Polypeptide-antigen conjugates with non-natural amino acids
Inventors
FAIRMAN, Jeffery • Heinrichs, Jon H. • Chan, Wei
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11998599-B2
Publication Date
2024-06-04
Expiration Date
Abstract
Methods for the production of immunogenic compositions containing a non-natural amino acid are disclosed. The non-natural amino acid can be a site for attachment of antigens, such as bacterial capsular polysaccharides, to make immunogenic conjugates. Bio-orthogonal attachment chemistry incorporated into the non-natural amino acids allows for more efficient and potent antigen presentation to the immune system, simplified purification, and more well-defined structure of these semi-synthetic immunogens.
Core Innovation
The invention provides immunogenic conjugate compositions containing at least 21 distinct crosslinked carrier protein-antigen conjugates. Each conjugate includes an antigen that is a distinct serotype of a Streptococcus pneumoniae capsular polysaccharide antigen, with a distinct crosslinked carrier protein-antigen conjugate for each of specified serotypes and at least eight additional capsular polysaccharide antigens selected from a defined serotype group.
The carrier protein comprises a polypeptide that includes at least one T-cell activating epitope and at least 95% sequence identity to SEQ ID NO: 1. The carrier protein is engineered by substituting 2-amino-3-(4-(azidomethyl)phenyl)propanoic acid (pAMF) for a naturally occurring amino acid at residues 34, 213, 245, 265, 386, and 527 numbered according to SEQ ID NO: 1, and the capsular polysaccharide antigen is conjugated to the non-natural amino acids in the carrier protein.
The compositions include multivalent sets of distinct pneumococcal serotype conjugates and further describe conjugation using defined linking moieties and carrier-engineering approaches. The document also refers to cyclooctyne-containing features, formula XI/XIa, and composition-level constraints, including a specified linkage parameter range and an overall polysaccharide-to-carrier weight ratio.
Claims Coverage
The independent claim coverage is directed to a multivalent immunogenic composition defined by crosslinked carrier protein-antigen conjugates, with five inventive features: at least 21 distinct pneumococcal serotype conjugates, an engineered carrier protein with T-cell activating epitopes and at least 95% sequence identity to SEQ ID NO: 1, pAMF substitution at specified residues, defined linkage structure, and composition constraints.
At least 21 distinct crosslinked carrier protein-antigen conjugates with defined pneumococcal serotype coverage
A composition comprising at least 21 distinct crosslinked carrier protein-antigen conjugates, where each conjugate comprises a Streptococcus pneumoniae capsular polysaccharide antigen from specified serotypes including a distinct conjugate for each of serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F and at least eight additional capsular polysaccharide antigens selected from a defined group.
Carrier protein with at least one T-cell activating epitope, at least 95% sequence identity to SEQ ID NO: 1, and pAMF substitution at specified residues
A carrier protein comprising a polypeptide with at least one T-cell activating epitope and at least 95% sequence identity to SEQ ID NO: 1, wherein pAMF non-natural amino acid substitutes for a naturally occurring amino acid at residues 34, 213, 245, 265, 386, and 527 numbered according to SEQ ID NO: 1.
Conjugation of the capsular polysaccharide antigen to the pAMF nnAAs in the carrier protein
The capsular polysaccharide antigen is conjugated to the nnAAs in the carrier protein.
Cyclooctyne/azide conjugation refinement via linkage structure and formula XI/XIa
The conjugation refinement specifies antigen-to-carrier linkage using formula XI or formula XIa with defined parameter meanings for R1, R2, W, y, n, and X, and includes a cyclooctyne group as a conjugation feature on the capsular polysaccharides.
Composition constraints on linkage parameter n and overall polysaccharide-to-carrier weight ratio
The linkage parameter n is defined within a specified range, and the overall weight-by-weight ratio of all serotype polysaccharides to the carrier protein is at least 1.0.
Overall claim coverage is directed to multivalent compositions of distinct crosslinked carrier protein-pneumococcal capsular polysaccharide conjugates for specified serotype sets, where the carrier protein contains T-cell activating epitopes and at least 95% sequence identity to SEQ ID NO: 1 while carrying pAMF substitutions at defined residues, with further refinement of linkage structure via formula XI/XIa and defined composition constraints.
Stated Advantages
Reduced carrier suppression.
Improved T-cell dependent response.
Documented Applications
Vaccine/immunogenic compositions using enhanced carrier protein-antigen conjugates.
Interested in licensing this patent?