# US 8,541,205 B2 · Variant forms of urate oxidase and use thereof

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- Number: US 8,541,205 B2
- Document ID: US8541205B2
- Status: Granted
- Kind: B2
- Application number: 13/461,170
- Filed: 2012-05-01
- Published: 2012-12-06
- Granted: 2013-09-24
- Earliest claimed: 2005-04-11
- Assignees: Savient Pharmaceuticals, Inc.
- Applicants: Jacob Hartman; Simona Mendelovitz
- Inventors: Jacob Hartman; Simona Mendelovitz
- Web page: https://patentgrep.com/patent/US8541205B2

## CPC

- C12N 9/0048: {Uricase (1.7.3.3)}
- A61K 38/44: Oxidoreductases (1)
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 13/12: of the kidneys
- A61P 19/06: Antigout agents, e.g. antihyperuricemic or uricosuric agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 9/0046: {with oxygen as acceptor (1.7.3)}
- C12Y 107/03003: Factor-independent urate hydroxylase (1.7.3.3), i.e. uricase
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12Y: ENZYMES

## Abstract

Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

## Claims

### Claim 1

An isolated nucleic acid comprising a nucleic acid sequence which encodes (a) a uricase comprising a mammalian uricase amino acid sequence truncated at the amino terminus or the carboxy terminus or both the amino and carboxy termini by 1-6 amino acids and further comprising an amino acid substitution with threonine at position 7 (D7T), an amino acid substitution at position 46 (S46T), an amino acid substitution with lysine at position 291 (R291K) and an amino acid substitution with serine at position 301 (T301S), said truncation and amino acid substitution being relative to a naturally occurring pig uricase having an amino acid sequence of SEQ ID NO:11;
(b) the uricase of (a) further comprising an amino terminal amino acid, wherein the amino terminal amino acid is alanine, glycine, proline, serine, or threonine;
(c) the uricase of (b) wherein the amino terminal amino acid is threonine;
(d) the uricase of (a) consisting of the amino acid sequence of SEQ ID NO. 8;
(e) the uricase of (a) wherein the N-terminal amino acid is methionine; or
(f) the uricase of (e) comprising the amino acid sequence of SEQ ID NO. 7.

### Claim 2 (depends on 1)

The isolated nucleic acid of claim 1, wherein the nucleic acid sequence is operatively linked to a heterologous promoter.

### Claim 3 (depends on 2)

The nucleic acid of claim 2, wherein the promoter is the osmB promoter.

### Claim 4 (depends on 2)

A nucleic acid vector comprising the nucleic acid of claim 2.

### Claim 5 (depends on 4)

A host cell comprising the vector of claim 4.

### Claim 6

An isolated nucleic acid comprising a nucleic acid sequence encoding a uricase comprising the amino acid sequence of SEQ ID NO. 7 or SEQ ID NO. 8.

### Claim 7 (depends on 6)

The isolated nucleic acid of claim 6, wherein the nucleic acid sequence comprises SEQ ID NO. 9 or SEQ ID NO. 10.

### Claim 8 (depends on 6)

The isolated nucleic acid of claim 6, wherein the nucleic acid sequence is operatively linked to a heterologous promoter.

### Claim 9 (depends on 8)

The nucleic acid of claim 8, wherein the promoter is the osmB promoter.