Beta-lactamases with improved properties for therapy

Patent metadata

Field	Value
Publication number	US-10336995-B2
Application number	US-201816112283-A
Country	US
Kind code	B2
Filing date	Aug 24, 2018
Priority date	Apr 17, 2014
Publication date	Jul 2, 2019
Grant date	Jul 2, 2019

Abstract

This invention relates to, in part, compositions of beta-lactamases and methods of using these enzymes in, for example, gastrointestinal tract (GI tract) disorders such as C. difficile infection (CDI).

First claim

What is claimed is:

1. A beta-lactamase comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1 and the following mutations according to Ambler classification:
an aliphatic hydrophobic residue other than glutamine (Q) at position 135.

2. The beta-lactamase of claim 1 , wherein the aliphatic hydrophobic residue is selected from glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V).

3. The beta-lactamase of claim 2 , wherein the aliphatic hydrophobic residue is methionine (M).

4. A polynucleotide comprising a polynucleotide sequence encoding the beta-lactamase of claim 1 .

5. A host cell comprising the polynucleotide of claim 4 .

6. A pharmaceutical composition, comprising the beta-lactamase of claim 1 and a pharmaceutically acceptable carrier or excipient.

7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is formulated for oral administration, optionally selected from a tablet, multi-particulate sprinkle, and a multi-particulate capsule.

8. A method for preventing an antibiotic-induced adverse effect in the gastrointestinal (GI) tract, comprising administering an effective amount of a beta-lactamase to a patient in need thereof, wherein the beta-lactamase comprises an amino acid sequence having at least 95% sequence identity with SEQ ID NO: 1 and the following mutations according to Ambler classification:
an aliphatic hydrophobic residue other than glutamine (Q) at position 135.

9. The method of claim 8 , wherein the aliphatic hydrophobic residue is selected from glycine (G), leucine (L), isoleucine (I), methionine (M), and valine (V).

10. The method of claim 9 , wherein the aliphatic hydrophobic residue is methionine (M).

11. The method of claim 8 , wherein the subject is being administered or will be administered an antibiotic.

12. The method of claim 8 , wherein the antibiotic-induced adverse effect in the gastrointestinal (GI) tract is selected from C. difficile infection (CDI), C. difficile -associated disease, and antibiotic-associated diarrhea (AAD).

Assignees

• Synthetic Biologics Inc

Inventors

• Kaleko Michael
• Connelly Sheila

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P39/02

  Antidotes · 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

• C12N9/86 Primary

  acting on amide bonds in cyclic amides, e.g. penicillinase {(3.5.2)} · CPC title

• C12Y305/02006

  Beta-lactamase (3.5.2.6) · CPC title