Patents Assigned to Magainin Pharmaceuticals Inc.
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Publication number: 20040204578Abstract: A new gene in the calcium-activated chloride channel family has been discovered that is induced by IL-9, thereby providing a therapeutic target in IL-9 mediated development of atopic allergy, asthma-related disorders and cystic fibrosis. A method for the identification and use of small molecule inhibitors of this gene and its products to treat these disorders has also been discovered. The invention also includes a method for diagnosing susceptibility to, and assessing treatment of atopic allergy, asthma-related disorders by measuring the level of gene expression in biologic samples using antibody specific for this protein.Type: ApplicationFiled: February 6, 2004Publication date: October 14, 2004Applicant: Magainin Pharmaceuticals Inc.Inventors: Kenneth J. Holroyd, Roy C. Levitt, W. Lee Maloy, Jamila Louahed, Mike McLane, Nicholas C. Nicolaides, Yuhong Zhou, Qu Dong
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Publication number: 20040076607Abstract: A C to T DNA variation at position 3365 in exon 5 of the human Asthma Associated Factor 1 (AAF1) produces the predicted amino acid substitution of a methionine for a threonine at codon 117 of AAF1. When this substitution occurs in both alleles in one individual, it is associated with less evidence of atopic allergy including asthma, fewer abnormal skin test responses, and a lower serum total IgE. Thus, applicant has identified the existence of a non-asthmatic, non-atopic phenotype characterized by methionine at codon 117 when it occurs in both AAF1 gene products in one individual.Type: ApplicationFiled: August 18, 2003Publication date: April 22, 2004Applicant: Magainin Pharmaceuticals Inc.Inventors: Roy Clifford Levitt, W. Lee Maloy, U. Prasad Kari, Nicholas C. Nicolaides
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Patent number: 6610866Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.Type: GrantFiled: April 12, 2001Date of Patent: August 26, 2003Assignee: Magainin Pharmaceuticals, Inc.Inventors: William A. Kinney, Steven Jones, Xuehai Zhang, Meena N. Rao, Michel Bulliard, Harold Meckler, Nancy Lee
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Publication number: 20030143687Abstract: This invention relates to the diagnosis, treatment and methods for discovery of new therapeutics for atopic asthma and related disorders based on variants of Asthma Associated Factor 2. One embodiment of the invention is a variant of AAF2 wherein codon 173 is deleted resulting in the loss of glutamine 173 from the mature protein precursor. This single amino acid deletion results in a non-functional AAF2 protein and therefore the presence of this phenotype should be associated with less evidence of atopic asthma. Correspondingly, the lack of susceptibility to an asthmatic, atopic phenotype is characterized by the loss of glutamine at codon 173. The invention includes isolated DNA molecules which are variants of the wild type sequence as well as the proteins encoded by such DNA and the use of such DNA molecules and expressed protein in the diagnosis and treatment of atopic asthma.Type: ApplicationFiled: December 17, 2002Publication date: July 31, 2003Applicant: Magainin Pharmaceuticals Inc.Inventors: Roy Clifford Levitt, Luigi Grasso, Nicholas C. Nicolaides, Kenneth J. Holroyd
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Publication number: 20030078409Abstract: A new gene in the calcium-activated chloride channel family has been discovered that is induced by IL-9, thereby providing a therapeutic target in IL-9 mediated development of atopic allergy, asthma-related disorders and cystic fibrosis. A method for the identification and use of small molecule inhibitors of this gene and its products to treat these disorders has also been discovered. The invention also includes a method for diagnosing susceptibility to, and assessing treatment of atopic allergy, asthma-related disorders by measuring the level of gene expression in biologic samples using antibody specific for this protein.Type: ApplicationFiled: October 16, 2002Publication date: April 24, 2003Applicant: Magainin Pharmaceuticals Inc.Inventors: Kenneth J. Holroyd, Roy C. Levitt, W. Lee Maloy, Jamila Louahed, Mike McLane, Nicholas C. Nicolaides, Yuhong Zhou, Qu Dong
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Publication number: 20020076393Abstract: The subject invention relates to a method for the stimulation of defensin production in eukaryotic cells such as, for example, mammalian cells. Furthermore, the invention includes said method for the prevention and treatment of infections and other various disease states and in the stimulation of the immune system.Type: ApplicationFiled: August 24, 2001Publication date: June 20, 2002Applicant: MAGAININ PHARMACEUTICALS, INC.Inventors: Pascale Fehlbaum, Mark Anderson, Meena Rao, Michael Zasloff
