Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Medimmune Limited

Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa

Istitute Di Ricerche Di Biologia Molecolare P. Angeletti S.p.a.

Whitehead Insitute of Biomedical Research

Whitehead Institute for Biomedical Research

Cambridge Antibody Technology Limited

John W Shiver

Andrew J Bett

Emilio A Emini

Margaret A Liu

David C Kaslow

Helen C Perry

Stefano Colloca

Alfredo Nicosia

Riccardo Cortese

Armin Lahm

Ling Chen

Danilo R Casimiro

Alessandra Luzzago

Daniel C Freed

Mary Ellen Davies

Elisabetta Bianchi

Michael D Miller

Victor M Garsky

Peter S Kim

John J Donnelly

Gene G Kinney

Paul M Keller

Joseph G Joyce

Debra Muir Eckert

Daria Hazuda

Xiaoping Liang

Michael P Caulfield

Michael J Root

Romas Geleziunas

Rima Youil

Michael A Chastain

Simon N Lennard

Timothy J Toner

Tong-Ming Fu

Daria J Hazuda

The present invention features Ad6 vectors and a nucleic acid encoding a Met-NS3-NS4A-NS4B-NS5A-NS5B polypeptide containing an inactive NS5B RNA-dependent RNA polymerase region. The nucleic acid is particularly useful as a component of an adenovector or DNA plasmid vaccine providing a broad range of antigens for generating an HCV specific cell mediated immune (CMI) response against HCV.

Hepatitis C virus vaccine

The invention provides compositions and methods for the treatment of diseases associated with amyloid deposits of A&#x3b2; in the brain of a patient, such as Alzheimer's disease. Such methods entail administering an immunogenic fragment of A&#x3b2;, lacking a T-cell epitope, capable of inducing a beneficial immune response in the form of antibodies to A&#x3b2;. In another aspect, the immunogenic fragment of A&#x3b2; is capable of elevating plasma A&#x3b2; levels. The immunogenic fragments comprise linear or multivalent peptides of A&#x3b2;. Pharmaceutical compositions comprise the immunogenic fragment chemically linked to a carrier molecule which may be administered with an adjuvant.

Peptide conjugate compositions and methods for the prevention and treatment of alzheimer's disease

Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as Vand Vchains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines.

Human antibodies interacting with HIV gp41

Nucleic acids, including DNA constructs and RNA transcripts, capable of inducing coordinate expression of two to three cistrons upon direct introduction into animal tissues, are bi- or tri-cistronic polynucleotides of this invention include those encoding and co-expressing HIV gene products, genes encoding antigens unrelated to HIV, and immunostimulatory gene products, including but not limited to GM-CSF, interleukins, interferon and members of the B7 family of proteins which act as T-cell costimulatory elements. The methods and polynucleotides of this invention are generally applicable to co-ordinate expression in vivo of any two or more genes in a single cell.

Coordinate in vivo gene expression

An adenoviral vector is described which carries a codon-optimized gag gene, along with a heterologous promoter and transcription terminator. This viral vaccine can effectively prevent HIV infection when administered to humans either alone or as part of a prime and boost regime also with a vaccine plasmid.

Adenovirus carrying gag gene HIV vaccine

First generation adenoviral vectors and associated recombinant adenovirus-based HIV vaccines which show enhanced stability and growth properties and greater cellular-mediated immunity are described within this specification. These adenoviral vectors are utilized to generate and produce through cell culture various adenoviral-based HIV-1 vaccines which contain HIV-1 gag, HIV-1 pol and/or HIV-1 nef polynucleotide pharmaceutical products, and biologically relevant modifications thereof. These adenovirus vaccines, when directly introduced into living vertebrate tissue, preferably a mammalian host such as a human or a non-human mammal of commercial or domestic veterinary importance, express the HIV1-Gag, Pol and/or Nef protein or biologically modification thereof, inducing a cellular immune response which specifically recognizes HIV-1. The exemplified polynucleotides of the present invention are synthetic DNA molecules encoding HIV-1 Gag, encoding codon optimized HIV-1 Pol, derivatives of optimized HIV-1 Pol (including constructs wherein protease, reverse transcriptase, RNAse H and integrase activity of HIV-1 Pol is inactivated), HIV-1 Nef and derivatives of optimized HIV-1 Nef, including nef mutants which effect wild type characteristics of Nef, such as myristylation and down regulation of host CD4. The adenoviral vaccines of the present invention, when administered alone or in a combined modality regime, will offer a prophylactic advantage to previously uninfected individuals and/or provide a therapeutic effect by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV-1 infection.

Enhanced first generation adenovirus vaccines expressing codon optimized HIV1-gag, pol, nef and modifications

Synthetic DNA molecules encoding HIV gag and modifications of HIV gag are provided. The codons of the synthetic molecules are codons preferred by the projected host cell. The synthetic molecules may be used as a polynucleotide vaccine which provides effective immunoprophylaxis against HIV infection through stimulation of neutralizing antibody and cell-mediated immunity.

Synthetic HIV gag genes

The present invention relates to polynucleotides comprising a DNA sequence encoding an HCV protein and fragments thereof that contain codons optimized for expression in a vertebrate host. Uses of the polynucleotides include eliciting an immune response specifically recognizing HCV.

Synthetic hepatitis C genes

Synthetic polynucleotides comprising a DNA sequence encoding a peptide or protein are provided. The DNA sequence of the synthetic polynucleotides comprise codons optimized for expression in a nonhomologous host. The invention is exemplified by synthetic DNA molecules encoding HIV env as well as modifications of HIV env. The codons of the synthetic molecules include the projected host cell's preferred codons. The synthetic molecules provide preferred forms of foreign genetic material. The synthetic molecules may be used as a polynucleotide vaccine which provides immunoprophylaxis against HIV infection through neutralizing antibody and cell-mediated immunity. This invention provides polynucleotides which, when directly introduced into a vertebrate in vivo, including mammals such as primates and humans, induces the expression of encoded proteins within the animal.

Vaccines comprising synthetic genes

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Doylestown, PA, United States of America

John W Shiver