# US 11,027,020 B2 · Delivery constructs for transcytosis and related methods

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- Number: US 11,027,020 B2
- Document ID: US11027020B2
- Status: Granted
- Kind: B2
- Application number: 16/902,256
- Filed: 2020-06-15
- Published: 2020-10-01
- Granted: 2021-06-08
- Earliest claimed: 2018-11-07
- Assignees: Applied Molecular Transport Inc.
- Applicants: Applied Molecular Transport Inc.
- Inventors: Randall J. Mrsny; Tahir Mahmood; Charles Olson; Weijun Feng; Sally Postlethwaite
- Web page: https://patentgrep.com/patent/US11027020B2

## CPC

- A61K 47/642: {the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate}
- A61K 38/20: Interleukins [IL]
- A61K 38/22: Hormones (derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35)
- A61K 47/6415: {Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- C07K 14/28: from Vibrionaceae (F)
- C07K 14/54: Interleukins [IL]
- C12N 15/62: DNA sequences coding for fusion proteins
- C07K 1/18: Ion-exchange chromatography
- C07K 2319/00: Fusion polypeptide
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure provides non-naturally occurring fusion molecules comprising therapeutic cargo moieties, such as IL-22 with a carrier. The disclosure also provides methods and compositions for the production, purification, refolding, formulation, and administration of fusion molecules. Methods and for using the purified molecules to treat and prevent diseases or disorders are also provided herein.

## Claims

### Claim 1

A delivery construct comprising a carrier coupled to a payload, wherein the delivery construct has at least 90% sequence identity to SEQ ID NO: 17, and wherein the carrier consists of the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 9, or an amino acid sequence having at least 95% sequence identity thereto.

### Claim 2 (depends on 1)

The delivery construct of claim 1, wherein the delivery construct comprises the amino acid sequence set forth in SEQ ID NO: 17.

### Claim 3 (depends on 1)

The delivery construct of claim 1, wherein the delivery construct comprises the amino acid sequence set forth in SEQ ID NO: 15.

### Claim 4 (depends on 1)

The delivery construct of claim 1, wherein the delivery construct has a glutamic acid at position 3 and an alanine at position 4.

### Claim 5 (depends on 4)

The delivery construct of claim 4, wherein the carrier is 266 amino acids in length.

### Claim 6 (depends on 1)

The delivery construct of claim 1, wherein the carrier consists of the amino acid sequence set forth in SEQ ID NO: 7.

### Claim 7 (depends on 1)

The delivery construct of claim 1, wherein the carrier consists of the amino acid sequence set forth in SEQ ID NO: 9.

### Claim 8 (depends on 1)

The delivery construct of claim 1, wherein the payload consists of the amino acid sequence set forth in SEQ ID NO: 11.

### Claim 9 (depends on 8)

The delivery construct of claim 8, wherein the carrier is coupled covalently to the payload via a spacer that consists of the amino acid sequence set forth in SEQ ID NO: 13.

### Claim 10 (depends on 1)

The delivery construct of claim 1, wherein the delivery construct consists of the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 17.

### Claim 11 (depends on 1)

A method of treating an inflammatory disease of the gastrointestinal tract in a subject, the method comprising administering to the subject an effective amount of the delivery construct of claim 1.

### Claim 12 (depends on 11)

The method of claim 11, wherein the inflammatory disease is Crohn's disease, ulcerative colitis, pouchitis, proctitis, or graft versus host disease.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disease is Crohn's disease or ulcerative colitis.

### Claim 14 (depends on 4)

The delivery construct of claim 4, wherein the carrier consists of the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 9, or an amino acid sequence having at least 95% sequence identity thereto.

### Claim 15 (depends on 4)

The delivery construct of claim 4, wherein the carrier consists of the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 9, or an amino acid sequence having at least 99% sequence identity thereto.
