Beta-lactamase formulations and uses thereof
Inventors
Bristol, Andrew • Kaleko, Michael • Connelly, Sheila
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12178917-B2
Publication Date
2024-12-31
Expiration Date
Abstract
The present invention provides, in part, formulations comprising a beta-lactamase. Particularly, modified-release formulations comprising a beta-lactamase are provided which release a substantial amount of the beta-lactamase in the intestines. Therapeutic uses of the beta-lactamase formulations are also provided.
Core Innovation
The invention concerns treating or preventing Clostridium difficile infection (CDI) and/or Clostridium difficile-associated disease in the gastrointestinal tract by administering a modified-release formulation. The formulation comprises at least one modified-release pellet designed to deliver beta-lactamase into the GI tract, and each modified-release pellet includes beta-lactamase, sucrose sphere, hydroxypropylcellulose, an enteric polymer, triethyl citrate, glyceryl monostearate, polysorbate-80, and buffer salt.
The modified-release pellet includes beta-lactamase defined by an amino acid sequence with at least 95% sequence identity to SEQ ID NO:1, 3, or 6, and in certain embodiments the sequence is further specified as SEQ ID NO:1 with an asparagine at Ambler position 276. The formulation architecture and ingredient selection are presented as enabling modified release.
The invention further supports delayed, location-targeted release in the gastrointestinal tract under gastric conditions, including modified-release coatings that remain stable in gastric fluid. The compositions are intended to delay release through gastric conditions and to release a substantial fraction in targeted GI regions such as the small and/or large intestine, while aiming not to interfere with systemic antibiotic efficacy.
Claims Coverage
The patent provides two independent methods for treating or preventing CDI and/or a CDI-associated gastrointestinal disease by administering a modified-release formulation containing specific modified-release pellets. The inventive features focus on modified-release pellet composition and beta-lactamase sequence requirements, with dependent refinements to pellet structure and coating stability in gastric fluid.
Modified-release pellets with defined beta-lactamase and excipient weight ranges
Administering a modified-release formulation comprising at least one modified-release pellet, wherein each modified-release pellet comprises beta-lactamase defined by at least 95% sequence identity to SEQ ID NO:1, 3 or 6, sucrose sphere, hydroxypropylcellulose, an enteric polymer, triethyl citrate, glyceryl monostearate, polysorbate-80, and buffer salt, with the components recited in weight ranges.
Modified-release pellets with specified ingredient amounts and Ambler position 276
Administering a modified-release formulation comprising at least one modified-release pellet, wherein each modified-release pellet comprises beta-lactamase, sucrose sphere, hydroxypropylcellulose, an enteric polymer, triethyl citrate, glyceryl monostearate, polysorbate-80, and buffer salt, and the beta-lactamase comprises the sequence of SEQ ID NO:1 with an asparagine at Ambler position 276.
Overall, the claim coverage is anchored in administering modified-release pellets with a defined composition of beta-lactamase and excipients that support delayed GI delivery, together with beta-lactamase sequence constraints. The claim set also includes refinements involving sequence-specific embodiments, pellet microstructure, and modified-release coating stability in gastric fluid.
Stated Advantages
Delayed, location-targeted release in the gastrointestinal tract under gastric conditions.
Release of a substantial fraction in targeted GI regions such as the small and/or large intestine.
Aiming not to interfere with systemic antibiotic efficacy.
Documented Applications
Treating Clostridium difficile infection (CDI).
Preventing Clostridium difficile infection (CDI).
Treating Clostridium difficile-associated disease in the gastrointestinal tract.
Preventing Clostridium difficile-associated disease.
Mitigating antibiotic-induced gastrointestinal adverse effects.
Interested in licensing this patent?