# US 5,708,141 A · Neutrophil inhibitors

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- Number: US 5,708,141 A
- Document ID: US5708141A
- Status: Granted
- Kind: A
- Application number: 08/249,041
- Filed: 1994-05-24
- Granted: 1998-01-13
- Earliest claimed: 1992-05-11
- Assignees: Corvas International, Inc.
- Inventors: Matthew Moyle; David L. Foster; George P. Vlasuk
- Web page: https://patentgrep.com/patent/US5708141A

## CPC

- C07K 14/535: Granulocyte CSF; Granulocyte-macrophage CSF
- C07K 14/4354: {from nematodes}
- 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

Compositions enriched for Neutrophil Inhibitory Factor which inhibit neutrophil activity including adhesion to vascular endothelial cells are provided. Such compositions may comprise a glycoprotein isolated from nematodes, particularly of the genus Ancylostoma. These compositions are useful in the therapy of conditions which involve abnormal or undesired inflammatory responses.

## Claims

### Claim 1

A glycoprotein isolated from Ancylostoma canium which has an apparent molecular weight of about 38,000 to 44,000 Daltons as determined by laser-desorption time-of-flight mass-spectrometry; and an isoelectric point of about 4.5 as determined by preparative isoelectric focusing and which has neutrophil inhibitory activity.

### Claim 2 (depends on 1)

A glycoprotein according to claim 1 which was isolated from a homogenate of Ancylostoma caninum using chromatography on Concanavalin-A, gel filtration chromatography using a gel filtration medium comprising a matrix of cross-linked agarose and dextran having a separation range of 10 to 600 KD, chromatography on hydroxyapatite and C4 reverse phase HPLC.

### Claim 3

A method of preparing a composition enriched for Neutrophil Inhibitory Factor from a homogenate of a parasitic worm of the genus Ancylostoma that has neutrophil inhibitory activity which comprises (a) subjecting the homogenate to chromatography on Concanavalin-A, (b) subjecting the material having neutrophil inhibitory activity from step (a) to chromatography on gel filtration media comprising a matrix of cross-linked agarose and dextran having a separation range of 10 to 600 KD, and (c) subjecting the material having neutrophil inhibitory activity from step (b) to column chromatography on hydroxyapatite.

### Claim 4 (depends on 3)

A method according to claim 3 further comprising (d) subjecting the material having neutrophil inhibitory activity from step (c) to reverse phase HPLC using a C4 column.