Patents Represented by Attorney Alysia A. Finnegan
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Patent number: 8216834Abstract: The present invention provides recombinant replication-defective adenoviral vectors derived from chimpanzee adenoviruses and methods for generating recombinant adenoviruses in human E1-expressing cell lines. The invention also provides compositions and methods suitable for use for the delivery and expression of transgenes encoding immunogens against which a boosted immune response is desired. The invention further provides methods of generating clinical grade vector stocks suitable for use in humans. In a particular embodiment the invention contemplates the use of vectors comprising transgenes which encode tumor associated antigens in vaccines and pharmaceutical compositions for the prevention and treatment of cancer.Type: GrantFiled: January 18, 2005Date of Patent: July 10, 2012Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti SPAInventors: Stefano Colloca, Alfredo Nicosia, Elisabetta Sporeno, Paolo Palazzolo, legal representative, Agostino Cirillo, Bruno Bruni Ercole, Annalisa Meola
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Patent number: 8198079Abstract: The present invention is directed at optimized expression vectors for the expression of native-like heterologous proteins in insect cells. Compositions of the invention are nucleotide sequences representing elements of an expression vector that when combined results in enhanced expression and secretion of heterologous proteins. The elements include sequences that define transcriptional activators, core promoters, secretion signals, and 3? untranslated regions that are functional in insect cells. The elements contained in the optimized vectors are all synthetically derived or are modified variants of naturally occurring insect sequences. The expression vectors are useful for the expression of native-like proteins when protein encoding nucleotide sequences are operatively linked to the vectors. These vectors can be used to transform insect cells, which can then be cultured to produce the desired protein product.Type: GrantFiled: April 28, 2008Date of Patent: June 12, 2012Assignee: Merck Sharp & Dohme Corp.Inventors: David Edward Clements, Gordon V. L. Wang, Carolyn Weeks-Levy
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Patent number: 8188244Abstract: Polynucleotides encoding carcinoembryonic antigen (CEA) fusion proteins are provided, the CEA fusion proteins comprising a CEA protein, or functional variant thereof, fused to a substantial portion of an immunoenhancing element. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type CEA. The gene encoding CEA is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the CEA tumor-associated antigen, wherein aberrant CEA expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying polynucleotides encoding CEA fusion proteins and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.Type: GrantFiled: February 3, 2005Date of Patent: May 29, 2012Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti SpAInventors: Nicola La Monica, Andrea Facciabene, Luigi Aurisicchio, Gennaro Ciliberto
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Patent number: 8124108Abstract: The present invention features polypeptides comprising an amino acid sequence structurally related to SEQ ID NO: 1 and uses of such polypeptides. SEQ ID NO: 1 is a truncated derivative of a full-length S. epidermidis polypeptide. The full-length naturally occurring polypeptide is referred to herein as full-length ORF1319e. A His-tagged derivative of SEQ ID NO: 1 was found to produce a protective immune response against S. epidermidis.Type: GrantFiled: January 18, 2008Date of Patent: February 28, 2012Assignee: Merck Sharp & Dohme Corp.Inventors: Annaliesa S. Anderson, Tessie McNeely, James C. Cook, III, William L. McClements, Donna L. Montgomery
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Patent number: 8106176Abstract: Compositions comprising matrix metalloproteinase 11 (MMP-11) or stromelysin-3 (ST-3) or the nucleic acid encoding the MMP-11 for use in vaccines for treating tumors and cancers, which overexpress MMP-11, are described. In particular embodiments, the compositions comprise a nucleic acid encoding a fusion polypeptide that includes the catalytically inactivated MMP-11 linked at the C-terminus to an immunoenhancing element wherein the codons encoding the MMP-11 and the immunoenhancing element have been optimized for enhanced expression of the fusion polypeptide in human cells. In other embodiments, the compositions comprise the catalytically inactivated MMP-11 linked at the C-terminus to an immunoenhancing element. The compositions can be used alone or in synergy with vaccines against other tumor associated antigens as well as with conventional therapies such as radiation therapy and chemotherapy.Type: GrantFiled: October 3, 2006Date of Patent: January 31, 2012Assignee: Instituto di Richerche di Biologia Molecolare P. Angeletti SpAInventors: Luigi Aurisicchio, Daniela Peruzzi, Nicola La Monica, Gennaro Ciliberto, Domenico Lazzaro, Federica Mori
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Patent number: 8026082Abstract: The present invention provides a synthetic gene control region which comprises a gene regulatory sequence comprising a binding site for a gene regulatory protein of a yeast strain, and a promoter from filamentous fungal strain located downstream of the gene regulatory sequence; wherein the promoter can be recognized by the general transcription factors and RNA polymerase of the yeast strain; wherein the gene regulatory sequence is capable of regulating transcription initiated by the filamentous fungal promoter in the yeast strain.Type: GrantFiled: June 9, 2006Date of Patent: September 27, 2011Assignee: Merck Sharp & Dohme Corp.Inventors: Janine Bryan, Michelle K. Brownlow, Loren D. Schultz, Maria C. Losada, Kathrin Ute Jansen, Myra Kurtz, Stuart Kurtz, legal representative
