New amphetamine derivatives, antibodies against them and pharmaceutical compositions containing them
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Abstract
Hapten-carrier conjugates capable of eliciting anti-hapten antibodies in vivo to amphetamines are disclosed. Methods of preparing the hapten-carrier conjugates and therapeutic compositions are also disclosed. A therapeutic composition containing the hapten-carrier conjugate is useful in the treatment of addiction to amphetamines. Passive immunization using antibodies raised against conjugates of the instant invention also is disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs for treatment of amphetamine abuse.
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Citations
51 Claims
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1. An (S)-enantiomer compound having the formula (I):
- 2. A compound having formula (II)
- 5. A compound having formula (IIIa):
- 7. A compound having formula (IIIb)
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15. An amphetamine-related immunogen comprising:
a compound having formula (I) covalently conjugated to a carrier. - View Dependent Claims (19, 21)
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16. An amphetamine-related immunogen I1 comprising:
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a compound having formula (II) covalently conjugated to a carrier,
wherein p is an integer between 1 and 6;
wherein R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —
OR9 and —
SR9, wherein R9 is hydrogen or a C1-C3 alkyl; and
R5 is selected from the group consisting of hydrogen, a polymethylene chain;
—
(CH)m—
R10 and an oxy-polymethylene chain;
—
O—
(CH2)m—
R10, wherein —
R10 is selected from the group consisting of carboxyl, thiol, —
CONHR13SH, and —
CONHCHR11SH, wherein R13 is selected from the group consisting of —
CH(COOH)CH2—
and —
(CH2)m— and
wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain;
—
(CH2)m—
COOH.
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17. An amphetamine-related immunogen 12 comprising:
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a compound having formula (IIIa) covalently conjugated to a carrier,
wherein R1 and R3 are selected from the group consisting of hydrogen, and C1-C3 alkyl;
R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain;
(CH2)n—
COOH, wherein n is an integer between 1 and 6;
R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —
OR9 and —
SR9, wherein R9 is hydrogen or a C1-C3 alkyl; and
,R11 is selected from the group consisting of a polymethylene chain;
—
(CH2)m— and
an oxy-polymethylene chain;
—
O(CH2)m—
, wherein m is an integer between 1 and 4, with the proviso that when R1 is a methyl, then R 1 is not a polymethylene chain;
—
(CH2)m—
.
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18. An amphetamine-related immunogen I3 comprising:
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a compound having formula (IIIb) covalently conjugated to a carrier,
wherein R1 and R3 are selected from the group consisting of hydrogen, and a C1-C3 alkyl;
R2 is selected from the group consisting of hydrogen, a C1-C3 alkyl and a polymethylene chain;
(CH2)n—
COOH, wherein n is an integer between 1 and 6;
R4, R6 and R7 are the same or different and are selected from the group consisting of hydrogen, a halogen, —
OR9 and —
SR9, wherein R9 is hydrogen or a C1-C3 alkyl; and
R12 is selected from the group consisting of a polymethylene chain;
(CH2)mCONHR13 and an oxy-polymethylene chain;
—
O(CH2)mCONHCH—
R13;
wherein R13 is selected from the group consisting of —
CH(COOH)CH2— and
—
(CH2)m—
, wherein m is an integer between 1 and 4, with the proviso that when R1 is hydrogen and R2 is a methyl or when R1 is a methyl and R2 is hydrogen, then R5 is not a polymethylene chain;
—
CH2)m. - View Dependent Claims (22, 41)
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20. The amphetamine-related immunogen TT-Met1 having the formula
- 23. Antibodies or fragments or chains of immunoglobulins having affinity for one or more amphetamine or derivative of amphetamine.
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28. A monoclonal antibody produced by hybridoma DASM243-6H5D1C4.
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29. A monoclonal antibody produced by hybridoma DASM243-3A10 A6A2.
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32. The murine hybridoma DASM243-645D1 C4 having accession number CNCM I-2750.
- 33. A cell line which produces monoclonal antibodies having the same antigenic specificity as that of monoclonal antibodies expressed by cell line DASM243-645D1C4.
- 43. Isolated nucleic acid encoding the heavy and light chains of monoclonal antibody DASM243-645D1C4 or DASM243-3A10A6A2.
- 44. Isolated nucleic acid encoding a polypeptide derived from monoclonal antibody DASM243-645D1C4 or DASM243-3A10A6A2.
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51. A process for producing an immunoglobulin specific for at least two amphetamines or amphetamine derivatives or an immunologically functional immunoglobulin fragment thereof comprising at least the variable domains of the heavy and light chains of said immunoglobulin, said method comprising:
growing a host cell comprising expression vectors comprising nucleic acid encoding respectively the heavy and light chains of monoclonal antibody DASM243-645D1C4 or DASM243-3A1 or functional fragments thereof, so that said nucleic acid is expressed, whereby said immunoglobulin is obtained.
Specification