# US 5,705,360 A · Chemokine N-terminal deletion mutations

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,705,360 A
- Document ID: US5705360A
- Status: Granted
- Kind: A
- Application number: 08/683,785
- Filed: 1996-07-16
- Granted: 1998-01-06
- Earliest claimed: 1993-11-12
- Assignees: Dana-Farber Cancer Institute, Inc.
- Inventors: Barrett Rollins; Yujun Zhang
- Web page: https://patentgrep.com/patent/US5705360A

## CPC

- C07K 14/521: {Chemokines}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 23/00: Anaesthetics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 14/523: {Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1, LDCF-2}
- 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 2319/00: Fusion polypeptide
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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 invention relates to mutant chemokines and pharmaceutical compositions thereof, wherein the mutant inhibits the corresponding endogenous chemokine from binding or activating a responsive receptor. The claimed mutant chemokines can be administered to a patient for the treatment or prophylaxis of a chemokine-mediated disease. The invention further relates to isolated DNAs encoding the mutant chemokines, vectors and recombinant host cells containing the same.

## Claims

### Claim 1

A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting the monocyte chemoattractant activity of endogenous MCP-1, with the proviso that the derivative has not been modified by the substitution of 28-tyrosine by leucine and/or the substitution of 30-arginine by valine.

### Claim 2 (depends on 1)

The modified nucleic acid molecule of claim 1 wherein the molecule is a DNA molecule.

### Claim 3 (depends on 1)

The modified nucleic acid molecule of claim 1 wherein the nucleic acid sequence substantially corresponds to a naturally occurring MCP-1 sequence.

### Claim 4 (depends on 1)

A vector comprising the nucleic acid of claim 1 operably linked to a regulatory sequence.

### Claim 5 (depends on 4)

A recombinant host cell comprising the vector of claim 4.

### Claim 6 (depends on 5)

A method of preparing a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting the monocyte chemoattractant activity of endogenous MCP-1 comprising culturing a recombinant host cell of claim 5; and expressing the MCP-1 derivative.

### Claim 7

A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting monocyte chemoattractant activity of endogenous MCP-1 wherein one or more of 24-arginine, 3-aspartate and the 2-8 amino acid sequence have been deleted or substituted by one or more amino acids.

### Claim 8 (depends on 7)

The modified nucleic acid molecule of claim 7 wherein the molecule is a DNA molecule.

### Claim 9 (depends on 7)

The modified nucleic acid molecule of claim 7 wherein the nucleic acid sequence substantially corresponds to a naturally occurring MCP-1 sequence.

### Claim 10 (depends on 9)

The modified nucleic acid molecule of claim 9 wherein the nucleic acid sequence corresponds to a naturally occurring MCP-1 sequence except in the codons coding for 24-arginine, 3-aspartate and amino acids between 2-8 of the MCP-1 sequence.

### Claim 11

A modified nucleic acid molecule which encodes a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting monocyte chemoattractant activity of endogenous MCP-1 wherein the MCP-1 has been modified in one or more of the following ways:
(a) the 28-tyrosine is substituted by aspartate;
(b) the 24-arginine is substituted by phenylalanine;
(c) the 3-aspartate is substituted by alanine; and/or
(d) the 2-8 amino acid sequence is deleted.

### Claim 12 (depends on 11)

The modified nucleic acid molecule of claim 11 wherein the molecule is a DNA molecule.

### Claim 13 (depends on 11)

A vector comprising the nucleic acid of claim 11 operably linked to a regulatory sequence.

### Claim 14 (depends on 13)

A recombinant host cell comprising the vector of claim 13.

### Claim 15 (depends on 14)

A method of preparing a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting the monocyte chemoattractant activity of endogenous MCP-1 comprising culturing a recombinant host cell of claim 14; and expressing the MCP-1 derivative.

### Claim 16 (depends on 11)

The modified nucleic acid molecule of claim 11 wherein the nucleic acid sequence substantially corresponds to a naturally occurring MCP-1 sequence.

### Claim 17 (depends on 16)

The modified nucleic acid molecule of claim 16 wherein the nucleic acid sequence corresponds to a naturally occurring MCP-1 sequence except in the codons coding for 28-tyrosine, 24-arginine, 3-aspartate and amino acids between 2-8 of the MCP-1 sequence.

### Claim 18 (depends on 17)

The modified nucleic acid of claim 17 wherein the 28-tyrosine is substituted by aspartate in the MCP-1 derivative.

### Claim 19 (depends on 17)

The modified nucleic acid of claim 17 wherein the 24-arginine is substituted by phenylalanine in the MCP-1 derivative.

### Claim 20 (depends on 17)

The modified nucleic acid of claim 17 wherein the 3-aspartate is substituted by alanine in the MCP-1 derivative.

### Claim 21 (depends on 17)

The modified nucleic acid of claim 17 wherein the 2-8 amino acids have been deleted in the MCP-1 derivative.

### Claim 22 (depends on 17)

A vector comprising the nucleic acid of claim 17 operably linked to a regulatory sequence.

### Claim 23 (depends on 22)

A recombinant host cell comprising the vector claim 22.

### Claim 24 (depends on 23)

A method of preparing a monocyte Chemoattractant Protein-1 (MCP-1) derivative capable of inhibiting the monocyte chemoattractant activity of endogenous MCP-1 comprising culturing a recombinant host cell of claim 23; and expressing the MCP-1 derivative.