Bradykinin; Kallidin; Related Peptides Patents (Class 530/314)
  • Patent number: 11141389
    Abstract: Methods are provided for treatment of cancer cells, in a regimen comprising contacting the cancer cells with an inhibitor on NGly1, optionally in combination with a direct proteasome inhibitor.
    Type: Grant
    Filed: January 26, 2018
    Date of Patent: October 12, 2021
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Carolyn Ruth Bertozzi, Frederick Tomlin, Ulla Gerling-Driessen
  • Patent number: 9758569
    Abstract: Novel collagen mimics are disclosed with a tripeptide unit having the formula (Xaa-Yaa-Gly)n, where one of the positions Xaa or Yaa is a bulky, non-electron withdrawing proline derivative. By substituting a proline derivative at either the Xaa or Yaa position in the native collagen helix, the stability of the helix is increased due solely to steric effects relative to prior known collagen-related triple helices. Methods are also disclosed for making the novel collagen mimics.
    Type: Grant
    Filed: May 25, 2007
    Date of Patent: September 12, 2017
    Assignee: WISCONSIN ALUMNI RESEARCH FOUNDATION
    Inventors: Ronald T. Raines, Matthew D. Shoulders, Jonathan A. Hodges
  • Patent number: 9018160
    Abstract: Peptide analogues of PYY, compositions comprising said analogues and methods of using said analogues for the treatment and prevention of metabolic disorders, for example disorders of energy metabolism such as diabetes and obesity, and for a reduction in appetite, reduction in food intake or reduction of calorie intake in a subject.
    Type: Grant
    Filed: January 27, 2011
    Date of Patent: April 28, 2015
    Assignee: Imperial Innovations Limited
    Inventor: Stephen Robert Bloom
  • Patent number: 8835602
    Abstract: Compounds having the Formula I and pharmaceutically acceptable salts thereof are provided in which the variables are described herein. Methods of making the compounds of Formula I are also disclosed.
    Type: Grant
    Filed: August 31, 2009
    Date of Patent: September 16, 2014
    Assignee: Indian Institute of Science
    Inventor: Erode N. Prabhakaran
  • Patent number: 8691941
    Abstract: Peptides may be produced by using (A) a first amino acid or peptide, which is converted into its ionic liquid form through the formation of an ionic bond, as a substance serving as both a reaction solvent and a reaction starting material; and reacting the first amino acid or peptide with (B) an ester of second amino acid or peptide, in the absence of any peptide hydrolase or any condensation agent, in the presence of water in an amount of not more than 20% by mass relative to the total mass of the reaction system to form a peptide bond between the first amino acid or peptide and the second amino acid or peptide. By means of this process, it is possible to synthesize a peptide at a high concentration and at a high yield, and this method is excellent for producing peptides on an industrial scale.
    Type: Grant
    Filed: January 25, 2013
    Date of Patent: April 8, 2014
    Assignee: Ajinomoto Co., Inc.
    Inventors: Shinya Furukawa, Hiroki Imai
  • Publication number: 20140038281
    Abstract: The present invention relates to a system for intracellular cargo delivery, named NickFect, comprising at least one component A, which is attached covalently to cell penetrating peptide B and/or peptide or non-peptide construct C. The said delivery system NickFect relates to chemically modified new cell-penetrating peptides (CPP) non-covalently or covalently complexed with cargo for efficient cellular.
    Type: Application
    Filed: February 22, 2012
    Publication date: February 6, 2014
    Applicant: CEPEP III AB
    Inventors: Ülo Langel, Piret Arukuusk, Nikita Oskolkov, Dana Maria Copolovici
  • Publication number: 20130136717
    Abstract: The present invention relates to bradykinin receptor modulators and pharmaceutical compositions thereof for use as a medicament for modulating collateral blood vessel growth of collateral arteries and/or other blood vessels of pre-existing arterial networks. The bradykinin receptor modulators of arteriogenesis are applicable in the treatment and/or prevention of disorders associated with defective blood flow or blood vessel malformation. A preferred aspect of the invention relates to bradykinin receptor agonists for use as a medicament for the prevention of cardiovascular ischemic disease in a patient at risk thereof. Further, the invention relates to a bradykinin receptor agonist for use in a method for treating a cardiovascular ischemic disease in a patient in need thereof, wherein said cardiovascular ischemic disease is a peripheral limb disease.
