US 10,703,810 B2Granted

Fusion polypeptides which bind vascular endothelial growth factor a (VEGF-A) and angiopoietin-2 (Ang-2)

AssigneePieris Australia Pty Ltd.

InventorsShane Olwill, Rachida-Siham Bel Aiba, Alexander Wiedenmann

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Abstract

The disclosure provides fusion polypeptides comprising a moiety specific for Ang-2 and another for VEGF-A, which fusion polypeptide can be useful for antagonizing Ang-2 and VEGF-A. In a preferred embodiment, the Ang-2-specific moiety is comprised of a human neutrophil gelatinase associated lipocalin (hNGAL) mutein. Such fusion polypeptide can be used in many pharmaceutical applications, for example, as an agent useful to inhibit or reduce angiogenesis. The present disclosure also concerns methods of making the fusion polypeptides described herein as well as compositions comprising such fusion polypeptides. The present disclosure further relates to nucleic acid molecules encoding such fusion polypeptides, their amino acid sequences and to methods for the generation of such fusion polypeptides and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of such fusion polypeptide as well as compositions comprising one or more of such fusion polypeptides.

Claims19

Dependent claims

A fusion protein comprising a first subunit and a second subunit, wherein the first subunit is comprised of an immunoglobulin or an antigen-binding domain thereof specific for vascular endothelial growth factor A (VEGF-A), wherein the second subunit is comprised of a human neutrophil gelatinase-associated lipocalin (hNGAL) mutein specific for angiopoietin-2 (Ang-2);

wherein said mutein comprises one or more of the following mutated amino acid residues in comparison with the linear polypeptide sequence of mature hNGAL (SEQ ID NO:
1):
Leu 36→Gln, Glu, His, Val, Met or Phe;
Ala 40→Val, Tyr, His or Trp;
Ile 41→His, Tyr, Trp, Val, Arg, Glu, or Asp;
Gln 49→Gly, Ile, Glu or Val;
Tyr 52→Trp, His, Thr or Ser;
Ser 68→Gly, Asp, Gln, Glu or Ile;
Leu 70→Ser, Thr, Gly, Arg, Tyr or Ala;
Arg 72→Gly, Ala, Trp, Thr or Glu;
Lys 73→Pro, Phe, Leu, Arg, Ala or Gln;
Asp 77→Asn, Lys, Ser or Val;
Trp 79→Thr, Arg, Ser or Asn;
Arg 81→Trp, His or Tyr;
Asn 96→Gly, Ala, Pro, Gln or Asp;
Tyr 100→Pro, Trp, Gly, Ser, Leu or Asp;
Leu 103→Gly, Glu, Asp, Met or Gln;
Tyr 106→Thr, Leu, Phe, or Pro;
Lys 125→His, Thr or Gly;
Ser 127→Leu, Met, or Tyr;
Tyr 132→Phe, Trp or Val;
and Lys 134→Ala, Glu or Trp;
and
wherein the second subunit is fused to the C-terminus of the immunoglobulin heavy chain constant region (CH) or light chain constant region (CL) of the first subunit via a peptide linker.

21 more elements

Dependencies are inferred from the claim text.