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Patent number: 8017387Abstract: Polynucleotides encoding telomerase reverse transcriptase (TERT) fusion proteins are provided, the TERT fusion proteins comprising a TERT protein, or functional variant thereof, fused to a substantial portion of the B subunit of heat labile enterotoxin (LTB). TERT variants useful in TERT-LTB fusion proteins of the invention comprise mutations that function to eliminate telomerase catalytic activity. The polynucleotides of the present invention can elicit an immune response in a mammal, which, in preferred embodiments, is stronger than the immune response elicited by a wild-type TERT. TERT expression is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the TERT tumor-associated antigen, wherein aberrant TERT expression is associated with a carcinoma or its development.Type: GrantFiled: October 11, 2007Date of Patent: September 13, 2011Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti SpAInventors: Elisa Scarselli, Carmela Mennuni, Nicola La Monica, Gennaro Ciliberto
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Patent number: 7976848Abstract: Synthetic DNA molecules encoding the HPV58 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV58 L1 protein, wherein said polynucleotides are codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV58 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV58 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity and are also useful for treatment of existing HPV infections.Type: GrantFiled: January 26, 2009Date of Patent: July 12, 2011Assignee: Merck Sharp & Dohme Corp.Inventors: Janine T. Bryan, Michelle K. Brownlow, Loren D. Schultz, Xin-Min Wang, Kathrin U. Jansen
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Patent number: 7756644Abstract: Methodology for the automated selection and/or optimization of T-cell epitopes is disclosed. The invention provides a data processing system which utilizes sequence-based statistical pattern recognition to compute an epitope selection matrix based on the informational content of epitopes known to bind to a particular major histocompatibility class I allele. The resulting Bayes-corrected scoring matrix is used to predict the relative binding affinities of candidate T-cell epitopes derived from immunologically relevant antigens of self or foreign origin. One aspect of the invention describes an analytical method for identification of modifications in known or predicted T-cell epitopes that confer upon the epitopes the ability to elicit stronger cellular immune response due to more efficient processing and/or presentation to T-cells.Type: GrantFiled: May 8, 2006Date of Patent: July 13, 2010Assignee: Merck & Co., Inc.Inventors: Arthur Fridman, Ansuman Bagchi, Wendy Bailey
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Patent number: 7744892Abstract: Synthetic DNA molecules encoding the HPV 52 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV 52 L1 protein, wherein said polynucleotides are codon-optimized for high level expression in a yeast cell. In alternative embodiments of the invention, the nucleotide sequence of the synthetic molecule is altered to eliminate transcription termination signals that are recognized by yeast. The synthetic molecules may be used to produce HPV 52 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV 52 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity and may also be useful for treatment of existing HPV infections.Type: GrantFiled: October 14, 2009Date of Patent: June 29, 2010Assignee: Merck Sharp & Dohme Corp.Inventors: Janine T. Bryan, Michelle K. Brownlow, Loren D. Schultz, Kathrin U. Jansen
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Patent number: 7718182Abstract: The present invention features polypeptides comprising an amino acid sequence structurally related to SEQ ID NO: 1 or a fragment thereof, S. aureus AhpC-AhpF compositions, and uses of such polypeptides and compositions. SEQ ID NO: 1 has a full length S. aureus AhpC sequence. A derivative of SEQ ID NO: 1 containing an amino His-tag and three additional carboxyl amino acids was found to produce a protective immune response against S. aureus.Type: GrantFiled: January 17, 2006Date of Patent: May 18, 2010Assignee: Merck Sharp & Dohme Corp.Inventors: Rosemarie Kelly, Loren D. Schultz, Mark A. Miller, Mark D. Yeager, Tessie McNeely
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Patent number: 7709010Abstract: The present invention relates to pharmaceutical compositions comprising virus-like particles (VLPs) of HPV, said VLPs adsorbed to an aluminum adjuvant, and an ISCOM-type adjuvant comprising a saponin, cholesterol, and a phospholipid. In preferred embodiments, the aluminum adjuvant comprises amorphous aluminum hydroxyphosphate sulfate. Another aspect of the invention provides multi-dose HPV vaccine formulations comprising HPV VLPs and an antimicrobial preservative selected from the group consisting of: m-cresol, phenol and benzyl alcohol. Also provided are methods of using the disclosed pharmaceutical compositions and formulations to induce an immune response against HPV in a human patient and to prevent HPV infection.Type: GrantFiled: March 6, 2008Date of Patent: May 4, 2010Assignee: Merck Sharp & Dohme Corp.Inventors: Janine T. Bryan, Michelle K. Brownlow, Li Shi, Danilo Casimiro, William L. McClements, Brian K. Meyer, Binghua Hu
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Patent number: 7700103Abstract: Synthetic DNA molecules encoding the HPV 52 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV 52 L1 protein, wherein said polynucleotides are codon-optimized for high level expression in a yeast cell. In alternative embodiments of the invention, the nucleotide sequence of the synthetic molecule is altered to eliminate transcription termination signals that are recognized by yeast. The synthetic molecules may be used to produce HPV 52 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV 52 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity and may also be useful for treatment of existing HPV infections.Type: GrantFiled: March 18, 2005Date of Patent: April 20, 2010Assignee: Merck & Co., Inc.Inventors: Janine T. Bryan, Michelle K. Brownlow, Loren D. Schultz, Kathrin U. Jansen
