The present invention provides methods of treating inflammation associated with infection, and methods of preventing or reducing the severity of sepsis caused by inflammation associated with infection, in an individual comprising, consisting essentially of or consisting of the steps of administering a therapeutically effective amount of idronoxil, or derivative, pharmaceutically acceptable salt, ester, amide, polymorph and/or prodrug thereof to the individual, wherein the individual is diagnosed with, or suspected of having, early stage organ damage caused by inflammation associated with infection.

Compounds of the general formula

##STR00001##

are disclosed with activity towards treating diseases related to inflammation, such as cancer, neurodegenerative and cardiovascular diseases. Pharmaceutical compositions and methods of use are also described.

Provided are, inter alia, multispecific antigen binding proteins, or antigen-binding fragments thereof, comprising one or more mutations in the VH/VL domains and/or CH1/CL domains, pharmaceutical compositions comprising same, isolated nucleic acids, vectors, and host cells encoding/expressing same, method of making the multispecific antigen binding proteins, computer readable media for evaluating multispecific antigen binding proteins, and libraries.

The present invention pertains to a novel and advantageous dosage regimen for a humanized pegylated monovalent anti-CD28 Fab′ antibody fragment, called “FR104”. This dosage regimen consists of between 0.05 and 1.5 mg/kg body weight of FR104, at a dosing schedule of once per week, once every two weeks, once every three weeks, once every four weeks, once every five weeks or once every 6 weeks, once every 7 weeks, once every 8 weeks or once every more than 8 weeks.

The present invention pertains to a novel and advantageous dosage regimen for a humanized pegylated monovalent anti-CD28 Fab′ antibody fragment, called “FR104”. This dosage regimen consists of between 0.05 and 1.5 mg/kg body weight of FR104, at a dosing schedule of once per week, once every two weeks, once every three weeks, once every four weeks, once every five weeks or once every 6 weeks, once every 7 weeks, once every 8 weeks or once every more than 8 weeks.

Provided is an isolated CTLA4 monoclonal antibody. The antibody can highly-specifically bind to CTLA4, and can effectively block the binding of CTLA4 to B7, reduce the activity or expression level of CTLA4, relieve the inhibition of CTLA4 on the immune function of an organism, activate T lymphocytes, and effectively treat tumors and immune system diseases. Also provided are a monoclonal antibody conjugate comprising the pharmaceutical composition and diagnostic composition of the antibody, and the use thereof in the preparation of a drug for preventing and/or treating and/or treating in combination tumors and immune system diseases.

Provided is an isolated CTLA4 monoclonal antibody. The antibody can highly-specifically bind to CTLA4, and can effectively block the binding of CTLA4 to B7, reduce the activity or expression level of CTLA4, relieve the inhibition of CTLA4 on the immune function of an organism, activate T lymphocytes, and effectively treat tumors and immune system diseases. Also provided are a monoclonal antibody conjugate comprising the pharmaceutical composition and diagnostic composition of the antibody, and the use thereof in the preparation of a drug for preventing and/or treating and/or treating in combination tumors and immune system diseases.

The invention relates to combination therapy involving two or more antibodies, wherein the Fc regions of the two antibodies have been modified such that hetero-oligomerization between the antibodies is strongly favored over self-oligomerization when antibodies are bound to their corresponding target antigens and such that hetero-oligomerization-independent effector functions of one or both antibodies are eliminated or strongly reduced. The invention also relates to antibodies, compositions, and kits suitable for use in the combination therapy of the invention.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.