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.

Provided herein are compositions which exhibit novel therapeutic capabilities and allow to reduce the off-target effect of therapeutic antibodies. The compositions include recombinant proteins that if expressed by a T cell can efficiently recruit therapeutic antibodies to their site of action.

This application discloses a nanobody polypeptide comprising at least 2 complementarity determining regions (CDRs) and an antimicrobial peptide, wherein the polypeptide binds specifically to a microbial surface antigen. Further, this application provides a nanobody polypeptide comprising 3 CDRs and an antimicrobial peptide, wherein the polypeptide binds specifically to a microbial surface antigen.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (MOD) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (Co-MOD). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Antitumor antagonists that bind specifically to immune checkpoint regulator and/or components of the angiogenesis pathways and/or components of the TGF pathway are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists.

Blood-brain barrier permeable peptide compositions that contain variable antigen binding domains from camelid and/or shark heavy-chain only single-domain antibodies are described. The variable antigen binding domains of the peptide compositions bind to therapeutic and diagnostic biomarkers in the central nervous system, such as the amyloid-beta peptide biomarker for Alzheimer's disease. The peptide compositions contain constant domains from human IgG, camelid IgG, and/or shark IgNAR. The peptide compositions include heavy-chain only single-domain antibodies and compositions with one or more variable antigen binding domain bound to one or more constant domains.

Antitumor antagonists that bind specifically to immune checkpoint regulator and/or components of the angiogenesis pathways and/or components of the TGF pathway are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists.

The present invention relates to a polypeptide binding to fibroblast growth factor receptor 3 isoforms 3b and 3c (FGFR3b and FGFR3c), wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDYEVYGPTPMLSFHKGEKFQIL(X.sup.1)(X.sup.2)(X.sup.3) (X.sup.4)GPYWEARSL(X.sup.5)TGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein amino acid positions (X1) to (X.sup.6) may be any amino acid sequence; (b) an amino acid sequence which is at least 95% identical to the amino acid sequence of (a), wherein the identity determination excludes amino acid positions (X.sup.1) to (X.sup.6) and provided that the amino acid sequence EVYGPTPM (SEQ ID NO: 2) in amino acid positions 12 to 19 of SEQ ID NO: 1 is conserved and the amino acids P and Y in amino acid positions 37 and 38 of SEQ ID NO: 1 are conserved; (c) GVTLFVALYDYEVMSTTALSFHKGEKF QILSQSPHGQYWEARSLTTGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 19), wherein the amino acid position (X.sup.6) may be any amino acid; and (d) an amino acid sequence which is at least 95% identical to the amino acid sequence of (c), wherein the identity determination excludes amino acid position (X.sup.6) and provided that the amino acid sequences EVMSTTA (SEQ ID NO: 20) in amino acid positions 12 to 18 of SEQ ID NO: 19 and SQSPH (SEQ ID NO: 21) in amino acid positions 31 to 35 of SEQ ID NO: 19 are conserved and the amino acids Q and Yin amino acid positions 37 and 38 of SEQ ID NO: 19 are conserved.

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.

A pharmaceutical comprising a therapeutic protein that binds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.