# US 2022/0031771 A1 · Microencapsulated and chromosome integrated compositions for l-dopa microbiome therapy

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- Number: US 2022/0031771 A1
- Document ID: US20220031771A1
- Status: Published application
- Kind: A1
- Application number: 17/304,444
- Filed: 2021-06-21
- Published: 2022-02-03
- Earliest claimed: 2020-07-31
- Assignees: Iowa State University Research Foundation, Inc.
- Applicants: Iowa State University Research Foundation, Inc.
- Inventors: Anumantha G. Kanthasamy; Gregory Phillips; Ahmed Abdalla; Nicholas John Backes; Piyush Padhi
- Web page: https://patentgrep.com/patent/US20220031771A1

## CPC

- A61K 35/741: Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06)
- 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 9/5036: {Polysaccharides, e.g. gums, alginate; Cyclodextrin}
- A61K 31/165: having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61P 25/16: Anti-Parkinson drugs
- 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
- C12N 9/0028: {with NAD or NADP as acceptor (1.5.1)}
- C12N 9/0071: {acting on paired donors with incorporation of molecular oxygen (1.14)}
- C12Y 114/14009: 4-Hydroxyphenylacetate 3-monooxygenase (1.14.14.9)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention generally provides methods and compositions for the treatment of Parkinson's disease, Alzheimer's disease, depression, anxiety, and memory deficits. The invention relates to recombinant microorganisms, particularly gut-colonizing probiotics, modified to produce L-DOPA as well as microcapsules and lyophilized formulations comprising the same.

## Claims

### Claim at position 1

1-38. (canceled)

### Claim 39

A recombinant microbial cell comprising a heterologous hpaB and hpaC nucleotide sequence stably integrated into the genome of the cell.

### Claim 40 (depends on 39)

The recombinant microbial cell of claim 39, wherein the recombinant microbial cell produces L-DOPA and is capable of colonizing the gut of a subject.

### Claim 41 (depends on 39)

The recombinant microbial cell of claim 39, wherein the recombinant microbial cell is a probiotic.

### Claim 42 (depends on 41)

The recombinant microbial cell of claim 41, wherein said probiotic is E. coli Nissle 1917.

### Claim 43 (depends on 39)

The recombinant microbial cell of claim 39, wherein the hpaB and hpaC nucleotide sequence comprises SEQ ID NO: 1.

### Claim 44 (depends on 39)

The recombinant microbial cell of claim 39, wherein the hpaB and hpaC nucleotide sequence is operably linked to a promoter sequence.

### Claim 45 (depends on 44)

The recombinant microbial cell of claim 44, wherein the promoter is a constitutive promoter or an inducible promoter.

### Claim 46 (depends on 45)

The recombinant microbial cell of claim 45, wherein the promoter is a rhamnose inducible promoter.

### Claim 47

(canceled)

### Claim 48 (depends on 39)

A microencapsulated composition comprising:
a core component comprising the recombinant microbial cell of claim 39; and
a coating material surrounding the core component.

### Claim 49 (depends on 48)

The microencapsulated composition of claim 48, wherein the core component further comprises an aromatic amino acid- or DOPA-decarboxylase inhibitor.

### Claim 50 (depends on 49)

The microencapsulated composition of claim 49, wherein the DOPA decarboxylase inhibitor is carbidopa or benserazide.

### Claim 51 (depends on 48)

The microencapsulated composition of claim 48, wherein the coating material comprises a polymer.

### Claim 52 (depends on 48)

The microencapsulated composition of claim 48, wherein the coating material comprises alginic acid or an alginate.

### Claim 53 (depends on 48)

The microencapsulated composition of claim 48, further comprising a pharmaceutically acceptable carrier.

### Claim 54 (depends on 39)

A method for treating Parkinson's disease, depression and/or anxiety, or mild cognitive impairment or improving motivational performance or memory and learning, the method comprising:
administering to a subject in need thereof an effective amount of the recombinant microbial cell of claim 39.

### Claim 55 (depends on 54)

The method of claim 54, wherein said composition is administered orally.

### Claim 56 (depends on 54)

The method of claim 54, wherein the composition is administered twice daily, daily, or on alternate days.

### Claim 57 (depends on 54)

The method of claim 54, wherein the subject is a mammal.

### Claim 58 (depends on 57)

The method of claim 57, wherein the mammal is a human.

### Claim 59 (depends on 54)

The method of claim 54, wherein the depression and/or anxiety or the mild cognitive impairment is associated with Parkinson's disease, Parkinsonism, Alzheimer's disease, or other memory disorder.
