Patents Represented by Attorney Elizabeth M. Barnhard
  • Patent number: 6017694
    Abstract: Methods of screening for modulators of respiratory syncytial virus matrix protein interaction are described. A host cell carrying a nucleic acid sequence encoding RSV matrix protein or fragments of RSV matrix protein which can bind to RSV matrix protein is cultured and the RSV matrix protein or RSV fragments are expressed. The interaction of the expressed RSV matrix protein or fragments is measured. A test sample is then added to the expressed RSV matrix protein or fragments and the effect of the test sample on RSV matrix protein interaction is measured.
    Type: Grant
    Filed: December 19, 1997
    Date of Patent: January 25, 2000
    Assignee: American Cyanamid Company
    Inventors: Paul Wai Mak, Bryan Mark O'Hara
  • Patent number: 5908780
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down-regulation of cell surface expression of MHC class I. A recombinant mutant HCMV which fails to down-regulate class I heavy chain expression is described. A method of controlling down-regulation of MHC class I expression in a cytomegalovirus infected cell, a pharmaceutical composition, a vaccine composition,a method of preventing or reducing susceptibility to acute cytomegalovirus in an individual, and a virus based gene therapy vector are also described.
    Type: Grant
    Filed: March 16, 1998
    Date of Patent: June 1, 1999
    Assignee: American Cyanamid Company
    Inventor: Thomas R. Jones
  • Patent number: 5906935
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which failed to down regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down regulation. In subregion B, the US11 gene product is involved. It encodes a endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.
    Type: Grant
    Filed: October 7, 1997
    Date of Patent: May 25, 1999
    Assignees: American Cyanamid Company, Eastern Virginia Medical School of the Medical College of Hampton Roads
    Inventors: Thomas R. Jones, Ann E. Campbell
  • Patent number: 5877296
    Abstract: This invention describes carrier-drug conjugates prepared from disulfide analogs of the calicheamicin family of potent antitumor antibiotics and their derivatives, as well as similar analogs from related antitumor antibiotics such as the esperamicins. The carrier can be an antibody, growth factor, or steroid which targets an undesired population of cells, such as those of a tumor. Whole protein carriers as well as their antigen-recognizing fragments and their chemically or genetically manipulated counterparts are useful for the targeting portion of the conjugates. This invention includes compounds required for the synthesis of these conjugates, appropriate pharmaceutical compositions of the carrier-drug conjugates, and their method of use.
    Type: Grant
    Filed: May 26, 1995
    Date of Patent: March 2, 1999
    Assignee: American Cyanamid Company
    Inventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
  • Patent number: 5877004
    Abstract: This invention relates to a method for identifying non-essential genes of the human cytomegalovirus (HCMV) genome through the insertion of a .beta.-glucuronidase marker gene into a specified HCMV gene, such that, if the product of the HCMV gene is not expressed, the gene is identified as non-essential for replication of HCMV. This invention also relates to a method of screening for compounds which inhibit HCMV by the insertion of the .beta.-glucuronidase marker gene into a HCMV gene, such that the enzyme marker is expressed and cleaves a conjugate chemical substrate in an assay system to yield a detectable fluorescing product or to result in a color change. This invention further provides the gene responsible in HCMV early cytopathic effect.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: March 2, 1999
    Assignee: American Cyanamid Compound
    Inventors: Thomas R. Jones, Viera P. Muzithras, Yakov Gluzman
  • Patent number: 5874264
    Abstract: The present invention relates to novel purified gibbon ape leukemia receptor proteins and purified DNA sequences encoding these receptor proteins.
    Type: Grant
    Filed: May 8, 1995
    Date of Patent: February 23, 1999
    Assignee: American Cyanamid Company
    Inventor: Bryan Mark O'Hara
  • Patent number: 5861301
    Abstract: A DNA sequence encoding a novel human growth factor receptor referred to as a type III receptor tyrosine kinase is described. The amino acid sequence of the receptor is also described. The receptor has a sequence which is similar to that of the kinase domains of known type III receptor tyrosine kinases, but which is unique in its kinase insert domain sequence. The receptor binds specifically to the vascular endothelial cell growth factor.
    Type: Grant
    Filed: November 23, 1992
    Date of Patent: January 19, 1999
    Assignee: American Cayanamid Company
    Inventors: Bruce Israel Terman, Miguel Eduardo Carrion
  • Patent number: 5846806
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which failed to down regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down regulation. In subregion B, the US11 gene product is involved. It encodes a endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.
