(19) TZZ_ Z__T (11) EP 1 920 781 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 39/02 (2006.01) A61K 39/40 (2006.01) 04.03.2015 Bulletin 2015/10 C12N 1/20 (2006.01) G01N 33/53 (2006.01) A61P 35/00 (2006.01) (21) Application number: 06090208.7 (22) Date of filing: 10.11.2006 (54) Compositions comprising a core-1 positive microorganism and their use for the treatment or prophylaxis of tumors Zusammensetzungen die ein Core- 1 positives Mikroorganismus enthalten und deren Verwendung zur Behandlung von Tumoren Compositions comprenant un microorganisme contenant core-1 et son utilisation pour le traitement des tumeurs (84) Designated Contracting States: • SPRINGER G F: "Immunoreactive T and Tn AT BE BG CH CY CZ DE DK EE ES FI FR GB GR epitopes in cancer diagnosis, prognosis, and HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI immunotherapy" JOURNAL OF MOLECULAR SK TR MEDICINE, SPRINGER VERLAG, DE, vol. 75, Designated Extension States: 1997, pages 594-602, XP002998516 ISSN: BA HR RS 0946-2716 • GOLETZ S ET AL: "THOMSEN-FRIEDENREICH (43) Date of publication of application: ANTIGEN: THE HIDDEN TUMOR ANTIGEN" 14.05.2008 Bulletin 2008/20 ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY, SPRING ST., NY, US, vol. 535, 2003, (73) Proprietor: Glycotope GmbH pages 147-162, XP009034310 ISSN: 0065-2598 13125 Berlin (DE) • KURTENKOV OLEG ET AL: "Better survival of Helicobacter pylori infected patients with early (72) Inventor: Goletz, Steffen gastric cancer is related to a higher level of 16548 Glienicke (DE) Thomsen-Friedenreich antigen-specific antibodies." IMMUNOLOGICAL (74) Representative: Roth, Carla et al INVESTIGATIONS, vol. 32, no. 1-2, February 2003 König-Szynka-Tilmann-von Renesse (2003-02), pages 83-93, XP009088439 ISSN: Patentanwälte Partnerschaft mbB 0882-0139 Postfach 11 09 46 • KLAAMAS K ET AL: "EXPRESSION OF TUMOR- 40509 Düsseldorf (DE) ASSOCIATED THOMSEN-FRIEDENREICH ANTIGEN (T AG) IN HELICOBACTER PYLORI (56) References cited: AND MODULATION OF T AG SPECIFIC IMMUNE WO-A-2006/012616 RESPONSE IN INFECTED INDIVIDUALS" IMMUNOLOGICAL INVESTIGATIONS, MARCEL • SPRINGER G F ET AL: "ORIGIN OF ANTI DEKKER, NEW YORK, NY, US, vol. 31, no. 3/4, THOMSEN FRIEDENREICH AND TN 2002, pages 191-204, XP009047359 ISSN: AGGLUTININS IN MAN AND IN WHITE LEGHORN 0882-0139 CHICKS" BRITISH JOURNAL OF • BUTSCHAK G ET AL: "ISOLATION AND HAEMATOLOGY, vol. 47, no. 3, 1981, pages CHARACTERIZATION OF THOMSEN- 453-460, XP009088436 ISSN: 0007-1048 FRIEDENREICH-SPECIFIC ANTIBODIES FROM HUMAN SERUM" TUMOR BIOLOGY, KARGER, BASEL, CH, vol. 23, no. 3, May 2002 (2002-05), pages 113-122, XP009034404 ISSN: 1010-4283 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 920 781 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 1 920 781 B1 • SUSANF SLOVIN ET AL:"Thomsen- Friedenreich • SHIGEOKA H ET AL: "INHIBITION OF LIVER (TF) antigen as a target for prostate cancer METASTASES FROM NEURAMINIDASE- vaccine: clinical trial results with TF cluster TREATED COLON 26 CELLS BY AN ANTI- (c)-KLH plus QS21 conjugate vaccine in patients THOMSEN-FRIEDENREICH-SPECIFIC with biochemically relapsed prostate cancer" MONOCLONAL ANTIBODY" TUMOR BIOLOGY, CANCER IMMUNOLOGY, IMMUNOTHERAPY, KARGER, BASEL, CH, vol. 20, 1999, pages SPRINGER-VERLAG, BE, vol. 54, no. 7, 1 July 139-146, XP008062447 ISSN: 1010-4283 2005 (2005-07-01), pages 694-702, XP019333138 ISSN: 1432-0851 2 EP 1 920 781 B1 Description FIELD OF THE INVENTION 5 [0001] The present invention relates to the field of prevention and treatment of gastrointestinal disorders and cancer. More particularly, the present invention relates to the prevention and treatment of Core-1-positive carcinomas. The invention provides nutraceuticals and pharmaceutical compositions comprising Core-1 positive microorganism and frac- tions thereof as defined in the appended claims. 10 DEFINITIONS [0002] In accordance with the present invention the term "nutraceutical" means any nutrient, composition of nutrients or formulation which can be taken orally by a human or animal such as but not limited to nutrients, nutrition additives, food additives, dietary supplements, medical food, clinical food, parenteral food, enteral food, food for special dietary 15 use, food of specified health use or functional food that can be applied orally in different forms, such as but not limited to capsules, tablets, emulsions, powder, liquids, as well as in form of any food or drink or as a part of it. In special cases the nutraceutical can be given parenterally (parenteral food). The nutraceutical can be given by itself or mixed with