    Type: Application
    Filed: May 16, 2011
    Publication date: May 30, 2013
    Applicant: MAX-DELBRUECK-CENTRUM FUER MOLEKULARE MEDIZIN
    Inventors: Philipp Hillmeister, Ivo Buschmann, Ferdinand Lenoble, Nora Gatzke
  • Patent number: 8288351
    Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a univalent vehicle, including peptides conjugated to univalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.
    Type: Grant
    Filed: April 8, 2008
    Date of Patent: October 16, 2012
    Assignee: Amgen Inc.
    Inventors: Gordon Ng, Yue-Sheng Li, Colin V. Gegg, Benny C. Askew, Jr., Thomas Storz, Yuelie Lu, Derin C. D'Amico, Mark A. Jarosinski, Chuan-Fa Liu, Qi Huang
  • Patent number: 8278280
    Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a multivalent vehicle, including peptides conjugated to multivalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.
    Type: Grant
    Filed: April 8, 2008
    Date of Patent: October 2, 2012
    Assignee: Amgen Inc.
    Inventors: Gordon Ng, Yue-Sheng Li, Colin V. Gegg, Benny C. Askew, Jr., Thomas Storz, Yuelie Lu, Derin C. D'Amico, Mark A. Jarosinski, Chuan-Fa Liu, Qi Huang
  • Publication number: 20120214742
    Abstract: A GABA (gamma-aminobutyric acid) release-inhibiting agent in the cerebellum and a composition for treating pathological symptoms caused by over-release of GABA in the cerebellum, each comprising a Bestrophin 1(Best1) channel inhibitor as an active ingredient; a GABA release-promoting agent in the cerebellum and a composition for treating pathological symptoms caused by the deficit of GABA in the cerebellum, each comprising a Best1 channel activator as an active ingredient; and a method for screening a GABA release-regulating agent in the cerebellum, which uses Best1 channel as target, are provided.
    Type: Application
    Filed: August 24, 2010
    Publication date: August 23, 2012
    Inventors: Changjoon Justin Lee, Soo-Jung Lee, Bo-Eun Yoon
  • Publication number: 20120065365
    Abstract: Stabilized radiopharmaceutical formulations are disclosed. Methods of making and using stabilized radiopharmaceutical formulations are also disclosed. The invention relates to stabilizers that improve the radiostability of radiotherapeutic and radiodiagnostic compounds and formulations containing them. In particular, it relates to stabilizers useful in the preparation and stabilization of targeted radiodiagnostic and radiotherapeutic compounds, and, in a preferred embodiment, to the preparation and stabilization of radiodiagnostic and radiotherapeutic compounds that are targeted to the Gastrin Releasing Peptide Receptor (GRP-Receptor).
    Type: Application
    Filed: October 25, 2011
    Publication date: March 15, 2012
    Applicant: BRACCO IMAGING S.P.A.
    Inventors: Jianqing Chen, Karen E. Linder, Edmund R. Marinelli, Edmund Metcalfe, Adrian D. Nunn, Rolf E. Swenson, Michael F. Tweedle
  • Publication number: 20110312522
    Abstract: The disclosed methods address the identification and monitoring of cancer in a subject using serum peptide profiles. Such profiles allow the detection of the differential presence of certain serum peptide markers in comparison with controls. The profiles can be determined employing mass spectrometry.
