# US 5,702,697 A · Treatment for biological damage using a colony stimulating factor and a biological modifier

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- Number: US 5,702,697 A
- Document ID: US5702697A
- Status: Granted
- Kind: A
- Application number: 08/457,629
- Filed: 1995-06-01
- Granted: 1997-12-30
- Earliest claimed: 1986-11-21
- Assignees: Chiron Corporation
- Inventors: Robert Zimmerman; Benedict J. Marafino, Jr.
- Web page: https://patentgrep.com/patent/US5702697A

## CPC

- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/2013: {IL-2}
- 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

Damage to cells, tissue and other body parts in a mammalian host may be treated by using a colony stimulating factor in conjunction with at least one biological modifier, which may be a free radical scavenger or a metabolic inhibitor. The biological modifier is preferably uric acid, buthionine sulphoximine, vitamin C, aspirin, or nordihydroguaiaretic acid. Such a combination may be used to treat, for example, cancer, infectious diseases, and damage caused by radiation therapy, high oxygen tension, and chemotherapy.

## Claims

### Claim 1

A method for the therapeutic or prophylactic treatment of biological damage to a mammalian host, said damage caused by free radical generation, which method comprises administering to the host in need of such treatment therapeutically effective amounts of a colony stimulating factor from a mammalian species and at least one biological modifier selected from the group consisting of a free radical scavenger and a metabolic inhibitor.

### Claim 2 (depends on 1)

The method of claim 1 wherein the colony stimulating factor and the biological modifier are administered separately to the host, and the biological modifier is administered first.

### Claim 3 (depends on 1)

The method of claim 1 wherein the biological modifier is selected from the group consisting of uric acid, buthionine sulphoximine, vitamin E, vitamin C, N-acetyl cysteine, a retinoid, gluathione, metronidazole, aspirin, indomethacin, ibuprofen, nordihydroguaiaretic acid, cis-8,11,14-eicosatrien-5-ynoic acid, synthetic prostaglandins, synthetic leukotrienes, and combinations thereof.

### Claim 4 (depends on 1)

The method of claim 1 wherein said biological modifier is administered to the host at least once prior to administration to the host of said colony stimulating factor.

### Claim 5 (depends on 1)

The method of claim 1 wherein the colony stimulating factor is selected from the group consisting of colony stimulating factor-1 (CSF-1) and granulocyte-macrophage colony stimulating factor (CSF-GM).

### Claim 6 (depends on 5)

The method of claim 5 wherein the colony stimulating factor is CSF-1.

### Claim 7 (depends on 1)

The method of claim 1 wherein the host is human and the biological damage results from a cause selected from the group consisting of infection, high oxygen tension, radiation therapy, and chemotherapy.

### Claim 8 (depends on 1)

The method of claim 1 wherein the biological modifier is a free radical scavenger.

### Claim 9 (depends on 8)

The method of claim 8 wherein the biological damage caused by free radical generation is caused by free radicals produced as a mechanism for killing cells.

### Claim 10 (depends on 1)

The method of claim 1 wherein the biological modifier is a metabolic inhibitor.

### Claim 11

A composition comprising therapeutically effective amounts of a colony stimulating factor from a mammalian species and of a biological modifier selected from the group consisting of a free radical scavenger and a metabolic inhibitor.

### Claim 12 (depends on 11)

The composition of claim 11 further comprising a pharmaceutically acceptable carrier medium.

### Claim 13 (depends on 11)

The composition of claim 11 wherein the colony stimulating factor is selected from the group consisting of colony stimulating factor-1 (CSF-1) and granulocyte-macrophage colony stimulating factor (CSF-GM).

### Claim 14 (depends on 13)

The composition of claim 13 wherein the colony stimulating factor is colony stimulating Factor-1.

### Claim 15 (depends on 13)

The composition of claim 13 wherein the colony stimulating factor is CSF-GM.

### Claim 16 (depends on 11)

The composition of claim 11 wherein the biological modifier is selected form the group consisting of uric acid, buthionine sulphoximine, vitamin E, vitamin C, N-acetyl cysteine, a retinoid, glutathione, metronidazole, aspirin, indomethacin, ibuprofen, nordihydroguaiaretic acid, cis-8,11,14-eicosatrien-5-ynoic acid, synthetic prostaglandins, synthetic leukotrienes, and combinations thereof.

### Claim 17 (depends on 11)

The composition of claim 11 wherein the biological modifier is a free radical scavenger.

### Claim 18 (depends on 11)

The composition of claim 11 wherein the biological modifier is a metabolic inhibitor.

### Claim 19

A method for treating biological damage in a host in need of such treatment, wherein said damage is caused by free radical generation, which method comprises administering to the host a therapeutically effective amount of a biological modifier in a first pharmaceutically acceptable carrier, said biological modifier selected from the group consisting of a free radical scavenger and a metabolic inhibitor, and administering to the host a therapeutically effective amount of a colony stimulating factor in a second pharmaceutically acceptable carrier.

### Claim 20 (depends on 19)

The method of claim 19 wherein the biological damage is cancer.

### Claim 21 (depends on 20)

The method of claim 20 wherein the colony stimulating factor is selected from the group consisting of colony stimulating factor-1 (CSF-1) and granulocyte-macrophage colony stimulating factor (CSF-GM).

### Claim 22 (depends on 20)

The method of claim 20 wherein the biological modifier is a free radical scavenger.

### Claim 23 (depends on 20)

The method of claim 20 wherein the biological modifier is a metabolic inhibitor.

### Claim 24

A unit dose comprising a first composition having a therapeutically effective amount of a colony stimulating factor from a mammalian species, and further comprising a second composition having a therapeutically effective amount of a biological modifier selected from the group consisting of a free radical scavenger and a metabolic inhibitor.

### Claim 25 (depends on 24)

The unit dose of claim 24 wherein said first composition and said second composition are cooperatively combined but not in admixture.

### Claim 26 (depends on 25)

The unit dose of claim 25 wherein the colony stimulating factor is selected from the group consisting of colony stimulating factor-1 (CSF-1) and granulocyte-macrophage colony stimulating factor (CSF-GM).

### Claim 27 (depends on 26)

The unit dose of claim 26 wherein the biological modifier is a free radical scavenger.

### Claim 28 (depends on 27)

The unit dose of claim 27 wherein the free radical scavenger is selected from the group consisting of uric acid, buthionine sulphoximine, N-acetyl cysteine, and vitamin C.

### Claim 29

A kit comprising a therapeutically effective amount of a colony stimulating factor from a mammalian species in association with a therapeutically effective amount of a biological modifier selected from the group consisting of a free radical scavenger and a metabolic inhibitor, said kit facilitating separate administration to a host of said therapeutically effective amount of a colony stimulating factor and said therapeutically effective amount of a biological modifier.

### Claim 30 (depends on 29)

The kit of claim 29 wherein the colony stimulating factor is selected from the group consisting of colony stimulating factor-1 (CSF-1) and granulocyte-macrophage colony stimulating factor (CSF-GM).

### Claim 31 (depends on 30)

The kit of claim 30 wherein the biological modifier is a free radical scavenger.

### Claim 32 (depends on 31)

The kit of claim 31 wherein the free radical scavenger is selected from the group consisting of uric acid, buthionine sulphoximine, N-acetyl cysteine, and vitamin C.
