Merck + Co., Inc.

Merck Sharp + Dohme Corp.

David B Volkin

Carl J Burke

Robert K Evans

Li Shi

Mark Bruner

Su-Pi Sheu

Henryk Mach

Zheng Xu

Lynne Isopi

C Russell Middaugh

Gautam Sanyal

Pei-Kuo Tsai

This invention relates to novel methods and formulations of nucleic acid pharmaceutical products, specifically formulations of nucleic acid vaccine products and nucleic acid gene therapy products. The formulations of the disclosure stabilize the conformation of DNA pharmaceutical products.

DNA vaccine formulations

The invention relates to viral formulations and related pharmaceutical products for use in gene therapy and/or vaccine applications. Especially preferred viral formulations disclosed herein are liquid adenovirus formulations, which show improved stability when stored in about the 2-8&#xb0; C. range while also being compatible with parenteral administration. These formulations comprise a buffer, a sugar, a salt, a divalent cation, a non-ionic detergent, as well as a free radical scavenger and/or a chelating agent to inhibit free radical oxidation.

Adenovirus formulations

The present invention provides liquid and lyophilized formulations of vaccines against rotavirus infection and methods of their preparation. The formulations include buffering agents appropriate for oral administration of rotavirus vaccines. The formulations also include compounds to stabilize of the vaccine compositions against loss of potency.

Rotavirus vaccine formulations

The present invention provides novel liquid and lyophilized formulations of vaccines against rotavirus infection and methods of their preparation. The formulations include buffering agents appropriate for oral administration of rotavirus vaccines. The formulations also include compounds to stabilize of the vaccine compositions against loss of potency.

The present invention relates to nucleic acid formulations of pharmaceutical products which comprise citrate and/or triethanolamine in concentrations which enhance stability of the nucleic acid. These formulations are suited for situations where prolonged storage occurs during the distribution and/or storage period prior to use.

DNA pharmaceutical formulations comprising citrate or triethanolamine and combinations thereof

Human papillomavirus (HPV) antigen formulations are disclosed which prevent protein aggregation and show prolonged stability as aqueous solutions. These formulations comprise a salt (such as sodium chloride) and a non-ionic surfactant (Polysorbate 80 such as Tween 80&reg;) in physiologically acceptable concentrations.

Stabilized human papillomavirus formulations

Vaccine stabilizers, vaccine formulations and lyophilized vaccines with enhanced thermostability are disclosed. The vaccine formulations comprise an increased amount of a 6-carbon polyhydric alcohol (such as sorbitol), an increase amount of a disaccharide (such as sucrose) and an amount of a physiologically active buffer to adjust the pH from about 6.0 to about 7.0.

Stabilizers for lyophilized vaccines

New human papilloma virus (HPV) vaccine formulations exhibit enhanced long-term stability. Formulation components can include: virus-like particles (VLPs) absorbed onto aluminum, a salt, non-ionic surfactant, and a buffer. Additional formulations also contain a polymeric polyanionic stabilizer and a salt either in the presence or absence buffering agents and nonionic detergent.

Human papillomavirus vaccine formulations

Human Papillomavirus vaccine formulations which contain virus-like particles (VLPs) can be made more stable and have an enhanced shelf-life, by treating the VLPs to a disassembly and reassembly process. Also provided are formulation buffers to long term stable storage of VLPs.

Human papilloma virus vaccine with disassembled and reassembled virus-like particles

Compositions are provided for improving the stability of live virus vaccines containing, e.g., live varicella zoster, measles, mumps, and rubella viruses. Such improved stabilizers are aqueous solutions containing recombinant human serum albumin (rHA) as a component at from 1-100 g/l. Live virus vaccines as well as methods of preparing live virus vaccines containing the stabilizers are also provided.

Stabilizers containing recombinant human serum albumin for live virus vaccines

Stabilizers for lyophilized mumps vaccines

Medicinal compositions containing fibroblast growth factor are stabilized against loss of biological activity by including in said composition a stabilizing amount of phytic add, phosvitin, phosphate buffer, (NH.sub.4).sub.6 P.sub.4 O.sub.13, Na.sub.5 P.sub.3 O.sub.10, Na.sub.4 P.sub.2 O.sub.7 and Na.sub.3 P.sub.3 O.sub.9, adenosine tetra, tri, di and mono phosphate and related diadenosine compounds plus other single and multi-phosphorylated mono and di-nucleotides, poly-aspartic acid, poly-adenylic-guanylic add and related compounds, double stranded deoxyribonucleic add, single stranded deoxyfibonucleic acid and poly-glutamic acid. Medicinal compositions for topical use are combined with a viscous excipient such as a water soluble polysaccharide with said combination with a second stabilizier.

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Doylestown, PA, United States of America

David B Volkin