Enzymatic large-scale synthesis of mucin glyconjugates, and immunogenic applications thereof

التفاصيل البيبلوغرافية
العنوان: Enzymatic large-scale synthesis of mucin glyconjugates, and immunogenic applications thereof
Patent Number: 9,657,074
تاريخ النشر: May 23, 2017
Appl. No: 12/160605
Application Filed: February 23, 2006
مستخلص: The present invention relates to mucin glycoconjugates, and to a process of producing mucin glycoconjugates. It relates to the biological, pharmaceutical and medical applications thereof. The invention notably provides mucin glycoconjugates which do not require a protein carrier, such as KHL, to induce an immune response (anti-Tn IgG).
Inventors: Bay, Sylvie (Paris, FR); Freire, Teresa (Montevideo, UY); Leclerc, Claude (Paris, FR); Lo-Man, Richard (Paris, FR)
Assignees: Institut Pasteur (Paris, FR), Institut National de la Santé et de la Recherche Médicale (INSERM) (Paris, FR), Centre National de la Recherche Scientifique (Paris, FR)
Claim: 1. An immunogenic Tn-based mucin glycoconjugate, wherein the Tn-based mucin glycoconjugate is prepared by enzymatically adding GaINAc moieties to at least 40% of the Ser and Thr residues of an apomucin backbone in vitro to produce a glycoconjugate containing only O-linked GaINAc residues, wherein the apomucin backbone comprises SEQ ID NO:12, SEQ ID NO:9, SEQ ID NO:6, SEQ ID NO:7, or SEQ ID NO:15.
Claim: 2. The immunogenic Tn-based mucin glycoconjugate of claim 1 , wherein the apomucin backbone comprises SEQ ID NO:12.
Claim: 3. The immunogenic Tn-based mucin glycoconjugate of claim 1 , wherein the apomucin backbone comprises SEQ ID NO:9.
Claim: 4. The immunogenic Tn-based mucin glycoconjugate of claim 1 , wherein the apomucin backbone comprises SEQ ID NO:6.
Claim: 5. The immunogenic Tn-based mucin glycoconjugate of claim 1 , wherein the apomucin backbone comprises SEQ ID NO:7.
Claim: 6. The immunogenic Tn-based mucin glycoconjugate of claim 1 , wherein the apomucin backbone comprises SEQ ID NO:15.
Claim: 7. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 1 to a human.
Claim: 8. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 2 to a human.
Claim: 9. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 3 to a human.
Claim: 10. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 4 to a human.
Claim: 11. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 5 to a human.
Claim: 12. A method for inducing an immune response comprising administering the immunogenic Tn-based mucin glycoconjugate of claim 6 to a human.
Patent References Cited: 2003/0138859 July 2003 Barbera-Guillem et al.
2008/0064059 March 2008 Schultz
WO2004069136 August 2004


























Other References: Skolnick and Fetrow. From genes to protein structure and function: novel applications of computational approaches in the genomic era. Trends in Biotechnology, 2000. vol. 18, pp. 34-39. cited by examiner
Burgess, Shaheen, Ravera, Jaye, Donohue, and Winkles. Possible dissociation of the heparin binding and mitogenic activities of heparin binding (acidic fibroblast) growth factor-1 from its receptor binding activities by site directed mutagenesis of a single lysine residue. Journal of Cell Biology, 1990. vol. 111, pp. 2129-2138. cited by examiner
Lazar, Watanabe, Dalton, and Sporn. Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities. Molecular and Cellular Biology, 1988. vol. 8, pp. 1247-1252. cited by examiner
De Bolòs et al. (Int. J. Cancer. Jul. 17, 1998; 77 (2): 193-9). cited by examiner
Brockhausen et al. (Biol. Chem. Feb. 2001; 382 (2): 219-32). cited by examiner
Van Klinken et al. (Am. J. Physiol. Aug. 1997; 273 (2 Pt 1): G296-302). cited by examiner
Grogan et al. (Annu. Rev. Biochem. 2002; 71: 593-634). cited by examiner
Pratt et al. (Chem. Soc. Rev. Jan. 2005; 34 (1): 58-68). cited by examiner
Freire et al. (Cancer Res. Sep. 1, 2005; 65 (17): 7880-7). cited by examiner
Hojo et al. (Curr. Protein Pept. Sci. Jul. 2000; 1 (1): 23-48). cited by examiner
Sames et al. (Nature. Oct. 9, 1997; 389 (6651): 587-910). cited by examiner
Freire et al. (J. Biol. Chem. Mar. 11, 2011; 286 (10): 7797-811). cited by examiner
Freire et al. (Glycobiology. May 2006; 16 (5): 390-401). cited by examiner
Reis et al. (J. Histochem. Cytochem. Mar. 2000; 48 (3): 377-88). cited by examiner
Stadie et al. (Eur. J. Biochem. 1995; 229: 140-7). cited by examiner
Nishimori et al. (Cancer Res. 1994; 54: 3738-44). cited by examiner
Sorensen et al. (Glycobiology. 2006; 16 (2): 96-107). cited by examiner
Hanisch et al. (J. Biol. Chem. 1999; 274 (15): 9946-54). cited by examiner
Freire et al. (Cancer Res. 2005; 65 (17): 7880-7). cited by examiner
Freire, Teresa et al., “Molecular Basis Of Incomplete O-Glycan Synthesis In MCF-7 Breast Cancer Cells: Putative Role Of MUC6 In Tn Antigen Expression”, Cancer Research, vol. 65, No. 17, pp. 7880-7887 (2005). cited by applicant
Ten Hagen, Kelly G. et al., “All In The Family: The UDP-GalNac: Polypeptide N-Acetylgalactosaminyltransferases”, Glycobiology, vol. 13, No. 1, pp. 1R-16R (2003). cited by applicant
Bartman, Allen et al., “Aberrant Expression Of MUC5AC And MUC6 Gastric Mucin Genes In Colorectal Polyps”, Int. J. Cancer, vol. 80, pp. 210-218 (1999). cited by applicant
De Bolos, Carme et al., “MUC6 Apomucin Shows A Distinct Normal Tissue Distribution That Correlates With Lewis Antigen Expression In The Human Stomach”, Gastroenterology, vol. 109, No. 3, pp. 723-734 (1995). cited by applicant
Guillem, Philippe et al., “Mucin Gene Expression And Cell Differentiation In Human Normal, Premalignant and Malignant Esophagus”, Int. J. Cancer, vol. 88, pp. 856-861 (2000). cited by applicant
Hamamoto, Atsushi et al., “Aberrant Expression Of The Gastric Mucin MUC6 In Human Pulmonary Adenocarcinoma Xenografts”, International Journal of Oncology, vol. 26, pp. 891-896 (2005). cited by applicant
Nishiumi, Noboru et al., “Use of 11p15 Mucins as Prognostic Factors In Small Adenocarcinoma Of The Lung”, Clinical Cancer Research, vol. 9, pp. 5616-5619 (2003). cited by applicant
Pereira, M. B. et al., “Immunohistochemical Study Of The Expression Of MUC5AC and MUC6 In Breast Carcinomas And Adjacent Breast Tissues”, J Clin. Pathol., vol. 54, pp. 210-213 (2001). cited by applicant
Primary Examiner: Rawlings, Stephen
Attorney, Agent or Firm: Arrigo, Lee & Guttman LLP
رقم الانضمام: edspgr.09657074
قاعدة البيانات: USPTO Patent Grants