Abstract: Hydroxamic acids having the formula are useful in treating disease conditions mediated by TNF-?, such as rheumatoid arthritis, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease or HIV infection.
Abstract: Mutant cholera holotoxins having single or double amino acid substitutions or insertions have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in antigenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.
Type:
Application
Filed:
December 19, 2007
Publication date:
December 18, 2008
Applicants:
Wyeth Holdings Corporation, The Gov. of the USA, as represented by the Uniformed Services University of Health Sciences
Inventors:
Bruce A. Green, Randall K. Holmes, Michael G. Jobling, Duzhang Zhu
Abstract: The expression of the lipidated form of the peptidoglycan-associated protein (PAL) of gram-negative bacteria is achieved through the use of a plasmid containing a tightly regulated promoter. A bacterial host cell is transformed, transduced or transfected with such a plasmid. The host cell is then cultured under conditions such that the lipidated recombinant PAL is expressed. The lipidated recombinant PAL is included in an antigenic composition administered to a mammalian host to immunize against a gram-negative bacterium.
Abstract: This invention relates to certain 6-aryl-7-halo-imidazo[1,2-a]pyrimidines or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts thereof, wherein said compounds are anti-cancer agents useful for the treatment of cancer in mammals by promotion of microtubule polymerization. This invention further relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal and further provides a method for the treatment or prevention of cancerous tumors that express multiple drug resistance (MDR) or are resistant because of MDR, in a mammal in need thereof which method comprises administering to said mammal an effective amount of said compounds or pharmaceutically acceptable salts thereof.
Abstract: The invention provides compounds of formula (I): wherein E, A, B?, R6, R7, R8, and R9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.
Type:
Application
Filed:
April 17, 2008
Publication date:
September 11, 2008
Applicant:
Wyeth Holdings Corporation
Inventors:
Arie Zask, Joshua Kaplan, Ayako Yamashita, Chuan S. Niu, Gary Harold Birnberg, Emily Norton, Kinwang Cheung, Ronald Suayan, Vincent Sandanayaka, Philip Ross Hamann, Semiramis Ayral-Kaloustian
Abstract: Mutant cholera holotoxins comprising a cholera toxin subunit A having single amino acid substitutions in the amino acid positions 16 or 72 or a double amino acid substitution in the amino acid positions 16 and 68 or 68 and 72 have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in immunogenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.
Type:
Application
Filed:
October 22, 2007
Publication date:
September 4, 2008
Applicants:
Wyeth Holdings Corporation, The Regents of the University of Colorado, A Body Corporate Health Science Center
Inventors:
Bruce A. Green, Randall K. Holmes, Michael G. Jobling, Duzhang Zhu
Abstract: The present invention relates to crystalline forms of 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine salts; processes for the production thereof; pharmaceutical compositions thereof; and methods for inhibiting tumor growth therewith.
Type:
Grant
Filed:
May 19, 2006
Date of Patent:
September 2, 2008
Assignee:
Wyeth Holdings Corporation
Inventors:
Fang Fang Qi, Mannching Sherry Ku, Yanzhong Wu, David M. Blum
Abstract: A mutant cholera holotoxin featuring a point mutation at amino acid 29 of the A subunit, wherein the glutamic acid residue is replaced by an amino acid other than aspartic acid, is useful as an adjuvant in an antigenic composition to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus or parasite. In a particular embodiment, the amino acid 29 is histidine. The mutant cholera holotoxin may contain at least one additional mutation in the A subunit at a position other than amino acid 29. The antigenic composition may include a second adjuvant in addition to the mutant cholera holotoxin.
Type:
Grant
Filed:
September 30, 1999
Date of Patent:
June 10, 2008
Assignees:
Wyeth Holdings Corporation, The United States of America as represented by the Uniformed Services University of the Health Sciences
Inventors:
Randall K. Holmes, Michael G. Jobling, John H. Eldridge, Bruce A. Green, Gerald E. Hancock, Joel A. Peek
Abstract: Adjuvant compositions comprising an effective amount IL-12 and QS-21 are disclosed. Immunogenic, vaccine and pharmaceutical compositions comprising a mixture of antigen and an adjuvant composition comprising an effective amount of IL-12 and QS-21 are also disclosed. These compositions elicit functional cell-mediated and humoral immune responses against at least one antigen. Methods of using the disclosed compositions are also disclosed.
