C07K2317/32

Antibodies directed to IL-17A/IL-17F heterodimers

The present invention is directed to a novel naturally occurring human cytokine that is comprised of a heterodimer of interleukin-17 and interleukin-17F designated herein as interleukin 17A/F (IL-17A/F). Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, specific antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

T CELL RECEPTOR LIKE ANTIBODIES HAVING FINE SPECIFICITY

An antibody capable of binding, with a human major histocompatibility complex (MHC)-restricted specificity, a MHC being complexed with an HLA-restricted peptide antigen is provided. The antibody having a binding specificity dictated by at least 4 amino acid residues in said HLA-restricted peptide such that at least 70% reduction in binding of said antibody to said complex is observed when each of said at least 4 amino acid residues is substituted as determined by FACS of cells loaded with said HLA-restricted peptide comprising said substitution, said at least 4 amino acid residues not being anchor residues.

AFFINITY ENTITIES COMPRISING A TCR-LIKE ANTIBODY BINDING DOMAIN WITH HIGH AFFINITY AND FINE SPECIFICITY AND USES OF SAME

Affinity binding entities having TCRL binding domain and methods of their use are provided. More specifically these compositions bind HLA-A2/WT1+, HLA-A2/MAGE-A4, HLA-A2/MAGE-A9, HLA-A2/PAP or HLA-A2/TyrD+ cells and as such can be used in diagnostics and therapy.

ANTIBODY

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

ANTIBODY EPITOPE

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

MODULATOR ASSAY

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.

ABERRANT CELL-RESTRICTED IMMUNOGLOBULINS PROVIDED WITH A TOXIC MOIETY

Described are immunoglobulins provided with a toxic moiety, comprising at least an immunoglobulin variable region that specifically binds to an MHC-peptide complex preferentially associated with aberrant cells. These immunoglobulins provided with a toxic moiety are preferably used in selectively modulating biological processes. The provided immunoglobulins provided with a toxic moiety are of particular use in pharmaceutical compositions for the treatment of diseases related to cellular aberrancies, such as cancers and autoimmune diseases.

ANTIBODIES

Antibodies having modified constant regions so as to permit conjugation of the antibody to a payload such as a therapeutic agent are described. Preferred antibodies include a mutation at light chain position 180 (positional numbering), most preferably the mutation is to a residue selected from C, K, Q, or a non-natural amino acid. Additional mutations may also be combined with a mutation at position 180; including one or more of light chain (LC) S208, LC S171, LC S182, LC A184, LC V191, LC S202, LC S203, LC T206, heavy chain (HC) S160, HC T190, HC S443, HC S447, HC S139, HC S168, HC V170, HC V176, HC T200, HC S445 according to a positional numbering convention.

Antibodies to Plasminogen Activator Inhibitor-1 (PAI-1) and Uses Thereof

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.

Regeneratable Biosensor and Methods of Use Thereof

A multiplex-able, regeneratable nucleic-acid linked immunoassay method and system for the detection of a single specific, or multiple, soluble analytes in solution and regeneratable biosensor devices for same are described.