 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: GrantFiled: July 8, 1999Date of Patent: March 2, 2004Assignee: Praecis Pharmaceuticals, Inc.Inventors: Malcolm L. Gefter, Nicholas Barker, Gary Musso, Christopher J. Molineaux
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Publication number: 20030211127Abstract: 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: ApplicationFiled: January 2, 2003Publication date: November 13, 2003Inventors: Alexey L. Margolin, Rose A. Persichetti, Nancy L. St. Clair, Nazer K. Khalaf, Bhami C. Shenoy
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Patent number: 6635739Abstract: 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: GrantFiled: August 28, 2001Date of Patent: October 21, 2003Inventor: Theresa Siler-Khodr
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Patent number: 6627609Abstract: 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: GrantFiled: March 14, 2000Date of Patent: September 30, 2003Assignee: Zentaris AGInventors: Michael Bernd, Bernhard Kutscher, Eckhard Günther, Peter Romeis, Thomas Reissmann, Thomas Beckers
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Patent number: 6610497Abstract: 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: GrantFiled: September 29, 1999Date of Patent: August 26, 2003Assignee: Millennium Pharmaceuticals, Inc.Inventors: Susan L. Acton, Keith Earl Robison, Frank Y. Hsieh
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Publication number: 20030059898Abstract: 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: ApplicationFiled: August 26, 2002Publication date: March 27, 2003Applicant: Genzyme CorporationInventors: Anton Beck, Edward Bernstine, Nancy Hsiung, Vermuni B. Reddy
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Patent number: 6528093Abstract: 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: GrantFiled: August 31, 1999Date of Patent: March 4, 2003Assignee: Takeda Chemical Industries, Ltd.Inventors: Shigeru Kamei, Yasutaka Igari, Yasuaki Ogawa
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Patent number: 6506730Abstract: 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: GrantFiled: August 15, 2000Date of Patent: January 14, 2003Inventors: Kang Choon Lee, Myung-Ok Park
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Patent number: 6492177Abstract: 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: GrantFiled: May 5, 1995Date of Patent: December 10, 2002Assignee: Applied Research Systems ARS Holding NVInventor: Bruno Lunenfeld
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Patent number: 6479063Abstract: 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: GrantFiled: December 26, 2000Date of Patent: November 12, 2002Inventors: Kenneth Weisman, Michael E. Goldberg
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Patent number: 6433135Abstract: 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: GrantFiled: October 30, 2000Date of Patent: August 13, 2002Assignee: Applied Research Systems ARS Holding N.V.Inventors: Nabil El-Tayar, Xuan Zhao, Michael D. Bentley
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Publication number: 20020028914Abstract: 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: ApplicationFiled: March 1, 1999Publication date: March 7, 2002Inventors: SHAI YARKONI, AMOTZ NECHUSHTAN, HAYA LORBERBOUM-GALSKI, IRINA MARIANOVSKY
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Patent number: 6323179Abstract: 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: GrantFiled: October 15, 1999Date of Patent: November 27, 2001Inventor: Theresa Siler-Khodr
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Patent number: 6303123Abstract: 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: GrantFiled: June 7, 1995Date of Patent: October 16, 2001Assignee: Aphton CorporationInventors: Stephen Grimes, Robert Scibienski
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Patent number: 6297354Abstract: 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: GrantFiled: August 12, 1999Date of Patent: October 2, 2001Assignee: Abbott LaboratoriesInventors: Fortuna Haviv, Wesley Dwight, Jonathan Greer
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Patent number: 6284733Abstract: 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: GrantFiled: March 22, 1999Date of Patent: September 4, 2001Assignee: DLO Instituut Voor Dierhouderij en DiergezondheidInventors: Robert Hans Meloen, Hendrica Berendina Oonk
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Patent number: 6258782Abstract: 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: GrantFiled: May 20, 1998Date of Patent: July 10, 2001Assignee: Trimeris, Inc.Inventors: Shawn Barney, Kelly I. Guthrie, Gene Merutka, Mohmed K. Anwer, Dennis M. Lambert
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Patent number: 6235712Abstract: 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: GrantFiled: February 28, 2000Date of Patent: May 22, 2001Assignee: ALZA CorporationInventors: Cynthia L. Stevenson, Steven J. Prestrelski
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Patent number: 6228987Abstract: 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: GrantFiled: April 30, 1999Date of Patent: May 8, 2001Assignee: United BIomedical, Inc.Inventor: Chang Yi Wang
