# US 6,723,701 B2 · Protein analogs of brain-derived neurotrophic factor

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- Number: US 6,723,701 B2
- Document ID: US6723701B2
- Status: Granted
- Kind: B2
- Application number: 09/742,600
- Filed: 2000-12-19
- Published: 2002-01-24
- Granted: 2004-04-20
- Earliest claimed: 1996-07-19
- Assignees: Amgen Inc.
- Inventors: Thomas Charles Boone; Ellen Ngoi Yin Cheung; Susan Irene Hershenson; John David Young
- Web page: https://patentgrep.com/patent/US6723701B2

## CPC

- C07K 14/50: Fibroblast growth factor [FGF]
- C07K 14/475: Growth factors; Growth regulators
- C07K 14/503: {basic FGF [bFGF]}
- C07K 14/54: Interleukins [IL]
- 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: 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)
- 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

The in vivo circulating life and/or absorption of cationic therapeutic proteins, including but not limited to basic proteins such as NT-3 and BDNF, can be increased by generating analogs that have a lower isoelectric point and, preferably, also a lower protein charge relative to the protein of native sequence.

## Claims

### Claim 1

An isolated brain-derived neurotrophic factor (BDNF) polypeptide analog having an amino acid sequence selected from the group consisting of SEQ ID NO: 9 and SEQ ID NO: 10, wherein the isoelectric point is lower and the in vivo circulating life and/or absorption is increased for said analog relative to those properties of a wild-type BDNF polypeptide having an amino acid sequence of SEQ ID NO:8.

### Claim 2 (depends on 1)

The BDNF polypeptide analog according to claim 1, which is also characterized by a lower charge under physiological conditions compared to the wild-type BDNF polypeptide of SEQ ID NO:8.

### Claim 3 (depends on 1)

The BDNF polypeptide analog according to claim 1 which is the product of expression in a eukaryotic or prokaryotic host cell.

### Claim 4 (depends on 1)

A pegylated derivative of the BDNF polypeptide analog according to claim 1.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the BDNF polypeptide analog according to claim 1 and a pharmaceutically acceptable carrier or diluent.

### Claim 6 (depends on 1)

The BDNF polypeptide analog according to claim 1, having the amino acid sequence of SEQ ID NO: 9.

### Claim 7 (depends on 1)

The BDNF polypeptide analog according to claim 1, having the amino acid sequence of SEQ ID NO: 10.