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Assignees
Member
BiosYnth s.r.l.BiosYnth s.r.l. is a biotechnology firm specializing in the research, development, and innovation of bacterial and viral vaccine platforms. With over 40 years of expertise, the company focuses on glycoconjugate, nanostructured vector, and synthetic peptide technologies to address invasive infectious diseases and antibiotic resistance. Operations comply with GLP and GMP standards and are supported by a robust patent portfolio and international collaborations.
BiosYnth s.r.l. is a biotechnology firm specializing in the research, development, and innovation of bacterial and viral vaccine platforms. With over 40 years of expertise, the company focuses on glycoconjugate, nanostructured vector, and synthetic peptide technologies to address invasive infectious diseases and antibiotic resistance. Operations comply with GLP and GMP standards and are supported by a robust patent portfolio and international collaborations.
Publication Number
US-11147872-B2
Publication Date
2021-10-19
Expiration Date
Abstract
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 S. pneumoniae, N. meningitidis, H. influenzae, K. pneumoniae, M. tuberculosis, S. aureus, or from intestinal infections due to S. typhi, V. cholerae and E. coli. The present invention additionally refers to new polyvalent glycoconjugate vaccines for the protection from C. albicans and E. coli systemic and genitourinary infections or for the protection from M. bovis infections in veterinary medicine.
Core Innovation
The invention relates to a conjugation process for preparing an antigenic multivalent molecular construct. A basic unit comprises a helper-T dependent carrier protein covalently bound to a minimum of three carbohydrate structures that are capsular polysaccharides of different serological specificity. Each carbohydrate structure comprises at least one repeating basic epitope consisting of a minimum of five to twelve monosaccharide residues, and the binding uses a linker comprising imine reduced bonds and amide bonds.
The invention provides a defined conjugation process to assemble multiple carbohydrate antigens on the carrier through a specified linker architecture and controlled epitope size. In the claimed process, the carbohydrate structures are chemically activated to mono-functionality or polyfunctionality by O-de-hydrogen uncoupling via oxidation and reductive amination forming imine reduced bonds with an alkyl diamine spacer, followed by derivatization to active esters of the carbohydrate structures.
The process then couples simultaneously coupling, or step-by-step coupling, of at least three ester-derivative carbohydrate structures to the amino groups of the polyfunctional carrier protein through formation of amide bonds. The carrier protein is selected from CRM197, diphtheria toxoid, tetanus toxoid, Protein D from Haemophilus influenzae, Pneumonococcal surface proteins, Pneumonococcal toxin and derivatives thereof.
Claims Coverage
The partial content provides one independent claim covering a conjugation process and the resulting antigenic multivalent molecular construct as obtained by that process. The core claim is built around at least three different capsular polysaccharides on a helper-T dependent carrier via a linker that includes imine reduced bonds and amide bonds, with carbohydrate epitopes sized as repeating basic epitopes of five to twelve monosaccharide residues. Dependent claims refine the chemistry, carrier selection, carbohydrate selection, and characterization criteria.
Conjugated multivalent construct on helper-T dependent carrier using imine-reduced and amide bond linker
A conjugation process for preparing the antigenic multivalent molecular construct consisting of a basic unit comprising a helper-T dependent carrier protein covalently bound to a minimum of three carbohydrate structures which are capsular polysaccharides of different serological specificity by a linker comprising imine reduced bonds and amide bonds, wherein each carbohydrate structure comprises at least one of the repeating basic epitopes consisting of a minimum of five to twelve monosaccharide residues, and wherein at least one mole or fraction thereof of protein carrier carries at least one mole or fraction thereof of each of the at least three different type-specific carbohydrate antigens in a physiologically acceptable vehicle, optionally together with an adjuvant or pharmaceutically acceptable excipients.
Carbohydrate activation to active esters via oxidation and reductive amination with alkyl diamine spacer
Chemical activation of the at least three antigenically different carbohydrate structures to mono-functionality or polyfunctionality by O-de-hydrogen uncoupling via oxidation and reductive amination forming imine reduced bonds with an alkyl diamine spacer, then derivatized to active esters of said carbohydrate structures.
Coupling of ester-derivative carbohydrates to carrier amino groups via amide bond formation
Simultaneously coupling, or a step-by-step coupling, of at least three ester-derivative carbohydrate structures to the amino groups of the polyfunctional carrier protein through the formation of amide bonds.
Helper-T dependent carrier selection including CRM197 and related proteins/toxoids
Carrier protein selected from the group consisting of natural diptheria mutant 6 protein CRM197, diptheria toxoid, tetanus toxoid, Protein D from Haemophilus influenzae, Pneumonococcal surface proteins, Pneumonococcal toxin and derivatives thereof including tetanus toxoid derivatized by an adipic acid dihydrazide spacer.
Characterized carbohydrate epitopes sized as 5–12 monosaccharide residues and assessed by MIC50 inhibition
Carbohydrate structures contain repeating basic epitopes made of 5–12 monosaccharide residues, characterized by molecular mass determination and NMR spectroscopy and assessed antigenically via MIC50 inhibition in a homologous Polysaccharide-Antibody reference system using type-specific or group-specific polyclonal or monoclonal antibodies.
Across the independent claim and its refined dependents, the inventive coverage centers on a conjugation process that activates at least three antigenically different capsular polysaccharides to active esters, links them to a helper-T dependent polyfunctional carrier protein via a linker architecture including imine reduced bonds and amide bonds, and requires carbohydrate repeating basic epitope size of five to twelve monosaccharide residues, with additional dependent coverage specifying characterization and MIC50 inhibition-based antigenic assessment.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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