Novel Angiopoietin 2, VEGF Dual Antagonists

• US 20200131260A1
• Filed: 01/13/2020
• Published: 04/30/2020
• Est. Priority Date: 05/13/2016
• Status: Active Grant

• Current Assignee: Askgene Pharma Inc. (Beijing Aosaikang Pharmaceutical Co., Ltd.)
• Original Assignee: Askgene Pharma Inc. (Beijing Aosaikang Pharmaceutical Co., Ltd.)
• Inventors: Lu, Yuefeng, Lu, Jian-Feng
• Granted Patent: US 11,746,147 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/515 Angiogenesic factors; Angiogenin
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction

Abstract

The present disclosure relates to chimeric molecules which are fusion proteins comprising two components: an Ang-2 binding peptide linked to either a VEGF antibody or a VEGF receptor-Fc fusion protein. The Ang2 peptide, VEGF antibody, and VEGF receptor-Fc fusion proteins are each defined below with reference to percent identity to a reference sequence. The chimeric molecule is a fusion protein, dual antagonist of Ang2 and VEGF for treatment of cancers, proliferative retinopathies, neovascular glaucoma, macular edema, AMD, and rheumatoid arthritis.

Claims

1. A chimeric molecule comprising:

a. a VEGF receptor-Fc-fusion; and

b. a peptide that binds to angiopoietin 2 (Ang2);

c. wherein the peptide that binds to Ang2 comprises a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO;

1; and

d. wherein the chimeric molecule inhibits the binding of VEGF to a VEGF receptor and inhibits binding of Ang2 to an Ang2 receptor.

2. The chimeric molecule of claim 1, wherein the VEGF receptor-Fc fusion comprises a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

5.

3. The chimeric molecule of claim 1, wherein the Ang2 binding protein is fused to the C-terminus of the VEGF receptor-Fc fusion.

4. The chimeric molecule of claim 2, wherein the polypeptide comprising the Ang2 binding peptide fused to the C-terminus of the VEGF-Fc fusion protein, wherein the chimeric molecule comprises a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to SEQ ID NO:

6.

5. Polynucleotides encoding the chimeric molecules of claim 1.

6. An expression vector comprising the polynucleotide of claim 5.

7. A host cell transfected with the vector of claim 6.

8. A method of producing a chimeric molecule comprising culturing the host cell of claim 7.

9. A pharmaceutical composition comprising a chimeric molecule of claim 1 and a pharmaceutically acceptable carrier.

10. A peptide-protein fusion molecule, wherein said peptide is fused to the N-terminal or C-terminal of said protein, optionally with a peptide linker, wherein the peptide has an amino acid sequence with at 80%, at least 85%, at least 90%, at least 95%, or 100% identity to a peptide selected from the group consisting of SEQ ID NOS:

7-12, and wherein said protein has an amino acid sequence of at least 95% identity to that of SEQ ID NO;

5.

11. The fusion molecule of claim 10, wherein the fusion molecule forms a homologous dimer, and wherein the dimer binds to both VEGF and Ang 2.

12. Polynucleotides encoding the fusion molecule of claim 10.

13. An expression vector comprising the polynucleotide of claim 12.

14. A host cell transfected with the vector of claim 13.

15. A method of producing a chimeric molecule comprising culturing the host cell of claim 14.