Adrenocorticotropic Hormone Or Derivatives Patents (Class 514/805)
  • Patent number: 9598714
    Abstract: Method for enzymatically synthesizing an oligopeptide, comprising the coupling of an (optionally N-protected) protected oligopeptide ester with an (optionally C-protected) protected oligopeptide nucleophile in an organic solvent or an organic solvent mixture having a water content of 0.1 vol % or less, by a subtilisin in any possible form.
    Type: Grant
    Filed: February 28, 2013
    Date of Patent: March 21, 2017
    Assignee: ENZYPEP B.V.
    Inventors: Peter Jan Leonard Mario Quaedflieg, Timo Nuijens
  • Patent number: 8758770
    Abstract: Methods and compositions for the enteral treatment of autoimmune disease such a multiple sclerosis with polypeptide therapeutics. Enteral therapeutics comprise monomeric alpha-MSH polypeptides such as ACTH. Therapeutic formulations of the invention may be used to reduce the incidence or severity of autoimmune disease. For instance methods for the oral treatment of multiple sclerosis with alpha-MSH and ACTH are described.
    Type: Grant
    Filed: October 4, 2010
    Date of Patent: June 24, 2014
    Assignee: Research Development Foundation
    Inventor: Staley A. Brod
  • Patent number: 7163694
    Abstract: Bioerodible poly(ortho esters) useful as orthopedic implants or vehicles for the sustained delivery of pharmaceutical, cosmetic and agricultural agents from dioxane-based di(ketene acetals). Block copolymers contain these bioerodible poly(ortho esters). These block copolymers have both hydrophilic and hydrophobic blocks. They form micelles in aqueous solution, making them suitable for encapsulation or solubilization of hydrophobic or water-insoluble materials; and they also form bioerodible matrices for the sustained release of active agents.
    Type: Grant
    Filed: March 8, 2006
    Date of Patent: January 16, 2007
    Assignee: A.P. Pharma, Inc.
    Inventors: Jorge Heller, Steven Y. Ng
  • Patent number: 6749866
    Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.
    Type: Grant
    Filed: January 3, 2002
    Date of Patent: June 15, 2004
    Assignee: Alkermes Controlled Therapeutics, Inc.
    Inventors: Howard Bernstein, Yan Zhang, M. Amin Khan, Mark A. Tracy
  • Patent number: 6559289
    Abstract: The invention relates to the use of compounds selected from GH, analogues thereof, and GH-releasing compounds, optionally in combination with lipid-lowering agents or therapy, for the preparation of a drug for treatment of mammals with familial hypercholesterolemia of homozygous form.
    Type: Grant
    Filed: April 23, 2001
    Date of Patent: May 6, 2003
    Assignee: Salhtech I Goteborg AB
    Inventors: Mats Rudling, Bo Angelin
  • Patent number: 6429195
    Abstract: Prolonged parenteral release into the circulatory system of a cow of a bioactive growth hormone releasing factor at desirably effective levels can be achieved using novel compositions in which the growth hormone releasing factor is present in an aqueous liquid at a dose of at least about 50 mg and at a concentration of at least about 20 mg/ml. Preferably, the growth hormone releasing factor is present in an aqueous liquid at a dose of about 200 mg and at a concentration of about 180 mg/ml. The aqueous bovine growth hormone releasing factor formulation provides for the sustained release of bovine somatotropin into the circulatory system of the animal for greater than seven (7) days.
    Type: Grant
    Filed: September 1, 2000
    Date of Patent: August 6, 2002
    Assignee: Pharmacia & Upjohn Company
    Inventors: Todd P. Foster, William M. Moseley, James F. Caputo, Michael J. Hageman
  • Patent number: 6417237
    Abstract: Macromolecular drug complexes containing a drug, like human growth hormone, and a polymer having a plurality of acid moieties, like carboxyl moieties or phosphonic acid moieties, and compositions containing the same, are disclosed. Compositions, particularly microemulsions, containing the macromolecular complexes are administered to individuals suffering from a disease or condition, and the complexes release the drug, in vivo, to treat the disease or condition, and to reduce, eliminate, or reverse complications associated with the disease.
