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US 5,310,535 AGranted
Carboxamide modified polyamine chelators and radioactive complexes thereof for conjugation to antibodies
AssigneesThe Dow Chemical Company, University of Texas
InventorsWilliam J. Kruper, Jr., William A. Fordyce, A. Dean Sherry
Life of this patent
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Abstract
A group of functionalized polyaminocarboxamide modified chelators that form complexes with rare earth-type metal ions are disclosed. The complexes, covalently attached to an antibody or antibody fragment, can be used for therapeutic and/or diagnostic purposes.
Claims6
A method for the treatment of a disease state in a mammal which comprises administering to said mammal in effective amount of a pharmaceutical formulation comprising a conjugate with a pharmaceutically acceptable carrier wherein the conjugate is a compound of the formula ##STR5## wherein:
- each Q is independently hydrogen, (CHR.sup.5).sub.p CO.sub.2 R;
- or (CHR.sup.5).sub.p C(O)N(R.sup.6).sub.2 with the proviso that at least one Q is (CHR.sup.5).sub.p C(O)N(R.sup.6).sub.2 ;
- R at each occurrence is independently hydrogen, benzyl or C.sub.1 -C.sub.4 alkyl;
- each R.sup.5 independently is hydrogen, C.sub.1 -C.sub.4 alkyl or -(C.sub.1 -C.sub.2 alkyl)phenyl;
- each R.sup.6 independently is hydrogen, C.sub.1 -C.sub.9 alkyl or -(C.sub.1 -C.sub.2 alkyl)phenyl;
- X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond to produce an alkene or alkyne;
- n is 0 or 1;
- m is an integer from 0 to 10 inclusive;
- p=1 or 2;
- r=0 or 1;
- with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond;
- R.sup.2 and R.sup.4 are independently hydrogen, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido or carboxyl;
- R.sup.3 is C.sub.1 -C.sub.4 alkoxy, --OCH.sub.2 CO.sub.2 H, hydroxy or hydrogen;
- with the proviso that R.sup.2 and R.sup.4 cannot both be hydrogen but one of R.sup.2 and R.sup.4 must be hydrogen;
- or
- a pharmaceutically acceptable salt thereof;
- complexed with an ion of a metal selected from .sup.153 Sm, .sup.166 Ho, .sup.90 Y, .sup.149 Pm, .sup.159 Gd, .sup.140 La, .sup.177 Lu, .sup.175 Yb, .sup.47 Sc or .sup.142 Pr and
- covalently attached to an antibody or antibody fragment.
15 more elements
A method for the diagnosis of a disease state in a mammal which comprises the steps of
- (a) administering to said mammal an effective amount of a pharmaceutical formulation comprising a conjugate with a pharmaceutically acceptable carrier wherein the conjugate is a compound of the formula ##STR6## wherein:
- each Q is independently hydrogen, (CHR.sup.5).sub.p CO.sub.2 R;
- or (CHR.sup.5).sub.p C(O)N(R.sup.6).sub.2 with the proviso that at least one Q is (CHR.sup.5).sub.p C(O)N(R.sup.6).sub.2 ;
- R at each occurrence is independently hydrogen, benzyl or C.sub.1 -C.sub.4 alkyl;
- each R.sup.5 independently is hydrogen, C.sub.1 -C.sub.4 alkyl or -(C.sub.1 -C.sub.2 alkyl)phenyl;
- each R.sup.6 independently is hydrogen, C.sub.1 -C.sub.9 alkyl or -(C.sub.1 -C.sub.2 alkyl)phenyl;
- X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond to produce an alkene or alkyne;
- n is 0 or 1;
- m is an integer from 0 to 10 inclusive;
- p=1 or 2;
- r=0 to 1;
- with the proviso that n is only 1 when X and/or Y form an additional carbon-carbon bond;
- R.sup.2 and R.sup.4 are independently hydrogen, amino, isothiocyanato, semicarbazido, thiosemicarbazido, maleimido, bromoacetamido or carboxyl;
- R.sup.3 is C.sub.1 -C.sub.4 alkoxy, --OCH.sub.2 CO.sub.2 H, hydroxy or hydrogen;
- with proviso that R.sup.2 and R.sup.4 cannot both be hydrogen but one of R.sup.2 and R.sup.4 must be hydrogen;
- or
- a pharmaceutically acceptable salt thereof;
- complexed with an ion of a radioisotope selected from .sup.153 Sm, .sup.166 Ho, .sup.90 Y, .sup.149 Pm, .sup.159 Gd, .sup.140 La, .sup.177 Lu, .sup.175 Yb, .sup.47 Sc or 142Pr and
- covalently attached to an antibody or antibody fragment;
- and
- (b) utilizing a radiation detection means to detect and locate radiation from the conjugate.
18 more elements
Dependencies are inferred from the claim text.