# US 7,410,799 B2 · In vivo production and delivery of erythropoietin or insulinotropin for gene therapy

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- Number: US 7,410,799 B2
- Document ID: US7410799B2
- Status: Granted
- Kind: B2
- Application number: 10/885,899
- Filed: 2004-07-07
- Published: 2005-06-23
- Granted: 2008-08-12
- Earliest claimed: 1991-11-05
- Assignees: Shire Human Genetic Therapies, Inc.
- Inventors: Richard F Selden; Douglas Treco; Michael W. Heartlein
- Web page: https://patentgrep.com/patent/US7410799B2

## CPC

- C12N 15/907: {in mammalian cells}
- A61K 47/6901: {Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P 5/18: of the parathyroid hormones
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 39/06: Free radical scavengers or antioxidants
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/505: Erythropoietin [EPO]
- C07K 14/605: Glucagons
- C07K 14/61: Growth hormone [GH], i.e. somatotropin
- C12N 15/85: for animal cells
- C07K 2319/02: containing a signal sequence
- C12N 2510/02: Cells for production
- C12N 2800/108: episomal vectors
- C12N 2830/002: inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
- C12N 2830/85: mammalian
- C12N 2840/20: translation of more than one cistron
- C12N 2840/44: being a specific part of the splice mechanism, e.g. donor, acceptor
- 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)

## Abstract

The present invention relates to transfected primary and secondary somatic cells of vertebrate origin, particularly mammalian origin, transfected with exogenous genetic material (DNA) which encodes erythropoietin or an insulinotropin [e.g., derivatives of glucagon-like peptide 1 (GLP-1)], methods by which primary and secondary cells are transfected to include exogenous genetic material encoding erythropoietin or an insulinotropin, methods of producing clonal cell strains or heterogenous cell strains which express erythropoietin or an insulinotropin, methods of gene therapy in which the transfected primary or secondary cells are used, and methods of producing antibodies using the transfected primary or secondary cells. The present invention also includes primary and secondary somatic cells, such as fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, other somatic cells, which can be cultured and somatic cell precursors, which have been transfected with exogenous DNA encoding EPO or an insulinotropin, which is stably integrated into their genomes or is expressed in the cells episomally.

## Claims

### Claim 1

A transfected primary or secondary cell of vertebrate origin having stably integrated into its genome:
a) exogenous DNA which encodes erythropoietin and
b) DNA sequences, sufficient for expression of the exogenous DNA in the transfected primary or secondary cell, the primary or secondary cell capable of expressing erythropoietin.

### Claim 2 (depends on 1)

The transfected primary or secondary cell of vertebrate origin of claim 1 selected from the group consisting of: transfected fibroblasts, transfected keratinocytes, transfected epithelial cells, transfected endothelial cells, transfected glial cells, transfected neural cells, transfected formed elements of the blood, transfected muscle cells, transfected hepatocytes, and transfected precursors thereof.

### Claim 3 (depends on 2)

The transfected primary or secondary cell of claim 2 which is of mammalian origin.

### Claim 4 (depends on 3)

The transfected primary or secondary cell of claim 3 selected from the group consisting of: transfected primary human cells, transfected secondary human cells, transfected primary rabbit cells and transfected secondary rabbit cells.

### Claim 5 (depends on 1)

The transfected primary or secondary cell of vertebrate origin of claim 1 which additionally includes DNA encoding a selectable marker.

### Claim 6 (depends on 5)

The transfected primary or secondary cell of claim 5 selected from the group consisting of: transfected fibroblasts, transfected keratinocytes, transfected epithelial cells, transfected endothelial cells, transfected glial cells, transfected neural cells, transfected formed elements of the blood, transfected muscle cells, transfected hepatocytes, and transfected precursors thereof.

### Claim 7 (depends on 6)

The transfected primary or secondary cell of claim 6 which is of mammalian origin.

### Claim 8 (depends on 7)

The transfected primary or secondary cell of claim 7 selected from the group consisting of: transfected primary human cells, transfected secondary human cells, transfected primary rabbit cells, and transfected secondary rabbit cells.

### Claim 9 (depends on 1)

The transfected primary or secondary cell of vertebrate origin of claim 1 selected from the group consisting of:
a) transfected primary or secondary cells which, in their untransfected state, do not make or contain erythropoietin;
b) transfected primary or secondary cells which, in their untransfected state, make or contain erythropoietin in abnormally low amounts or in defective form; and
c) transfected primary or secondary cells which, in their untransfected form, make or contain erythropoietin in physiologically normal amounts.

### Claim 10

A primary or secondary cell of vertebrate origin transfected with:
a) exogenous DNA which encodes erythropoietin; and
b) DNA sequences, sufficient for expression of the exogenous DNA in the primary or secondary cell, the sequences of (a) and (b) present in the cell in an episome.

### Claim 11 (depends on 10)

The primary or secondary cell of vertebrate origin of claim 10 selected from the group consisting of: fibroblasts, keratinocytes, epithelial cells, endothelial cells, glial cells, neural cells, formed elements of the blood, muscle cells, hepatocytes, and precursors thereof.

### Claim 12 (depends on 11)

The primary or secondary cell of claim 11 which is of mammalian origin.

### Claim 13 (depends on 12)

The primary or secondary cell of claim 12 selected from the group consisting of: primary human cells, secondary human cells, primary rabbit cells, and secondary rabbit cells.