This invention relates to the incorporation of one, or more, heterologous antibody epitopes into the AB, EF, or CD structural loops of the constant heavy domain 3 (“CH3 domain”) of an engineered antibody or Fc-linked therapeutic agent. The heterologous epitopes serve as “epitope tags” that are specifically detectable by epitope tag-specific detector antibodies, irrespective of the tagged agent's target specificity. Therefore, the epitope tags are useful for the rapid detection of any tagged antibody or Fc-linked agent in biological samples, including samples, which also contain endogenous antibodies.

Binding members for sodium channel Nav1.7 and their use in medicine including for treatment of pain or epilepsy. Binding members comprise a fusion protein containing a Nav1.7-binding peptide, e.g., venom toxin peptide or knottin (“donor diversity scaffold domain”) inserted within an antibody variable domain (“recipient diversity scaffold domain”), and a partner domain (e.g., antibody variable domain), optionally wherein the partner domain enhances specificity of binding to Nav1.7 over other sodium channels.

Antibodies that bind to αv⊖8 are provided.

Provided herein are methods and compositions relating to adenosine A2A receptor libraries having nucleic acids encoding for a scaffold comprising an adenosine A2A binding domain. adenosine A2A receptor libraries described herein encode for immunoglobulins including antibodies and single domain antibodies. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.

The present invention relates to an antibody or a fragment thereof comprising at least one heterologous amino acid sequence incorporated within at least one CDR region of said antibody or fragment thereof, wherein said at least one heterologous amino acid sequence comprises an N-terminal linker sequence (Ntls), a Brain Natriuretic Peptide (BNP) and a C-terminal linker sequence (Ctls). Optionally, at least a portion of said at least one CDR region is replaced by said at least one heterologous amino acid sequence incorporated therein. The present invention further relates to such antibody or fragment thereof for use in a method for treatment, a composition comprising such antibody or fragment thereof, a nucleic acid or a mixture of nucleic acids encoding such antibody or fragment thereof, a host cell comprising such nucleic acid or such mixture of nucleic acids and to a process for producing such antibody or fragment thereof.

The present disclosure provides multispecific binding molecules that specifically bind to a first tumor-associated antigen that is expressed on cancerous B cells, a second tumor-associated antigen that is expressed on cancerous B cells, and a component of a human T-cell receptor complex, conjugates comprising the trispecific binding molecules, and pharmaceutical compositions comprising the multispecific binding molecules and the conjugates. The disclosure further provides methods of using the multispecific binding molecules to treat cancers that express the tumor-associated antigens. The disclosure yet further provides recombinant host cells engineered to express the multispecific binding molecules and methods of producing the multispecific binding molecules by culturing the host cells under conditions in which the multispecific binding molecules are expressed.

The present invention relates to an antibody or a fragment thereof comprising at least one heterologous amino acid sequence incorporated within at least one CDR region of said antibody or fragment thereof, wherein said at least one heterologous amino acid sequence comprises an N-terminal linker sequence (Nils), an Atrial Natriuretic Peptide (ANP) and a C-terminal linker sequence (Ctls). Optionally, at least a portion of said at least one CDR region is replaced by said at least one heterologous amino acid sequence incorporated therein. The present invention further relates to such antibody or fragment thereof for use in a method for treatment, a composition comprising such antibody or fragment thereof, a nucleic acid or a mixture of nucleic acids encoding such antibody or fragment thereof, a host cell comprising such nucleic acid or such mixture of nucleic acids and to a process for producing such antibody or fragment thereof.

Antitumor antagonists that bind specifically to immune checkpoint regulators, angiogenesis pathway regulators and/or TGF pathway regulators are disclosed. Also disclosed are methods for treating proliferative disorders, infections, and immunological disorders with the antitumor antagonists described herein.

In one aspect, the invention provides an isolated antibody, or antigen-binding fragment thereof, comprising a bioactive peptide amino acid sequence, wherein the bioactive peptide amino acid sequence is an inhibitor of the complement system and is fused to at least one of: (i) the amino terminal region of at least one of: a light chain variable region and/or a heavy chain variable region; or (ii) the carboxy terminal region of at least one of: a light chain constant region and/or a heavy chain constant region, wherein the antibody inhibits complement activation.

The present invention provides methods for generating functional derivatives of effector polypeptides (e.g., hormones and receptor ligands) embedded in a different protein scaffold (e.g., antibody scaffolds). The methods involve modifying the effector polypeptide with a combinatorial library of terminal linker sequences, inserting the modified sequences into the host scaffold, and then selecting functional derivatives from the library of modified polypeptide sequences embedded in the host scaffold. As exemplifications, the invention also provides specific functional derivatives of leptin, scFSH and scRelaxin embedded in an antibody scaffold, as well as therapeutic applications of such functional fusion molecules.