    Type: Grant
    Filed: June 8, 2000
    Date of Patent: July 9, 2002
    Assignee: The Board of Trustees of the University of Illinois
    Inventors: Eric J. Dadey, Camillia Zamiri
  • Patent number: 6368630
    Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.
    Type: Grant
    Filed: March 23, 1999
    Date of Patent: April 9, 2002
    Assignee: Alkermes Controlled Therapeutics, Inc.
    Inventors: Howard Bernstein, Yan Zhang, M. Amin Khan, Mark A. Tracy
  • Patent number: 6326463
    Abstract: Novel cyclic CRF agonist peptides have the amino acid sequence: (cyclo 30-33)Ac-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Glu-Ala-R32-R33-Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH2 wherein R32 is His, D-His or an equivalent &agr;-amino acid; R33 is Lys or Orn. The N-terminus may be extended by Tyr, D-Tyr or Ile. Lys may be substituted for Arg23, and its side chain connected by a lactam bridge to Glu20 to form a bicyclic peptide. Certain disclosed CRF agonists include: (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Glu30, Lys33]r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(7-41); (bicyclo 20-23, 30-33)[Ac-Ser7, D-Phe12, Nle21,38, Lys23,33, Glu30, D-His32]-r/hCRF(7-41); (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle18,21, Glu30, D-Ala32, Lys33]&agr;-helicale CRF(7-41); and (cyclo 30-33)[Ac-Ser7, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33]r/hCRF(7-41).
    Type: Grant
    Filed: November 29, 1999
    Date of Patent: December 4, 2001
    Assignee: The Salk Institute For Biological Studies
    Inventor: Jean E. F. Rivier
  • Patent number: 6150330
    Abstract: Prolonged parenteral release into the circulatory system of a cow of a bioactive growth hormone releasing factor at desirably effective levels can be achieved using novel compositions in which the growth hormone releasing factor is present in an aqueous liquid at a dose of at least about 50 mg and at a concentration of at least about 20 mg/ml. Preferably, the growth hormone releasing factor is present in an aqueous liquid at a dose of about 200 mg and at a concentration of about 180 mg/ml. The aqueous bovine somatotropin formulation provides for the sustained release of bovine somatotropin into the circulatory system of the animal for greater than seven (7) days.
    Type: Grant
    Filed: December 13, 1996
    Date of Patent: November 21, 2000
    Assignee: Pharmacia & Upjohn Company
    Inventors: Todd P. Foster, William M. Moseley, James F. Caputo, Michael J. Hageman
  • Patent number: 5976569
    Abstract: Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and either (b)(1) a carrier of (i) at least one amino acid and (ii) at least one diketopiperazine or (b)(2) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.
    Type: Grant
    Filed: April 29, 1997
    Date of Patent: November 2, 1999
    Assignee: Emisphere Technologies, Inc.
    Inventor: Sam J. Milstein
  • Patent number: 5912015
    Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.
    Type: Grant
    Filed: April 7, 1998
    Date of Patent: June 15, 1999
    Assignee: Alkermes Controlled Therapeutics, Inc.
    Inventors: Howard Bernstein, Yan Zhang, M. Amin Khan, Mark A. Tracy
  • Patent number: 5874227
    Abstract: Novel cyclic CRF antagonist peptides have the amino acid sequence: ##STR1## wherein Y is Ac, H, Ac-Thr or H-Thr; R.sub.30 is Glu or Cys; R.sub.32 is His or preferably a basic and/or aromatic D-amino acid such as D-His or D-Arg; R.sub.33 is Lys, Orn or Cys. The N-terminus may be extended by Leu or Asp-Leu. CML may be substituted for Leu.sup.27, and D-Tyr may be substituted for D-Phe to facilitate labelling. Lys may be substituted for Arg.sup.23, and its side chain connected by a lactam bridge to Glu.sup.20 to form a bicyclic peptide. Disclosed CRF antagonists include:(cyclo 30-33)?D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 !r/hCRF(12-41),(cyclo 30-33)?Ac-Thr.sup.11, D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 !r/hCRF(11-41),(cyclo 30-33)?D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33 !r/hCRF(12-41),(bicyclo 20-23,30-33)?D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30 !-r/hCRF(12-41),(cyclo 30-33)?D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, D-His.sup.32, Lys.sup.
