Abstract: The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Abstract: Described is a conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. Also described are a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

Abstract: Described is a conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. Also described are a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

Abstract: Described is a conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. Also described are a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

Abstract: The present invention relates to the conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

Abstract: Provided herein is the conjugation of an amanita toxin compound to a cell-binding molecule with branched linkers for having better targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of an amanita molecule to a cell-binding ligand, as well as methods of using the conjugate in targets treatment of cancer, infection and autoimmune disease.

Abstract: The present invention relates to a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (a dual-linker) containing a 2,3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

Abstract: A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease. wherein “” is an optional bond; X, Y, Z1, and Z2 are a functional group; m1 and n are a integer; L1 and L2 are a linker.

Abstract: The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease. wherein “” is an optional bond; X, Y, Z1, and Z2 are a functional group; m1 and n are a integer; L1 and L2 are a linker.

Abstract: A conjugation of a cytotoxic drug to a cell-binding molecule with a bis-linker (dual-linker) as shown in Formula (I). Bis-linkage methods of making a conjugate of a cytotoxic drug/molecule to a cell-binding agent in a specific manner are also described, as well as application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease. wherein “” is an optional bond; X, Y, Z1, and Z2 are a functional group; m1 and n are a integer; L1 and L2 are a linker.

Abstract: The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Abstract: The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Abstract: The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)-butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

Abstract: Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

Abstract: The present invention relates to novel cross-linked cytotoxic agents, pyrrolobenzodiazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.

Abstract: Cell binding agent-drug conjugates comprising hydrophilic linkers, and methods of using such linkers and conjugates are provided.

Abstract: The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.