Abstract: Novel compounds, compositions and methods comprising modified antibodies are provided. In preferred embodiments the disclosed modified antibodies comprise antibodies having one or more of the constant region domains altered or deleted to afford beneficial physiological properties such as enhanced target localization and rapid blood clearance. The disclosed compounds are particularly useful for the treatment of neoplastic disorders in myelosuppressed patients.

Abstract: The instant invention describes methods of separating or preferentially synthesizing dimers which are linked via at least one interchain disulfide linkage from dimers which are not linked via at least one interchain disulfide linkage from a mixture comprising the two types of polypeptide dimers. These forms can be separated from each other using hydrophobic interaction chromatography. In addition, the invention pertains to connecting peptides that result in the preferential biosynthesis of dimers that are linked via at least one interchain disulfide linkage or that are not linked via at least one interchain disulfide linkage. The invention also pertains to compositions in which a majority of the dimers are linked via at least one interchain disulfide linkage or are not linked via at least one interchain disulfide linkage. The invention still further pertains to novel binding molecules, e.g., comprising connecting peptides of the invention.

Abstract: Novel compounds, compositions and methods comprising modified antibodies are provided. In preferred embodiments the disclosed modified antibodies comprise antibodies having one or more of the constant region domains altered or deleted to afford beneficial physiological properties such as enhanced target localization and rapid blood clearance. The disclosed compounds are particularly useful for the treatment of neoplastic disorders in myelosuppressed patients.

Abstract: Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).

Abstract: Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).

Abstract: Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).

Abstract: Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).

Abstract: Methods, compositions and kits comprising dimeric antibodies for the treatment of neoplastic, autoimmune or other disorders are provided. The dimeric antibodies of the instant invention may comprise two antibody molecules (H4L4) having the same antigen binding specificity (homodimers) or, alternatively, may comprise two different antibody molecules having binding specificity for two distinct antigens (heterodimers). In preferred embodiments the antibody molecules comprising the dimers are non-covalently associated.

Abstract: The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

Abstract: The present invention relates to a novel process for the preparation of biologically active antibody dimers in a pharmaceutically acceptable composition. The dimers can be composed of two antibody molecules having the same antigen binding specificity and linked through reducible, disulfide, or a non-reducible thioether, bond (homodimer). Alternatively, the dimers can be composed of two different antibody molecules having binding specificity for two distinct antigens (heterodimer). These dimers are useful for inducing hyper-cross-linking of membrane antigens. The present invention further relates to the use of biologically active antibody dimers for the preferential killing or inhibition of selected cell populations in the treatment of diseases such as cancer and autoimmune disorders.

Abstract: The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

Abstract: Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).

Abstract: The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

Abstract: The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

Abstract: Provided are drug/ligand compounds of Formula (I): ##STR1## (I) in whichD is a drug moiety;n is an integer from 1 to 10;p is an integer from 1 to 6;Y is O or NH.sub.2.sup.+ C1.sup.- ;z is 0 or 1;q is about 1 to about 10;X is a ligand; and,A is a Michael Addition Adduct.In a preferred embodiment, the ligand is an immunoglobulin, preferably a chimeric antibody or fragment thereof. Also provided are formulations comprising as an active ingredient a compound of Formula (I), intermediates useful for preparing the compounds of Formula (I), processes for preparing the compounds of Formula (I), and methods for using the compounds of the invention.

Abstract: Provided are drug/ligand compounds of Formula (I): ##STR1## in which D is a drug moiety;n is an integer from 1 to 10;p is an integer from 1 to 6;Y is O or NH.sub.2.sup.+ C1.sup.- ;z is 0 or 1;q is about 1 to about 10;X is a ligand; and,A is a Michael Addition Adduct.In a preferred embodiment, the ligand is an immunoglobulin, preferably a chimeric antibody or fragment thereof. Also provided are formulations comprising as an active ingredient a compound of Formula (I), intermediates useful for preparing the compounds of Formula (I), processes for preparing the compounds of Formula (I), and methods for using the compounds of the invention.

Abstract: Provided are drug/ligand compounds of Formula (I): ##STR1## in which D is a drug moiety;n is an integer from 1 to 10;p is an integer from 1 to 6;Y is O or NH.sub.2.sup.+ Cl.sup.- ;z is 0 or 1;q is about 1 to about 10;X is a ligand; and,A is a Michael Addition Adduct.In a preferred embodiment, the ligand is an immunoglobulin, preferably a chimeric antibody or fragment thereof. Also provided are formulations comprising as an active ingredient a compound of Formula (I), intermediates useful for preparing the compounds of Formula (I), processes for preparing the compounds of Formula (I), and methods for using the compounds of the invention.

Abstract: The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-substituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the preferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.

Abstract: The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-subhstituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the perferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.

Abstract: The invention relates to anthracycline conjugates comprising at least one anthracycline molecule linked to a molecule that is reactive with a cell population to be eliminated such as antibody, bombesin, EGF and transferrin. Each anthracycline molecule, having a keto group at the C-13 position, is conjugated to the antibody via a linker arm and is bound to that linker arm via an acid-sensitive acylhydrazone bond at the 13-keto position of the anthracycline. The linker additionally contains a disulfide or thioether linkage as part of the antibody or ligand attachment to the immunoconjugate. The novel anthracycline acylhydrazone derivatives are useful in the preparation of the conjugates of this invention. The acid-sensitive hydrazone bond of the conjugates of this invention allows the release of free anthracycline from the conjugates in the acidic external or internal environment of the target cell.