    Type: Grant
    Filed: November 10, 1995
    Date of Patent: February 23, 1999
    Assignee: The Salk Institute for Biological Studies
    Inventor: Jean E. F. Rivier
  • Patent number: 5869081
    Abstract: The present invention relates to a method of administering progesterone to a normogonadal or a functionally agonadal human female undergoing an assisted reproduction technique. The invention further provides a method of hormone replacement for a human female. In a preferred embodiment of the present invention, progesterone is provided by intravaginal administration of a progesterone-containing polysiloxane ring.
    Type: Grant
    Filed: June 28, 1996
    Date of Patent: February 9, 1999
    Assignee: The Population Council
    Inventors: Theodore Jackanicz, Horacio B. Croxatto Avoni, Leopoldo Glasser Drexler, Fernando Zegers-Hochschild
  • Patent number: 5844074
    Abstract: Novel cyclic CRF agonist peptides have the amino acid sequence: (cyclo 30-33)Ac-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu -Glu-Nle-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-R.sub.30 -Ala-R.sub.32 -R.sub.33 -Asn-Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2 wherein R.sub.30 is Glu or Cys; R.sub.32 is His or a D-amino acid such as D-His, D-Arg or similar; R.sub.33 is Lys, Orn or Cys. The N-terminus may be extended by Ser-Glu-Glu. Lys may be substituted for Arg.sup.23, and its side chain connected by a lactam bridge to Glu.sup.20 to form a bicyclic peptide. Certain disclosed CRF agonists include:(cyclo 30-33)?Ac-Pro.sup.4, D-Phe.sup.12, Nle.sup.21,38, D-His.sup.32, Glu.sup.30, Lys.sup.33 !r/hCRF(4-41),(cyclo 30-33)?Ac-Pro.sup.4, D-Phe.sup.12, Nle.sup.21,38, D-His.sup.32, Glu.sup.30, Orn.sup.33 !r/hCRF(4-41),(cyclo 30-33)?Ac-Pro.sup.4, D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33, D-His.sup.32 !r/hCRF(4-41),(bicyclo 20-23,30-33)?Ac-Pro.sup.4, D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30, D-His.sup.
    Type: Grant
    Filed: December 19, 1995
    Date of Patent: December 1, 1998
    Assignee: The Salk Institute for Biological Studies
    Inventor: Jean E. F. Rivier
  • Patent number: 5656297
    Abstract: The present invention relates to a composition for the modulated release of a biologically active agent. The composition comprises a biocompatible polymeric matrix, a biologically active agent which is dispersed within the polymeric matrix, and a metal cation component which is separately dispersed within the polymeric matrix, whereby the metal cation component modulates the release of the biologically active agent from the polymeric matrix. The present invention also relates to a method for modulating the release of a biologically active agent from a biocompatible polymeric matrix, comprising the steps of dissolving a biocompatible polymer in a solvent to form a polymer solution and also separately dispersing a metal cation component and a biologically active agent within the polymer solution.
    Type: Grant
    Filed: May 3, 1994
    Date of Patent: August 12, 1997
    Assignee: Alkermes Controlled Therapeutics, Incorporated
    Inventors: Howard Bernstein, Yan Zhang, M. Amin Khan, Mark A. Tracy
  • Patent number: 5413797
    Abstract: ACTH polymeric controlled release systems are described wherein the ACTH retains good biological activity and is released over an extended period of time following administration by injection. In the preferred embodiment, the ACTH polymeric microspheres are made using very cold temperatures to freeze the polymer-ACTH mixtures into polymeric microspheres with very high retention of biological activity and material. Sustained release of biologically active ACTH is achieved when the microspheres are tested in vitro, extending over a period of greater than one day to several months. Altered release can be achieved by inclusion of degradation modifiers, pore forming agents, and stabilizers of the ACTH.
