RELEASABLE ANTIBODY CONJUGATES

1 - 67 . (canceled)

68 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

the antibody moiety is selected from:

antibody-L-(CH 2 ) q — and antibody-L-(aliphatic moiety)-;

the aliphatic moiety is selected from a polymer, R P , and a group selected from:

polymer-L-(CH 2 ) m — and -polymer-L-(CH 2 —CH 2 —O) p —(CH 2 ) m —;

R P is selected from optionally substituted C 1-6 alkyl, optionally substituted C 1-3 alkyl-O—(CH 2 —CH 2 —O) p —(CH 2 ) m —, and optionally substituted C 3-7 cycloalkyl;

each L is independently a linking group;

m and p are each independently an integer from 1 to 10;

D is a residue of a cytotoxic or chemotherapeutic compound;

Z 1 is selected from O, S, and N(R N );

Z 3 is selected from O and N(R N ), or Z 3 is absent;

A is O or N, wherein when A is O then R 3 is absent;

R N is selected from H and optionally substituted C 1-6 alkyl;

R 3 is selected from H and C 1-6 alkyl, or

R 3 and R 1 , together with A and the carbon atom to which R 1 is attached, form an optionally substituted 4 to 7 membered aliphatic heterocyclic ring; or

R 3 and R 2 , together with A, the carbon atom to which R 1 is attached, and the carbon atom to which R 2 is attached, form an optionally substituted 4 to 8 membered aliphatic heterocyclic ring;

M A is a self-immolative group having any one of formulae (a)-(i):

wherein x denotes a point of attachment to Z 1 and y denotes a point of attachment to Z 3 ;

R 1 and R 2 are independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl and optionally substituted 5- to 14-membered heteroaryl;

or R 1 and R 2 are joined together with the carbon atoms to which they are attached to form an optionally substituted C 3-7 cycloalkyl ring, an optionally substituted 4 to 7 membered aliphatic heterocyclic ring, an optionally substituted C 6-10 aryl or an optionally substituted 5- to 14-membered heteroaryl;

or R 1 and R 2 are joined together to form a ribose ring system;

R 7 and R 8 are independently selected from H and C 1-6 alkyl; and

E is a cleavable moiety.

69 . The compound of claim 68 , wherein the cytotoxic compound is selected from the group consisting of alkylating agents, antimetabolites, inhibitors of mitosis, and topoisomerase inhibitors.

70 . The compound of claim 68 , wherein E is selected from:

(i) a group cleavable by an enzyme selected from the group consisting of an esterase, a specific or an unspecific peptidase, a reductase, an oxidase, a glycosidase, a hydrolase, a glycosyl transferase, and a transaminase;

(ii) a group non-enzymatically cleavable at acidic pH; and

(iii) a group containing a dithio group which is cleavable by a biogenic thiol.

71 . The compound of claim 70 , wherein E is selected from:

(i) a group cleavable by a glycoside hydrolase enzyme which is a residue of a sugar selected from glucose, galactose, mannose and glucuronic acid;

(ii) a group cleavable by an intracellular esterase enzyme which is selected from an acyl group, a carbonate ester, and a O-methyl-acyl ester; and

(iii) a group that is non-enzymatically cleavable at acidic pH selected from a methyl azido group, a protected acetal, an acetal, an ortho-ester, and a substituted triphenyl methylether.

72 . The compound of claim 70 , wherein E is selected from a group of any one of the following formulae:

wherein R E is selected from the group consisting of C 1-6 alkyl and benzyl.

73 . The compound of claim 68 , wherein a cleavable moiety E is attached to A using a group of formula (L E ):

wherein a denotes a point of attachment to A, and b denotes a point of attachment to E.

74 . The compound of claim 68 , wherein R 1 and R 2 together form C 3-7 cycloalkyl ring selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

75 . The compound of claim 68 , wherein R 1 and R 2 together form a 4 to 7 membered aliphatic heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, tetrahydrofuran, and tetrahydropyran.

76 . The compound of claim 68 , wherein R 1 and R 2 together form a ribose ring system of a ribonucleoside of formula:

wherein either a denotes a point of attachment to O and b denotes a point of attachment to A, a denotes a point of attachment to A and b denotes a point of attachment to O, and wherein W is selected from the group consisting of H, an acyl group, a protecting group, antibody-L-(CH 2 ) q — and antibody-L-(aliphatic moiety)-.

