Abstract: The present invention relates to immunoglobulins that specifically bind CD40L and more in particular to polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes. In particular, the immunoglobulins of the present invention inhibit the activity of CD40L and are safe.

Abstract: The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

Abstract: The present invention relates to amino acid sequences and polypeptides binding to the P2X7 receptor. In particular, the present invention relates to improved heavy-chain immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVD's”) binding to the P2X7 receptor, as well as to proteins, polypeptides and other constructs, compounds, molecules or 5 chemical entities that comprise such ISVD's.

Abstract: The present invention relates to amino acid sequences binding to serum albumin. In particular, the present invention relates to improved immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVD's”), and more in particular improved heavy-chain immunoglobulin single variable domains, binding to serum albumin, as well as to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise such improved serum albumin binders.

Abstract: The present invention relates to amino acid sequences that are directed against IL-23. The amino acid sequences of the present invention comprise two Nanobodies against IL-23 and one Nanobody against serum albumin, linked by two linkers (9GS linkers). In particular, the invention relates to the amino acid sequences of SEQ ID NO: 2 and SEQ ID NO: 3 (listed in Table 1 and FIG. 1) (also referred to herein as “anti-IL 23 polypeptides of the invention”).

Abstract: The present invention relates to glycosylated immunoglobulin variable domains, and in particular to glycosylated immunoglobulin single variable domains (the latter also being referred to herein by means of the abbreviation “ISF” or “ISVD”). The present invention relates to glycosylated immunoglobulin heavy-chain variable domains (also referred to herein as “VH domains”), and in particular to glycosylated immunoglobulin heavy-chain ISVD's. The invention in particular relates to immunoglobulin (single) variable domains that are glycosylated in such a way that the binding of said immunoglobulin (single) variable domains by so-called “pre-existing antibodies” is prevented and/or reduced (i.e. partially or essentially completely) compared to the same immunoglobulin (single) variable domain without the glycosylation of the invention being present.

Abstract: The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

Abstract: This invention provides, and in certain specific but non-limiting aspects relates to: assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay).

Abstract: This invention provides, and in certain specific but non-limiting aspects relates to: —assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay).

Abstract: This invention provides, and in certain specific but non-limiting aspects relates to: —assays that can be used to predict whether a given ISV will be subject to protein interference as described herein and/or give rise to an (aspecific) signal in such an assay (such as for example in an ADA immunoassay).

Abstract: The present invention relates to amino acid sequences, compounds and polypeptides binding to tumor necrosis factor alpha (“TNF” or “TNF-alpha”). In particular, the present invention relates to improved heavy-chain immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVDs”) binding to tumor necrosis factor alpha, as well as to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise such ISVDs, collectively TNF binders. Other aspects, embodiments, features, uses and advantages of the invention will be clear to the skilled person based on the disclosure herein.

Abstract: Bispecifc binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

Abstract: The present invention relates to amino acid sequences, compounds and polypeptides binding to tumor necrosis factor alpha (“TNF” or “TNF-alpha”). In particular, the present invention relates to improved heavy-chain immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVDs”) binding to tumor necrosis factor alpha, as well as to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise such ISVDs, collectively TNF binders. Other aspects, embodiments, features, uses and advantages of the invention will be clear to the skilled person based on the disclosure herein.

Abstract: The present invention relates to amino acid sequences, compounds and polypeptides binding to tumor necrosis factor alpha (“TNF” or “TNF-alpha”). In particular, the present invention relates to improved heavy-chain immunoglobulin single variable domains (also referred to herein as “ISV's” or “ISVDs”) binding to tumor necrosis factor alpha, as well as to proteins, polypeptides and other constructs, compounds, molecules or chemical entities that comprise such ISVDs, collectively TNF binders. Other aspects, embodiments, features, uses and advantages of the invention will be clear to the skilled person based on the disclosure herein.

Abstract: The present invention relates to polypeptides directed against or specifically binding to chemokine receptor CXCR2 and in particular to polypeptides capable of modulating signal transduction from CXCR2. The invention also relates to nucleic acids, vectors and host cells capable of expressing the polypeptides of the invention, pharmaceutical compositions comprising the polypeptides and uses of said polypeptides and compositions for treatment of diseases involving aberrant functioning of CXCR2.

Abstract: The invention provides novel biparatopic LRP5/LRP6 cross-reactive binding polypeptides, and more specifically novel biparatopic LRP5/LRP6 cross-reactive immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

Abstract: The present invention provides multispecific molecules, e.g., comprising more than one ISVD or Nanobody, that bind to PD1 and CTLA4. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to CTLA4 or human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: The present invention provides molecules, such as ISVDs and Nanobodies, that bind to PD1 and LAG3 and, optionally to human serum albumin. These molecules have been engineered so as to reduce the incidence of binding by pre-existing antibodies in the bodies of a subject administered such a molecule. Methods for increasing immune response, treating cancer and/or treating an infectious disease with such molecules are provided.

Abstract: VH domain, in which: (i) the amino acid residue at position 1 12 is one of K or Q; and/or (ii) the amino acid residue at position 89 is T; and/or (iii) the amino acid residue at position 89 is L and the amino acid residue at position 1 10 is one of K or Q; and (iv) in each of cases (i) to (hi), the amino acid at position 1 1 is preferably V; and in which said VH domain contains a C-terminal extension (X)n, in which n is 1 to 10, preferably 1 to 5, such as 1, 2, 3, 4 or 5 (and preferably 1 or 2, such as 1); and each X is an (preferably naturally occurring) amino acid residue that is independently chosen, and preferably independently chosen from the group consisting of alanine (A), glycine (G), valine (V), leucine (L) or isoleucine (I).