    Type: Grant
    Filed: July 29, 1994
    Date of Patent: December 8, 1998
    Assignees: American Cyanamid Company, Eastern Virginia Medical School
    Inventors: Thomas R. Jones, Ann E. Campbell
  • Patent number: 5843637
    Abstract: This invention relates to a method for identifying non-essential genes of the human cytomegalovirus (HCMV) genome through the insertion of a .beta.-glucuronidase marker gene into a specified HCMV gene, such that, if the product of the HCMV gene is not expressed, the gene is identified as non-essential for replication of HCMV. This invention also relates to a method of screening for compounds which inhibit HCMV by the insertion of the .beta.-glucuronidase marker gene into a HCMV gene, such that the enzyme marker is expressed and cleaves a conjugate chemical substrate in an assay system to yield a detectable fluorescing product or to result in a color change. This invention further provides the gene responsible in HCMV early cytopathic effect.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: December 1, 1998
    Assignee: American Cyanamid Company
    Inventors: Thomas R. Jones, Viera P. Muzithras, Yakov Gluzman
  • Patent number: 5843458
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down-regulation of cell surface expression of MHC class I. A recombinant mutant HCMV which fails to down-regulate class I heavy chain expression is described. A method of controlling down-regulation of MHC class I expression in a cytomegalovirus infected cell, a pharmaceutical composition, a vaccine composition, a method of preventing or reducing susceptibility to acute cytomegalovirus in an individual, and a virus based gene therapy vector are also described.
    Type: Grant
    Filed: July 31, 1995
    Date of Patent: December 1, 1998
    Assignee: American Cyanamid Company
    Inventor: Thomas R. Jones
  • Patent number: 5824318
    Abstract: Isolated tumoricidal herpetic viruses, in particular neurotrophic herpes viruses, T-lymphotrophic viruses, and B-lymphotrophic viruses, which are avirulent and capable of selectively replicating in and destroying neoplastic cells, and pharmaceutical compositions, vaccines, and methods of destroying neoplastic cells employing the isolated tumoricidal herpetic viruses are described. A method of isolating tumoricidal herpetic viruses by sequentially passaging attenuated, avirulent herpetic viruses on neoplastic cells which fail to support replication of the herpetic viruses and isolating the viruses which grow on the neoplastic cells is also described. Herpes simplex virus mutants having a genome from which the .gamma.34.5 genes have been deleted and which require at least one additional mutation to produce a non-neurovirulent herpes simplex virus which selectively replicates in and destroys neoplastic cells are also described.
    Type: Grant
    Filed: July 24, 1996
    Date of Patent: October 20, 1998
    Assignee: American Cyanamid Company
    Inventors: Ian J. Mohr, Yakov Gluzman, deceased
  • Patent number: 5789188
    Abstract: A method for detecting a tetracycline efflux pump inhibitor in the presence of tetracycline using a reporter gene system where the tetA promoter directs transcription of a reporter gene (lacZ) while the tetA is under the control of the tet repressor encoded by the tetR gene is described. The method uses a cell having a reporter gene system where the tetA promoter directs transcription of a reporter gene (lacZ) and an active efflux system in which relatively modest levels of the efflux protein encoded by the tetA gene are produced in a constitutive manner, i.e., not under the control of the tet repressor encoded by the tetR gene. Test samples which are inhibitors of the TetA efflux protein will allow accumulation of tetracycline inside the cells at levels which will induce expression of the tetA-lacZ transcriptional fusion to give a positive signal.
    Type: Grant
    Filed: May 13, 1996
    Date of Patent: August 4, 1998
    Assignee: American Cyanamid Company
    Inventors: David Michael Rothstein, Gordon Gerald Guay
  • Patent number: 5773001
    Abstract: This invention describes carrier-drug conjugates prepared from disulfide analogs of the calicheamicin family of potent antitumor antibiotics and their derivatives, as well as similar analogs from related antitumor antibiotics such as the esperamicins. The carrier can be an antibody, growth factor, or steroid which targets an undesired population of cells, such as those of a tumor. Whole protein carriers as well as their antigen-recognizing fragments and their chemically or genetically manipulated counterparts are useful for the targeting portion of the conjugates. This invention includes compounds required for the synthesis of these conjugates, appropriate pharmaceutical compositions of the carrier-drug conjugates, and their method of use.
