Abstract: The present invention provides a variant of an immunoglobulin variable domain including (A) at least one CDR region and (B) framework regions flanking the CDR region, wherein the variant also contains (a) a CDR region having added or substituted therein at least on binding sequence and (b) the flanking framework regions, wherein the binding sequence is heterelogous to the CDR and is an antigenic sequence from a MUC-1 binding sequence.

Abstract: The present invention relates to a synthetic variable region of an immunoglobin construct which contains in at least one of its CDRs a sequence of thrombopoietin, <i>e.g.</i>, IEGPTLRQWLAARA or its derivatives. This construct can efficiently bind and activate a thrombopoientin receptor (MPL) leading to stimulation of proliferation, growth or differentiation or modulation of apoptosis of hematopoietic cells, especially platelet progenitor cells. The invention further relates to the use of the synthebody to treat hematopoietic or immune disorders, and particularly thrombocytopenia resulting from chemotherapy, radiation therapy, or bone marrow transfusions.

Abstract: Variants of an immunoglobulin variable domain, said immunoglobulin variable domain comprising (A) at least one CDR region and (B) framework regions flanking said CDR, said variant comprising: (a) said CDR region havind added or substituted therein at least one binding sequence and (b) said flanking framework regions, wherein said binding sequence is heterologous to said CDR and is a binding sequence from a binding site of a binding pair, and wherein said binding sequence is a receptor-binding portion of angiogenin. Additionally, amino acid residues in the flanking and/or non-flanking framework regions may have been deleted, substituted or inserted. Also claimed are molecules comprising said variants. Said molecules may be immunoglobulins. Nucleic acids encoding said variants, and cells and recombinant non-human hosts containing said nucleic acids. Pharmaceutical compositions comprising an effective amount of said variants.