Children's Hospital Research Center at Oakland

Children's Hospital & Research Center Oakland

Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

Children's Hospital Medical Center of Northern California

Other

Childern's Hospital & Research Center at Oakland

Children's Hospital Oakland Research Institute

Gregory R Moe

Dan M Granoff

Brent T Hagen

Charles Paul Plested

Rino Rappuoli

The present invention generally provides compositions methods and composition relating to the diagnosis and/or treatment of cancers having a cell surface de-N-acetylated sialic acid antigen, e.g., an at least partially de-N-acetylated ganglioside and/or a de-N-acetylated sialic acid-modified cell surface protein.

DE-N-acetyl sialic acid antigens, antibodies thereto, and methods of use in cancer therapy

The invention relates to methods of producing, and compositions comprising, an isolated alpha (2&#x2192;8) or (2&#x2192;9) oligosialic acid derivative bearing a non-reducing end enriched for one or more de-N-acetyl residues and resistant to degradation by exoneuraminidase. A representative production method involves: (i) treating an alpha (2&#x2192;8) or (2&#x2192;9) oligosialic acid precursor having a reducing end and a non-reducing end with sodium borohydride under conditions for de-N-acetylating the non-reducing end; and (ii) isolating alpha (2&#x2192;8) or (2&#x2192;9) oligosialic acid derivative having one or more de-N-acetylated residues and a non-reducing end that is resistant to degradation by exoneuraminidase. Isolated alpha (2&#x2192;8) or (2&#x2192;9) oligosialic acid derivatives that comprise a non-reducing end de-N-acetyl residue are provided, as well as antibodies specific for the derivatives, compositions comprising the derivatives, kits, and methods of use including protection against and detection ofK1 andbacterial infection, and in diagnosing and treating cancer.

Oligosialic acid derivatives, methods of manufacture, and immunological uses

De-N-acetyl sialic acid antigens, antibodies thereto, and methods of use in cancer therapy

The invention relates to inhibitors of polysialic (PSA) de-N-acetylase, methods of their production and use. The methods involve use of a PSA de-N-acetylase inhibitor for modifying the growth of cells, such as inhibiting the growth of cancer cells. The compositions include an inhibitor of a PSA de-N-acetylase, such as N-substituted derivatives of the amino sugars hexosamine and neuraminic acid, as well as conjugates and aggregates. Also provided are pharmaceutical compositions that include a PSA de-N-acetylase inhibitor of the invention. Kits containing one or more inhibitor compositions of the invention, as well as methods of preparing the compositions also are provided.

Inhibitors of polysialic acid de-N-acetylase and methods for using the same

The present invention generally provides methods and vaccines for the prevention of diseases caused bybacteria, particularly serogroup B strains.

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The present invention relates to compositions and methods of their production and use, including use in increasing de-N-acetyl sialic acid antigen of a mammalian cell and methods that exploit the increase in deNAc sialic acid antigen on such cells.

Polysialic acid derivatives, methods of production, and uses in enhancing cancer antigen production and targeting

Polypeptides that can elicit antibodies that bind to T-cell stimulating protein B (TspB) of, and methods of use, are provided.

T-cell stimulating protein B and methods of use

The present invention generally provides compositions comprising a polysaccharide derivative, and methods of their preparation and use for the prevention or treatment of diseases caused bybacteria, particularly group B (NmB) strains, and byK1. The invention provides a de-N-acetylated PS derivative in which one or more residues of the PS has been modified by de-N-acetylation. The invention also includes derivatives in which one or more of the N-acetyl groups of PS containing de-N-acetylated PS are replaced with other N-acyl groups, usually a lower acyl group of C-C. Further, the invention includes de-N-acetylated PS derivatives containing long chain hydrocarbons, as well as conjugates in which the de-N-acetylated PS derivative is linked to a carrier, e.g., a carrier protein.

Polysaccharide derivatives and uses in induction of an immune response

Molecular mimetics of a surface-exposed epitope on loop 4 of PorA ofserogroup B (MenB) P1.2 serosubtype and antibodies produced against the same are disclosed. Compositions containing such molecular mimetics or the antibodies thereto can be used to prevent MenB disease, as well as for diagnosis of MenB infection.

Molecular mimetics of meningococcal B epitopes which elicit functionally active antibodies

Novel bactericidal antibodies againstserogroup B ('MenB') are disclosed. The antibodies either do not cross-react or minimally cross-react with host tissue polysialic acid and hence pose minimal risk of autoimmune activity. The antibodies are used to identify molecular mimetics of unique epitopes found on MenB orK1. Examples of such peptide mimetics are described that elicit serum antibody capable of activating complement-mediated bacteriolysis of MenB. Vaccine compositions containing such mimetics can be used to prevent MenB orK1 disease without the risk of evoking autoantibody.

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Alameda, CA, United States of America

Gregory R Moe