Merck Sharp + Dohme Corp.

The Liposome Company, Inc.

Transave Limited

Rutgers, the State University of New Jersey

Biodelivery Sciences International, Inc.

Elan Pharmaceuticalstechnologies, Inc.

Patrick L Ahl

Andrew S Janoff

Michael Albert Winters

Patrick McHugh

Akhilesh Bhambhani

Sharma R Minchey

Jessica Sinacola

Emily Wen

Morrisa C Jones

Matthew P Watson

Justin Stanbro

Christopher Jon Farrell

Daniel D Roth

Donna J Cabral-Lilly

Paul R Meers

Raphael J Mannino

Lawrence T Boni

Suresh K Bhatia

Susan Gould-Fogerite

Christine E Swenson

Walter R Perkins

Sara L Krause-Elsmore

Tong Shangguan

Ravi Erukulla

Thomas S Davis

Jayme L Cannon

Zi Wei Chen

Gaofeng Shang

Shaukat Ali

J Craig Franklin

Jeffrey T Blue

Charles Pak

Michael J Caulfield

Gabriel M Lobel

David S Thiriot

Jayme Cannon

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

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

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 present invention relates to methods for preparing amorphous aluminum hydroxyphosphate. An aluminum salt and a phosphate solution are co-mixed at a constant ratio in the presence of a buffer. Preferably, an excess of the phosphate solution is used to act as a buffer. Due to the presence of a buffer, the pH is maintained constant during reaction (after initial rapid equilibration) without active adjustment. The methods are particularly applicable for the large scale manufacturing of aluminum phosphate adjuvant. Aluminum phosphate is used as an adjuvant in vaccine formulations, particularly those including a protein or saccharide antigen.

Method for preparation of aluminum hydroxyphosphate adjuvant

Disclosed herein are novel siRNA-cochleate and morpholino-cochleate compositions. Also disclosed are methods of making and using siRNA-cochleate and morpholino-cochleate compositions.

Cochleate compositions directed against expression of proteins

The present invention provides a multivalent immunogenic composition having 15 distinct polysaccharide-protein conjugates. Each conjugate consists of a capsular polysaccharide prepared from a different serotype of(1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F or 33F) conjugated to a carrier protein, preferably CRM. The immunogenic composition, preferably formulated as a vaccine on an aluminum -based adjuvant, provides broad coverage against pneumococcal disease, particularly in infants and young children.

15-valent pneumococcal polysaccharide-protein conjugate vaccine composition

This invention provides a method to prepare liposome-encapsulated bioactive agents such as nucleic acids, comprising complexation of the bioactive agents in reverse micelles prior to forming liposomes, as well as methods of using the liposomes so formed and formulations to deliver nucleic acids to cells.

Encapsulation of bioactive complexes in liposomes

A liposome including a fusogenic liposome, a linking moiety and a targeting moiety. The fusogenic liposome is a lipid bilayer encapsulating contents. The linking moiety is electrostatically bound to the lipid bilayer, and the targeting moiety is covalently bound to the linking moiety. The liposome may also include a stabilizing moiety interposed between the linking and targeting moieties, and covalently bound to both. Alternatively, the stabilizing and targeting moieties may be covalently bound to separate linking moieties, the linking moieties being electrostatically bound to the lipid bilayer.

Modular targeted liposomal delivery system

Peptide-lipid conjugates are incorporated into liposomes so as to selectively destabilize the liposomes in the vicinity of target peptidase-secreting cells, and hence, to deliver the liposomes to the vicinity of the target cells, or directly into the cells. The liposomes can thus be used to treat mammals for diseases, disorders or conditions, e.g., tumors, microbial infection and inflammations, characterized by the occurrence of peptidase-secreting cells.

Peptide-lipid conjugates, liposomes and lipsomal drug delivery

This invention provides a composition containing a sized liposome comprising a lipid and an inducer; the sized liposome has a diameter of at most about 1 micron and the inducer is present in an amount effective to induce interdigitation-fusion of the sized liposome. Also provided herein are interdigitation-fusion liposomes and gels, and methods of making the same.

Pharmaceutical compositions containing interdigitation-fusion liposomes

This invention provides a composition containing a sized liposome comprising a lipid and an induce; the sized liposome has a diameter of at most about 1 micoron and the induces is present in an amount effective to induce interdigitation-fusion of the sized liposome. Also provided herein are interdigitation-fusion liposomes and gels, and methods of making the same.

Methods of preparing interdigitation-fusion liposomes and gels which

Provided herein is a method of administering a liposome composition to an animal, the method involving adminstering to the animal a liposome composition containing an adverse physiological reaction-reducing effective amount of a liposome which has, in addition to a bioactive agent, a lipid bilayer containing a lipid and a surface agent-modified molecule. An adverse physiological reaction which may be experienced by the animal upon administration of a liposome composition is reduced by way of the presence of the surface agent-modified molecule in the liposome's lipid bilayer.

Reduction of liposome-induced adverse physiological reactions

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Yardley, PA, United States of America

Patrick L Ahl