Bispecific binding molecules binding to vegf and ang2
AssigneeBoehringer Ingelheim International GmbH
InventorsAndreas GSCHWIND, Rene Georg OTT, Joachim BOUCNEAU, Marie-Ange BUYSE, Erik DEPLA
Life of this patent
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Abstract
Bispecifc binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.
Claims18
1-26. (canceled)
An Ang2-binding VHH with an amino acid sequence selected from acid sequences shown in SEQ ID NOs:
- 214, 215, 216, 217, 218, 219, 220, 221, 222, or 223.
29-37. (canceled)
A method of treating a disease that is associated with VEGF- and/or Ang2-mediated effects on angiogenesis comprising administering to a patient an effective amount of a pharmaceutical composition comprising at least one binding molecule as the active ingredient and a pharmaceutically acceptable carrier, diluent or excipient, wherein the said binding molecule comprises:
- at least one VEGF-binding component,
- at least one serum albumin binding component, and
- at least one Angiopoietin-2 (Ang2) binding component,
- wherein said VEGF-, serum albumin and Ang2-binding components are immunoglobulin single variable domains, each immunoglobulin single variable domain consisting of four framework regions and three complementarity determining regions (CDRs), and
- wherein:
- said VEGF binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 450)
- CDR1:
- SYSMG
- (SEQ ID NO:
- 465)
- CDR2:
- AISKGGYKYDAVSLEG
- (SEQ ID NO:
- 4)
- CDR3:
- SRAYGSSRLRLADTYEY
- said serum albumin binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 255)
- CDR1:
- SFGMS
- (SEQ ID NO:
- 256)
- CDR2:
- SISGSGSDTLYADSVKG
- (SEQ ID NO:
- 257)
- CDR3:
- GGSLSR;
- and
- said Ang2-binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 248)
- CDR1:
- DYAIG
- (SEQ ID NO:
- 49)
- CDR2:
- AIRSSGGSTYYADSVKG
- (SEQ ID NO:
- 250)
- CDR3:
- VPAGRLRYGEQWYPIYEYDA.
An isolated nucleic acid molecule encoding a bispecific binding molecule, wherein said binding molecule comprises:
- at least one VEGF-binding component,
- at least one serum albumin binding component, and
- at least one Angiopoietin-2 (Ang2) binding component,
- wherein said VEGF-, serum albumin and Ang2-binding components are immunoglobulin single variable domains, each immunoglobulin single variable domain consisting of four framework regions and three complementarity determining regions (CDRs), and
- wherein:
- said VEGF binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 450)
- CDR1:
- SYSMG
- (SEQ ID NO:
- 465)
- CDR2:
- AISKGGYKYDAVSLEG
- (SEQ ID NO:
- 4)
- CDR3:
- SRAYGSSRLRLADTYEY
- said serum albumin binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 255)
- CDR1:
- SFGMS
- (SEQ ID NO:
- 256)
- CDR2:
- SISGSGSDTLYADSVKG
- (SEQ ID NO:
- 257)
- CDR3:
- GGSLSR;
- and
- said Ang2-binding immunoglobulin single variable domain, comprises the following CDR sequences:
- (SEQ ID NO:
- 248)
- CDR1:
- DYAIG
- (SEQ ID NO:
- 249)
- CDR2:
- AIRSSGGSTYYADSVKG
- (SEQ ID NO:
- 250)
- CDR3:
- VPAGRLRYGEQWYPIYEYDA.
An isolated nucleic acid molecule encoding a bispecific binding molecule, wherein said bispecific binding molecule comprises:
- a VEGF-binding VHH, comprising the following CDR sequences:
- (SEQ ID NO:
- 450)
- CDR1:
- SYSMG
- (SEQ ID NO:
- 465)
- CDR2:
- AISKGGYKYDAVSLEG
- (SEQ ID NO:
- 4)
- CDR3:
- SRAYGSSRLRLADTYEY
- a serum albumin binding VHH, comprising the following CDR sequences:
- (SEQ ID NO:
- 255)
- CDR1:
- SFGMS
- (SEQ ID NO:
- 256)
- CDR2:
- SISGSGSDTLYADSVKG
- (SEQ ID NO:
- 257)
- CDR3:
- GGSLSR;
- and
- an Ang2-binding VHH, comprising the following CDR sequences:
- (SEQ ID NO:
- 248)
- CDR1:
- DYAIG
- (SEQ ID NO:
- 249)
- CDR2:
- AIRSSGGSTYYADSVKG
- (SEQ ID NO:
- 250)
- CDR3:
- VPAGRLRYGEQWYPIYEYDA.
An isolated nucleic acid molecule encoding a bispecific binding molecule comprising the amino acid sequence shown in SEQ ID NO:
- 207.
Dependencies are inferred from the claim text.