    Type: Application
    Filed: May 26, 2011
    Publication date: December 22, 2011
    Applicant: Sloan-Kettering Institute for Cancer Research
    Inventors: Paul Tempst, Josep Villanueva
  • Patent number: 8039227
    Abstract: Methods for diagnosing a kidney disease, or the risk thereof, in a subject are provided. The methods comprise determining an amount of at least one peptide biomarker disclosed herein in a biological sample from the subject and comparing the amount of the at least one peptide in the sample with a control level, wherein if the amount determined is different than the control level, the subject is diagnosed as having, or at an increased risk of developing, the kidney disease.
    Type: Grant
    Filed: September 19, 2008
    Date of Patent: October 18, 2011
    Assignee: University of Louisville Research Foundation, Inc.
    Inventors: Jon B. Klein, Michael Merchant, Grzegorz Boratyn
  • Patent number: 7932228
    Abstract: Provided is a method for the use of a bradykinin B1 receptor antagonist of formula I: X-CO-Aaa0-Aaa1-Aaa2-Aaa3-Gly-?(Me)Phe-Ser-D-?Nal-Aaa8-OH (I) or a pharmaceutically acceptable salt or hydrate thereof wherein: X is CnH2n+1 or CiH2i—C6H5, where n is an integer from 1 to 3, and i is an integer from 0 to 3; Aaa0 is Lys, Orn or Cit; Aaa1 is Arg or Cit, and preferably Arg; Aaa2 is Oic, Hyp or Pro, and preferably Oic; Aaa3 is Pro or Oic, and preferably Pro; and Aaa8 is Ile, Leu or Nle, and preferably Ile, for the treatment of metastases, cancers and/or chemotherapy-induced neuropathies, comprising the administration of the compound to a patient in need of such treatment. Also provided are compositions containing such antagonists and their thereof.
    Type: Grant
    Filed: June 12, 2006
    Date of Patent: April 26, 2011
    Assignee: Societe de Commercialisation des Produits de la Recherche Applique Socpra Sciences Sante et Humaines S.E.C.
    Inventors: François Nantel, Roger Chammas, Pierre Sirois, Bruno Joseph Battistini
  • Patent number: 7858349
    Abstract: The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.
    Type: Grant
    Filed: September 17, 2008
    Date of Patent: December 28, 2010
    Assignee: The Regents of the University of Colorado
    Inventors: John M. Stewart, Daniel C. F. Chan, Lajos Gera, Paul A. Bunn, Jr.
  • Patent number: 7807629
    Abstract: The invention provides methods for treating and/or preventing ocular disorders associated with increased intraocular pressure comprising administering a bradykinin B2 receptor agonist to a patient in need thereof.
    Type: Grant
    Filed: June 5, 2008
    Date of Patent: October 5, 2010
    Assignee: Alcon Research, Ltd.
    Inventor: Najam A. Sharif
  • Publication number: 20090137452
    Abstract: The present invention relates to composition of matter involving bradykinin B1 receptor antagonist peptides conjugated to a multivalent vehicle, including peptides conjugated to multivalent PEG. These compositions can be used as therapeutics or prophylactics against diseases or conditions, such as inflammation or pain, linked to the bradykinin B1 receptor.
    Type: Application
    Filed: April 8, 2008
    Publication date: May 28, 2009
    Inventors: Gordon Ng, Yue-Sheng Li, Colin V. Gegg, Benny C. Askew, JR., Thomas Storz, Yuelie Lu, Derin C. D'Amico, Mark A. Jarosinski, Chuan-Fa Liu, Qi Huang
  • Patent number: 7427496
    Abstract: The invention provides bradykinin antagonists and pharmaceutically acceptable salts thereof having anti-cancer activity. These anti-cancer compounds are particularly useful for inhibiting the growth of lung and prostate cancers.
    Type: Grant
    Filed: December 14, 2005
    Date of Patent: September 23, 2008
    Assignee: The Regents of the University of Colorado
    Inventors: John M. Stewart, Daniel C. F. Chan, Lajos Gera, Paul A. Bunn, Jr.
