Noelle Mistretta has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
Abstract: The invention relates to SAEP II peptide dimers that mimic polymyxin B i.a. in its ability to bind non-covalently the lipopolysaccharide (LPS) of Gram-negative bacteria with high affinity, and therefore to detoxify LPS as polymyxin B does. The dimeric structure is maintained by a pair of disulphide bonds involving the two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. In the dimers of the invention, peptides may have a parallel or anti-parallel orientation. As a matter of example, a dimer of the invention is constituted by a peptide of formula NH2-Lys-Thr-Lys-Cysl-Lys-Phe-Leu-Leu-Leu-Cys2-COOH, either in a parallel or antiparallel dimeric form. SAEP II dimers are useful for treating or preventing septic shock and related disorders generated by Gram-negative bacteria infection. The invention also relates to LPS-peptide complexes in which LPS and SAEP II diners are non-covalently bound together.
Abstract: The invention relates to conjugates derived from the reductive amination of the pneumococcus serotype 5 capsular polysaccharide. The conditions for reductive amination differ from conventional conditions in that they make it possible to avoid the appearance of an undesirable compound which harms the immunogenicity of the conjugates. In carbon NMR spectrum, this undesirable compound is characterized by a resonance signal between 13 and 14 ppm. The aminated polysaccharides used to produce the conjugates therefore have a carbon NMR spectrum lacking a resonance signal between 13 and 14 ppm. The invention offers two conditions for reductive amination. According to a first method, the reductive amination is carried out at a slightly acidic pH (4-6.5) for at the very most 4 hours. According to a second method, the polysaccharide is first of all reduced, then fragmented and, finally, subjected to a reductive amination per se, under conditions which may or may not be conventional.
Abstract: The invention relates to a polysaccharide-peptide conjugate wherein the polysaccharide is advantageously immunogenic, which comprises a polysaccharide chain composed of repeat units and a plurality of peptide moieties, each moiety containing a cysteine residue and being covalently attached at random along the polysaccharide chain, through an indirect bond being achieved through either a linker or a spacer-linker moiety provided that the spacer entity of the spacer-linker moiety is linked to the amino, hydroxyl or carboxyl group of the polysaccharide. To this end a useful linker may be, e.g., N-(&ggr;-maleimidobutyrloxy)succinimide ester. Such a conjugate may typically exhibit a “Rake” configuration. Conjugation processes are also disclosed. Conjugates of the invention are in particular useful in the vaccinal field to elicit a protective long term immune response against a pathogenic microorganism from which the Immunogenic polysaccharide is derived.