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Publication number: 20020068834Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.Type: ApplicationFiled: April 12, 2001Publication date: June 6, 2002Applicant: Magainin Pharmaceuticals, Inc.Inventors: William A. Kinney, Steven Jones, Xuehai Zhang, Meena N. Rao, Michel Bulliard, Harold Meckler, Nancy Lee
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Patent number: 6399370Abstract: The invention relates to mammalian beta defensin and methods of use thereof for treatment of microbial infection.Type: GrantFiled: January 12, 1999Date of Patent: June 4, 2002Assignees: The Trustees of the University of Pennsylvania, Magainin Pharmaceuticals, Inc.Inventors: James M. Wilson, Mitchell Goldman, Robert Bals, Ethan D. Stolzenberg, Mark Anderson, Michael Zasloff, Prasad Kari
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Patent number: 6348445Abstract: The present invention relates to biologically active peptides with reduced toxicity and methods of preparing them. The peptides of the invention, which can be unsubstituted or N-terminal substituted have the formula: wherein X is a biologically active amphiphilic ion channel-forming peptide or protein, T is a lipophilic moiety or hydrogen, and W is T or hydrogen. Preferably T is: wherein R is a hydrocarbon (alkyl or aromatic or alkylaromatic) having at least 2 and no more than 10 carbon atoms. T is preferably an octanoyl group. The peptides and proteins of the invention have improved antimicrobial and anti-tumor biological activity while exhibiting reduced toxicity. A preferred method of reducing toxicity involves the formation of related methane sulfonate derivatives or analogues. Additionally, the compounds of the invention may be used to treat sepsis, septic shock, and lung infections, such as those occurring in cystic fibrosis.Type: GrantFiled: July 15, 1998Date of Patent: February 19, 2002Assignee: Magainin Pharmaceuticals, Inc.Inventors: U. Prasad Kari, Taffy J. Williams, Michael McLane
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Patent number: 6262283Abstract: A method is described for stereoselectively reducing an unsaturated alkyl ketone substituent attached to a fused ring base. In this method, the unsaturated alkyl ketone reacts with a chiral oxazaborolidine reagent. This reaction stereoselectively reduces the unsaturated alkyl ketone to an unsaturated alkyl alcohol. The unsaturated alkyl alcohol can be further reduced, if desired, to produce a saturated alkyl alcohol. The fused ring base can be, for example, a steroid ring base or a base of a vitamin D analog. The process in accordance with the invention can be used with an alkeneone substituent (e.g., a 22-ene-24-one substituent) or an alkyneone substituent (e.g., a 22-yne-24-one substituent) on a steroid ring base to make squalamine or other useful aminosterol compounds and intermediates for making aminosterol compounds.Type: GrantFiled: December 5, 1997Date of Patent: July 17, 2001Assignee: Magainin Pharmaceuticals Inc.Inventors: William A. Kinney, Steven Jones, Xuehai Zhang, Meena N. Rao, Michel Bulliard, Harold Meckler, Nancy Lee
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Patent number: 6143738Abstract: A pharmaceutical composition includes, as an active ingredient, a compound according to formula 1436 as shown in FIG. 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Various pharmaceutical products may be produced including this pharmaceutical composition. Such pharmaceutical products may be used for the treatment of cancers, such as leukemia; inflammation; arthritis; and viruses, such as HSV. Methods for using the pharmaceutical compositions also are described. In these methods, various diseases are treated or other body functions are activated or inhibited by administering an effective amount of the pharmaceutical composition. For example, inflammation, arthritis, herpes simplex virus, melanoma, and leukemia may be treated by administering an effective amount of the pharmaceutical compositions. Viral replication, weight gain, and growth factor production can be inhibited by administering an effective amount of these pharmaceutical compositions.Type: GrantFiled: May 16, 1997Date of Patent: November 7, 2000Assignee: Magainin Pharmaceuticals, Inc.Inventor: Michael Zasloff
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Patent number: 6037149Abstract: A C to T DNA variation at position 3365 in exon 5 of the human Asthma Associated Factor 1 (AAF1) produces the predicted amino acid substitution of a methionine for a threonine at codon 117 of AAF1. When this substitution occurs in both alleles in one individual, it is associated with less evidence of atopic allergy including asthma, fewer abnormal skin test responses, and a lower serum total IgE. Thus, applicant has identified the existence of a non-asthmatic, non-atopic phenotype characterized by methionine at codon 117 when it occurs in both AAF1 gene products in one individual.Type: GrantFiled: August 23, 1996Date of Patent: March 14, 2000Assignee: Magainin Pharmaceuticals Inc.Inventors: Roy Clifford Levitt, Nicholas C. Nicolaides