  • Patent number: 7371810
    Abstract: Tachykinin peptide isolated and purified from the posterior salivary gland of the mollusk Octopus vulgaris. The tachykinin peptide provides a new approach for developing medicaments and pesticides through studies on the structural activity correlation at the molecular level, is characterized by: (1) number of amino acid residues is 12; (2) N terminal of the peptide is Lys; (3) an amino acid sequence of 5 amino acids from C-terminal is represented by the following amino acid sequence: Phe-Xaa-Gly-Leu-Met (SEQ ID NO: 6), (wherein, Xaa is Val, lie, Phe or Tyr), especially following amino acid sequences are provided: Lys-Pro-Pro-Ser-Ser-Ser-Glu-Phe-Val-Gly-Leu-Met (SEQ ID NO: 1), Lys-Pro-Pro-Ser-Ser-Ser-Glu-Phe-Ile-Gly-Leu-Met (SEQ ID NO: 2).
    Type: Grant
    Filed: July 25, 2000
    Date of Patent: May 13, 2008
    Assignee: Suntory Limited
    Inventors: Hiroyuki Minakata, Eiko Iwakoshi, Kyoko Kuroda
  • Patent number: 7276251
    Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.
    Type: Grant
    Filed: July 26, 2002
    Date of Patent: October 2, 2007
    Assignee: LG Life Sciences, Ltd., Inc.
    Inventors: Myung-Jin Kim, Sun-Jin Kim, Oh-Ryong Kwon
  • Patent number: 7235531
    Abstract: The present invention relates to amino acid sequences for novel tachykinin polypeptides and base sequences encoding them, agonists and antagonists of such polypeptides, pharmaceutical compositions comprising them, and the like.
    Type: Grant
    Filed: December 21, 2000
    Date of Patent: June 26, 2007
    Assignee: Takeda Pharmaceutical Company
    Inventors: Yasuaki Itoh, Kazunori Nishi, Chieko Kitada
  • Patent number: 7074765
    Abstract: The invention relates to compounds and methods for inhibiting human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4 using peptide analogs of Arg-Pro-Pro-Gly-Phe that contain one or more amino acid substitutions. The invention also includes screening methods for identifying compounds that inhibit thrombin mediated activities.
    Type: Grant
    Filed: May 1, 2003
    Date of Patent: July 11, 2006
    Assignees: The Regents of the University of Michigan, Thromgen, Inc.
    Inventors: Alvin H. Schmaier, Ahmed A. K. Hasan
  • Patent number: 7071168
    Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X[Formula I] wherein X is a linker group having 2–5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.
    Type: Grant
    Filed: December 28, 2001
    Date of Patent: July 4, 2006
    Assignee: The Regents of the University of Colorado
    Inventors: John M. Stewart, Daniel C. F. Chan, Lajos Gera, Eunice York, Paul Bunn
  • Patent number: 7041785
    Abstract: The present invention relates to novel antagonists to a B1-bradykinin (B1-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B1 receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B1-BK receptors in these two models. B1-BK antagonists abolished the vasocontraction induced by B1-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels.
    Type: Grant
    Filed: August 14, 1997
    Date of Patent: May 9, 2006
    Assignee: Université de Sherbrooke
    Inventors: Domenico Recoli, Gerard E. Plante, Fernand Gobeil, Witold A. Neugebauer, Adriana Zucollo, Orlando L. Catanzaro
  • Patent number: 6995236
    Abstract: An object of the present invention is to provide a protein useful as a sphingomyelin detecting probe, which specifically recognizes sphingomyelin and has low cytotoxicity. The present invention provides a protein which has an amino acid sequence having, as the amino acid sequence from the 1st to the 48th amino acid, the amino acid sequence from the 1st to the 48th amino acid in Lysenin 1, and as the amino acid sequence from the 49th to the 298th amino acid, the amino acid sequence from the 51st to the 300th amino acid in Lysenin 3; and a protein which is obtained by deleting N terminal and/or C terminal from earthworm toxins Lysenin 1 or 3, and which specifically recognizes sphingomyelin.
