The invention relates to specific binding members that bind CD137. The specific binding members comprise a CD137 antigen-binding site located in a constant domain of the specific binding member and find application in the treatment of cancer and infectious diseases, for example.

The present disclosure provides methods for treating bone disease, such as bone cancers or bone metastasis of cancers, by administering an engineered bone-targeting compositions, such as an antibody or one or more polypeptides, such as an antibody or polypeptide engineered to comprise bone-homing peptide(s). Further provided herein are bone-targeting compositions, such as an antibody or one or more polypeptides, such as an antibody or polypeptide engineered to comprise bone-homing peptide(s).

Provided are bispecific or multispecific antibodies that include an anti-CEACAM5 portion and one or more anti-4-1BB nanobodies whose agonist activity is dependent on the presence of the CEACAM5 antigen. Such bispecific or multispecific antibodies are safe, and are efficacious in treating cancer and have long-term protective immunological memory against tumors. Methods of using the antibodies for treating diseases such as cancer are also provided.

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.

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 such as antibodies.

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.

The present invention provides engineered antibodies and antigen binding fragments, in which an additional functional domain is inserted into the elbow region of the antibody or antigen binding fragment. The present invention also provides nucleic acid molecules, such as vectors, encoding such antibodies and antigen binding fragments, host cells and compositions comprising such antibodies, antigen binding fragments or nucleic acid molecules and uses thereof. For example a multispecific antibody format is provided, in which an additional binding site (specificity) is inserted into the elbow region of an antibody or antigen binding fragment.

The present disclosure provides polypeptide constructs that act as agonists of immune cell function when exposed to sufficient levels of ATP to cause their assembly into dimers or higher level complexes (e.g., trimers, tetramers, etc.). The complexes of the constructs are capable of stimulating immune cells (e.g., cytotoxic CD8+ T cell and/or NK cells) that function to promote anti-tumor immune responses. The constructs may be employed as anticancer agents/therapeutics for the treatment of solid tumors that have elevated levels of ATP.

The present disclosure provides Transforming Growth Factor Beta (TGF-) polypeptide constructs and complexes that find use in, for example, therapeutic treatment of diseases including autoimmune diseases. Also described are nucleic acids that encode the constructs and complexes and methods of preparing the constructs and complexes in cell-based expression systems.

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 C-Type Natriuretic Peptide (CNP) 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.