Modified beta-lactamases and methods and uses related thereto

Patent metadata

Field	Value
Publication number	US-9587234-B2
Application number	US-201615054292-A
Country	US
Kind code	B2
Filing date	Feb 26, 2016
Priority date	May 24, 2010
Publication date	Mar 7, 2017
Grant date	Mar 7, 2017

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 composition, comprising a beta-lactamase comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and a hydrophilic amino acid residue other than aspartic acid (D) at a position corresponding to position 276 according to Ambler classification, wherein the hydrophilic amino acid residue is selected from asparagine (N) and arginine (R).

2. The beta-lactamase according to claim 1 , wherein the hydrophilic amino acid residue is located in an alpha helix.

3. The beta-lactamase according to claim 1 , wherein the beta-lactamase further comprises at least one amino acid selected from a leucine (L) at a position corresponding to position 220 and an arginine (R) at a position corresponding to position 244 according to Ambler classification.

4. The beta-lactamase according to claim 1 , wherein the beta-lactamase hydrolyzes a penicillin and a cephalosporin.

5. The beta-lactamase according to claim 4 , wherein the cephalosporin is selected from cefoperazone and ceftriaxone.

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

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

8. A pharmaceutical composition for oral administration comprising an effective amount of a beta-lactamase comprising an amino acid sequence having at least 97% sequence identity with SEQ ID NO: 1 and a hydrophilic amino acid residue other than aspartic acid (D) at a position corresponding to position 276 according to Ambler classification, wherein the hydrophilic amino acid residue is selected from asparagine (N) and arginine (R).

9. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase comprises an amino acid sequence of at least 98% sequence identity with SEQ ID NO: 1.

10. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase comprises an amino acid sequence of at least 99% sequence identity with SEQ ID NO: 1.

11. The pharmaceutical composition according to claim 8 , wherein the beta-lactamase hydrolyzes a penicillin and a cephalosporin.

12. The pharmaceutical composition according to claim 11 , wherein the cephalosporin is selected from cefoperazone and ceftriaxone.

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

• A61K38/50

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

• A61P1/12

  Antidiarrhoeals · CPC title

• A61K31/43

  Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula [IMAGE cpc-sch-A61K-0952.gif], e.g. penicillins, penems · CPC title