Millennium Pharmaceuticals Limited

Pfizer Corporation

Millennium Biotherapeutics, Inc.

Myco Pharmaceuticals, Incorporated

Christine Ellen Bulawa

Sean Anthony McCarthy

Steven Bossone

Michael Joseph Kuranda

Benjamin Stone Amidon

Patrick K Dorr

James Allan Fleming

Tanya Parkinson

W James Cook

The present invention relates to pharmaceutical compositions and methods of treatment comprising administering to a patient in need thereof a combination of a benzoxazole derivative transthyretin stabilizer or a pharmaceutically acceptable salt or prodrug thereof and an additional therapeutic agent for the treatment of transthyretin amyloidosis. Particularly, the present invention relates to pharmaceutical compositions and methods of treatment comprising administering to a patient in need thereof 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid or a pharmaceutically acceptable salt or prodrug thereof and one or more additional therapeutic agent for the treatment of transthyretin amyloidosis.

Pharmaceutical compositions and methods comprising a combination of a benzoxazole transthyretin stabilizer and an additional therapeutic agent

Disclosed is a yeast cell whose genetic complement includes an inactive allele of the yeast CDC7 gene, a first nucleic acid that encodes a mammalian Cdc7 protein, and a second nucleic acid that encodes a mammalian Dbf4 protein. The yeast cell is dependent on the mammalian Cdc7 and Dbf4 proteins for viability. The yeast cell can be used to identify potential anti-proliferative agents by virtue of their inhibition of the mammalian Cdc7 and Dbf4 proteins. In some embodiments, a control yeast cell which does not depend on Cdc7 for viability is used in a secondary screen.

Screen for CDC7 inhibitors

Disclosed are coenzyme-A carboxylase genes and polypeptides and their use in identifying antifungal agents, for example.

Aspergillus fumigatus acetyl coenzyme-A carboxylase genes and polypeptides and uses thereof

Disclosed is an,N-myristoyltransferase gene and its use in identifying antifungal agents, for example.

Aspergillus N-myristoyl transferase genes and polyeptides and uses thereof

Methods of detecting inhibitors of fungal pathgenicity are disclosed. These methods are based on the discovery that pathogenicity is diminished when chitin synthase III is inhibited. The inhibitors of fungal pathogenicity are detected with mutant strains of,or other mutant fungal strains, whose mutation causes diminished growth of the fungus when combined with the inhibition of chitin synthase III.

Methods for identifying inhibitors of fungal pathogenicity

The invention involves a method of identifying nucleic acid sequences encoding signal peptide-containing proteins. The method features chimeric constructs containing a KRE9 gene that lacks a signal sequence. Yeast containing chimeric KRE9 plasmid constructs that encode signal sequences are selected based on their ability to grow on media in which sucrose is the sole carbon source.

Method for identifying genes encoding signal sequences

Methods of detecting inhibitors of fungal pathogenicity are disclosed. These methods are based on the discovery that pathogenicity is diminished when chitin synthase III is inhibited. The inhibitors of fungal pathogenicity are detected with mutant strains of Saccharomyces cerevisiae or other mutant fungal strains, whose mutation causes diminished growth of the fungus when combined with the inhibition of chitin synthase III.

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Arlington, MA, United States of America

Christine Ellen Bulawa