Abstract: Mutant cholera holotoxins comprising a cholera toxin subunit A having single amino acid substitutions in the amino acid positions 16 or 72 or a double amino acid substitution in the amino acid positions 16 and 68 or 68 and 72 have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in immunogenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.
Type:
Grant
Filed:
December 15, 2006
Date of Patent:
April 22, 2008
Assignees:
Wyeth Holdings Corporation, The Regents of the University of Colorado, A Body Corporate
Inventors:
Bruce A. Green, Randall K. Holmes, Michael G. Jobling, Duzhang Zhu
Abstract: The present invention discloses the existence of two novel proteins UspA1 and UspA2, and their respective genes uspA1 and uspA2. Each protein encompasses a region that is conserved between the two proteins and comprises an epitope that is recognized by the MAb 17C7. One or more than one of these species may aggregate to form the very high molecular weight form (i.e. greater than 200 kDa) of the UspA antigen. Compositions and both diagnostic and therapeutic methods for the treatment and study of M. catarrhalis are disclosed.
Type:
Grant
Filed:
June 21, 2004
Date of Patent:
March 18, 2008
Assignees:
Board of Regents, The University of Texas System, Wyeth Holdings Corporation
Inventors:
Eric J. Hansen, Christoph Aebi, Leslie D. Cope, Isobel Maciver, Michael J. Fiske, Ross A. Fredenburg
Abstract: Mutant cholera holotoxins having single or double amino acid substitutions or insertions have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in antigenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.
Type:
Grant
Filed:
June 5, 2002
Date of Patent:
February 19, 2008
Assignees:
Wyeth Holdings Corporation, The United States of America as represented by the Uniformed Services University of Health Sciences
Inventors:
Bruce A. Green, Randall K. Holmes, Michael G. Jobling, Duzhang Zhu
Abstract: This invention discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile comprising combining an amine compound with a cyanoacetic acid and an acid catalyst to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline in an alcoholic solvent and a trialkylorthoformate to yield a 3-amino-2-cyanoacrylamide; combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 4-amino-3-quinolinecarbonitrile and also discloses a process for the preparation of a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile comprising combining a disubstituted 3-amino thiophene with a cyanoacetamide and trialkylorthoformate in an alcoholic solvent to obtain a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride and acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 7-amino-
Type:
Application
Filed:
October 5, 2007
Publication date:
February 7, 2008
Applicant:
Wyeth Holdings Corporation
Inventors:
Karen Sutherland, Gregg Feigelson, Diane Boschelli, David Blum, Henry Strong
Abstract: There is provided a process for the preparation of bicyclicheteroaryl carboxaldehydes having the structural Formula I where X and Y are defined in the specification The bicyclic heteroaryl carboxaldehydes are useful as intermediates in the preparation of ?-lactamase inhibitors.
Type:
Application
Filed:
June 18, 2007
Publication date:
January 10, 2008
Applicant:
Wyeth Holdings Corporation
Inventors:
Michael Winkley, Anita Chan, Ivo Jirkovsky, Kenneth Kremer, Joseph Zeldis, Antonia Nikitenko, Henry Strong, Tarek Mansour, Gulnaz Khafizova, Aranapakam Venkatesan
Abstract: The invention relates to an enzymatic process for the production of an intermediate, bicyclic-heteroaryl-2-carboxylic acid 7, of the formula wherein X and Y are defined in the specification and which are useful in the preparation of beta-lactamase inhibitors, by selective enzymatic hydrolysis of a mixture of positional hydrolyzable esters of the formulae where X, Y, and R1 are defined in the specification.