    Type: Grant
    Filed: May 6, 2002
    Date of Patent: February 7, 2006
    Assignee: Riken
    Inventors: Toshihide Kobayashi, Etsuko Kiyokawa, Akiko Hasegawa
  • Patent number: 6770741
    Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.
    Type: Grant
    Filed: December 20, 1994
    Date of Patent: August 3, 2004
    Assignee: Scios Inc.
    Inventors: Donald James Kyle, Roger Neal Hiner
  • Patent number: 6458923
    Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.
    Type: Grant
    Filed: September 12, 1994
    Date of Patent: October 1, 2002
    Assignee: Scios Inc.
    Inventor: Donald James Kyle
  • Patent number: 6388054
    Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X  [Formula I] wherein X is a linker group having 2-5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.
    Type: Grant
    Filed: August 19, 1999
    Date of Patent: May 14, 2002
    Inventors: John M. Stewart, Daniel C. F. Chan, Lajos Gera, Eunice York, Paul Bunn
  • Patent number: 6288036
    Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.
    Type: Grant
    Filed: December 16, 1993
    Date of Patent: September 11, 2001
    Assignee: Scios Inc.
    Inventors: Donald James Kyle, Roger Neal Hiner
  • Patent number: 6245736
    Abstract: The invention relates to the use of bradykinin antagonists for the production of pharmaceuticals for the treatment and prevention of Alzheimer's disease. Suitable bradykinin antagonists are peptides which inhibit the effects of the Alzheimer's protein amyloid (&bgr;/A4) on isolated endothelial cells. A particularly suitable peptide is H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH (HOE 140) and its physiologically tolerable salts.
    Type: Grant
    Filed: October 14, 1997
    Date of Patent: June 12, 2001
    Assignee: Aventis Pharma Deutschland GmbH
    Inventors: Holger Heitsch, Stephan Henke, Gerhard Breipohl, Jochen Knolle, Klaus Wirth, Gabriele Wiemer
  • Patent number: 6242573
    Abstract: A regenerated collagen fiber is subjected to water-insolubilizing treatment with a monofunctional epoxy compound to produce a water-insolubilized regenerated collagen fiber which can substantially maintain the color and the high knot tenacity, inherent in the collagen. Where the monofunctional epoxy compound is an epihalohydrin, a regenerated collagen fiber can be treated with this epihalohydrin and a sulfur compound to produce a water-insolubilized regenerated collagen fiber which can be permanent-wave set. In addition, the water-insolubilized regenerated collagen fiber can be converted into a fiber which can be permanent-wave set, by introducing a disulfide linkage into carboxylic groups of the collagen, which remain unmodified by the insolubilizing treatment.
    Type: Grant
    Filed: November 1, 1999
    Date of Patent: June 5, 2001
    Assignee: Kaneka Corporation
    Inventors: Masaoki Goto, Shinichi Sakashita, Kunihiko Matsumura
  • Patent number: 6075120
    Abstract: A bradykinin antagonist of the formula:(BKAn)(X)(Y)where BKAn is a bradykinin antagonist peptide; Y is a pharmacore; and X is a bridging link chemically joining the BKAn and Y components.
    Type: Grant
    Filed: May 12, 1995
    Date of Patent: June 13, 2000
    Assignee: Cortech, Inc.
    Inventors: John C. Cheronis, James K. Blodgett, Val Smith Goodfellow, Manoj Vinayak Marathe, Lyle W. Spruce, Eric T. Whalley
  • Patent number: 5935932
    Abstract: The present invention provides bradykin antagonists containing pentafluorophenylalanine which are therapeutically useful. Moreover, the present invention provides methods to antagonize bradykinin receptors in a mammal in need of such antagonism, comprising administering a bradykinin antagonist containing pentafluorophenylalanine. Also provided are methods to treat inflammation in a mammal in need of such inhibition, comprising administering a bradykinin antagonist containing pentafluorophenylalanine. Lastly, a method to treat cancer in a mammal in need of such inhibition, comprising administering a bradykinin antagonist containing pentafluorophenylalanine.
