Microbiome-based informed method to formulate live biotherapeutics

Patent metadata

Field	Value
Publication number	US-10967012-B2
Application number	US-202016917661-A
Country	US
Kind code	B2
Filing date	Jun 30, 2020
Priority date	Oct 16, 2019
Publication date	Apr 6, 2021
Grant date	Apr 6, 2021

Abstract

Methods of formulating live biotherapeutics are disclosed in which a deficiency or excess of a specific bacterial strain in a person's microbiome is identified by comparing a gene-specific characterization of the person's microbiome against a comprehensive, non-redundant reference gene catalog, and the biotherapeutic is formulated by selecting bacteria to address the deficiency or excess. Embodiments include the formulation of live biotherapeutics for improving the health of a person's vaginal microbiome, i.e. using a vaginal reference gene catalog, and may be suitable for ameliorating, treating, or preventing a malignancy such as a cancer of the female genitourinary system.

First claim

The invention claimed is:

1. A method for treating bacterial vaginosis in a female human subject, comprising:
administering a remedial live biotherapeutic formulation to the subject,
wherein the remedial live biotherapeutic formulation comprises bacteria adapted to remedy a deficiency or excess of at least one bacterial strain in the subject's vaginal microbial community, and
wherein the bacteria comprise a selected strain or consortium of strains comprising at least one of:
(i) Lactobacillus crispatus bacteria configured to express at least one of the asparagine synthase B (asnB) gene of SEQ ID NO: 2 and the asparagine synthase B (asnB) gene of SEQ ID NO: 3; and
(ii) Lactobacillus crispatus bacteria containing an asparagine synthase B (asnB) gene encoding at least one of a polypeptide of SEQ ID NO: 5 and a polypeptide of SEQ ID NO: 6.

2. The method of claim 1 , wherein the Lactobacillus crispatus bacteria are configured to express the asparagine synthase B (asnB) gene of SEQ ID NO: 2.

3. The method of claim 1 , wherein the live biotherapeutic formulation further comprises a pharmaceutically acceptable carrier.

4. The method of claim 1 , wherein the live biotherapeutic formulation further comprises an agent adapted to reduce or remove free ammonia from the vaginal environment.

5. The method of claim 1 , wherein the Lactobacillus crispatus bacteria are configured to express the asparagine synthase B (asnB) gene of SEQ ID NO: 3.

6. The method of claim 1 , wherein the Lactobacillus crispatus bacteria containing an asparagine synthase B (asnB) gene encode the polypeptide of SEQ ID NO: 5.

7. The method of claim 1 , wherein the Lactobacillus crispatus bacteria containing an asparagine synthase B (asnB) gene encode the polypeptide of SEQ ID NO: 6.

Assignees

• Univ Maryland

Inventors

• Ravel Jacques
• France Michael
• Rutt Lindsay
• Ma Bing

Classifications

• A61K35/74

  Bacteria (therapeutic use of a bacterial protein A61K38/00) · CPC title

• C12N1/20

  Bacteria; Culture media therefor · CPC title

• A61K35/742 Primary

  Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes · CPC title

• A61K35/747 Primary

  Lactobacilli, e.g. L. acidophilus or L. brevis · CPC title

• A61P15/02

  for disorders of the vagina · CPC title