Stable and soluble antibodies inhibiting VEGF

Patent metadata

Field	Value
Publication number	US-10590193-B2
Application number	US-201715814784-A
Country	US
Kind code	B2
Filing date	Nov 16, 2017
Priority date	Jun 25, 2008
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

The present invention relates to soluble and stable anti-VEGF imunobinders comprising CDRs from rabbit monoclonal antibodies. Said antibodies are designed for the diagnosis and/or treatment of VEGF-mediated disorders. The hybridomas, nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

First claim

The invention claimed is:

1. A humanized antibody or antigen-binding fragment thereof comprising a variable heavy chain (VH), and a variable light chain (VL), wherein:
the VH comprises CDRH1, CDRH2 and CDRH3 sequences of SEQ ID NO: 8, SEQ ID NO: 20 and SEQ ID NO: 32, respectively, and the VL comprises CDRL1, CDRL2, and CDRL3 sequences of SEQ ID NO: 43, SEQ ID NO: 55 and SEQ ID NO: 66, wherein the antibody or antigen-binding fragment thereof binds human VEGF 165 with an affinity (K d ) of ≤1×10 −9 M.

2. The humanized antibody or antigen-binding fragment thereof of claim 1 , wherein the fragment is an scFv, a Fab fragment, a Fab′ fragment, or a F(ab′) 2 fragment.

3. A composition comprising the humanized antibody or antigen-binding fragment of claim 1 , and a pharmaceutically acceptable carrier.

4. The composition of claim 3 , formulated for topical, intraocular, oral, nasal, rectal or parental administration.

5. The humanized antibody or antigen-binding fragment of claim 1 comprising a heavy chain variable region variable region framework sequence having at least 95% sequence identity to the sequence of SEQ ID NO: 164.

6. The humanized antibody or antigen-binding fragment of claim 5 , wherein the heavy chain variable region framework comprises a sequence having 100% identity to SEQ ID NO: 164.

7. The humanized antibody or antigen-binding fragment of claim 1 , comprising a light chain variable region framework sequence having at least 95% sequence identity to the sequence of SEQ ID NO: 87.

8. The humanized antibody or antigen-binding fragment of claim 7 , wherein the light chain variable region framework comprises a sequence having 100% identity to SEQ ID NO: 87.

9. The humanized antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a variable heavy chain comprises the sequence of SEQ ID NO: 164 and wherein the antibody or antigen-binding fragment comprises a variable light chain comprising the sequence of SEQ ID NO: 87.

10. The humanized antibody or antigen-binding fragment of claim 9 , further comprising a linker sequence having the sequence of SEQ ID NO: 181 linking the heavy chain variable region and the light chain variable region.

11. The antigen-binding fragment of claim 10 , which is a single-chain antibody (scFv).

12. The antigen-binding fragment of claim 11 , comprising an N-terminal methionine derived from a start codon present in an expression vector that expresses the antigen-binding fragment.

13. The humanized antibody or antigen-binding fragment of claim 5 , 6 , 7 , 8 , 9 , 10 , 11 , or 12 , wherein the antibody or antigen-binding fragment thereof binds human VEGF 165 with an affinity (K d ) of ≤1×10 −10 M.

14. A composition comprising the humanized antibody or antigen-binding fragment of claim 13 , and a pharmaceutically acceptable carrier.

Assignees

• Esbatech Alcon Biomed Res Unit
• Novartis Ag

Inventors

• Borras Leonardo
• Urech David
• Gunde Tea

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title

• A61P33/14

  Ectoparasiticides, e.g. scabicides · CPC title