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Patent number: 7662586Abstract: Synthetic polynucleotides encoding human HER2/neu or a truncated form thereof, are provided, the synthetic polynucleotides being codon-optimized for expression in a human cellular environment. The gene encoding hHER2 is commonly associated with the development of human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the hHER2 tumor-associated antigen, wherein aberrant hHER2 expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector and plasmid constructs carrying codon-optimized human HER2 and codon-optimized truncated HER2, and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.Type: GrantFiled: November 14, 2008Date of Patent: February 16, 2010Assignee: Instituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.Inventors: Paolo Monaci, Pasquale Gallo, Maurizio Nuzzo
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Patent number: 7498036Abstract: Synthetic DNA molecules encoding the HPV58 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV58 L1 protein, wherein said polynucleotides are codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV58 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV58 VLPs. The vaccines of the present invention provide effective imnunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity and are also useful for treatment of existing HPV infections.Type: GrantFiled: November 10, 2004Date of Patent: March 3, 2009Assignee: Merck & Co., Inc.Inventors: Janine T. Bryan, Michelle K. Brownlow, Loren D. Schultz, Xin-Min Wang, Kathrin U. Jansen
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Patent number: 7482015Abstract: Synthetic DNA molecules encoding the HPV45 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV45 L1 protein, wherein said polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV45 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV45 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity.Type: GrantFiled: May 23, 2007Date of Patent: January 27, 2009Assignee: Merck & Co., Inc.Inventors: Janine T. Bryan, Michelle K. Brownlow, Loren D. Schultz, Kathrin U. Jansen
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Patent number: 7482428Abstract: Synthetic DNA molecules encoding the HPV31 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV31 L1 protein, wherein said polynucleotides are free from internal transcription termination signals that are recognized by yeast. Also provided are synthetic polynucleotides encoding HPV31 L1 wherein the polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV31 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV31 VLPs. The vaccines of the present invention provide effective immunoprophylaxis against papillomavirus infection through neutralizing antibody and cell-mediated immunity.Type: GrantFiled: July 19, 2007Date of Patent: January 27, 2009Assignee: Merck & Co., Ltd.Inventors: Kathrin U. Jansen, Loren D. Schultz, Michael P. Neeper, Henry Z. Markus
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Patent number: 7326555Abstract: A process for purifying virus particles, especially recombinant adenovirus vector particles, is presented. The process relies on various combinations of cell lysis, detergent-based precipitation of host cell contaminants away from the virus, depth filtration or centrifugation, ultrafiltration, nuclease digestion and chromatography to robustly and economically produce highly purified product. This process results in contaminating DNA levels which are consistently below detectable levels.Type: GrantFiled: May 13, 2003Date of Patent: February 5, 2008Assignee: Merck & Co., Inc.Inventors: John O. Konz, Jr., Ann L. Lee, Chi Shung Brian To, Aaron R Goerke
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Patent number: 7282365Abstract: Polynucleotides encoding rhesus monkey HER2/neu have been isolated, cloned and sequenced. The gene encoding the HER2/neu is commonly associated with the development of epithelial-derived human carcinomas. The present invention provides compositions and methods to elicit or enhance immunity to the protein product expressed by the HER2/neu tumor-associated antigen, wherein aberrant HER2/neu expression is associated with a carcinoma or its development. This invention specifically provides adenoviral vector constructs carrying rhHER2/neu and discloses their use in vaccines and pharmaceutical compositions for preventing and treating cancer.Type: GrantFiled: December 29, 2003Date of Patent: October 16, 2007Assignee: Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.Inventors: Paolo Monaci, Maurizio Nuzzo, Nicola La Monica, Gennaro Ciliberto, Armin Lahm
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Patent number: 7276243Abstract: Synthetic DNA molecules encoding the HPV31 L1 protein are provided. Specifically, the present invention provides polynucleotides encoding HPV31 L1 protein, wherein said polynucleotides are free from internal transcription termination signals that are recognized by yeast. Also provided are synthetic polynucleotides encoding HPV31 L1 wherein the polynucleotides have been codon-optimized for high level expression in a yeast cell. The synthetic molecules may be used to produce HPV31 virus-like particles (VLPs), and to produce vaccines and pharmaceutical compositions comprising the HPV31 VLPs.Type: GrantFiled: March 19, 2004Date of Patent: October 2, 2007Assignee: Merck & Co., Inc.Inventors: Kathrin U. Jansen, Loren D. Schultz, Michael P. Neeper, Henry Z. Markus