# US 2019/0316089 A1 · Synthetic membrane-receiver complexes

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- Number: US 2019/0316089 A1
- Document ID: US20190316089A1
- Status: Published application
- Kind: A1
- Application number: 16/409,576
- Filed: 2019-05-10
- Published: 2019-10-17
- Earliest claimed: 2013-11-18
- Assignees: Rubius Therapeutics, Inc.
- Applicants: Rubius Therapeutics, Inc.
- Inventors: Avak Kahvejian; Jordi Mata-Fink; John Round; David Arthur Berry; Noubar B. Afeyan
- Web page: https://patentgrep.com/patent/US20190316089A1

## CPC

- C12N 5/0641: {Erythrocytes}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/5068: {Cell membranes or bacterial membranes enclosing drugs (liposomes with additional exogenous lipids A61K9/127)}
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 35/18: Erythrocytes (haemoglobin A61K38/42)
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/001: {Preparations to induce tolerance to non-self, e.g. prior to transplantation}
- A61K 39/385: Haptens or antigens, bound to carriers
- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/082: Hepadnaviridae (F), e.g. hepatitis B virus
- C12N 9/88: Lyases (4.)
- C07K 2317/622: Single chain antibody (scFv)
- C12N 2510/00: Genetically modified cells
- C12Y 204/02004: Thymidine phosphorylase (2.4.2.4)
- C12Y 304/22: Cysteine endopeptidases (3.4.22)
- C12Y 403/01024: Phenylalanine ammonia-lyase (4.3.1.24)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- 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)
- C12Y: ENZYMES
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

## Claims

### Claim 1

An enucleated erythroid cell comprising an exogenous polypeptide comprising phenylalanine ammonia lyase (PAL) or a functional fragment thereof,
wherein the enucleated erythroid cell is made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into a nucleated erythroid cell precursor.

### Claim 2 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the enucleated erythroid cell further comprises a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.

### Claim 3 (depends on 1)

The enucleated erythroid cell of claim 1, which comprises at least 1,000 copies of the exogenous polypeptide.

### Claim 4 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide is intracellular.

### Claim 5 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide consists essentially of PAL.

### Claim 6 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the exogenous polypeptide consists of PAL.

### Claim 7 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the exogenous nucleic acid comprises DNA.

### Claim 8 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the exogenous nucleic acid comprises RNA.

### Claim 9 (depends on 1)

The enucleated erythroid cell of claim 1, which is a reticulocyte.

### Claim 10 (depends on 1)

The enucleated erythroid cell of claim 1, which is an erythrocyte.

### Claim 11 (depends on 1)

The enucleated erythroid cell of claim 1, which lacks A and B antigens.

### Claim 12 (depends on 1)

The enucleated erythroid cell of claim 1, wherein the nucleated erythroid cell precursor is a CD34+ hematopoietic stem cell.

### Claim 13 (depends on 1)

The enucleated erythroid cell of claim 1, which is a human cell.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of claim 1.

### Claim 15 (depends on 14)

The pharmaceutical composition of claim 14, wherein at least about 90% of enucleated erythroid cells in the pharmaceutical composition comprise the exogenous polypeptide.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of claim 1, wherein at least 70% of the cells in the pharmaceutical composition are the enucleated erythroid cells.

### Claim 17

A nucleated erythroid cell precursor comprising an exogenous polypeptide comprising PAL or a functional fragment thereof,
wherein the nucleated erythroid cell precursor was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell precursor.

### Claim 18 (depends on 17)

The nucleated erythroid cell precursor of claim 17, wherein the exogenous polypeptide is intracellular.

### Claim 19 (depends on 17)

The nucleated erythroid cell precursor of claim 17, which has been cultured after the introduction of the exogenous nucleic acid.

### Claim 20 (depends on 17)

The nucleated erythroid cell precursor of claim 17, which further comprises a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.

### Claim 21

A method of reducing phenylalanine concentration in the blood of a subject, comprising administering to the subject a pharmaceutical composition comprising a plurality of enucleated erythroid cells comprising an exogenous polypeptide comprising PAL, wherein each of the enucleated erythroid cells of said plurality was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into a nucleated erythroid cell precursor.

### Claim 22 (depends on 21)

The method of claim 21, wherein the exogenous polypeptide is intracellular.

### Claim 23 (depends on 21)

The method of claim 21, wherein the enucleated erythroid cells further comprise a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.

### Claim 24

A method of reducing phenylalanine concentration in the blood of a subject, comprising administering to the subject a pharmaceutical composition comprising a plurality of nucleated erythroid cell precursors comprising an exogenous polypeptide comprising PAL, wherein each of the nucleated erythroid cell precursors of said plurality was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell precursor.

### Claim 25 (depends on 24)

The method of claim 24, wherein the exogenous polypeptide is intracellular.

### Claim 26 (depends on 24)

The method of claim 24, wherein the nucleated erythroid cell precursor has been cultured after the introduction of the exogenous nucleic acid.

### Claim 27 (depends on 24)

The method of claim 24, wherein the nucleated erythroid cell precursors further comprise a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.