Abstract: A protein comprising (i) a domain of the Platelet-Derived Growth Factor receptor (PDGFR) and (ii) a domain of the Vascular Endothelial Growth Factor receptor (VEGFR) is provided. In a preferred embodiment, said domain of PDGFR and said domain of VEGFR are attached by a linker consisting of proline, alanine and serine. The domain of PDGFR and said domain of VEGFR can also be attached by a linker consisting of proline and alanine. Compositions comprising the proteins, as well as therapeutic uses thereof are also provided.

Abstract: The present invention relates to a nucleic acid molecule comprising a low repetitive nucleotide sequence encoding a proline/alanine-rich amino acid repeat sequence. The encoded polypeptide comprises a repetitive amino acid sequence that forms a random coil. The nucleic acid molecule comprising said low repetitive nucleotide sequences can further comprise a nucleotide sequence encoding a biologically or pharmacologically active protein. Further, the present invention provides for selection means and methods to identify said nucleic acid molecule comprising said low repetitive nucleotide sequence. The present invention also relates to a method for preparing said nucleic acid molecules. Also provided herein are methods for preparing the encoded polypeptide or drug conjugates with the encoded polypeptide using the herein provided nucleic acid molecules. The drug conjugate may comprise a biologically or pharmacologically active protein or a small molecule drug.

Abstract: A protein comprising (i) a domain of the Platelet-Derived Growth Factor receptor (PDGFR) and (ii) a domain of the Vascular Endothelial Growth Factor receptor (VEGFR) is provided. In a preferred embodiment, said domain of PDGFR and said domain of VEGFR are attached by a linker consisting of proline, alanine and serine. The domain of PDGFR and said domain of VEGFR can also be attached by a linker consisting of proline and alanine. Compositions comprising the proteins, as well as therapeutic uses thereof are also provided.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, in which the biosynthetic random coil polypeptide, the biosynthetic random coil polypeptide segment, or the biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein the amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. The at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) fconstituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or conjugates are described.

Abstract: The present invention relates to conjugates of a protein drug and two or more P/A peptides, and pharmaceutical compositions comprising them. The conjugates of the invention exhibit an advantageously reduced immunogenicity as compared to the respective unmasked protein drugs as well as a favorable safety and tolerability profile, which render them particularly suitable for therapeutic use. The conjugates further show an enhanced plasma half-life and, thus, a prolonged duration of action as compared to the respective unmasked protein drugs, which allows for a reduction in the dosing frequency and, thus, side-effect burden. The invention also provides processes of preparing such conjugates as well as activated P/A peptides that are useful as synthetic intermediates in the preparation of the conjugates.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: The present invention relates to a nucleic acid molecule comprising a low repetitive nucleotide sequence encoding a proline/alanine-rich amino acid repeat sequence. The encoded polypeptide comprises a repetitive amino acid sequence that forms a random coil. The nucleic acid molecule comprising said low repetitive nucleotide sequences can further comprise a nucleotide sequence encoding a biologically or pharmacologically active protein. Further, the present invention provides for selection means and methods to identify said nucleic acid molecule comprising said low repetitive nucleotide sequence. The present invention also relates to a method for preparing said nucleic acid molecules. Also provided herein are methods for preparing the encoded polypeptide or drug conjugates with the encoded polypeptide using the herein provided nucleic acid molecules. The drug conjugate may comprise a biologically or pharmacologically active protein or a small molecule drug.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, wherein said biosynthetic random coil polypeptide, said biosynthetic random coil polypeptide segment or said biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein said amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. Said at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or said conjugates are described.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, in which the biosynthetic random coil polypeptide, the biosynthetic random coil polypeptide segment, or the biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein the amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. The at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituent(s) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or conjugates are described.

Abstract: The present invention relates to a biosynthetic random coil polypeptide or a biosynthetic random coil polypeptide segment or biosynthetic conjugate, wherein said biosynthetic random coil polypeptide, said biosynthetic random coil polypeptide segment or said biosynthetic conjugate comprises an amino acid sequence consisting solely of proline and alanine amino acid residues, wherein said amino acid sequence consists of at least about 50 proline (Pro) and alanine (Ala) amino acid residues. Said at least about 50 proline (Pro) and alanine (Ala) amino acid residues may be (a) constituents) of a heterologous polypeptide or an heterologous polypeptide construct. Also uses and methods of use of these biosynthetic random coil polypeptides or polypeptide segments or said conjugates are described.

Abstract: We discovered that a biosynthetic polypeptide, consisting of at least about 50 proline (Pro) and alanine (Ala) amino acid residues, forms a random coil, and increases the stability of other compounds to which it is conjugated, such as small molecules and polypeptides. We describe such biosynthetic polypeptides, constructs containing such polypeptides, ways of making them, and their use.