Merck Sharp + Dohme Corp.

Patrick McHugh

Michael Albert Winters

Chitrananda Abeygunawardana

Luwy Kavuka Musey

Julie Marie Skinner

Emily Wen

Patrick L Ahl

Yadong Adam Cui

Michael J Kosinski

Akhilesh Bhambhani

Jian He

Jessica Sinacola

William J Smith

Morrisa C Jones

Matthew P Watson

Justin Stanbro

Christopher Jon Farrell

Daniel D Roth

Janelle Konietzko

John M Williams

Joseph G Joyce

Richard J Porambo

John E MacNair

Hari Pujar

Catherine Lancaster

A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized, the separately lyophilized polysaccharides and carrier protein are separately reconstituted in an organic solvent, and the reconstituted polysaccharide and carrier protein are then combined together by Tee-mixing and conjugated together to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

Methods for producingcapsular polysaccharide carrier protein conjugates

The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides frombacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.

Enhancing immunogenicity ofpolysaccharide-protein conjugates

A non-grid energy marketplace system is provided for at least one unit, e.g., a dwelling, building, or other structure that shelters an entity such as a person, family, or business that consumes energy. The system comprises at least one gateway coupled to a plurality of sensors configured to collect time-series energy data for each unit at a site that has at least one non-grid energy system. The time-series energy data can include unit-level non-grid energy consumption data and, if available, unit-level grid energy consumption data. An energy information processor is configured to communicate with at least one gateway via a remote network to receive and process the time-series energy data to determine time-based non-grid energy consumption for each unit. The system can be configured to perform a non-grid energy marketplace method that carries out the above processes and functions.

Non-grid energy marketplace system and method

The present invention provides a number of process improvements related to the conjugation of capsular polysaccharides fromto a carrier protein. These process are serotype specific and include acid hydrolysis, addition of sodium chloride to the reductive amination reaction, and addition of sucrose to dissolve polysaccharides. Polysaccharide-protein conjugates prepared using the processes of the invention can be included in multivalent pneumococcal conjugate vaccines.

Processes for the formulation of pneumococcal polysaccharides for conjugation to a carrier protein

A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized in the form of lyospheres of carrier protein and lyospheres of the one or more polysaccharides. A predetermined amount of carrier protein lyospheres and activated polysaccharide lyospheres are mixed together and the mixture reconstituted in an organic solvent to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

Methods for producing streptococcus pneumoniae capsular polysaccharide carrier protein conjugates from lyospheres

The invention is related to multivalent immunogenic compositions comprising more than onepolysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from anserotype conjugated to a carrier protein, wherein the serotypes ofare as defined herein. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection againstinfection and diseases caused by. The compositions of the invention are also useful as part of treatment regimes that provide complementary protection for patients that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.

Compositions comprisingpolysaccharide-protein conjugates and methods of use thereof

A method is described for reconstituting lyophilized mutant diphtheria toxin in dimethyl sulfoxide for use in producing pneumococcal capsular polysaccharide mutant diphtheria toxin conjugates.

Methods for providing a homogenous solution of lyophilized mutant diptheria toxin in dimethylsulfoxide

The invention is related to multivalent immunogenic compositions comprising more than onepolysaccharide protein conjugates, wherein each of the conjugates comprises a polysaccharide from anserotype conjugated to a carrier protein, wherein the serotypes ofare as defined herein. In some embodiments, at least one of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. In further embodiments, each of the polysaccharide protein conjugates is formed by a conjugation reaction comprising an aprotic solvent. Also provided are methods for inducing a protective immune response in a human patient comprising administering the multivalent immunogenic compositions of the invention to the patient. The multivalent immunogenic compositions are useful for providing protection againstinfection and diseases caused by. The compositions of the invention are also useful as part of treatment regimes that provide complementary protection for patients that have been vaccinated with a multivalent vaccine indicated for the prevention of pneumococcal disease.

The present invention provides capsular polysaccharides fromserotypes identified using NMR. The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additionalserotypes.

Growing community of inventors

Pipersville, PA, United States of America

Patrick McHugh