The present invention is directed to a combination therapy involving a type II anti-CD20 antibody and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a CD20-expressing cancer.

The present invention provides bispecific antibodies that bind to CD3 and tumor antigens and methods of using the same. According to certain embodiments, the bispecific antibodies of the invention exhibit reduced effector functions and have a unique binding profile with regard to Fcγ receptors. The bispecific antibodies are engineered to efficiently induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, a second antigen-binding molecule that specifically binds human CD20, and an Fc domain that binds Fcγ receptors with a specific binding pattern. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell or melanoma tumors expressing CD20. The bispecific antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) that binds B-cell maturation antigen (BCMA) and uses thereof for treating multiple myeloma, for example, refractory and/or relapsed multiple myeloma. The genetically engineered T cells may comprise a disrupted endogenous TRAC gene and/or a disrupted endogenous β2M gene.

The object of the present invention is to provide a synthetic method for ADC synthesis with controllable regioselectivity and number of drugs introduced, as well as synthetic intermediates and synthetic raw materials for such methods. The object can be solved by a sugar compound having a polyethylene glycol chain, of the following general formula (1).

##STR00001##

wherein each X is independently a single bond, an oxygen atom, —NH—, —COHN—, —COO—, or a group of formula (5) or (6), (wherein R.sup.1 is trivalent branched hydrocarbon group having 1 to 6 carbon atoms, R.sup.2 and R.sup.3 are each independently an alkylene group having 1 to 3 carbon atoms), any one or more of Y1 to Y3 are present and are independently a PEG chain, a substituted PEG chain, or a PEG chain containing an oxygen atom, —NH—, —COHN—, or —COO— in the main chain, a structure of the PEG chain is linear or branched, and the number of branches is 2 to 10 in the case of branched structure, Z is independently a hydroxy group, a methoxy group, an azido group, a tetrazine group which may be optionally substituted, a norbornene group, a trans-cyclooctene group, a dibenzylcyclooctyl group, or a bicyclo[6.1.0]nona-4-yn-9-ylmethyl group, or a cyanobenzothiazole group which may be optionally substituted, wherein at least one of Z is not a hydroxy group or methoxy group, when any of Y1 to Y3 is not present, Z is hydrogen and X is oxygen, when X is the group of formula (5) or (6), Y1 to Y3 are bonded to each of R.sup.2 and R.sup.3 of the branched chains thereof, when the PEG chain is branched structure, Z is bonded to each of branched chains.

The present invention concerns modified recombinant J-chain polypeptides, binding molecules, such as antibodies comprising the same, and their uses.

PD1-CD70 fusion proteins are provided. Accordingly, there is provided a PD1-CD70 fusion protein comprising a single amino acid linker between the PD1 and the CD70. Also there is provided a PD1-CD70 fusion protein, wherein the PD1 amino acid is 123-166 amino acids in length and/or wherein the PD1 amino acid sequence comprises SEQ ID NO: 2 and/or wherein the fusion protein is in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the PD1-CD70 fusion protein, host-cells expressing the PD1-CD70 fusion protein and methods of use thereof.

The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human CD20. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

Provided herein are methods of using 2-(2,6-dioxopiperidin-3-yl)-4-((2-fluoro-4-((3-morpholinoazetidin-1-yl)methyl)benzyl)amino)isoindoline-1,3-dione, or an enantiomer, a mixture of enantiomers, a tautomer, an isotopolog, or a pharmaceutically acceptable salt thereof, alone or in combination with obinutuzumab, for treating, preventing or managing chronic lymphocytic leukemia/small lymphocytic lymphoma.

Provided is a mutant of an antibody or fragment thereof, characterized in that the antibody or fragment thereof contains a light-chain constant region, and according to the Kabat numbering system, the amino acid at position 166 is mutated to cysteine.