    Type: Grant
    Filed: June 3, 1994
    Date of Patent: June 30, 1998
    Assignee: American Cyanamid Company
    Inventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
  • Patent number: 5770710
    Abstract: A process is described for producing substituted disulfide analogs of the family of antibacterial and antitumor agents known collectively as the LL-E33288 complex.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: June 23, 1998
    Assignee: American Cyanamid Company
    Inventors: William James McGahren, Martin Leon Sassiver, George A. Ellestad
  • Patent number: 5766860
    Abstract: A DNA sequence encoding a novel human growth factor receptor referred to as a type III receptor tyrosine kinase is described. The amino acid sequence of the receptor is also described. The receptor has a sequence which is similar to that of the kinase domains of known type III receptor tyrosine kinases, but which is unique in its kinase insert domain sequence. The receptor binds specifically to the vascular endothelial cell growth factor.
    Type: Grant
    Filed: February 25, 1997
    Date of Patent: June 16, 1998
    Assignee: American Cyanamid Company
    Inventors: Bruce Israel Terman, Miguel Eduardo Carrion
  • Patent number: 5767285
    Abstract: This invention describes carrier-drug conjugates prepared from disulfide analogs of the calicheamicin family of potent antitumor antibiotics and their derivatives, as well as similar analogs from related antitumor antibiotics such as the esperamicins. The carrier can be an antibody, growth factor, or steroid which targets an undesired population of cells, such as those of a tumor. Whole protein carriers as well as their antigen-recognizing fragments and their chemically or genetically manipulated counterparts are useful for the targeting portion of the conjugates. This invention includes compounds required for the synthesis of these conjugates, appropriate pharmaceutical compositions of the carrier-drug conjugates, and their method of use.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: June 16, 1998
    Assignee: American Cyanamid Company
    Inventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
  • Patent number: 5753476
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which failed to down regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down regulation. In subregion B, the US11 gene product is involved. It encodes a endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: May 19, 1998
    Assignee: American Cyanamid Company
    Inventors: Thomas R. Jones, Ann E. Campbell
  • Patent number: 5739116
    Abstract: This invention describes carrier-drug conjugates prepared from disulfide analogs of the calicheamicin family of potent antitumor antibiotics and their derivatives, as well as similar analogs from related antitumor antibiotics such as the esperamicins. The carrier can be an antibody, growth factor, or steroid which targets an undesired population of cells, such as those of a tumor. Whole protein carriers as well as their antigen-recognizing fragments and their chemically or genetically manipulated counterparts are useful for the targeting portion of the conjugates. This invention includes compounds required for the synthesis of these conjugates, appropriate pharmaceutical compositions of the carrier-drug conjugates, and their method of use.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: April 14, 1998
    Assignee: American Cyanamid Company
    Inventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
  • Patent number: 5720957
    Abstract: Infection of human fibroblast cells with human cytomegalovirus (HCMV) causes down regulation of cell surface expression of MHC class I. The present invention is directed to a mutant with a 9-kb deletion in the S component of the HCMV genome (including open reading frames IRS1-US9 and US11) which failed to down regulate class I heavy chains. By examining the phenotypes of mutants with smaller deletions with this portion of the HCMV genome, a 7-kb region containing at least 9 open reading frames was shown to contain the genes required for reduction in heavy chain expression. Furthermore, it was determined that two subregions (A and B) of the 7-kb region each contained genes which were sufficient to cause heavy chain down regulation. In subregion B, the US11 gene product is involved. It encodes a endoglycosidase H-sensitive glycoprotein which is intracytoplasmic, similar to the adenovirus type 2 E3-19K glycoprotein which inhibits surface expression of class I heavy chains.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: February 24, 1998
    Assignee: American Cyanamid Company
    Inventors: Thomas R. Jones, Ann E. Campbell
  • Patent number: 5714586
    Abstract: A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution, a cosolvent selected from the group consisting of propylene glycol, ethanol, DMSO, and combinations thereof, and an additive comprising at least one C.sub.6 -C.sub.18 carboxylic acid having a pH in the range from about 4.0 to 8.5 and at a temperature ranging from about 25.degree. C. to about 37.degree. C. for a period of time ranging from about 15 minutes to about 24 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution and a cosolvent comprising t-butanol.
    Type: Grant
    Filed: May 28, 1996
    Date of Patent: February 3, 1998
    Assignee: American Cyanamid Company
    Inventors: Martin P. Kunstmann, Irwin J. Hollander, Philip Hamann, Arthur Kunz