# US 12,214,002 B2 · Compositions and methods for treating antibiotic resistance

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- Number: US 12,214,002 B2
- Document ID: US12214002B2
- Status: Granted
- Kind: B2
- Application number: 16/760,757
- Filed: 2018-10-30
- Published: 2020-11-12
- Granted: 2025-02-04
- Earliest claimed: 2017-10-30
- Assignees: Seres Therapeutics, Inc.
- Applicants: Seres Therapeutics, Inc.
- Inventors: Christopher Burton Ford; Jessica Bryant; Edward J. O'Brien
- Web page: https://patentgrep.com/patent/US12214002B2

## CPC

- A61K 35/742: Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 31/04: Antibacterial agents
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to compositions and methods for reducing the carriage of antibiotic resistance genes.

## Claims

### Claim 1

A method of reducing an abundance of at least one antibiotic-resistance gene in the microbiome of a mammalian subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising a combination of bacteria, the combination comprising Blautia wexlerae and Anaerotruncus colihominis, wherein after the administration of the composition, the abundance of the at least one antibiotic-resistance gene in the microbiome of the subject is reduced as compared to a corresponding subject who did not receive the administration of the composition, wherein the at least one antibiotic-resistance gene is capable of conferring resistance to beta-lactam antibiotics and at least one additional antibiotic drug class, and wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 2

A method of treating a mammalian subject at risk for or diagnosed with an undesirable level of bacteria that are resistant to multiple antibiotic drug classes, comprising administering to the subject a therapeutically effective amount of a composition comprising a combination of bacteria, wherein the combination comprises Blautia wexlerae and Anaerotruncus colihominis, wherein the undesirable level is a level significantly greater than that in a healthy subject population and the multiple antibiotic drug classes comprise beta-lactam antibiotics and at least one additional antibiotic drug class, and wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 97% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more bacterial species.

### Claim 4 (depends on 1)

The method of claim 1, wherein the bacteria are in a spore form, a vegetative form, or a mixed vegetative form and spore form.

### Claim 5 (depends on 1)

The method of claim 1, wherein, prior to the administration, the subject has been unresponsive to antibiotic treatment, has or is at risk of developing Clostridium difficile infection, or has or is at risk of developing colitis.

### Claim 6 (depends on 1)

The method of claim 1, wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 98% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 98% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 7 (depends on 1)

The method of claim 1, wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 99% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 99% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 8 (depends on 1)

The method of claim 1, wherein:
(a) the Blautia wexlerae comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 9 (depends on 2)

The method of claim 2, wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 98% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 98% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 10 (depends on 2)

The method of claim 2, wherein:
(a) the Blautia wexlerae comprises a 16S rDNA sequence that is at least 99% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises a 16S rDNA sequence that is at least 99% identical to the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 11 (depends on 2)

The method of claim 2, wherein:
(a) the Blautia wexlerae comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 104-110 and 255; and
(b) the Anaerotruncus colihominis comprises the 16S rDNA sequence set forth in any one of SEQ ID NOs: 89-92.

### Claim 12 (depends on 2)

The method of claim 2, wherein the composition comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more bacterial species.

### Claim 13 (depends on 2)

The method of claim 2, wherein the bacteria are in a spore form, a vegetative form, or a mixed vegetative form and spore form.

### Claim 14 (depends on 1)

The method of claim 1, wherein the bacteria are cultured.

### Claim 15 (depends on 2)

The method of claim 2, wherein the bacteria are cultured.

### Claim 16 (depends on 1)

The method of claim 1, wherein the composition is administered to the subject via oral delivery, colonoscopic delivery, or nasogastric delivery.

### Claim 17 (depends on 2)

The method of claim 2, wherein the composition is administered to the subject via oral delivery, colonoscopic delivery, or nasogastric delivery.

### Claim 18 (depends on 1)

The method of claim 1, wherein the abundance of 2, 3, 4, 5, 6, 7, 8, 9, 10, or more antibiotic-resistance genes in the microbiome of the subject is reduced as compared to the corresponding subject who did not receive the administration of the composition.

### Claim 19 (depends on 1)

The method of claim 1, wherein the at least one additional antibiotic drug class is selected from aminocoumarin antibiotic, aminoglycoside antibiotic, cephalosporin, cephamycin, fluoroquinolone antibiotic, glycylcycline, macrolide antibiotic, nitroimidazole antibiotic, nucleoside antibiotic, penam, peptide antibiotic, phenicol antibiotic, rifamycin antibiotic, benzalkonium chloride, monobactam, penem, streptogramin antibiotic, rhodamine, triclosan, lincosamide antibiotic, acridine dye, carbapenem, tetracycline antibiotic, and fosfomycin.

### Claim 20 (depends on 2)

The method of claim 2, wherein the at least one additional antibiotic drug class is selected from aminocoumarin antibiotic, aminoglycoside antibiotic, cephalosporin, cephamycin, fluoroquinolone antibiotic, glycylcycline, macrolide antibiotic, nitroimidazole antibiotic, nucleoside antibiotic, penam, peptide antibiotic, phenicol antibiotic, rifamycin antibiotic, benzalkonium chloride, monobactam, penem, streptogramin antibiotic, rhodamine, triclosan, lincosamide antibiotic, acridine dye, carbapenem, tetracycline antibiotic, and fosfomycin.
