New conjugates associating, by covalent bond, an enzyme with an antibody, and medicinal associations using the said conjugates

Claim 2

An immunoenzymic conjugate comprising an antibody or a fragment thereof having the capacity to recognize a specific antigen, covalently bonded to an enzyme capable of producing ammonium ions from natural substrates well tolerated in higher animal organisms.

Claim 3

A conjugate as claimed in claim 1 wherein the covalent bond is a disulfide bond.

Claim 4

A conjugate as claimed in claim 1, wherein the covalent bond is a thioether bond.

Claim 5

A conjugate as claimed in claim 1, wherein the enzyme covalently bonded to the antibody or fragment thereof, is selected from the group consisting of a sub-group 1-4 containing amino-acids-dehydrogenase and amino-oxydase, a sub-group 3-5 enzyme comprising the enzymes hydrolizing amines, amidines, and other C--N nonpeptidic bonds, a sub-group 4-2 and 4-3 enzyme catalyzing degradation reactions with formation of nonsaturated compounds.

Claim 6

A conjugate as claimed in claims 4 wherein the enzyme covalently bonded to the antibody or a fragment thereof, is 1-4-1-1:alanine dehydrogenase, 1-4-1-3:glutamate dehydrogenase NAD (P) + , 1-4-1-5:L-amino-acids dehydrogenase, 1-4-3-2:L-amino-acids oxydase, 3-5-1-1:asparaginase, 3-5-1-2:glutaminase, 3-5-1-4:amidase, adenosine deaminase, 3-5-4-66:adenosine monophosphate deaminase, 3-5-4-21:creatinine deaminase, 4-2-1-13:L-serine dehydratase, 4-2-1-16:L-threomine dehydratase, 4-3-1-1:aspartate-ammonia-lyase, 4-3-1-3:histidine-ammonia-lyase or 4-3-1-5:phenylalanine-ammonia-lyase.

Claim 7

A conjugate as claimed in claim 5 wherein the covalent bond is a disulfide bond.

Claim 8

A conjugate as claimed in claim 5 wherein the covalent bond is a thioether bond.

Claim 9

A pharmaceutical composition comprising a therapeutically effective amount of at least one immunotoxin formed between the A chain of ricin and an antibody or an antibody fragment and a potentiating amount of at least one immunoenzymic conjugate as claimed in claim 1, and an pharmaceutically acceptable carrier.

Claim 10

A pharmaceutical composition as claimed in claim 8 in injectible form.

Claim 11

A method of potentiating an immunotoxin formed between the A-chain of ricin and an antibody or an antibody fragment, at the immediate environment of a mammalian target-cell for said immunotoxin, which comprises administering a potentiating effective amount of the immunoenzymic conjugate of claim 1 to a patient having target-cells, to cause reaction of said immunoenzymic conjugate with a natural substrate located in the area of the target-cells to generate a potentiating amount of ammonium ions for said immunotoxin.

Claim 12

A method of potentiating an immunotoxin formed between the A-chain of ricin and an antibody or an antibody fragment; at the immediate environment of a mammalian target-cell for said immunotoxin, which comprises administering a potentiating effecting amount of the immunoenzymic conjugate of claim 1 to a patient having target-cells for said immunotoxin, and wherein a substrate for the enzyme of the immunoenzyme conjugate is not present in the blood and the extra cellular liquid in a high enough concentration to effect a potentiating reaction between the substrate and the immunoenzymic conjugate, and administering an effective amount of a substrate to the patient being treated with the immunotoxin and immunoenzymic conjugate to cause reaction of said immunoenzymic conjugate with the substrate located in the area of the target-cells to generate a potentiating amount of ammonium ions for said immunotoxin.