# US 5,349,055 A · Nerve growth factor having altered receptor binding specificities

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- Number: US 5,349,055 A
- Document ID: US5349055A
- Status: Granted
- Kind: A
- Application number: 07/847,369
- Filed: 1992-03-06
- Granted: 1994-09-20
- Earliest claimed: 1992-03-06
- Inventors: Hakan B. Persson; Carlos F. I. Moliner
- Web page: https://patentgrep.com/patent/US5349055A

## CPC

- C07K 14/48: Nerve growth factor [NGF]
- C07K 14/475: Growth factors; Growth regulators
- 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)
- Y10S 930/12: Growth hormone, growth factor other than t-cell or b-cell growth factor, and growth hormone releasing factor; related peptides
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A method of altering the receptor binding properties and the stability of neurotrophic factors is set forth. Mutant neurotrophic factors having altered receptor binding specificities are described. Specific embodiments include neurotrophic factors that bind trk receptors but do not bind to the low affinity NGF receptor.

## Claims

### Claim 1

Mutant nerve growth factor having essentially the same biological activity as wild-type nerve growth factor, wherein at least one positively charged amino acid in amino acids 30 through 34 or amino acids 93 to 98 of wild-type nerve growth factor is replaced with an uncharged or negatively charged amino acid, wherein said replacement reduces the ability of the mutant nerve growth factor to bind p75.sup.NGFR as compared to wild-type nerve growth factor.

### Claim 2 (depends on 1)

The mutant neurotrophic factor of claim 1 wherein Lys95 is replaced.

### Claim 3 (depends on 2)

The mutant neurotrophic factor of claim 2 wherein said Lys95 is replaced by Ala.

### Claim 4 (depends on 1)

The mutant neurotrophic factor of claim 1 wherein Lys32 is replaced.

### Claim 5 (depends on 4)

The mutant neurotrophic factor of claim 4 wherein Lys34 is replaced.

### Claim 6 (depends on 4)

The mutant neurotrophic factor of claim 4 wherein Lys95 is replaced.

### Claim 7 (depends on 1)

The mutant neurotrophic factor of claim 1 wherein Lys34 is replaced.

### Claim 8

A method of selecting for nerve growth factor mutants with reduced ability to bind p75.sup.NGFR comprising
a) replacing a least one positively charged amino acid in amino acids 30 through 34 or amino acids 93 to 98 of the factor with an uncharged or negatively charged amino acid; and
b) selecting those factors that demonstrate essentially the same biological activity as wild-type nerve growth molecule.