Gilead Sciences, Inc.

Lung-Chi J Yuan

Terrence C Dahl

The invention provides compositions comprising the nucleotide analog 9-&lsqb;2-&lsqb;&lsqb;bis&lsqb;(pivaloyloxy)methyl&rsqb;phosphono&rsqb;methoxy&rsqb;ethyl&rsqb;adenine and an alkaline excipient with or without L-carnitine-L-tartrate. The compositions are more stable those previously described. The invention also provides methods to make the compositions and their intermediates.

Pharmaceutical formulations

The invention provides compositions and methods to prevent the appearance of visually detectable precipitate in the composition upon storage of an aqueous solution of the composition containing 5-250 mg/mL of the phosphonate nucleotide analog for at least 6 months at 22.degree. where the composition comprises a phosphonate nucleotide analog and a sufficient amount of a divalent or trivalent metal cation sequestering agent such as about 0.1% w/v EDTA, and/or a sufficiently low concentration of a divalent or trivalent metal cation, e.g., about 3-10 ppm, and/or a sufficient pH in water, e.g., a pH of about 7.0-7.5.

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Foster City, CA, United States of America

Lung-Chi J Yuan