The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

A targeted therapeutic agent comprising a compound of formula I:
B-L-D(I),
wherein: B is a low molecular weight binding moiety for Carbonic Anhydrase IX (CAIX); D is a drug moiety; and L is a linker group that undergoes cleavage in vivo for releasing said drug moiety in an active form. The drug moiety is suitably a cytotoxic agent for targeted delivery to cancer cells expressing CAIX. The binding moiety B suitably comprises a sulfonamidothiadiazole moiety. The binding moiety B may comprise one, two or more groups capable of binding to CAIX. The linker group suitably comprises a disulfide bond and/or a triazole group and/or a cleavable peptide group.

A binding moiety (B) for Carbonic Anhydrase IX (CAIX), the binding moiety comprising:

##STR00001##

The binding moiety is univalent, bivalent, or multivalent. A targeted therapeutic agent may comprise the binding moiety. The invention also includes a method for treating a disease expressing elevated levels of CAIX by administering the targeted therapeutic agent.

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

A targeted therapeutic agent comprising a compound of formula I:

B-L-D(I),

wherein: B is a low molecular weight binding moiety for Carbonic Anhydrase IX (CAIX); D is a drug moiety; and L is a linker group that undergoes cleavage in vivo for releasing said drug moiety in an active form. The drug moiety is suitably a cytotoxic agent for targeted delivery to cancer cells expressing CAIX. The binding moiety B suitably comprises a sulfonamidothiadiazole moiety. The binding moiety B may comprise one, two or more groups capable of binding to CAIX. The linker group suitably comprises a disulfide bond and/or a triazole group and/or a cleavable peptide group.

Methods employing chemiluminescent agents as therapeutically active agents in the treatment of proliferative disorders are disclosed. The chemiluminescent agents are used in the disclosed method without a therapeutically effective amount of a photosensitizer. Novel chemiluminescent agents having the general formula:

##STR00001##

are also disclosed, wherein X, Y, Z, R.sub.3 and R.sub.5-R.sub.9 are as defined herein.

A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure: ##STR00001##
wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, SO.sub.3H, PO.sub.3H, OH, NH.sub.2, and -halogen; wherein Y.sub.1 and Y.sub.2 is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, -alkylaminium, -alkynyl, PEGyl, PEGylcarboxylate, -PEGylaminium, -acyl-NH, -acyl-lysinyl-, -acyl-triazole, -PEGylcarboxyl-NH, -PEGylcarboxyl-lysinyl, and -PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH.sub.2, SH and OH; and R.sub.3 and R.sub.4 are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.

Provided herein are dye-drug conjugate (DDC) compounds comprising: a tumor-targeting near-infrared dye; a chemotherapeutic drug; and a cleavable linker, and methods of use thereof.