# US 11,439,671 B2 · Therapeutic bacterial composition

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- Number: US 11,439,671 B2
- Document ID: US11439671B2
- Status: Granted
- Kind: B2
- Application number: 17/324,898
- Filed: 2021-05-19
- Published: 2021-09-09
- Granted: 2022-09-13
- Earliest claimed: 2021-05-19
- Assignees: Microbiotica Limited
- Applicants: Microbiotica Limited
- Inventors: Matthew Robinson; Trevor Lawley; Michael Romanos; Kevin Vervier; Simon Harris; Ghaith Bakdash; Amy Popple; Dominika Klisko
- Web page: https://patentgrep.com/patent/US11439671B2

## CPC

- A61K 35/74: Bacteria (therapeutic use of a bacterial protein A61K38/00)
- C12Q 1/689: for bacteria
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- G01N 33/4833: {of solid biological material, e.g. tissue samples, cell cultures (tissue in vivo A61B5/00; cell suspensions G01N33/48735)}
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- G01N 2333/195: from bacteria
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to bacterial compositions useful in the treatment of cancer. In particular, the compositions can be used as a co-therapy with an immune checkpoint therapy. The invention also relates to methods for identifying a subject that will respond to therapy with an immune checkpoint inhibitor comprising determining the abundance of bacteria in a biological sample from said subject.

## Claims

### Claim 1

A method for treating melanoma or non-small cell lung cancer in a subject in need thereof, comprising administering to the subject a composition comprising isolated bacteria selected from at least two species wherein the bacteria from the first species comprise a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1, and the bacteria from the second species comprise a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2 wherein said subject is receiving, has received or will receive therapy with an anti-PD-1 or anti-PD-L1 antibody, thereby treating the melanoma or non-small cell lung cancer in the subject.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said composition further comprises one or more bacteria comprising a 16S rDNA sequence selected from SEQ ID NOs: 3 to 15 or a sequence having at least 98.7% sequence identity thereto.

### Claim 3 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria from 7 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NO: 3 to 15 or a sequence having at least 98.7% sequence identity thereto.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria from 4 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NO: 3 to 15 or a sequence having at least 98.7% sequence identity thereto.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the subject has melanoma.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the melanoma is Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, acral-lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, nodular melanoma, subungual melanoma, cutaneous melanoma, uveal/intraocular melanoma, superficial spreading melanoma, or cutaneous or intraocular malignant melanoma.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the immune checkpoint inhibitor is selected from nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, spartalizumab camrelizumab sintilimab, or tislelizumab.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the composition is administered by oral administration or rectal administration.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the composition is in the form of a capsule, tablet, gel or liquid.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the subject has received prior anti-cancer therapy with an anti-PD-1 or anti-PD-L1 antibody.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the anti-PD-1 or anti-PD-L1 antibody is administered before, after or at the same time as the bacterial composition.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the composition comprises live, attenuated or killed bacteria.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the composition is lyophilised.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the composition does not comprise bacterial spores.

### Claim 15 (depends on 1)

The method according to claim 1, further comprising surgical, radiation, and/or chemotherapeutic cancer intervention or administration of an anti-cancer therapeutic.

### Claim 16 (depends on 1)

The method according to claim 1, wherein the subject has been determined to be a non-responder to the previous anti-cancer treatment with an anti-PD-1 or anti-PD-L1 antibody.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the subject has been determined to have a microbial profile in the gut microbiome with an abundance of one or more bacteria comprising a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity thereto at or below a reference value from subjects that do not respond to therapy with an anti-PD-1 or anti-PD-L1 antibody.

### Claim 18 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 or a sequence having at least 98.7% sequence identity thereto.

### Claim 19 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 3, 4, 5, 6, 7, 8 and 9 or a sequence having at least 98.7% sequence identity thereto.

### Claim 20 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 3, 6, 7, 8, 9, 11, 12, 13, 14 and 15 or a sequence having at least 98.7% sequence identity thereto.

### Claim 21 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 3, 6, 7, 8, 9, 11 and 14 or a sequence having at least 98.7% sequence identity thereto.

### Claim 22 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 7, 9, 13, 16, 18, 19 and 20 or a sequence having at least 98.7% sequence identity thereto.

### Claim 23 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 7, 9, 18 and 20 or a sequence having at least 98.7% sequence identity thereto.

### Claim 24 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria comprising a 16S rDNA sequence of SEQ ID NO: 7 or a sequence having at least 98.7% sequence identity thereto.

### Claim 25 (depends on 1)

The method according to claim 1, wherein said composition further comprises bacteria species comprising a 16S rDNA sequence from each of SEQ ID NOs: 3, 5, 7, 10, 11, 12, 13 and 14 or a sequence having at least 98.7% sequence identity thereto.