Cambridge Biotech Corporation

Galenica Pharmaceuticals, Inc.

Cambridge Bioscience Corporation

Adjuvantys, Inc.

Dante J Marciani

Charlotte A Kensil

Sean Soltysik

Chung-Ho Hung

Gerald A Beltz

Richard M Thorn

Charles H Riggin

William A Haseltine

Richard T Coughlin

Jeffery Bruce Press

Joanne Recchia

The present invention relates to polysaccharide conjugates that comprise: a polysaccharide that binds to surface-receptors present on Antigen Presenting Cells, conjugated to one or more compounds having stable carbonyl groups covalently attached, either directly or via a bifunctional linker. The conjugates are useful as immuno-stimulants and adjuvants.

Imine-forming polysaccharide adjuvants and immunostimulants

Use of imine-forming polysaccharides as adjuvants and immunostimulants

The present invention is directed to chemical conjugates (herein referred to as polysaccharide adjuvant-antigen conjugates) that have a polysaccharide backbone capable of binding to the cell surface of Antigen Presenting Cells (APCs), to which is covalently attached (a) one or more molecules having a stable carbonyl group (i.e. an aldehyde and ketone group that is capable of reacting with amino groups to form an imine or Schiff base), and (b) one or more polypeptides or peptides that are capable of eliciting an immunogenic response when covalently attached to polysaccharide backbone. Also disclosed are methods for making the conjugates and methods of using the conjugates to enhance the potentiation of an immune response in a mammal. Also disclosed is a method of vaccination, and pharmaceutical and veterinary compositions comprising one or more of the polysaccharide adjuvant-antigen conjugates of the present invention.

Modified polysaccharide adjuvant-protein antigen conjugates, the preparation thereof and the use thereof

The present invention is directed to novel bidesmosidic saponin derivatives comprising a triterpene aglycone core substituted at positions 3 and 28 with a monosaccharide or an oligosaccharide which can be the same or different, and having an aldehyde group attached to the core, preferably at the 4-position. The novel derivatives include a lipophilic group that is covalently attached to the 4-position of a fucosyl group that is required in the 28-oligosaccharide substituent. These derivatives preferably have Formula I:

Chemically modified saponins and the use thereof as adjuvants

The present invention is directed to vaccines comprising (1) one or more bacterial, viral or tumor-associated antigens; and (2) one or more saponin-lipophile conjugate in which a lipophilic moiety such as a lipid, fatty acid, polyethylene glycol or terpene is covalently attached to a non-acylated or desacylated triterpene saponin via a carboxyl group present on the 3-O-glucuronic acid of the triterpene saponin. The attachment of a lipophile moiety to the 3-O-glucuronic acid of a saponin such as Quillaja desacylsaponin, lucyoside P, or saponin from Gypsophila, Saponaria and Acanthophyllum enhances their adjuvant effects on humoral and cell mediated immunity. Additionally, the attachment of a lipophile moiety to the 3-O-glucuronic acid residue of non- or des-acylsaponin yields a saponin analog that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin.

Immunostimulating and vaccine compositions employing saponin analog

The present invention is directed to novel chemical compounds in which a lipophilic moiety such as a lipid, fatty acid, polyethylene glycol or terpene is covalently attached to a non-acylated or desacylated triterpene saponin via a carboxyl group present on the 3-O-glucuronic acid of the triterpene saponin. The attachment of a lipophile moiety to the 3-O-glucuronic acid of a saponin such as Quillaja desacylsaponin, lucyoside P, or saponin from Gypsophila, Saponaria and Acanthophyllum enhances their adjuvant effects on humoral and cell mediated immunity. Additionally, the attachment of a lipophile moiety to the 3-O-glucuronic acid residue of non- or des-acylsaponin yields a saponin analog that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin.

Triterpene saponin analogs having adjuvant and immunostimulatory activity

Disclosed herein are modified saponins or fractions thereof obtainable by modification of a crude Quillaja saponaria extract or by modification of purified saponins obtainable from a crude Quillaja saponaria extract useful in pharmaceutical compositions for enhancing the transport of pharmacologically active substances across mucous membranes of an animal. Also disclosed are modified saponins having reduced irritability wherein the aldehyde group is reduced and the fatty acid moiety may be removed by hydrolysis. Also disclosed are pharmaceutical compositions comprising the modified saponins of the invention.

Drug delivery enhancement via modified saponins

Saponin/antigen conjugates and the use thereof for enhancing immune responses in individuals are disclosed. The saponins may be substantially pure or mixtures of saponins.

Saponin-antigen conjugates and the use thereof

Modified saponins isolated from Quillaja saponaria

The invention relates to antigenic preparations useful for inducing the production of antibodies in a cat which will bind to epitopes on feline leukemia virus. Also disclosed are immunogenic compositions and methods for immunizing a cat to enable the production of antibodies to feline leukemia virus.

Vaccine comprising recombinant feline leukemia antigen and saponin

Methods for enhancing the transport of pharmacologically active substances across mucous membranes of an animal by administration of pharmaceutical compositions comprising modified saponins or fractions thereof obtainable by modification of a crude Quillaja saponaria extract or by modification of purified saponins obtainable from a crude Quillaja saponaria extract. Also disclosed are modified saponins having reduced irritability wherein the fatty acid moiety is removed by hydrolysis or the aldehyde group is reduced. Also disclosed are pharmaceutical compositions comprising the modified saponins of the invention.

Methods for enhancing drug delivery with modified saponins

Monoclonal antibodies specific for Toxin B of Clostridium difficile are provided. Further, methods for making and using the antibodies are given, particularly the use of the antibodies for the detection of C. difficile.

Monoclonal antibodies specific for Toxin B of Clostridium difficile

Substantially pure saponins are disclosed. The saponins of the present invention are useful as immune adjuvants. Disclosed as well are immune response-provoking compositions comprising an antigen in admixture with the substantially pure saponins.

Saponin adjuvant

The present invention relates to an assay for determinng the presence of antibodies in a sample to human immunodeficiency virus (HIV) comprising mixing a sample suspected of containing antibodies to HIV with HIV-specific antigen coated, hydroxylated microbeads, evaluating whether agglutination occurs, and determining therefrom the presence of the antibodies to HIV in the sample.

Detection of antibodies to human immunodeficiency virus by agglutination

Certain peptide fragments of the human T-cell leukemia (lymphotropic) virus (HTLV-III) are particularly immunoreactive to HTLV-III antibodies, and can therefore be applied to immunodiagnostic tests for the detection of antibodies to HTLV-III.

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Birmingham, AL, United States of America

Dante J Marciani