    Type: Grant
    Filed: June 12, 1998
    Date of Patent: August 10, 1999
    Assignee: University Technology Corporation
    Inventors: John M. Stewart, Lajos Gera
  • Patent number: 5874529
    Abstract: Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N.sup..alpha. (.omega.-functionalized)amino acids constructed to include a spacer and a terminal functional group. One or more of these N.sup..alpha. (.omega.-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.
    Type: Grant
    Filed: December 5, 1996
    Date of Patent: February 23, 1999
    Assignees: Peptor Ltd., Yissum Research Development Company of the Hebrew University
    Inventors: Chaim Gilon, Doron Eren, Irina Zeltser, Alon Seri-Levy, Gal Bitan, Dan Muller
  • Patent number: 5863901
    Abstract: This invention relates to a method of treating a chronic fibrogenetic liver disorder and/or an acute liver disorder and/or complications associated therewith, comprising administering to a patient a therapeutically effective amount of a bradykinin antagonist. Particular complications associated with said liver disorders include portal hypertension, decompensation phenomena such as ascites, edema formation, hepatorenal syndrome, hypertensive gastropathy and colopathy, splenomegaly and hemorrhagic complications in the gastrointestinal tract due to portal hypertension, collateral circulation and hyperemia and a cardiopathy as a result of a chronically hyperdynamic circulatory situation and its consequences.
    Type: Grant
    Filed: March 4, 1997
    Date of Patent: January 26, 1999
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Gerhard Breipohl, Stephan Henke, Jochen Knolle, Klaus Wirth, Max Hropot, Martin Bickel
  • Patent number: 5863899
    Abstract: A bradykinin antagonist of the formula:(BKAn) (X) (Y)where BKAn is a bradykinin antagonist peptide; Y is a Pharmacophore; and X is a bridging link chemically joining the BKAn and Y components.
    Type: Grant
    Filed: August 29, 1994
    Date of Patent: January 26, 1999
    Assignee: Cortech, Inc.
    Inventors: John C. Cheronis, James K. Blodgett, Val Smith Goodfellow, Manoj Vinayak Marathe, Lyle W. Spruce, Eric T. Whalley
  • Patent number: 5849863
    Abstract: The present invention provides bradykinin antagonists effective to inhibit cancer cell growth. Also provided are methods of inhibiting lung cancer cell growth by administering a therapeutically effective amount of a dimerized bradykinin antagonist.
    Type: Grant
    Filed: September 8, 1995
    Date of Patent: December 15, 1998
    Assignees: University of Colorado, Cortech, Inc.
    Inventors: John M. Stewart, Daniel C. Chan, Eric T. Whalley, Lajos Gera
  • Patent number: 5843903
    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 Q.sup.14 --O--R--P wherein Q has the general formula ##STR1## wherein: Q.sup.14 signifies a Q moiety with a side chain at the 14 position, R-- is H or --C(O)--(CH.sub.2).sub.n --C(O)-- and n=0-7, R' is NH.sub.2 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. Nevertheless where R' is NH.sub.
    Type: Grant
    Filed: November 27, 1995
    Date of Patent: December 1, 1998
    Assignee: The Administrators of the Tulane Educational Fund
    Inventors: Andrew V. Schally, Attila A. Nagy, Ren-Zhi Cai
  • Patent number: 5843900
    Abstract: The present invention relates to pharmaceutically effective heterodimers comprising a bradykinin antagonist component covalently linked to a mu-opioid agonist component.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: December 1, 1998
    Assignee: Cortech, Inc.