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Patent number: 6217844Abstract: 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: GrantFiled: April 27, 1998Date of Patent: April 17, 2001Assignee: Praecis Pharmaceuticals, Inc.Inventor: Marc B. Garnick
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Patent number: 6214798Abstract: 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: GrantFiled: January 3, 2000Date of Patent: April 10, 2001Assignee: Ferring BVInventors: Graeme Semple, Guangcheng Jiang
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Patent number: 6214969Abstract: 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: GrantFiled: January 25, 1993Date of Patent: April 10, 2001Assignee: The Administrators of the Tulane Educational FundInventors: Tamas Janaky, Attila Juhasz, Sandor Bajusz, Andrew V. Schally
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Patent number: 6211333Abstract: 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&mdaType: GrantFiled: December 18, 1998Date of Patent: April 3, 2001Assignee: Takeda Chemical Industries, Ltd.Inventors: Chitoshi Hatanaka, Yasuaki Abe, Mitsuhisa Yamano
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Patent number: 6210927Abstract: 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: GrantFiled: June 30, 1997Date of Patent: April 3, 2001Assignee: University of Maryland Biotechnology InstituteInventors: Yonathan Zohar, Yoav Gothilf
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Patent number: 6191115Abstract: 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: GrantFiled: January 15, 1999Date of Patent: February 20, 2001Assignee: Abbott LaboratoriesInventors: Fortuna Haviv, Wesley J. Dwight, Charles J. Nichols, Jonathan Greer
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Patent number: 6184374Abstract: 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: GrantFiled: July 15, 1998Date of Patent: February 6, 2001Assignee: The Administrators of the Tulane Educational FundInventors: Andrew V. Schally, Attila A. Nagy, Ren-Zhi Cai
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Patent number: 6180608Abstract: 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: GrantFiled: December 11, 1997Date of Patent: January 30, 2001Assignee: Praecis Pharmaceuticals, Inc.Inventors: Malcolm L. Gefter, Nicholas Barker, Gary Musso, Christopher J. Molineaux
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Patent number: 6156731Abstract: 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: GrantFiled: December 5, 1995Date of Patent: December 5, 2000Assignee: G. D. Searle & Co.Inventors: George M. Grass, Stephanie A. Sweetana
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Patent number: 6153587Abstract: 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: GrantFiled: May 24, 1999Date of Patent: November 28, 2000Assignee: Laboratoire THERAMEXInventors: Remi Delansorne, Jacques Paris
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Patent number: 6132720Abstract: 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: GrantFiled: November 17, 1997Date of Patent: October 17, 2000Assignee: Aphton Corp.Inventors: Stephen Grimes, Robert Scibienski
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Patent number: 6124261Abstract: 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: GrantFiled: April 19, 1999Date of Patent: September 26, 2000Assignee: ALZA CorporationInventors: Cynthia L. Stevenson, Steven J. Prestrelski
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Patent number: 6106805Abstract: 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: GrantFiled: October 30, 1997Date of Patent: August 22, 2000Assignee: Asta Medica AktiengesellschaftInventors: Jurgen Engel, Klaus Diedrich, Ricardo Felberbaum
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Patent number: 6103881Abstract: 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: April 7, 1998Date of Patent: August 15, 2000Assignee: Colorado State University Research FoundationInventors: Torrance M. Nett, Leonard Michael Glode, Marat Karpeisky
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Patent number: 6066619Abstract: 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: GrantFiled: April 16, 1999Date of Patent: May 23, 2000Assignee: Alza CorporationInventors: Cynthia L. Stevenson, Sally A. Tao, Steven J. Prestrelski, James B. Eckenhoff, Jeremy C. Wright, John J. Leonard, Jr.
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Patent number: 6054555Abstract: 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: GrantFiled: October 22, 1999Date of Patent: April 25, 2000Assignee: Asta Medica AktiengesellschaftInventors: Jurgen Engel, Wolfgang Deger, Thomas Reissmann, Gunter Losse, Wolfgang Naumann, Sandra Murgas
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Patent number: 6025468Abstract: 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: GrantFiled: June 20, 1998Date of Patent: February 15, 2000Assignee: United Biomedical, Inc.Inventor: Chang Yi Wang
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Patent number: RE37710Abstract: 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: GrantFiled: May 18, 2000Date of Patent: May 21, 2002Assignee: Immunomedics, Inc.Inventors: William J. McBride, Habibe Karacay, Gary L. Griffiths