at least one other ingredient. The nutraceutical by itself or its mixture with at least one other ingredient can be given by itself or mixed into a food or a drink. The term nutraceutical also means any food, beverage, capsule, tablet, emulsion, 20 powder, or liquid. [0003] In accordance with the present invention the term "nutraceutical" means any nutrient, composition of nutrients or formulation which can be taken orally by a human or animal such as but not limited to nutrients, nutrition additives, food additives, dietary supplements, clinical food or nutrition, medical food or nutrition, enteral food, enteral clinical nutrition, health care nutrition or food, food for special dietary use, food of specified health use or functional food that 25 can be applied orally in different forms, such as but not limited to capsules, tablets, emulsions, powder, liquids, as well as in form of any food or drink or as a part of it. In special cases the nutraceutical can be given parenterally (parenteral food). The nutraceutical can be given by itself or mixed with at least one other ingredient. The nutraceutical by itself or its mixture with at least one other ingredient can be given by itself or mixed into a food or a drink. The term nutraceutical also means any food, beverage, capsule, tablet, emulsion, powder, or liquid. 30 [0004] In accordance with the present invention the term "pharmaceutical composition" means any composition which can be used as a drug, or a pharmaceutical, or a biological, or is a component of a drug or a pharmeutical or a biological. [0005] In accordance with the present invention the term "Core-1" means the carbohydrate structure galactose beta 1-3 linked to N-Acetyl-galactosamine alpha 1- linked (Gal betal-3GalNAc alpha1-; TF alpha, TFa, TF α). On the protein or polypeptide Core-1 is covalently linked via a O-glycosidic linkage to serine or threonine amino acids (Gal 35 beta1-3GalNAc alpha1-O-Ser/Thr). Core-1 can also be linked via various linkers and various densities to natural or synthetic carriers, such as polyacrylamide (herein also called PAA), or other molecules such as chromatographic bed materials (e.g. sepharose), biotin or proteins, such as bovine serum albumin (BSA), ovalbumin (Ova), human serum albumin (HSA) or Keyhole limpet hemocyanin (KLH), toxins, toxoids, beads or nanoparticles. [0006] In the sense of this invention the term Core-1 means also Core-1 mimickry structures such as polypeptides, 40 peptides, lipids or carbohydrates or combinations thereof of a chemical structure different from Core-1 but which have a conformational structure which can be recognized by Core-1 specific antibodies of the invention. [0007] In accordance with the present invention the term"Core-1 specific antibody" means (i) any antibody which specifically binds to Gal beta1-3GalNAc alpha1-PAA (TFa-PAA, TF α-PAA, Core-1-PAA) but not to any of the substances of #list 1#. 45 #list1# [0008] 50 GlcNAcß1-2Galß1-3GalNAcα-PAA (GlcNAcß1-2’ TF) Fucα1-2Galß1-3GalNAcα-PAA (H type 3) GalNAcα1-3Galβ-PAA (Adi) Galα1-3-GalNAcβ-PAA (Tαβ) 55 which were obtained from Lectinity holdings, Inc. [0009] Alternatively all structures can be generated by one skilled in the art, who also can select another suitable polyacrylamide for conjugation or another suitable carrier molecule as well as the suitable conjugation methods for coupling of the according carbohydrate structures and the synthesis of the necessary intermediates. 3 EP 1 920 781 B1 (ii) or any antibody which binds to asialoglycophorin but not glycophorin, and this binding is periodate sensitive, (iii) more preferably any antibody which binds to TFa-PAA and less or not to TFb-PAA (Gal betal-3GalNAc betal- PAA) but not to any of the substances of #list 2#: 5 #list2# proteins: 10 [0010] Glycophorin BSA (bovine serum albumin) 15 PAA-conjugates: [0011] Aminoglucitol 20 β-N-acetylneuraminic acid (beta-N-acetymeuraminic acid) α-D-glucose (alpha-D-glucose) β-glucose (beta-D-glucose) α-D-galactose (alpha-D-galactose) β-D-galactose (beta-D-galactose) 25 α-D-mannose (alpha-D-mannose) α-D-mannose-6-phosphate (alpha-D-mannose-6-phosphate) α-L-fucose (alpha-L-fucose) β-N-acetyl-D-glucosamine (beta-N-acetyl-D-glucosamine α-N-acetyl-D-galactosamine (alpha-N-acetyl-D-galactosamine, Tn, Tn) 30 β-D-galactose-3-sulfate (beta-D-galactose-3-sulfate) α-N-acetylneuraminic-acid (alpha-N-acetylneuraminic-acid) β-N-acetyl-D-glucosamine-6-sulfate (beta-N-acetyl-D-glucosamine-6-sulfate) Lac-di-NAc (GalNAcβ1-4GlcNAcβ-, GalNAcbeta1-4GlcNAcbeta-) GlcNAcβ3Gal (GlcNAcβ1-3Galβ-, GlcNAcbeta1-3Galbeta-)