    Inventors: John C. Cheronis, Albert Gyorkos, Lyle W. Spruce, Eric T. Whalley
  • Patent number: 5834431
    Abstract: The present invention provides des-Arg.sup.9 bradykinin analogs which are selective B1 receptor antagonists.
    Type: Grant
    Filed: September 8, 1995
    Date of Patent: November 10, 1998
    Assignees: Cortech, Inc., University of Colorado
    Inventors: John M. Stewart, Eric T. Whalley, Lajos Gera
  • Patent number: 5811392
    Abstract: Novel backbone cyclized peptide analogs are formed by means of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units disclosed are N.sup..alpha. (.omega.-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these N.sup..alpha. (.omega.-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The invention is exemplified by backbone cyclized bradykinin antagonists having biological activity. Further embodiments of the invention are somatostatin analogs having one or two ring structures involving backbone cyclization.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: September 22, 1998
    Assignees: Yissum research Development Co. of the Hebrew University, Peptor Limited
    Inventors: Chaim Gilon, Doron Eren, Irina Zeltser, Alon Seri-Levy, Gal Bitan, Dan Muller
  • Patent number: 5789383
    Abstract: Bradykinin antagonists and their physiologically tolerated salts are suitable for the treatment or prophylaxis of virus diseases.
    Type: Grant
    Filed: December 29, 1994
    Date of Patent: August 4, 1998
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Klaus Wirth, Irvin Winkler, Fred Lembeck, Gerhard Breipohl, Stephan Henke, Jochen Knolle
  • Patent number: 5777073
    Abstract: Novel cyclic CRF antagonist peptides are created by shortening the N-terminus of a CRF family peptide by 8-11 residues and adding an acyl group. CML is preferably present in what would be the 27-position of the native CRF sequence, and D-Tyr may be incorporated at the N-terminus to facilitate labelling. The cyclizing bond is preferably created between the side chains of the residues in positions 30 and 33; but it may alternatively be created between the residues in either of positions 28 and 29 with those in positions 31 and 32 or with those in positions 32 and 33, respectively. The side chain of Lys in position 33 is preferably linked to the side chain of Glu in position 30 by a lactam bridge to form the cyclic peptide. Disclosed CRF antagonists include:(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,40, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41),(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.12, Nle.sup.21,38, CML.sup.27,37, Glu.sup.30, Lys.sup.33 !r/hCRF(9-41),(cyclo 30-33) ?Ac-Asp.sup.9, D-Phe.sup.
    Type: Grant
    Filed: May 30, 1997
    Date of Patent: July 7, 1998
    Assignee: The Salk Institute for Biological Studies
    Inventor: Jean E. F. Rivier
  • Patent number: 5750506
    Abstract: Bradykinin antagonists, particularly Cys.sup.6 analogs, which have an extended hydrophobic side chain.
    Type: Grant
    Filed: May 13, 1996
    Date of Patent: May 12, 1998
    Assignee: Cortech, Inc.
    Inventors: Val S. Goodfellow, Heather B. Kroona, Eric T. Whalley, Francine E. Wincott, Dana A. Zummach
  • Patent number: 5750646
    Abstract: A linear peptide which is an analog of a naturally occurring, biologically active peptide having an active site and a binding site responsible for the binding of the peptide to a receptor on a target cell, cleavage of a peptide bond in the active site to the naturally occurring peptide being unnecessary for in vivo biological activity, the analog having a non-peptide bond instead of a peptide bond between an amino acid of the active site and an adjacent amino acid, and having the same binding site as the naturally occurring peptide, so that the analog is capable of acting as a competitive inhibitor of the naturally occurring peptide by binding to the receptor and, by virtue of the non-peptide bond, failing to exhibit the in vivo activity of the naturally occurring peptide.
    Type: Grant
    Filed: March 22, 1995
    Date of Patent: May 12, 1998
    Assignees: The Administrators of the Tulane Educational Fund, Biomeasure, Inc.