Type:
Grant
Filed:
May 12, 2004
Date of Patent:
January 8, 2008
Assignee:
Wyeth Holdings Corporation
Inventors:
Ramesh Venkat Matur, Mark Edward Ruppen
Abstract: The present invention provides immunogenic and pharmaceutical compositions for the treatment and prevention of human papillomavirus (HPV)-associated cancers and in particular, cervical cancer. In particular, this invention relates to fusion proteins, and the nucleic acids encoding these fusion proteins, used to generate immune responses against HPV. Specifically, this invention provides for fusions of HPV E6 and E7 in which the E6 and/or E7 contains one or more mutations. These mutations abrogate the transformation activity of these oncogenic proteins and, thus, confer safety to the E6/E7 fusions. In addition, these fusions maintain or increase the immunogenic efficacy of E6 and E7. Any gene or protein delivery method can be used to deliver or package the immunogenic compositions of the present invention.
Type:
Application
Filed:
January 26, 2007
Publication date:
November 29, 2007
Applicant:
Wyeth Holdings Corporation
Inventors:
Maria Cassetti, Larry Smith, Jeffrey Pullen, Susan McElhiney
Abstract: This invention discloses a process for the preparation of a 4-amino-3-quinolinecarbonitrile comprising combining an amine compound with a cyanoacetic acid and an acid catalyst to yield a cyanoacetamide; condensing the cyanoacetamide with an optionally up to tetra-substituted aniline in an alcoholic solvent and a trialkylorthoformate to yield a 3-amino-2-cyanoacrylamide; combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride in acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 4-amino-3-quinolinecarbonitrile and also discloses a process for the preparation of a 7-amino-thieno[3,2-b]pyridine-6-carbonitrile comprising combining a disubstituted 3-amino thiophene with a cyanoacetamide and trialkylorthoformate in an alcoholic solvent to obtain a 3-amino-2-cyanoacrylamide; and combining the 3-amino-2-cyanoacrylamide with phosphorus oxychloride and acetonitrile, butyronitrile, toluene or xylene, optionally in the presence of a catalyst to yield a 7-amino-
Type:
Grant
Filed:
August 16, 2004
Date of Patent:
November 20, 2007
Assignee:
Wyeth Holdings Corporation
Inventors:
Karen Wiggins Sutherland, Gregg Brian Feigelson, Diane Harris Boschelli, David Michael Blum, Henry Lee Strong
Abstract: The construction of recombinant respiratory syncytial virus (RSV) strains deleted of the region of G protein most likely to induce unwanted type 2 T cell responses in susceptible recipients is disclosed. Using reverse genetics, recombinant RSV strains were engineered with deletions of amino acids 151-221 and 178-219. Both RSV strains replicated in the respiratory tract of BALB/c mice and elicited serum neutralization and anti-F protein IgG titers that were equivalent to cp-RSV and contributed to a 3.9 log 10 reduction in RSV A2 four days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either recombinant RSV strain. These findings are important for the development of immunogenic compositions against RSV.
Abstract: The disclosure is drawn to a method of using novel 7-substituted-9-(substituted amino)-6-demethyl-6-deoxytetracycline compounds to treat infections caused by a wide spectrum of bacterial organisms, including those which are resistant to tetracycline.
Type:
Grant
Filed:
December 23, 2005
Date of Patent:
February 19, 2008
Assignee:
Wyeth Holdings Corporation
Inventors:
Joseph J. Hlavka, Phaik-Eng Sum, Yakov Gluzman, Ving J. Lee, Adma A. Ross
Abstract: The invention is drawn to 7-substituted-9-(substituted amino)-6-demethyl-6-deoxytetracycline compounds of the formula wherein R, X, R5 and R6 are defined in the specification. The compounds of the invention are useful as broad spectrum antibiotics.
Type:
Grant
Filed:
June 3, 2005
Date of Patent:
March 25, 2008
Assignee:
Wyeth Holdings Corporation
Inventors:
Joseph J. Hlavka, Phaik-Eng Sum, Yakov Gluzman, Ving J. Lee, Adma A. Ross