# US 10,767,171 B2 · Beta-lactamases with improved properties for therapy

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- Number: US 10,767,171 B2
- Document ID: US10767171B2
- Status: Granted
- Kind: B2
- Application number: 16/751,734
- Filed: 2020-01-24
- Published: 2020-05-21
- Granted: 2020-09-08
- Earliest claimed: 2014-04-17
- Assignees: Synthetic Biologics, Inc.
- Applicants: Synthetic Biologics, Inc.
- Inventors: Michael Kaleko; Sheila Connelly
- Web page: https://patentgrep.com/patent/US10767171B2

## CPC

- C12N 9/86: acting on amide bonds in cyclic amides, e.g. penicillinase {(3.5.2)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/546: containing further heterocyclic rings, e.g. cephalothin
- A61K 38/50: acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12Y 305/02006: Beta-lactamase (3.5.2.6)
- A61K 38/00: 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## 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).

## Claims

### Claim 1

A beta-lactamase comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1 and a mutation at all of positions 232, 237, 238, and 240, according to Ambler classification,
wherein the beta-lactamase demonstrates greater cephalosporin antibiotic degradation activity as compared to a beta-lactamase having the amino acid sequence of SEQ ID NO: 1.

### Claim 2 (depends on 1)

The beta-lactamase of claim 1, wherein the beta-lactamase has a further mutation at position 276 according to Ambler classification.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 3)

A host cell comprising the polynucleotide of claim 3.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is formulated for oral administration, optionally selected from a tablet, multi-particulate sprinkle, and a multi-particulate capsule.

### Claim 7

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 98% sequence identity with SEQ ID NO: 1 and a mutation at all of positions 232, 237, 238, and 240, according to Ambler classification,
wherein the beta-lactamase demonstrates greater cephalosporin antibiotic degradation activity as compared to a beta-lactamase having the amino acid sequence of SEQ ID NO: 1.

### Claim 8 (depends on 7)

The method of claim 7, wherein the beta-lactamase has a further mutation at position 276 according to Ambler classification.

### Claim 9 (depends on 7)

The method of claim 7, wherein the subject is being administered or will be administered an antibiotic.

### Claim 10 (depends on 7)

The method of claim 7, 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).