Merck Sharp + Dohme Corp.

Vaxinnate Corporation

Merck + Co., Inc.

Robert K Evans

Akhilesh Bhambhani

Thomas J Powell

David B Volkin

Langzhou Song

Lynda G Tussey

James W Huleatt

Valerian Nakaar

Lynne Isopi

Albert E Price

Jessica Sinacola

Mark Bruner

David C Kaslow

Zheng Xu

Pranav Gupta

Morrisa C Jones

Brian K Meyer

David Krah

Jennifer Kriss

Colleen Barr

Channing R Beals

Rebecca Lizzano

Donna M Williams

Ronald L Smith

Erica L Strable

The present invention relates to thermally stable oral rotavirus vaccine formulations comprising one or more rotavirus reassortant or attenuated rotavirus strains, a pharmaceutically acceptable calcium salt, adipic acid, sucrose, and sodium phosphate, wherein each of the one or more rotavirus reassortant or attenuated rotavirus strain is stable for 7 days at 37&#xb0; C., for 45 days at 25&#xb0; C. and for 2 years or more at 2-8&#xb0; C. The calcium containing formulations of the invention may further comprise one or more excipients which are present in an amount that is effective to optimize the calcium ions free in solution to stabilize the rotavirus particles. In embodiments of the invention, the formulation comprises a surfactant, such as polysorbate 80. The invention also relates to methods of using the rotavirus vaccine compositions of the invention to prevent rotavirus infection, or to reduce the likelihood of infection or to prevent, ameliorate, or delay the onset or progression of the clinical manifestations thereof.

Thermally stable rotavirus vaccine formulations and methods of use thereof

The present invention provides a process for preparing enterically-coated lyospheres comprising a therapeutic agent comprising: a.) providing lyospheres comprising the therapeutic agent; b.) coating said lyospheres with an enteric polymer coating composition; and c.) isolating said enterically-coated lyospheres. In other embodiments, the invention provides dosage forms comprising a lyosphere comprising an effective amount of a therapeutic agent and an enteric polymer coating. In some embodiments, the therapeutic agent in the process or dosage form is a polypeptide, a protein, a peptide, a lipopeptide, a glycoprotein, a fusion protein, a protein conjugate, a cytokine, an enzyme, an antibody, an oligonucleotide, a vaccine vector, small molecule, a live virus, an inactivated virus, a virus-like particle, a viral protein subunit, an adjuvant, microbiome, a prebiotic, a probiotic, or an ectobiotic. In some embodiments of the present invention, after oral administration the dosage forms containing the enterically-coated lyospheres provide a method of delivering a therapeutic agent to the ileum, ileo-caecal junction, colon or a combination thereof in a subject.

Process for preparing formulations for gastrointestinal-targeted therapies

Methods for preparing dried pellets of biological materials are described. The pellets can have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a solid surface followed by microwave vacuum drying the frozen droplets. These methods are useful for preparing dried pellets having a high concentration of a desired biological material, in particular a therapeutic protein or vaccine, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials.

Method of microwave vacuum drying spherical-shaped pellets of biological materials

Methods for improving the drying yield and stability of RSV vaccines comprising a highly thermolabile enveloped live virus and/or one or more RSV protein subunits, are described. Methods for rapid drying of RSV formulations containing between 17.5% and 60% w/w of a non-polymeric sugar and using either conduction or radiation dominant drying mechanisms, are disclosed. The disclosed methods provide for; 1) a dried RSV formulation with improved stability profile; 2) faster drying; and 3) integration of dried RSV into a primary device (such as dual chamber cartridges, foil-pouch devices etc.), pre- as well as post-drying.

Thermostable respiratory synctial virus (RSV) vaccine compositions

The present invention relates to a method of vaccinating a patient against varicella zoster virus (VZV) by delivery of an effective amount of a live attenuated VZV vaccine to the epidermis or the dermis of a patient's skin at a depth of between about 100 and about 700 microns from the surface of the skin, which is useful for preventing herpes zoster or reducing the severity or duration thereof. In embodiments of the invention, the patient is 50 years of age or older and has been previously exposed to VZV. The invention also relates to a method of preventing VZV infection in an individual who was not previously infected with VZV comprising administering an effective amount of a live attenuated VZV vaccine to the epidermis or the dermis of the individual's skin at a depth of between about 100 and about 700 microns from the surface of the skin.

Methods of immunization with varicella zoster virus antigen

Methods for preparing lyophilized pellets of biological materials are described. The pellets have a substantially spherical shape and are prepared by freezing droplets of a liquid composition of a desired biological material on a flat, solid surface, in particular, a surface that does not have any cavities, followed by lyophilizing the frozen droplets. These methods are useful for preparing lyophilized pellets having a high concentration of a desired biological material, in particular a therapeutic protein or vaccine, and which have a faster reconstitution time than lyophilized powder cakes prepared in vials.

Methods of preparing lyophilized spherical-shaped pellets of biological materials

This present invention relates to compositions and methods for stabilizing a dried vaccine formulations. In particular, the invention provides a method for producing a vaccine composition comprising the steps of providing an aqueous composition comprising a buffer, the vaccine components and between 17.5% w/w and 60% w/w of a non-polymeric sugar, freezing the composition, and applying microwave radiation under a pressure lower than atmospheric pressure in order to sublimate the composition and obtain a dried vaccine formulation. The invention also provides a product obtainable by this method.

Method of obtaining thermostable dried vaccine formulations

Methods of making a protein that stimulates a protective immune response in a subject include separating a portion of a protein from a naturally occurring influenza viral hemagglutinin to form a protein portion.

Flagellin fusion proteins

Methods of making a protein that stimulates a protective immune response in a subject include separating a portion of a protein from a naturally occurring influenza viral hemagglutinin to form a protein portion. The protein portion includes at least a portion of a globular head, and at least a portion of at least one secondary structure having at least one &#x3b2;-sheet at a bottom of the globular head that causes the globular head to essentially retain its tertiary structure. The protein portion made by the methods of the invention lacks a transmembrane domain, a cytoplasmic domain and an HA2 subunit. A nucleic acid sequence encoding the protein portion is transformed into a prokaryotic host cell.

Methods of making hemagglutinin proteins

Methods that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the protein portion includes at least a portion of a globular head and at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and wherein the protein portion lacks a transmembrane domain, a cytoplasmic domain and an HA2 subunit. Compositions administered to the subject can further include a carrier and can be administered in single or multiple doses.

Methods of treatment with compositions that include hemagglutinin

Methods of making and compositions that stimulate a protective immune response in a subject include a portion of a protein from a naturally occurring viral hemagglutinin, wherein the protein portion includes at least a portion of a globular head and at least a portion of at least one secondary structure that causes the globular head to essentially retain its tertiary structure, and wherein the protein portion lacks a membrane fusion domain, a transmembrane domain and a cytoplasmic domain. Compositions can further include a Toll-like Receptor agonist and a carrier protein.

Compositions that include hemagglutinin

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 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.

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Souderton, PA, United States of America

Robert K Evans