# US 5,705,153 A · Glycolipid enzyme-polymer conjugates

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- Number: US 5,705,153 A
- Document ID: US5705153A
- Status: Granted
- Kind: A
- Application number: 08/735,961
- Filed: 1996-10-23
- Granted: 1998-01-06
- Earliest claimed: 1992-12-10
- Assignees: The United States of America as represented by the Department of Health and Human Services
- Inventors: Robert G. L. Shorr; Carl W. Gilbert; Brian M. Martin; Myung-Ok Cho; Edward J. Ginns
- Web page: https://patentgrep.com/patent/US5705153A

## CPC

- C12N 9/2402: {hydrolysing O- and S- glycosyl compounds (3.2.1)}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 49/001: {Preparation for luminescence or biological staining}
- C12N 9/96: Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
- C12Y 302/01045: Glucosylceramidase (3.2.1.45), i.e. beta-glucocerebrosidase
- 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)
- 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)
- C12Y: ENZYMES

## Abstract

Conjugates containing glucocerebrosidase and non-antigenic polymers such as polyethylene glycol are disclosed. The conjugates circulate for extended times and have prolonged activity in vivo when compared to unmodified enzymes. The conjugates are useful in the treatment of Gaucher's Disease and have improved enzyme activity at the pH ranges associated with lysosomal, arterial and capillary regions.

## Claims

### Claim 1

A method of treating Gaucher's Disease comprising administering an effective amount of a glucocerebrosidase conjugate having enhanced enzymatic activity at pH ranges of from about 4.0-5.0 and about 6.5-7.5, comprising recombinant glucocerebrosidase and from about 1 to about 25 poly(alkylene oxide) strands, each strand having a molecular weight of from about 1,000 to about 15,000, and each strand being covalently linked via a urethane linkage to an amino group on said recombinant glucocerebrosidase.

### Claim 2 (depends on 1)

The method of claim 1, wherein each of said poly(alkylene oxide)s is terminally substituted with a C.sub.1-4 alkyl group distal to said recombinant glucocerebrosidase.

### Claim 3 (depends on 1)

The method of claim 1, wherein said poly(alkylene oxide) is selected from the group consisting of polyethylene glycol homopolymers, polypropylene glycol homopolymers, alkyl-capped polyethylene oxides, bis-activated polyethylene oxides and copolymers or block copolymers of poly(alkylene oxides).

### Claim 4 (depends on 1)

The method of claim 1, wherein said poly(alkylene oxide) has a molecular weight of from about 1,000 to about 12,500.

### Claim 5 (depends on 4)

The method of claim 4, wherein said polymer has a molecular weight of from about 2,000 to about 12,500.

### Claim 6 (depends on 5)

The method of claim 5, wherein said polymer has a molecular weight of about 5,000.

### Claim 7 (depends on 1)

The method of claim 1, wherein about 5 to about 20 poly(alkylene oxide) strands are attached to each molecule of said recombinant glucocerebrosidase.

### Claim 8 (depends on 7)

The method of claim 7, wherein about 7 to about 18 poly(alkylene oxide) strands are attached to each molecule of said recombinant glucocerebrosidase.

### Claim 9 (depends on 3)

The method of claim 3, wherein said poly(alkylene oxide) is polyethylene glycol.

### Claim 10 (depends on 3)

The method of claim 3, wherein said polyethylene glycol is a monomethoxy polyethylene glycol.