Immunological materials

Claim 2

A cytotoxic agent comprising an immunoglobulin specific for antigens on the surface of cells to be killed having 1-10 polymer carrier molecules convalently bound thereto, said polymer carrier having about 5-500 molecules of a cytotoxic drug covalently bound thereto and said polymer carrier having a molecular weight of 5000-500,000 and free carboxyl, amino or cycloimidocarbonate groups for covalently bonding, said cytotoxic drug also having amino or carboxyl groups available for covalent bonding.

Claim 3

A cyctotoxic agent according to claim 1 represented by the formula ##STR43## wherein Ig represents an immunoglobulin specific to antigens on the surface of cells to be killed; the polymer carrier has a molecular weight of 5000-500,000 and is selected from the group of polymers comprising: a. dextran activated with cyanogen bromide to form cycloimidocarbonate and functionalized with --NH(CH 2 ) x CO 2 H, --NH--(CH 2 ) x --NH 2 , wherein x is 3-8, b. aminoethylated dextran, c. polyglutamic acid, d. polyaspartic acid, e. polyarginine, f. serum albumen, g. fibrinogen, h. γ-globulin, h. polylysine (solubilized by reaction with citraconic anhydride), j. copolymers of lysine-phenylalanine, lysinetryrosine, and glutamic acid-tyrosine; CD represents a covalently bound cytotoxic drug selected from the group comprising: p-[N,N-bis(2-chloroethyl)]phenylenediamine, p-[bis(2-chloroethyl)amino]phenylalanine, 4-{p-[bis(2-chloroethyl)amino]phenyl}butyric acid, 2-amino-N-[p-bis(2-chloroethylamino]phenyl-3-hydroxypropionamide, 2-amino-N-[p-bis(2-chloroethyl)amine]phenyl-3-hydroxy-2-hydroxymethyl propionamide, N-{p{[(2,4-diamino-6-pteridinyl)methyl]methylamino}benzyl}-L-glutamic acid, cytosine arabinoside, cytosine arabinoside monophosphate, O-[n,n-bis(2-chloropropyl)]carbamoylglycollic acid, daunomycin, doxorubicin, and diphtheria toxin; B 1 represents a covalent bond between Ig and polymer carrier of the formula ##STR44## B 2 represents a covalent bond between the polymer carrier and CD of the formula ##STR45## m = 5-500; n = 1-10.

Claim 4

A cytotoxic agent according to claim 2 wherein the polymer carrier is dextran, molecular weight 5000-500,000, activated with cyanogen bromide to form cycloimidocarbonate and functionalized with 1,6-diaminohexane; CD represents covalently bound p-[N,N-bis(2-chloroethyl)]phenylenediamine, p-[bis(2-chloroethyl)amino]phenyl-3-hydroxypropionamide, or 2-amino-N-[p-bis(2-chloroethyl)amino]phenyl-3-hydroxy-2-hydroxymethyl propianamide; B 1 represents -- N═CH--(CH 2 ) 3 --CH═N--; B 2 represents ##STR46## m = 5-500; n = 1-10.

Claim 5

A cytotoxic agent according to claim 3 wherein the dextran has a molecular weight 5,000-50,000.

Claim 6

A cytotoxic agent according to claim 13 wherein the dextran has a molecular weight of about 17,000.

Claim 7

A cytotoxic agent according to claim 2 wherein the polymer carrier is polyglutamic acid, molecular weight 5000-500,000; CD represents covalently bound p-[N,N-bis(2-chloroethyl)]phenylenediamine, p-[bis(2-chloroethyl)amino]phenylalanine, 2-amino-N-[p-bis(2-chloroethyl)amino]phenyl-3-hydroxypropionamide, or 2-amino-N-[p-bis(2-chloroethyl)amino]phenyl-3-hydroxy-2-hydroxymethyl propionamide; B 1 represents ##STR47## B 2 represents ##STR48## m = 5-500; and n = 1-10.

Claim 8

A cytotoxic agent according to claim 6 wherein the polyglutamic acid has a molecular weight of 5,000-100,000.

Claim 9

A cytotoxic agent according to claim 6 wherein the polyglutamic acid has a molecular weight of about 35,000.

Claim 10

A cytotoxic agent according to claim 2 wherein the polymer carrier is polylysine solubilized by reaction with citraconic anhydride and having a molecular weight of 5,000-100,000; Cd represents p-[bis(2-chloroethyl)amino[phenylalanine, 4-{p-[bis(2-chloroethyl)amino]phenyl}butyric acid, or N-{p{[2,4-diamino-6-pteridinyl)methyl]methylamino}benzyl}-L-glutamic acid; B 1 is ##STR49## or --N═CH--(CH 2 ) 3 --CH═N--; B 2 is ##STR50## m = 5-500 and n = 1-10.

Claim 11

A cytotoxic agent according to claim 2 wherein the polymer carrier is polyethyleneimine having a molecular weight of 5,000-500,000; Cd represents p-[bis(2-chloroethyl)amino]phenylalanine, 4-{p-[bis(2-chloroethyl)amino]phenyl}butyric acid or N-{p{[2,4-diamino-6-pteridinyl)methyl]methylamino}benzyl}-L-glutamic acid; B 1 is ##STR51## or --N═CH--(CH 2 ) 3 --CH═N--; B 2 is ##STR52## m = 5-500 and n = 1-10.

Claim 12

A cytotoxic agent according to claim 10 wherein the polymer carrier is polyethyleneimine having a molecular weight of 5,000-100,000.

Claim 13

A cytotoxic agent according to claim 10 wherein the polymer carrier has a molecular weight of about 20,000.

Claim 14

A cytotoxic agent according to claim 1 represented by the formula ##STR53## wherein the polymer carrier is polyglutamic acid of molecular weight 5000-500,000; Cd represents covalently bound p-[N,N-bis(2-chloroethyl)]phenylenediamine, p-[bis(2-chloroethyl)amino]phenylalanine, 2-amino-N-[p-bis(2-chloroethyl)amino]phenyl-3-hydroxypropionamide, or 2-amino-N-[p-bis(2-chloroethyl)amino]phenyl-3-hydroxy-2-hydroxymethyl propionamide; B 1 represents ##STR54## B 2 represents ##STR55## m = 5-500; and n = 1-10.