Abstract: The present invention relates to macrocyclic compounds of formula (I): wherein W, n, m, R1, R2, R3, R4, R5, Ra, M, Z and ring B are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.

Abstract: The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention.

Abstract: N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R1, R2, R3 and R4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

Abstract: 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.

Abstract: Recombinant adenoviruses comprising modified fiber proteins which expand the tropism of the adenovirus in comparison to wild-type virus are disclosed. The modified fiber proteins described herein contain a peptide ligand for a cell surface binding site other than CAR comprising a 14 amino acid core sequence containing both fixed and variable amino acid residues. The invention includes isolated nucleic acid molecules encoding the modified adenovirus fiber proteins disclosed, as well as recombinant vectors and host cells containing said nucleic acid molecules. Methods of identifying peptide ligands that bind to cell binding sites other than CAR are included comprising screening a phage-display library of peptide ligands expressed within an adenovirus fiber knob context on CAR-negative cells.

Abstract: The present invention relates to the molecular biology and virology of the hepatitis C virus (HCV). An object of the present invention is a method to reproduce in vitro the RNA-dependent RNA polymerase activity of HCV that makes use of sequences contained in the HCV NS5B protein.

Abstract: The subject matters of this invention are the hormone-dependent forms of Rep 78 and Rep 68 proteins of the Adeno-associated virus (AAV), obtained by the fusion of their specific mutants with the hormone binding domain (HBD) of steroid hormone receptors, and the DNA sequences coding for them. The invention also refers to a method for the hormonal regulation of the activity of the fusion products Rep78/68-HBD, inserted into eucaryotic cells utilizing viral or non-viral systems, in order to direct the stable integration of DNA sequences in specific regions of the host human genome for therapeutic purposes. The fusion products Rep78/68-HBD are also utilized to generate viral hybrid vectors (i.e. adenovirus vectors AAV) and for generating recombinant vectors AAV.

Abstract: The subject of the present invention are variants of ciliary neurotrophic factor with enhanced receptor selectivity (CNTFR), useful for the treatment of diseases and disorders including motor neuron diseases and muscle degenerative diseases. Another subject of the invention is to provide a method for identifying the above mentioned CNTF variants. The hCNTF variants with the amino acid substitutions in accordance with the present invention, have a reduced ability, as compared to the human CNTF, to elicit biological effects through soluble CNTFR, without affecting its ability to activate membrane-bound neuronal CNTF receptors, thereby improving its therapeutic properties. FIG. 1 shows the reduced CNTFR binding affinity of a CNTF variant according to the invention (IA-CNTF; SEQ ID NO: 2). It is evident that the binding affinity of this variant to the CNTFR is reduced as compared to the wild-type human CNTF molecule.