This invention relates generally to monoclonal antibodies or antigen binding fragments thereof that specifically bind Toll-like Receptor 4 (TLR-4), to methods of using the anti-TLR4 antibodies to treat or prevent symptoms of Acute Respiratory Distress Syndrome (ARDS). This invention also relates to monoclonal antibodies or antigen binding fragments thereof that specifically bind to IP-10 and methods of using anti-IL-10 antibodies to treat or prevent symptoms of ARDS. The invention further provides routes of administrations and formulations for said methods.

The invention provides antibodies that specifically bind to Plasminogen Activator Inhibitor type-1 (PAI-1), The invention also provides pharmaceutical compositions, as well as nucleic acids encoding anti-PAI-1 antibodies, recombinant expression vectors and host cells for making such antibodies, or fragments thereof. Methods of using antibodies to modulate PAI-1 activity or detect PAI-1, either in vitro or in vivo, are also provided. The disclosure further provides methods of making antibodies that specifically bind to PAI-1 in the active conformational state.

The present disclosure relates to proteins that bind to CD83 and uses thereof, for example, in therapy, prophylaxis, diagnosis, or prognosis.

The present invention generally relates to antigen binding receptors capable of specific binding to mutated Fc domains with reduced Fc receptor binding and T cells expressing these antigen binding receptors. More precisely, the present invention relates to T cells, transfected/transduced with an antigen binding receptor which is recruited by specifically binding to/interacting with the mutated Fc domain of therapeutic antibodies. Furthermore, the invention relates to a kit comprising the T cells of the invention and/or nucleic acid molecules, vectors expressing antigen binding receptors of the present invention and (a) tumor targeting antibody/antibodies comprising a mutated Fc domain. The invention also provides the production and use of T cells in a method for the treatment of particular diseases in conjunction with tumor-specific antibodies as well as pharmaceutical compositions/medicaments comprising T cells and/or therapeutic antibodies, wherein T cells are to be administered in combination with therapeutic-tumor targeting antibody/antibodies comprising a mutated Fc domain with reduced Fc receptor binding.

The present invention relates to peptides that bind with high specificity and which functionally interact with the transferrin receptor (“TfR”) and which may be used in making molecular vehicles that carry biomolecules across membranes, including, e.g., across the blood brain barrier or the gastrointestinal tract. TfR specific binding moieties may also be used alone or as components in specific molecules that target the transferrin/transferrin receptor transport system. The invention relates more specifically to VNAR single chain antibodies derived from nurse shark that bind to TfR, compounds and compositions comprising a TfR specific VNAR binding moiety, methods for preparing them, diagnostic and therapeutic methods of use in vitro or in vivo, e.g., to diagnose, treat and/or prevent a pathological condition, disorder or disease in which it is beneficial to deliver a heterologous biomolecule across the blood brain barrier by association with a TfR specific VNAR binding moiety. Other uses for TfR specific VNAR binding moieties of the invention include, e.g., regulating the interaction of iron-charged transferrin with TfR (receptor cycling or cell surface presentation), such as may be therapeutic in treatment of certain cancer cells and tumors of various tissue types.

The invention provides novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule and methods for producing novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule. The antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other of a Lambda constant domain. The invention provides methods for the isolation of antibodies of different specificities but sharing a common heavy chain. The invention also provides methods for the controlled co-expression of two light chains and a single heavy chain leading to the assembly of monospecific and bispecific antibodies. The invention provides a mean of producing a fully human bispecific and bivalent antibody that is unaltered in sequence and does not involve the use of linkers or other non-human sequences, as well as antibody mixtures of two monospecific antibodies and one bispecific antibody. The invention also provides the means of efficiently purifying the bispecific antibody.

The invention is directed to methods of treatment of Alzheimer's disease and other tauopathies, via the administration of antibodies having specificity to abnormal forms of tau protein, the antibodies showing no binding and/or reactivity to a normal tau protein and being administered under conditions and in amounts effective to prevent or treat Alzheimer's disease or other tauopathies. In certain embodiments, the antibodies are selective for soluble truncated tau protein truncated at (i) its C-terminus after the glutamic acid residue Glu391, or (ii) at the aspartic acid residue Asp421, or (iii) at its N-terminus at the aspartic acid residue Asp13, or (iv) a combination of (i)-(iii). Further aspects of the invention are directed to the administration of an immunogen comprising an abnormal tau, preferably a soluble truncated tau.

A new, stable trimeric TNFα structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNFα/TNFR1 interaction. Membrane-bound TNFα is not affected in its ability to signal through TNFR2, and thus the new structure of TNFα may be used in therapies which do not significantly raise the risk of infection or malignancy.

This invention provides fully human monoclonal antibodies that recognize the IL-6/IL-6R complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Provided here are antibodies that bind Protein S, and methods of making and using such antibodies. In some embodiments, the Protein S antibodies provided herein are useful for treating a bleeding disorder or platelet disorder, or a condition characterized by reduced or impaired blood coagulation and/or clotting, e.g. by depleting the circulating levels of TFPI, by disrupting a Protein S-TFPI complex, and/or by preventing the formation of a Protein S-TFPI complex.