# US 8,465,948 B2 · Long-acting veterinary polypeptides and methods of producing and administering same

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- Number: US 8,465,948 B2
- Document ID: US8465948B2
- Status: Granted
- Kind: B2
- Application number: 13/192,542
- Filed: 2011-07-28
- Published: 2012-01-05
- Granted: 2013-06-18
- Earliest claimed: 2006-02-03
- Assignees: Prolor Biotech Ltd.
- Applicants: Fuad Fares; Udi Eyal Fima
- Inventors: Fuad Fares; Udi Eyal Fima
- Web page: https://patentgrep.com/patent/US8465948B2

## CPC

- C07K 14/505: Erythropoietin [EPO]
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 5/06: of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/06: Antianaemics
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/555: Interferons [IFN]
- C07K 14/59: Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
- C07K 14/61: Growth hormone [GH], i.e. somatotropin
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/31: fusions, other than Fc, for prolonged plasma life, e.g. albumin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.

## Claims

### Claim 1

A polynucleotide consisting of a nucleic acid encoding a polypeptide, said polypeptide consisting of a non-human growth hormone, one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus of said non-human growth hormone, and two chorionic gonadotrophin CTPs attached to the carboxy terminus of said non-human growth hormone, wherein said polypeptide optionally comprises a signal peptide attached to the amino terminus of said one CTP, and wherein at least one CTP is optionally attached to said non-human growth hormone via a linker.

### Claim 2 (depends on 1)

The polynucleotide of claim 1, wherein at least one CTP is glycosylated.

### Claim 3 (depends on 1)

The polynucleotide of claim 1, wherein at least one CTP is truncated.

### Claim 4 (depends on 1)

The polynucleotide of claim 1, wherein at least one CTP is attached to said non-human growth hormone via a linker.

### Claim 5 (depends on 4)

The polynucleotide of claim 4, wherein said linker is a peptide bond.

### Claim 6 (depends on 1)

The polynucleotide of claim 1, wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.

### Claim 7 (depends on 1)

The polynucleotide of claim 1, wherein said polypeptide further comprises a signal peptide attached to the amino terminus of said one CTP.

### Claim 8 (depends on 1)

An expression vector comprising the polynucleotide of claim 1.

### Claim 9 (depends on 8)

An isolated cell comprising the expression vector of claim 8.

### Claim 10 (depends on 8)

A composition comprising the expression vector of claim 8 and a pharmaceutically acceptable carrier.

### Claim 11

A method of producing a non-human growth hormone with an improved biological half life in an isolated cell, comprising the step of transfecting said cell with an expression vector comprising a polynucleotide consisting of a nucleic acid encoding a polypeptide, said polypeptide consisting of a non-human growth hormone, one chorionic gonadotrophin carboxy terminal peptide (CTP) attached to the amino terminus of said non-human growth hormone, and two chorionic gonadotrophin CTPs attached to the carboxy terminus of said non-human growth hormone, wherein said polypeptide optionally comprises a signal peptide attached to the amino terminus of said one CTP, and wherein at least one CTP is optionally attached to said non-human growth hormone via a linker, thereby producing a non-human growth hormone with an improved biological half life in an isolated cell.

### Claim 12 (depends on 11)

The method of claim 11, wherein the sequence of at least one CTP consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 17 and SEQ ID NO: 18.

### Claim 13 (depends on 11)

The method of claim 11, wherein said polypeptide further comprises a signal peptide attached to the amino terminus of said one CTP.

### Claim 14 (depends on 11)

The method of claim 11, wherein at least one CTP is glycosylated.

### Claim 15 (depends on 11)

The method of claim 11, wherein at least one CTP is truncated.

### Claim 16 (depends on 11)

The method of claim 11, wherein at least one CTP is attached to said non-human growth hormone via a linker.

### Claim 17 (depends on 16)

The method of claim 16, wherein said linker is a peptide bond.
