562 results about "Antibody-drug conjugate" patented technology

Antibody drug conjugates with predetermined sites and stoichiometries of drug attachment are provided. Also provided are methods of using antibody drug conjugates.

Methods of treating a refractory or drug resistant cancer, cell proliferative disorder and tumor cells are provided. Also provided are antibody drug conjugate metabolites.

The present disclosure provides antibody-drug conjugates that are potent cytotoxins, wherein the drug is linked to the antibody through a linker. The disclosure is also directed to compositions containing the antibody-drug conjugates, and to methods of treatment using them.

Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.

Linker-drug intermediates of Formula I are conjugated to antibodies to form antibody-drug conjugates where the drug moiety is an N-methylalaninyl-maytansinoid.

Methods for preparing monomeric cytotoxic drug/carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative/antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative/anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.

Methods to detect, screen, and quantitate biological samples after administration of antibody conjugates, antibody-drug conjugates of Formula I, antibodies, and fragments and metabolites thereof, by affinity separation, chromatography, and mass spectrometry are disclosed.

Ab-(L-D)_p   I

wherein Ab is an antibody; D is a drug moiety; L is a linker covalently attached to Ab, and covalently attached to D; and p is 1, 2, 3, 4, 5, 6, 7, or 8;

The invention relates to antibody drug conjugate (ADC) compounds represented by Formula I:

Ab-(L-D)_p  I

where one or more 1,8 bis-naphthalimide drug moieties (D) having Formulas IIa and IIb are covalently linked by a linker (L) to an antibody (Ab). The invention also relates to pharmaceutical compositions comprising an effective amount of a Formula I ADC for treatment of hyperproliferative disorders and other disorders. The invention also relates to methods for killing or inhibiting the multiplication of a tumor cell or cancer cell including administering to a patient an effective amount of a Formula I ADC.

The invention relates to bis 1,8 naphthalimide compounds including antibody drug conjugate (ADC) compounds represented by Formula I:

Ab-(L-D)_p   I

where one or more 1,8 bis-naphthalimide drug moieties (D) having Formulas IIa and IIb are covalently linked, through the wavy line, by a linker (L) to an antibody (Ab).

The invention also relates to heterocyclic-substituted 1,8 bis-naphthalimide compounds having Formula XV

The invention also relates to pharmaceutical compositions comprising an effective amount of a Formula I ADC or Formula XV heterocyclic-substituted 1,8 bis-naphthalimide compound for treatment of hyperproliferative disorders and other disorders. The invention also relates to methods for killing or inhibiting the proliferation of tumor cells or cancer cells including administering to a patient an effective amount of a Formula I ADC or Formula XV compound.

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

The present invention provides antibodies that bind to the IL-3 receptor alpha subunit alpha (Il3Rα) chain, and compositions comprising such antibodies. The present invention provides methods for inhibiting or reducing an IL3Rα-expressing cell population, the methods comprising contacting a population of IL3Rα-expressing cells (e.g., cancer cells and/or cancer stem cells) with an antibody that binds to IL3Rα. The present invention also provides antibody conjugates comprising an antibody that binds to an IL3Rα chain linked to a cytotoxic agent or anticellular agent and compositions comprising such conjugates. The present invention also provides methods for preventing, treating and/or managing a disorder associated with IL3Rα-expressing cells (e.g., a hematological cancer), the methods comprising administering to a subject in need thereof an antibody that binds to IL3Rα.

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, immunosuppressive, or other therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the disclosed pharmaceutical compositions.

Methods to detect, characterize, and quantitate biological samples after administration of antibody conjugates, antibody-drug conjugates of Formula I, antibodies, and fragments and metabolites thereof, by immunoaffinity bead separation, chromatography, and mass spectrometry are disclosed.

Ab-(L-D)_p  I

• • wherein
  • Ab is an antibody;
  • D is a drug moiety;
  • L is a linker covalently attached to Ab, and covalently attached to D; and
  • p is 1, 2, 3, 4, 5, 6, 7, or 8;

Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

Conjugates of an antibody that binds to CD19 with PBD dimers.

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to B7H4 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided, immunoconjugates, including antibody-drug conjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of this disclosure are also provided. This disclosure also provides methods for treating cancer.

The invention relates to 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 using the same to reduce ocular toxicity associated with administration of antibody drug conjugates.

The present invention relates to antibody-drug conjugate compounds of Formula I: Ab (L D)p I where one or more macrocyclic depsipeptide drug moieties (D), selected from Aplidin, Didemnin B, Kahalalide F, and analogs and derivatives therefrom, are covalently attached by a linker (L) to an antibody (Ab) which binds to one or more tumor-associated antigens or cell-surface receptors. These compounds may be useful in methods of diagnosis or treatment of cancer, and other diseases and disorders.

Provided are novel multispecific antibody constructs and multispecific antibody drug conjugates (ADCs), and methods of using such antibodies and ADCs to treat cancer. IgG-like bispecific antibodies have different binding specificities on each arm of the antibody. They are similar in structure to monospecific IgGs in that they contain two heavy chains with VH, CH1, CH2 and CH3 regions, and two light chains with VL and CL regions.

[Problem to be solved] The present invention provides an antibody-drug conjugate (ADC). The present invention also provides a conjugate of an anti-CD71 antibody or an antigen-binding fragment thereof with a drug. The present invention further provides a conjugate of Fab′ with a drug. The present invention further provides a composition comprising the conjugate for delivering the drug to a tissue or a cell of muscle or the like.

[Solution] A conjugate of an anti-CD71 antibody or an antigen-binding fragment thereof with a drug, and a conjugate of Fab′ of an antibody with a drug.

The present invention is directed to antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation. The invention relates to engineered antibody constant region (Fc, Cγ, Cκ, and Cλ) polypeptides, and portions thereof, and antibodies comprising the polypeptides. Further, the invention relates to Fc fusion proteins comprising an engineered Fc region. The invention also relates to methods and uses of the engineered antibodies and portions for, among other things, production of antibody-drug conjugate therapeutics.