Compositions containing multivalent and monovalent multispecific complexes having scaffolds such as antibodies that support such binding functionalities are described. The use of and methods of compositions containing multivalent and monovalent multispecific complexes having scaffolds, such as antibodies, that support such binding functionalities are also described.

The instant invention provides for a new method of treating bone metastasis diseases in subjects, wherein said method preferably depends on whether the subject shows certain specific proteins levels in one or more body fluids prior to or during treatment, wherein said treatment comprises the administration of at least one pan αv integrin inhibitor to a subject, a medicament for use in said new methods, and a method of predicting the outcome of a treatment with at least one pan αv integrin inhibitor based on said specific protein levels in one or more body fluids of the subject.

The instant invention provides for a new method of treating colorectal cancer (CRC) and metastases thereof in subjects, and preferably also of other solid cancers and metastases thereof in subjects, wherein said method preferably depends on whether the patient shows certain specific proteins levels in one or more body fluids prior to or during treatment, wherein said treatment comprises the administration of at least one pan αv integrin inhibitor to a patient, a medicament for use in said new methods, and a method of predicting the outcome of a treatment with at least one pan αv integrin inhibitor based on said specific protein levels in one or more body fluids of the patient.

The present invention provides antagonists and methods of use thereof in the treatment of cancer and abnormal immune suppression diseases.

The invention generally relates to immunotherapy using immune cells such as chimeric antigen receptor (CAR)-engineered T cells. In particular, the invention relates to immunotherapy using chimeric antigen receptor (CAR)-engineered T cells that carry a novel, IgG3-Hinge-based spacer domain, allowing a finely modulated response to target antigens. In addition, the invention relates to the introduction of one or more IgG3-Hinge-based multi-function sites (MFs) into CARs and other immunoreceptors, allowing purification, stimulation, expansion and depletion of CAR T cells. The invention includes also the sequence of an antibody targeting this motif, allowing the execution of the before-mentioned functions.

Disintegrin variants that bind specifically to one or more of α5β1 and αv integrins, such as αvβ1, αvβ3, αv7β5, αvβ6 and αvβ8, but with reduced binding activity to αIIbβ3, are described. Also described are uses of the disintegrin variants for the treatment or prevention of a disease associated with an αv integrin or an α5β1 integrin.

The present inventors have successfully prepared a library consisting essentially of a plurality of antigen-binding molecules differing in sequence from each other, the antigen-binding molecules each comprising an antibody variable region that has binding activity against a first antigen and a second antigen different from the first antigen, but does not bind to the first antigen and the second antigen at the same time. Use of the library of the present invention allows the obtainment of a variable region having enhanced ability to bind to the first antigen and the production of a bispecific antibody against the first antigen and a cancer antigen. Moreover, the present inventors have also successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against three different antigens, but does not bind to these antigens at the same time.

The present disclosure relates to methods of modifying the isoelectric point of an antibody. The method includes providing an antibody comprising a first polypeptide comprising a heavy chain variable region and a second polypeptide comprising heavy chain variable region and substituting, in at least one of the first and second polypeptides of the antibody, one or more amino acid residues of the heavy chain variable region (V.sub.H) at positions 7, 9, 11, 14, 41, 70, 74, 82a, 84, and 113, according to the Kabat numbering system, wherein the substituting increases or decreases the isoelectric point of the antibody.

This invention concerns a process for making a lyophilized pharmaceutical formulation of a therapeutic protein, which comprises (a) providing a formulation of a bulk amount of the therapeutic protein, (b) measuring the concentration of the therapeutic protein in said bulk formulation, (c) adjusting the fill weight of the protein in said bulk formulation to achieve a fixed dose of the protein, and (d) lyophilizing the protein fill weight-adjusted formulation to achieve a final formulation in a container, wherein the product concentration post reconstitution with a fixed volume is within a predetermined acceptance range. The process is particularly suitable for formulations with low protein concentrations (e.g., 0.05 mg/mL to 20 mg/mL).

The present invention relates to a neovascular-targeting contrast medium composition and a method for preparing same. The neovascular-targeting contrast medium composition according to the present invention exhibits high binding force to neovascularization-associated α.sub.vβ.sub.3 integrin, excellent tissue permeability and biostability, enables simple measurement in vitro, in vivo, or ex vivo, and thus is effective in the detection of neovascularization and in diagnosing diseases associated therewith, and therefore may be usefully employed in the relevant industries.