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.

The present inventors have successfully prepared an antigen-binding molecule comprising an antibody variable region that has binding activity against a molecule expressed on the surface of a T cell and a molecule expressed on the surface of any other immunocyte, but does not bind to these molecules at the same time. The present invention allows the preparation of an antigen-binding molecule capable of circumventing adverse reactions that may be caused by the cross-linking of T cells to other immunocytes, and provides an antigen-binding molecule suitable as a drug.

Disclosed herein are non-naturally existing novel platelet variants or platelet like cells (PLCs), extracellular vesicles (EVs), and derivatives thereof. Composition comprising the same and methods for treatment or prevention of diseases or disorders therewith is also disclosed.

Methods are provided for targeting cells for depletion, including without limitation tumor cells, in a regimen comprising contacting the targeted cells with a combination of agents that modulate immunoregulatory signaling. Immunoregulatory modulating agents include (i) an agent that blockades CD47 activity; and (ii) an agent that agonizes an immune costimulatory molecule, e.g. CD137. The regimen may further comprise an agent that specifically binds to the target cell, e.g. an antibody or biologically active fragment or derivative thereof. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single immunoregulatory modulating agent is used; and the effect may be synergistic relative to a regimen in which a single immunoregulatory modulating agent is used.

Provided is an isolated antibody that specifically binds to HPA-1a. Also provided is a nucleic acid molecule that encodes the antibody, and compositions comprising the antibody. Also provided is a method of producing the antibody and methods and uses which employ the antibody. Also provided are therapeutic uses of the antibody, for example in the treatment or prophylaxis of fetal and neonatal alloimmune thrombocytopenia (FNAIT).

A method is used for treating bone metastasis diseases in subjects. The method preferably depends on whether the subject shows certain specific proteins levels in one or more body fluids prior to or during treatment. The treatment includes 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 the specific protein levels in one or more body fluids of the subject.

Disclosed are an α.sub.vβ.sub.3 integrin targeting single-domain antibody and various applications thereof. The α.sub.vβ.sub.3 integrin targeting single-domain antibody exhibits high binding ability to α.sub.vβ.sub.3 integrin related to angiogenesis, excellent tissue permeability, and biostability compared to conventional antibodies. Further, the single-domain antibody may be combined with fluorescent particles and thus may be easily measured in vitro, in vivo or ex vivo, and may be effective in detecting angiogenesis and diagnosing angiogenesis related diseases, therefore it may be usefully used in related industries.

Chimeric clotting factors which localize the therapeutic to sites of coagulation (e.g., by being targeted to platelets or being activatable at sites of coagulation), have reduced clearance rates, have improved manufacturability, have reduced thrombogenicity, have enhanced activity, or have more than one of these characteristics are described as are methods for making chimeric clotting factors and methods for improving hemostasis using these clotting factors.

Activated cardiac fibroblasts are essential for the production of extracellular matrix proteins that accumulate during cardiac fibrosis, and PW1.sup.+ cardiac adult stem cells were recently proposed as a cellular source of fibroblasts in the ischemic hearts. Here the inventors identify αV-integrin (or CD51) as an essential regulator of PW1.sup.+ cardiac adult stem cells fibrogenic behavior. Inhibition of αV-integrin reduce the profibrotic gene expression profile and the ability to differentiate into fibroblasts of cardiac PW1.sup.+ cells. The pharmacological blockade of αV-containing integrins improved cardiac function and survival after MI by reducing infarct size and attenuating the extension of reactive cardiac fibrosis. Notably, the total cardiac fibrotic area as well as interstitial fibrosis in the remote myocardial area are significantly reduced after pharmacological blockade of αV-containing integrins. These data identify a new mechanism that regulates cardiac fibrosis in response to an ischemic injury and suggest that pharmacological targeting of αV-integrin may provide clinical benefit in the treatment of cardiac fibrosis.

A method can treat a patient suffering from at least one of fibrosis and a fibrotic disorder. The method includes administering a therapeutically effective amount of an anti-αv integrin antibody DI17E6, or a biologically active variant or modification thereof, to the patient.