77 . The compound of claim 76 , wherein the nucleobase is selected from the group consisting of adenine, cytosine, guanine, thymine, uracil, 5-methylcytosine, pseudouridine, dihydrouridine, inosine, 7-methylguanosine, hypoxanthine, and xanthine.

78 . The compound of claim 68 , wherein R 1 and R 2 together form a ribose ring system of a ribonucleoside of formula:

wherein the polymer is optionally substituted with antibody-L-(CH 2 ) q —.

79 . The compound of claim 68 , wherein R 3 and R 1 , together with A and the carbon atom to which R 1 is attached, form an optionally substituted 4 to 7 membered aliphatic heterocyclic ring selected from the group consisting of:

wherein x denotes a point of attachment to E, and y denotes a point of attachment to the carbon atom to which R 1 is attached.

80 . The compound of claim 68 , wherein the aliphatic moiety is selected from a polymer, R P , and a group of formula:

-polymer-L-(CH 2 ) m —;

R P is selected from optionally substituted C 1-6 alkyl and optionally substituted C 3-7 cycloalkyl; and

m is an integer from 1 to 10.

81 . The compound of claim 68 , wherein each L is independently selected from a linking group comprising a heterocycloakylene or a heteroarylene, a linking group comprising a succinimide or a triazole, and a linking group of any one of the following formulae:

wherein ring C is selected from the group consisting of an optionally substituted C 8-16 cycloalkyl and an optionally substituted 8-16-membered heterocycloalkyl, and indicates a point of attachment of the linking group to the polymer or to the CH 2 group.

82 . The compound of claim 68 , wherein the polymer is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(α-hydroxy acid), poly(vinyl alcohol), polyoxazoline, and copolymers thereof.

83 . The compound of claim 82 , wherein the polymer is linear or branched polyethylene glycol.

84 . The compound of claim 68 , wherein Z 1 is S and M A is a self-immolative group of formula (a):

wherein x denotes a point of attachment to Z 1 and y denotes a point of attachment to Z 3 .

85 . A pharmaceutical composition comprising the compound of claim 68 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

86 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 68 , or a pharmaceutically acceptable salt thereof.

87 . A compound of Formula (II):

or a pharmaceutically acceptable salt thereof, wherein:

each aliphatic moiety is independently selected from a polymer, R P , and a group selected from:

polymer-L-(CH 2 ) m — and polymer-L-(CH 2 —CH 2 —O) p —(CH 2 ) m —;

R P is selected from optionally substituted C 1-6 alkylene, optionally substituted C 1-3 alkylene-O—(CH 2 —CH 2 —O) p —(CH 2 ) m —, and optionally substituted C 3-7 cycloalkylene;

each L is independently a linking group;

m and p are each independently an integer from 1 to 10;

D is a residue of a cytotoxic or chemotherapeutic compound;

Z 1 is selected from O, S, and N(R N );

Z 3 is selected from O and N(R N ), or Z 3 is absent;

A is O or N, wherein when A is O then R 3 is absent;

R N is selected from H and optionally substituted C 1-6 alkyl;

R 3 is selected from H and C 1-6 alkyl, or

R 3 and R 1 , together with A and the carbon atom to which R 1 is attached, form an optionally substituted 4 to 7 membered aliphatic heterocyclic ring; or

R 3 and R 2 , together with A, the carbon atom to which R 1 is attached, and the carbon atom to which R 2 is attached, form an optionally substituted 4 to 8 membered aliphatic heterocyclic ring;

M A is a self-immolative group having any one of formulae (a)-(i):

wherein x denotes a point of attachment to Z 1 and y denotes a point of attachment to Z 3 ;

R 1 and R 2 are independently selected from the group consisting of hydrogen, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl and optionally substituted 5- to 14-membered heteroaryl;

or R 1 and R 2 are joined together with the carbon atoms to which they are attached to form an optionally substituted C 3-7 cycloalkyl ring, an optionally substituted 4 to 7 membered aliphatic heterocyclic ring, an optionally substituted C 6-10 aryl or an optionally substituted 5- to 14-membered heteroaryl;

or R 1 and R 2 are joined together to form a ribose ring system;

wherein one of R 1 or R 2 is substituted with antibody-L-(CH 2 ) q — and antibody-L-(aliphatic moiety)-;

R 7 and R 8 are independently selected from H and C 1-6 alkyl; and

E is a cleavable moiety.