Alanine Peptide Composition for Soluble Injectable NFL-TBS40-63
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Solution Overview
Problem
The low solubility, insolubility in common buffer systems, and self-association into fibrillar structures of NFL-TBS 40-63 peptide pose challenges for formulating a stable, injectable pharmaceutical composition suitable for parenteral administration, complicating industrial production and sterilization.
Innovation Solution
Incorporating alanine at specific concentrations (25-120 mM) with pharmaceutically acceptable excipients in a multistep process, including pre-filtration and sterilization, enhances solubility and reduces fibril size and number, enabling easy filtration and sterilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TBS40-63 peptide is used as a tuberculosis vaccine candidate, then it shows promise as a novel antigen, but it forms aggregates that are difficult to solubilize and exhibit poor immunogenicity
Solution Approach 1:
Alanine acts as a mediator between the TBS40-63 peptide and the aqueous environment. The N-terminal alanine residues solubilize the hydrophobic peptide aggregate, enabling it to dissolve in water while maintaining its immunogenic properties. This intermediary approach resolves the contradiction by allowing the peptide to remain soluble without losing its antigenic characteristics.
Solution Approach 2:
The patent changes the physical-chemical parameters of the peptide by adding N-terminal alanine residues. This modification alters the solubility characteristics and aggregate formation tendency of the peptide, transforming it from an insoluble aggregate-forming molecule to a soluble form with improved immunogenicity while preserving the core antigenic sequence.
2Manufacturing precision
If TBS40-63 peptide is purified to homogeneity, then it forms aggregates, but aggregation makes it difficult to purify and store
Solution Approach 1:
N-terminal alanine residues serve as a solubilizing intermediary that prevents aggregate formation during purification and storage. This allows the peptide to be purified to homogeneity without the problematic aggregate formation that would otherwise occur, facilitating easier manufacturing and storage.
3Productivity
If conventional tuberculosis vaccines (BCG, ACW) are used, then they are widely administered, but they have limited efficacy and do not protect against all Mycobacterium species
Solution Approach 1:
The patent focuses on a specific local region of the antigen - the C-terminal 40-63 amino acid sequence of the 6kDa early secreted antigenic target. This local quality approach identifies a specific epitope region that elicits protective immunity against multiple Mycobacterium species, improving upon the broad but less effective coverage of conventional vaccines.
Solution Approach 2:
The vaccine composition combines the TBS40-63 peptide antigen with aluminum salt adjuvant to create a composite vaccine formulation. This composite approach enhances the immunogenicity and protective efficacy against multiple Mycobacterium species, overcoming the limitations of single-component conventional vaccines.
Data Source
Figure 1A~2A
Figure 2B
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AI summary
The present invention provides a pharmaceutical composition comprising NFL-TBS40-63 peptide, biologically active variants or pharmaceutically acceptable salts thereof, an alanine and pharmaceutically acceptable excipients, wherein the alanine is at concentrations comprised between 25 mM and 120 mM. The present invention further provides a manufacturing method of said composition and said pharmaceutical composition for its use as a medicament, particularly for treating cancer.