# US 2002/0004208 A1 · Hapten-carrier conjugates for treating and preventing nicotine addiction

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- Number: US 2002/0004208 A1
- Document ID: US20020004208A1
- Status: Published application
- Kind: A1
- Application number: 09/784,139
- Filed: 2001-02-16
- Published: 2002-01-10
- Earliest claimed: 1998-11-30
- Assignees: Nabi
- Inventors: Sofiane Ennifar; Ali Ibrahim Fattom; Robert B. Naso
- Web page: https://patentgrep.com/patent/US20020004208A1

## CPC

- A61K 39/0013: {Therapeutic immunisation against small organic molecules, e.g. cocaine, nicotine}
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61P 25/34: Tobacco-abuse
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- A61K 2039/6068: {Other bacterial proteins, e.g. OMP}
- Y10S 435/975: Kit
- Y10S 436/816: Alkaloids, amphetamines, and barbiturates
- Y10S 530/807: Hapten conjugated with peptide or protein
- 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
- 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)
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Novel hapten-carrier conjugates are capable of inducing the production of antibodies, in vivo, that specifically bind to nicotine. These conjugates comprise a nicotine hapten conjugated to an immunogenic carrier protein. The novel conjugates preserve the chirality of nicotine in its native (S)-(−) state, and have good stability properties. The conjugates are useful in formulating vaccines for active immunization, that are used to prevent and treat nicotine addiction. The antibodies raised in response to the nicotine hapten-carrier conjugate are used for passive immunization. These antibodies are administered for prevention and treatment of nicotine addiction.

## Claims

### Claim 1

A hapten-carrier conjugate of the following formula:
11
wherein
m is 1 to 2500,
n is 0 to 12,
y is 1 to 12,
X is selected from the group consisting of NH—CO, CO—NH, CO—NH—NH, NH—NH—CO, NH—CO—NH, CO—NH—NH—CO, and S—S;
Y is selected from the group consisting of NH—CO, CO—NH, CO—NH—NH, NH—NH—CO, NH—CO—NH, CO—NH—NH—CO, and S—S,
and the —(CH2)n—X—(CH2)y—Y— moiety is bonded to the 3′, 4′ or 5′ position.

### Claim 2 (depends on 1)

The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH—CO, Y is CO—NH, wherein the carrier protein is exoprotein A and the —(CH2)n—X—(CH2)y—Y— is bonded to the 3′ position.

### Claim 3 (depends on 1)

The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH—CO, Y is CO—NH, wherein the carrier protein is exoprotein A and the —(CH2)n—X—(CH2)y—Y— is bonded to the 4′ position.

### Claim 4 (depends on 1)

The conjugate of claim 1, wherein m is 11 to 17, n is 1, y is 2, X is NH—CO, Y is CO—NH, wherein the carrier protein is exoprotein A and the —(CH2)n—X—(CH2)y—Y— is bonded to the 5′ position.

### Claim 5 (depends on 1)

The conjugate of claim 1, wherein m is selected from the group consisting of 1 to 20 and 1 to 200.

### Claim 6

A hapten-carrier conjugate of the following formula:
12
wherein n is 0 to 12, j is 1 to 1000, k is 1 to 20, and E is an amino acid-containing matrix.

### Claim 7 (depends on 6)

The hapten-carrier conjugate of claim 6, wherein the matrix is poly-L-glutamic acid.

### Claim 8 (depends on 1)

An antibody produced in response to the hapten-carrier conjugate of claim 1.

### Claim 9 (depends on 8)

A functional fragment of the antibody of claim 8.

### Claim 10 (depends on 8)

The antibody of claim 8, which is a monoclonal antibody.

### Claim 11 (depends on 8)

The antibody of claim 8, which is a polyclonal antibody.

### Claim 12 (depends on 6)

An antibody produced in response to the hapten-carrier conjugate of claim 6.

### Claim 13 (depends on 12)

A functional fragment of the antibody of claim 12.

### Claim 14 (depends on 12)

The antibody of claim 12, which is a monoclonal antibody.

### Claim 15 (depends on 12)

The antibody of claim 12, which is a polyclonal antibody.

### Claim 16 (depends on 1)

A method of treating nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the hapten-carrier conjugate of claim 1.

### Claim 17 (depends on 8)

A method of treating nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the antibody of claim 8.

### Claim 18 (depends on 1)

A method of preventing nicotine addiction in a patient in need of such prevention, comprising administering a therapeutically effective amount of the hapten-carrier conjugate of claim 1.

### Claim 19 (depends on 8)

A method of preventing nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the antibody of claim 8.

### Claim 20 (depends on 16)

The method of claim 16, further comprising administering a compound that is useful in the treatment of addiction.

### Claim 21 (depends on 6)

A method of treating nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the hapten-carrier conjugate of claim 6.

### Claim 22 (depends on 21)

The method of claim 21, further comprising administering a compound that is useful in the treatment of addiction.

### Claim 23 (depends on 12)

A method of treating nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the antibody of claim 12.

### Claim 24 (depends on 6)

A method of preventing nicotine addiction in a patient in need of such prevention, comprising administering a therapeutically effective amount of the hapten-carrier conjugate of claim 6.

### Claim 25 (depends on 12)

A method of preventing nicotine addiction in a patient in need of such treatment comprising administering a therapeutically effective amount of the antibody of claim 12.

### Claim 26 (depends on 1)

A process for producing an antibody, comprising immunizing a host mammal with the hapten-carrier conjugate of claim 1.

### Claim 27 (depends on 26)

The process of claim 26, wherein the antibody is monoclonal.

### Claim 28 (depends on 26)

The process of claim 26, wherein the antibody is polyclonal.

### Claim 29 (depends on 6)

A process for producing an antibody, comprising immunizing a host mammal with the hapten-carrier conjugate of claim 6.

### Claim 30 (depends on 29)

The process of claim 29, wherein the antibody is monoclonal.

### Claim 31 (depends on 29)

The process of claim 29, wherein the antibody is polyclonal.

### Claim 32 (depends on 1)

A vaccine composition comprising at least one conjugate of claim 1.

### Claim 33 (depends on 6)

A vaccine composition comprising at least one conjugate of claim 6.

### Claim 34 (depends on 8)

A kit for determining the presence of nicotine in a sample, comprising an antibody of claim 8.

### Claim 35 (depends on 12)

A kit for determining the presence of nicotine in a sample, comprising an antibody of claim 12.