    Type: Grant
    Filed: June 30, 1994
    Date of Patent: May 9, 1995
    Assignee: Alkermes Controlled Therapeutics, Inc.
    Inventors: M. Amin Khan, Howard Bernstein
  • Patent number: 5348729
    Abstract: The present invention is directed to a method for testing the susceptibility of a mammal to inflammatory diseases which comprises the steps of:administering to a mammal a compound selected from the group consisting of Type 1 mineralocorticoid receptor antagonists, opiate antagonists, estrogen antagonists or mixed estrogen agonists/antagonists, progesterone agonists; or a combination of an estrogen antagonist with one or a combination of a Type I glucocorticoid receptor antagonist, a Type II glucocorticoid agonist or a progesterone agonist which is effective in stimulating the hypothalamic-pituitary-adrenal (HPA) axis; andmeasuring the level of at least one hormone secreted by the hypothalamus, pituitary or adrenal glands of said mammal.The present invention is also directed to methods of treating inflammatory diseases.
    Type: Grant
    Filed: May 5, 1992
    Date of Patent: September 20, 1994
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Esther M. Sternberg, Philip W. Gold, Samuel W. Page
  • Patent number: 5209920
    Abstract: Inbred Lewis (LEW/N) female rats develop an arthritis in response to Group A streptococcal cell wall peptidoglycanpolysaccharide (SCW) which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats, on the other hand, do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammatory reactivity between the two strains, the function of the hypothalamic-pituitary-adrenal axis and its ability to modulate the development of the inflammatory response was studied. It has been found that, in contrast to F344/N rats, LEW/N rats had markedly impaired plasma ACTH and corticosterone responses to SCW, recombinant human Interleukin-1 alpha (IL-1 alpha), the serotonin agonist, quipazine, and synthetic rat corticotropin-releasing hormone (CRH). In addition, LEW/N rats compared to F344/N rats had smaller adrenal glands and larger thymuses. Treatment of LEW/N rats with replacement doses of dexamethasone decreased the severity of their SCW-induced arthritis.
    Type: Grant
    Filed: September 25, 1989
    Date of Patent: May 11, 1993
    Assignee: The United States of America as represented by the United States Department of Health and Human Services
    Inventors: Esther M. Sternberg, Ronald L. Wilder, Philip W. Gold, George P. Chrousos
  • Patent number: 5132111
    Abstract: Agonists and antagonists of rCRF are disclosed that exhibit good binding affinity to CRF receptors. One exemplary agonist is: H-Ser-Gln-Glu-Pro-Pro-Ile-Ser- Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Met-Leu-Glu-Met- Ala-Arg-Ala-Glu-Gln-Glu-Ala-Glu-Gln-Ala-Ala-Leu-Asn-Arg- Leu-Leu-Leu-Glu-Glu-Ala-NH.sub.2. In the agonists, one or more of the first five N-terminal residues may be deleted or may be substituted by a peptide up to 10 amino acids long. A number of other substitutions may also be made throughout the chain. Similar peptides which function as CRF antagonists are created by deleting the first 7, 8 or 9 N-terminal residues. These analogs are coupled to a cytotoxin, such as gelonin, by a dialdehyde or the like, e.g., glutaraldehyde. The conjugates may be used to eliminate CRF Target Cells, and thus to regulate secretion of ACTH, .beta.-lipotropin and the like.
    Type: Grant
    Filed: April 11, 1990
    Date of Patent: July 21, 1992
    Assignee: The Salk Institute for Biological Studies
    Inventors: Wylie W. Vale, Jr., Jean E. F. Rivier, Jeffrey Schwartz
  • Patent number: 5109111
    Abstract: Several known members of the corticotropin releasing factor (CRF) family have been synthesized and tested, including human and rat CRF which have the formula: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His- Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln- Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu- Ile-Ile-NH.sub.2. Peptides are herein disclosed that are potent competitive antagonists of CRF in mammals. One which has been found to be particularly potent is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-Leu-Nle-Glu-Ile-Ile-NH.sub.2. One that has shown particularly prolonged duration of potency is: H-D-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Nle-Ala- Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn- Arg-Lys-CML-Nle-Glu-Ile-Ile-NH.sub.2.
