# US 11,433,106 B2 · Compositions comprising bacterial strains

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- Number: US 11,433,106 B2
- Document ID: US11433106B2
- Status: Granted
- Kind: B2
- Application number: 16/598,699
- Filed: 2019-10-10
- Published: 2020-05-07
- Granted: 2022-09-06
- Earliest claimed: 2015-06-15
- Assignees: 4D Pharma Research Limited
- Applicants: 4D Pharma Research Limited
- Inventors: George Grant; Angela Margaret Patterson; Imke Mulder; Seanin McCluskey; Emma Raftis
- Web page: https://patentgrep.com/patent/US11433106B2

## CPC

- A61K 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00)
- A23L 33/135: Bacteria or derivatives thereof, e.g. probiotics
- A23L 33/30: {Dietetic or nutritional methods, e.g. for losing weight (A23L33/10 takes precedence)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 35/747: Lactobacilli, e.g. L. acidophilus or L. brevis
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/00: Drugs for disorders of the senses
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 1/205: Bacterial isolates
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- A61K 2035/11: {Medicinal preparations comprising living procariotic cells}
- C12R 2001/01: Bacteria or Actinomycetales {; using bacteria or Actinomycetales}
- 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)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- C12R: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention provides compositions comprising bacterial strains for treating and preventing inflammatory and autoimmune diseases.

## Claims

### Claim 1

A method of treating inflammation characterized by an elevated level of interferon-γ (IFN-γ) and interleukin-10 (IL-10) in a subject in need thereof, comprising:
administering to said subject a therapeutically effective amount of a pharmaceutical composition that comprises at least 1×103 colony forming units (CFU)/g of a bacteria strain of the species Parabacteroides distasonis with respect to a total weight of said pharmaceutical composition;
wherein said bacteria strain comprises a 16s rRNA gene sequence with at least 99.5% sequence identity to the sequence of SEQ ID NO:1 or at least 99% sequence identity to the sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:9, as determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2; and
wherein said therapeutically effective amount is effective to reduce said level of IFN-γ and IL-10, as compared to prior to said administering, thereby treating said inflammation in said subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein said subject has a condition that comprises uveitis, multiple sclerosis, an arthritis, neuromyelitis optica, psoriasis, systemic lupus erythematosus, celiac disease, an asthma, allergic asthma, neutrophilic asthma, chronic obstructive pulmonary disease (COPD), scleritis, vasculitis, Behcet's disease, atherosclerosis, atopic dermatitis, emphysema, periodontitis, allergic rhinitis, and allograft rejection.

### Claim 3 (depends on 2)

The method of claim 2, wherein said condition is uveitis; and
wherein said administering results in a reduction in retinal damage in uveitis.

### Claim 4 (depends on 2)

The method of claim 2, wherein said condition is asthma; and
wherein said administering results in a reduction in neutrophilia or eosinophilia.

### Claim 5 (depends on 2)

The method of claim 2, wherein said condition is arthritis, and wherein said arthritis comprises rheumatoid arthritis, osteoarthritis, psoriatic arthritis, spondyloarthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.

### Claim 6 (depends on 1)

The method of claim 1, wherein said bacteria strain is dried.

### Claim 7 (depends on 1)

The method of claim 1, wherein said pharmaceutical composition further comprises a pharmaceutically acceptable excipient, diluent, or carrier.

### Claim 8 (depends on 1)

The method of claim 1, wherein said pharmaceutical composition comprises from about 1×106 to about 1×1011 colony forming units (CFU)/g of said bacteria strain with respect to a total weight of said pharmaceutical composition.

### Claim 9 (depends on 1)

The method of claim 1, wherein said administering further results in a reduction of at least one cytokine of the Th17 pathway that comprises IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, or TNFα.

### Claim 10 (depends on 1)

The method of claim 1, wherein said bacteria strain is the Parabacteroides distasonis strain MRX005 deposited as NCIMB 42382.

### Claim 11

A method of treating inflammation characterized by an elevated level of interleukin-10 (IL-10) in a subject in need thereof, comprising:
administering to said subject a therapeutically effective amount of a pharmaceutical composition that comprises at least 1×103 colony forming units (CFU)/g of a bacteria strain of the species Parabacteroides distasonis with respect to a total weight of said pharmaceutical composition; wherein said bacteria strain totally or partially colonizes the intestine when administered to said subject;
wherein said bacteria strain comprises a 16s rRNA gene sequence with at least 99.5% sequence identity to the sequence of SEQ ID NO:1 or at least 99% sequence identity to the sequence of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:9, as determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2; and
wherein said therapeutically effective amount is effective to reduce said level of IL-10, as compared to prior to said administering, thereby treating said inflammation in said subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein said pharmaceutical composition is encapsulated.

### Claim 13 (depends on 1)

The method of claim 1, wherein said bacteria strain comprises a 16s rRNA gene sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:9.

### Claim 14 (depends on 1)

The method of claim 1, wherein said pharmaceutical composition comprises a second bacteria strain.

### Claim 15 (depends on 14)

The method of claim 14, wherein said second bacteria strain is of the species Parabacteroides merdae.

### Claim 16 (depends on 14)

The method of claim 14, wherein said second bacteria strain is of the species Parabacteroides goldsteinii.

### Claim 17 (depends on 1)

The method of claim 1, wherein said pharmaceutical composition is in the form of a tablet or powder.

### Claim 18 (depends on 1)

The method of claim 1, wherein the bacteria strain is non-spore forming.