Modified beta-lactamases and methods and uses related thereto

Patent metadata

Field	Value
Publication number	US-10253306-B2
Application number	US-201715661416-A
Country	US
Kind code	B2
Filing date	Jul 27, 2017
Priority date	May 24, 2010
Publication date	Apr 9, 2019
Grant date	Apr 9, 2019

Abstract

The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects.
Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

First claim

The invention claimed is:

1. A method for reducing the likelihood of a Clostridium difficile infection in a subject in need thereof, comprising administering an effective amount of a beta-lactamase to the subject, wherein:
the subject is receiving or will receive ceftriaxone; and
the beta-lactamase comprises an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and an asparagine (N) or arginine (R) residue at a position corresponding to position 276 according to Ambler classification.

2. The method of claim 1 , wherein the Clostridium difficile infection is caused by unabsorbed ceftriaxone in the subject's intestinal tract.

3. The method of claim 1 , wherein the method maintains an ecological balance of normal intestinal microbiota.

4. The method of claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1.

5. The method of claim 1 , wherein the beta-lactamase comprises an amino acid sequence having at least 99% sequence identity with SEQ ID NO: 1.

6. The method of claim 1 , wherein the beta-lactamase comprises the amino acid sequence of SEQ ID NO: 1.

7. The method of claim 1 , wherein the beta-lactamase is administered simultaneously to or sequentially with the ceftriaxone.

8. The method of claim 1 , wherein the ceftriaxone is administered intravenously.

9. A method for reducing the likelihood of a Clostridium difficile infection in a subject in need thereof, comprising administering an effective amount of a beta-lactamase to the subject, wherein:
the subject is receiving or will receive ceftriaxone; and
the beta-lactamase comprises the amino acid sequence of SEQ ID NO: 1 and an asparagine (N) residue at a position corresponding to position 276 according to Ambler classification.

10. The method of claim 9 , wherein the Clostridium difficile infection is caused by unabsorbed ceftriaxone in the subject's intestinal tract.

11. The method of claim 9 , wherein the method maintains an ecological balance of normal intestinal microbiota.

12. The method of claim 9 , wherein the beta-lactamase is administered simultaneously to or sequentially with the beta-lactam antibiotic.

13. The method of claim 9 , wherein the ceftriaxone is administered intravenously.

Assignees

• Synthetic Biologics Inc

Inventors

• Koski Pertti
• Airaksinen Ulla
• Valimaki Katja

Classifications

• A61P7/10

  Antioedematous agents; Diuretics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K9/4891

  Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004) · CPC title

• A61K38/50

  acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title