    Type: Grant
    Filed: March 23, 1990
    Date of Patent: April 28, 1992
    Assignee: The Salk Institute for Biological Studies
    Inventors: Jean E. F. Rivier, Wylie W. Vale, Jr., Catherine L. Rivier, Jean-Francois Hernandez
  • Patent number: 5049547
    Abstract: A pharmaceutically active composition comprising a pharmaceutically acceptable carrier and one or more alpha-MSH or analogues thereof for use in the stimulation of integumental melanocytes in vertebrates in order to bring about the production of melanin is disclosed.
    Type: Grant
    Filed: April 19, 1989
    Date of Patent: September 17, 1991
    Assignee: University Patents, Inc.
    Inventors: Victor J. Hruby, Mac E. Hadley, Robert Dorr, Norman Levine, Elizabeth Sugg, Wayne L. Cody
  • Patent number: 5043321
    Abstract: A method for alleviating stress induced immunosuppression is accomplished by application of low doses of ANF[1-28] or other ANF analogs having intact N-terminal sequences. Atrial natriuretic factors (ANFs) with intact N-terminal sequences are shown to be effective inhibitors of CRF 41-stimulated ACTH secretion when the ANFs are present in low concentrations. ANF[1-28] significantly inhibited ACTH release stimulated by 1-5 nM CRF. At the most effective concentration of 100 pM, ACTH release was inhibited by 40.1% (p<0.001). This effect was manifested after three hours, but not after only one half or one hour of incubation. Conversely, ANF[5-28], at concentrations of 10 to 10,000 pM, had no effect on ACTH secretion after one half, one, or three hours. ANF[1-11] weakly inhibited ACTH secretion at concentrations of 100 pM and 1000 pM. Again, three hours of incubation was required to manifest these effects.
    Type: Grant
    Filed: July 11, 1988
    Date of Patent: August 27, 1991
    Assignees: Center for Innovative Technology, University of Virginia
    Inventor: Alex J. Baertschi
  • Patent number: 4918055
    Abstract: A method for stimulating integumental melanocytes by the topical application of alpha-MSH analogs, and compositions comprising said analogs for use in the method are described.
    Type: Grant
    Filed: February 11, 1988
    Date of Patent: April 17, 1990
    Inventors: Victor J. Hruby, Mac E. Hadley, Robert Dorr, Norman Levine
  • Patent number: 4866038
    Abstract: A method for stimulating integumental melanocytes by the topical application of alpha-MSH analogs, and compositions comprising said analogs for use in the method are described.
    Type: Grant
    Filed: July 22, 1988
    Date of Patent: September 12, 1989
    Assignee: University Patents, Inc.
    Inventors: Victor J. Hruby, Mac E. Hadley, Robert Dorr, Norman Levine, Elizabeth Sugg, Wayne L. Cody
  • Patent number: 4762820
    Abstract: A novel therapeutic method for treating human and animal subjects afflicted with congestive heart failure is provided by administering effective dosages of a selective antagonist for arginine vasopressin to the subject. The antagonist is an effective and potent inhibitor for vasopressin and is a therapeutic agent selected from the class consisting of analogues of previously prepared compositions synthesized in a conventionally known manner. The administration of such selective antagonist as a therapeutic agent results in a demonstrated beneficial change in approximately thirty percent of tested individuals.
    Type: Grant
    Filed: March 3, 1986
    Date of Patent: August 9, 1988
    Assignee: Trustees of Boston University
    Inventor: Haralambos Gavras
  • Patent number: 4594239
    Abstract: A technique is described for neutralizing unishiol. The technique involves contacting urushiol with a chlorine-containing compound in a liquid medium. In one embodiment the chlorine-containing compound is sodium or calcium hypochlorite in an aqueous solution. In another embodiment the chlorine-containing compound is a chloramine in a liquid organic medium.
    Type: Grant
    Filed: March 14, 1984
    Date of Patent: June 10, 1986
    Inventor: Arthur W. Pluim, Jr.