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Patent number: 5994336Abstract: A method of inhibiting the proliferation of a wide variety of cells is described. This method includes administering an effective amount of a compound having the following structure: ##STR1## or a pharmaceutically acceptable salt thereof. The proliferation of the following types of cells can be inhibited by this method: lymphocytes, fibroblasts, epithelial cells, smooth muscle cells, and human ovarian cancer cells.Type: GrantFiled: June 7, 1995Date of Patent: November 30, 1999Assignee: Magainin Pharmaceuticals Inc.Inventors: Michael Zasloff, Ann Shinnar, William Kinney, Meena Rao
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Patent number: 5908839Abstract: A C to T DNA variation at position 3365 in exon 5 of the human Asthma Associated Factor 1 (AAF1) produces the predicted amino acid substitution of a methionine for a threonine at codon 117 of AAF1. When this substitution occurs in both alleles in one individual, it is associated with less evidence of atopic allergy including asthma, fewer abnormal skin test responses, and a lower serum total IgE. Thus, applicant has identified the existence of a non-asthmatic, non-atopic phenotype characterized by methionine at codon 117 when it occurs in both AAF1 gene products in one individual.Type: GrantFiled: August 23, 1996Date of Patent: June 1, 1999Assignee: Magainin Pharmaceuticals, Inc.Inventors: Roy Clifford Levitt, Nicholas C. Nicolaides
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Patent number: 5874597Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.Type: GrantFiled: June 7, 1995Date of Patent: February 23, 1999Assignee: Magainin Pharmaceuticals, Inc.Inventor: Steven Jones
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Patent number: 5856535Abstract: An aminosterol compound according to the following formula: ##STR1## wherein: R.sub.1 is a member selected from the group of: ##STR2## R.sub.2 is H or OH; R.sub.3 is H or OH;R.sub.4 is H or OH; andR.sub.5 is a C.sub.1 to C.sub.12 alkyl group.Preferably, R.sub.5 is a C.sub.1 to C.sub.6 alkyl group, and a methyl group is particularly preferred.Type: GrantFiled: December 18, 1996Date of Patent: January 5, 1999Assignee: Magainin Pharmaceuticals, Inc.Inventors: Michael Zasloff, William Kinney, Steven Jones
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Patent number: 5849490Abstract: The present invention relates to an inducible antimicrobial peptide designated lingual antimicrobial peptide (LAP) which has antibacterial and antifungal activity and which can be obtained from mammalian epithelium. The prepro- and the pro- precursors of LAP are also provided. The present invention also relates to cDNA encoding LAP, the prepro- precursor or the pro-lingual precursor. In addition, methods of treating microbial infection of the epithelia are provided. Such infections can be treated by contacting the epithelia with an antimicrobially effective amount of a purified mammalian epithelial LAP or by administering a component which cause endogenous production or up-regulation of LAP.Type: GrantFiled: September 13, 1996Date of Patent: December 15, 1998Assignee: Magainin Pharmaceuticals, Inc.Inventors: Barry S. Schonwetter, Michael A. Zasloff
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Patent number: 5847172Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.Type: GrantFiled: June 7, 1995Date of Patent: December 8, 1998Assignee: Magainin Pharmaceuticals Inc.Inventors: Michael Zasloff, Ann Shinnar, William Kinney, Steven Jones
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Patent number: 5840936Abstract: Aminosterol compounds are described that are useful as inhibitors of the sodium/proton exchanger (NHE). Methods of using such aminosterols compounds are also enclosed, including those employing compounds that are inhibitors of a spectrum of NHEs as well as those using compounds that are inhibitors of only one specific NHE. Advantageous screening techniques and assays for evaluating a compound's therapeutic activity are also disclosed.Type: GrantFiled: June 7, 1995Date of Patent: November 24, 1998Assignee: Magainin Pharmaceuticals Inc.Inventors: Michael Zasloff, Ann Shinnar, Meena Rao, William Kinney
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Patent number: 5840740Abstract: Disclosed are aminosterol compounds 1360 and 1361: ##STR1## which can be obtained in isolated or purified form from the liver of the dogfish shark.Type: GrantFiled: June 7, 1995Date of Patent: November 24, 1998Assignee: Magainin Pharmaceuticals Inc.Inventors: Michael Zasloff, Ann Shinnar, William Kinney, Meena Rao