Patents Represented by Attorney Elizabeth M. Barnhard
-
Patent number: 6017694Abstract: 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: GrantFiled: December 19, 1997Date of Patent: January 25, 2000Assignee: American Cyanamid CompanyInventors: Paul Wai Mak, Bryan Mark O'Hara
-
Patent number: 5908780Abstract: 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: GrantFiled: March 16, 1998Date of Patent: June 1, 1999Assignee: American Cyanamid CompanyInventor: Thomas R. Jones
-
Patent number: 5906935Abstract: 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: GrantFiled: October 7, 1997Date of Patent: May 25, 1999Assignees: American Cyanamid Company, Eastern Virginia Medical School of the Medical College of Hampton RoadsInventors: Thomas R. Jones, Ann E. Campbell
-
Patent number: 5877296Abstract: 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: GrantFiled: May 26, 1995Date of Patent: March 2, 1999Assignee: American Cyanamid CompanyInventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
-
Patent number: 5877004Abstract: 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: GrantFiled: June 5, 1995Date of Patent: March 2, 1999Assignee: American Cyanamid CompoundInventors: Thomas R. Jones, Viera P. Muzithras, Yakov Gluzman
-
Patent number: 5874264Abstract: The present invention relates to novel purified gibbon ape leukemia receptor proteins and purified DNA sequences encoding these receptor proteins.Type: GrantFiled: May 8, 1995Date of Patent: February 23, 1999Assignee: American Cyanamid CompanyInventor: Bryan Mark O'Hara
-
Patent number: 5861301Abstract: 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: GrantFiled: November 23, 1992Date of Patent: January 19, 1999Assignee: American Cayanamid CompanyInventors: Bruce Israel Terman, Miguel Eduardo Carrion
-
Patent number: 5846806Abstract: 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: GrantFiled: July 29, 1994Date of Patent: December 8, 1998Assignees: American Cyanamid Company, Eastern Virginia Medical SchoolInventors: Thomas R. Jones, Ann E. Campbell
-
Patent number: 5843458Abstract: 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: GrantFiled: July 31, 1995Date of Patent: December 1, 1998Assignee: American Cyanamid CompanyInventor: Thomas R. Jones
-
Patent number: 5843637Abstract: 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: GrantFiled: June 5, 1995Date of Patent: December 1, 1998Assignee: American Cyanamid CompanyInventors: Thomas R. Jones, Viera P. Muzithras, Yakov Gluzman
-
Patent number: 5824318Abstract: 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: GrantFiled: July 24, 1996Date of Patent: October 20, 1998Assignee: American Cyanamid CompanyInventors: Ian J. Mohr, Yakov Gluzman, deceased
-
Patent number: 5789188Abstract: 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: GrantFiled: May 13, 1996Date of Patent: August 4, 1998Assignee: American Cyanamid CompanyInventors: David Michael Rothstein, Gordon Gerald Guay
-
Patent number: 5773001Abstract: 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: GrantFiled: June 3, 1994Date of Patent: June 30, 1998Assignee: American Cyanamid CompanyInventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
-
Patent number: 5770710Abstract: 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: GrantFiled: June 5, 1995Date of Patent: June 23, 1998Assignee: American Cyanamid CompanyInventors: William James McGahren, Martin Leon Sassiver, George A. Ellestad
-
Screening method using a recombinant kinase insert domain containing receptor and gene encoding same
Patent number: 5766860Abstract: 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: GrantFiled: February 25, 1997Date of Patent: June 16, 1998Assignee: American Cyanamid CompanyInventors: Bruce Israel Terman, Miguel Eduardo Carrion -
Patent number: 5767285Abstract: 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: GrantFiled: June 5, 1995Date of Patent: June 16, 1998Assignee: American Cyanamid CompanyInventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
-
Patent number: 5753476Abstract: 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: GrantFiled: June 2, 1995Date of Patent: May 19, 1998Assignee: American Cyanamid CompanyInventors: Thomas R. Jones, Ann E. Campbell
-
Patent number: 5739116Abstract: 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: GrantFiled: June 5, 1995Date of Patent: April 14, 1998Assignee: American Cyanamid CompanyInventors: Philip Ross Hamann, Lois Hinman, Irwin Hollander, Ryan Holcomb, William Hallett, Hwei-Ru Tsou, Martin J. Weiss
-
Patent number: 5720957Abstract: 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: GrantFiled: June 2, 1995Date of Patent: February 24, 1998Assignee: American Cyanamid CompanyInventors: Thomas R. Jones, Ann E. Campbell
-
Patent number: 5714586Abstract: 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: GrantFiled: May 28, 1996Date of Patent: February 3, 1998Assignee: American Cyanamid CompanyInventors: Martin P. Kunstmann, Irwin J. Hollander, Philip Hamann, Arthur Kunz