Biosynth S.r.l.

American Cyanamid Company

Sanofi Pasteur Inc.

Sclavo Spa

Osterreichische Akademie Der Wissenschaften

Pba3 Biomed Gmbh

Massimo Porro

Sylvie E Blondelle

Monique Moreau

Noëlle Mistretta

Karl Lohner

Dagmar Zweytick

Klaus Brandenburg

Roman Jerala

Massimo Velucchi

Andreja Majerle

Tino Krell

Mateja Zorko

Paolo Costantino

Bostjan Japelj

Gunter Deutsch

Primoz Pristovsek

Alessandro Rustici

Martti Varra

Jorg Andra

Ignacio Moriyon Uria

Jose Leiva Leon

Guillermo Martinez De Tejada De Garaizabal

Guenter Deutsch

Joerg Andrae

The present invention refers to new glycoconjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines intended for the protection of mammalians, and particularly for the protection of the human population from enteropathogenic bacteria, such as the Gram-positive anaerobic bacteriumand the Gram-negative bacteriaA,and/or from viral gastrointestinal infections due to human noroviruses.

Glycoconjugate vaccines comprising basic units of a molecular construct expressing built-in multiple epitopes for the formulation of a broad-spectrum vaccine against infections due to enteropathogenic bacteria

The present invention refers to new conjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines and formulations containing the same. In addition, the present invention concerns the use of these vaccines in particular for the protection of the human population, and in particular for the protection of the paediatric population from pulmonary and systemic infections due to, or from intestinal infections due toand. The present invention additionally refers to new polyvalent glycoconjugate vaccines for the protection fromandsystemic and genitourinary infections or for the protection frominfections in veterinary medicine.

Multivalent glycoconjugate vaccines

The present invention refers to new glycoconjugate antigens expressing built-in multiple epitopes and to polyvalent glycoconjugate vaccines intended for the protection of mammalians, and particularly for the protection of the human population from enteropathogenic bacteria, such as the Gram-positive anaerobic bacteriumand the Gram-negative bacteriaand/or from viral gastrointestinal infections due to human noroviruses.

The present invention relates to families of polypeptides and lipopolypeptides that have antimicrobial and endotoxin-neutralizing activities. These molecules show a broad spectrum of activity against various pathogens (including bacteria, viruses, fungi etc.) These compounds can be used alone or in combination therapy with conventional antibiotics or antiendotoxic agents. In addition, the present invention discloses processes for making and using of the compounds.

Antimicrobial peptides

The present invention concerns a conjugation process for coupling a endotoxin (LPS) free polyfunctional polysaccharide with a polyfunctional carrier protein with quantitative yields. The invention also provides for vaccine formulations comprising the glyconjugate antigen manufactured by the process.

Polysaccharide and glycoconjugate vaccines

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. The dimeric structure is maintained by a pair of disulphide bonds between two cystein residues present in the peptide sequence, which does not exceed 17 amino acids and essentially comprises cationic and hydrophobic amino acid residues. The peptides in the dimers may have a parallel or anti-parallel orientation. 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. These complexes are useful as vaccinal agents against Gram-negative bacteria infection.

Polymyxin B analogs for LPS detoxification

A vaccine is disclosed which is useful for protecting a host from Gram negative infections and the effects of endotoxin, therefore preventing sepsis and septic shock. The vaccine is prepared by combining LPS free or in conjugate form with a stoichiometric excess of a peptide of the formula:

Vaccine for prevention of gram-negative bacterial infections and endotoxin related diseases

The present invention is concerned with methods of potentiating an antibiotic. The invention also includes compositions of an antibiotic and a peptide having units of the formula:

Potentiation of antibiotics

The present invention is concerned with a peptide composition which includes a peptide having units of the formula: (a) (A).sub.n wherein A is Lysine or Arginine and n is an integer with a minimum value of 7. (b) (AB).sub.m wherein A is Lysine or Arginine and B is a hydrophobic amino acid selected from the group consisting of Valine, Leucine, Isoleucine, Tyrosine, Phenylalanine and Tryptophan; m is an integer with a minimum value of 3; and (c) (ABC).sub.p wherein A is a cationic amino acid which Is Lysine or Arginine; B and C are hydrophobic amino acids which may be the same or different and are selected from the group consisting of Valine, Leucine, Isoleucine, Tyrosine, Phenylalanine and Tryptophan; p is an integer with a minimum value of 2. The compositions of the invention bind Lipid-A of endotoxins.

Peptides for neutralizing the toxicity of Lipid A

The present invention provides methods of using peptides of the formula R.sub.1 --(A--B--C).sub.n --R, wherein R.sub.1 and R are independently H or an amino acid residue or a fatty acid residue; A is an amino acid residue selected from the group consisting of Lys and Arg; B is an amino acid selected from the group consisting of Phe, Tyr, and Trp; C is an amino acid selected from the group consisting of Leu, Ile and Val; n is an integer of 1-100. The peptides are used for the removal of endotoxin from blood or sera; the detoxification of bacterial endotoxin; and the prevention of the contamination of products with endotoxin.

Synthetic peptides for detoxification of bacterial endotoxins and for

The present invention provides novel peptides of the formula R.sub.1 -(A-B-C).sub.n -R, where R.sub.1 and R are independently H or an amino acid residue or a fatty acid residue; A is an amino acid residue selected from the group consisting of Lys, Arg, and His; B is an amino acid selected from the group consisting of Phe, Tyr, and Trp; C is an amino acid selected from the group consisting of Leu, Ile and Val; n is an integer of 1-100. The peptides are used inter alia for the prevention and/or treatment of septic shock, for the detection of endotoxin and the preparation of antigenic complexes of Lipid A.

Novel peptides are disclosed which are based on the formula:

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Rapolano Terme, Italy

Massimo Porro