    Inventors: David H. Coy, Jacques-Pierre Moreau, John E. Taylor, Sun Hyuk Kim
  • Patent number: 5700779
    Abstract: The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.
    Type: Grant
    Filed: June 20, 1996
    Date of Patent: December 23, 1997
    Assignee: Cortech, Inc.
    Inventors: Val S. Goodfellow, Manoj V. Marathe, Eric T. Whalley, Timothy D. Fitzpatrick, Karen G. Kuhlman
  • Patent number: 5686416
    Abstract: Peptides called receptor mediated permeabilizers (RMP) increase the permeability of the blood-brain barrier to molecules such as therapeutic agents or diagnostic agents. The permeabilizer A-7 or conformational analogues can be intravenously co-administered to a host together with molecules whose desired destination is the interstitial fluid compartment of the brain. Alternatively, the permeabilizer A-7 or conformational analogues can be administered sequentially with the molecule(s) of interest and these molecules can also be administered by routes other than intravascular. The permeabilizer A-7 or conformational analogues allow these molecules to penetrate the blood-brain barrier and arrive in the interstitial fluid.
    Type: Grant
    Filed: November 12, 1993
    Date of Patent: November 11, 1997
    Assignee: Alkermes, Inc.
    Inventors: John W. Kozarich, Gary F. Musso, Bernard Malfroy-Camine
  • Patent number: 5670619
    Abstract: The invention relates to the use of bradykinin-antagonists of the formulaR.sup.1 -A-B-C-E-F-G-J-K-R.sup.2wherein R.sup.1 represents hydrogen, C.sub.1 -C.sub.4 -alkanoyl which can be substituted by mercapto, hydroxyphenyl, (4-benzoyl)phenoxy or represents (4-benzoyl)benzoyl-Lys; A represents D-Arg or D-Lys or stands for a direct bond; B represents Arg which can be substituted by NO.sub.2 or toluol-4-sulfonyl or represents Lys which can be substituted by toluol-4-sulfonyl or CO--NH--C.sub.6 H.sub.5, or stands for a direct bond; C represents Hyp-Pro-Gly, Pro-Hyp-Gly, Pro-Pro-Gly or dehydroPro-Hyp-Gly; E represents Thi, Phe, Leu or Cha; F represents Ser or Cys; G represents D-Tic, D-Phe or D-Hyp substituted by C.sub.1 -C.sub.4 -alkoxy; J represents Tic, Aoc or Oic; K represents Arg or Ahx or stands for a direct bond; R.sup.
    Type: Grant
    Filed: April 22, 1994
    Date of Patent: September 23, 1997
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Thomas Griesbacher, Fred Lembeck
  • Patent number: 5648336
    Abstract: The present invention pertains to modified bradykinin antagonist peptides of the formula X-A.sup.0 -B.sup.1 -C.sup.2 -D.sup.3 -E.sup.4 -F.sup.5 -G.sup.6 -H.sup.7 -J.sup.8 -K.sup.9, where at least one of F.sup.5, H.sup.7 and J.sup.8 is an indane substituted amino acids.
    Type: Grant
    Filed: November 18, 1994
    Date of Patent: July 15, 1997
    Assignee: University of Colorado
    Inventors: John M. Stewart, Lajos Gera, Eric T. Whalley
  • Patent number: 5648333
    Abstract: Peptides of the formula IA-B-C-E-F-K-P-G-M-F'-I (I),wherein the terms A, B, C, E, F, K, P, G, M, F', and I are defined in the specification, have bradykinin antagonist action. Their therapeutic utility includes all pathological states which are mediated, caused or supported by bradykinin and bradykinin-related peptides.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: July 15, 1997
    Assignee: Hoechst Aktiengesellschaft
    Inventors: Stephan Henke, Hiristo Anagnostopulos, Gerhard Breipohl, Jochen Knolle, Jens Stechl, Bernward Scholkens, Hans-Wolfram Fehlhaber, Hermann Gerhards, Franz Hock