Optimized variants of anti-vegf antibodies
AssigneeGenentech, Inc.
InventorsPatrick KOENIG, Chingwei Vivian LEE, Karthikan RAJAGOPAL, Amin FAMILI, Germaine FUH
Life of this patent
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Abstract
The present invention provides anti-VEGF antibodies and compositions that include anti-VEGF antibodies (e.g., antibody conjugates, fusion proteins, and polymeric formulations), and uses thereof, for example for treatment of disorders associated with pathological angiogenesis. The present invention also provides methods of identifying antibody variants with improved properties, for example, enhanced binding affinity, stability, pharmacokinetics, and/or expression.
Claims53
1-317. (canceled)
An antibody conjugate comprising (i) an antibody that specifically binds vascular endothelial growth factor (VEGF) and (ii) a hyaluronic acid (HA) polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 1 megadalton (MDa) or lower, and wherein the antibody comprises the following six hypervariable regions (HVRs):
- (a) an HVR-H1 comprising the amino acid sequence of DYWIH (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of GX1TPX2GGX3X4X5YX6DSVX7X8 (SEQ ID NO:
- 2), wherein X1 is Ile or His, X2 is Ala or Arg, X3 is Tyr or Lys, X4 is Thr or Glu, X5 is Arg, Tyr, Gln, or Glu, X6 is Ala or Glu, X7 is Lys or Glu, and X8 is Gly or Glu;
- (c) an HVR-H3 comprising the amino acid sequence of FVFFLPYAMDY (SEQ ID NO:
- 3);
- (d) an HVR-L1 comprising the amino acid sequence of RASQX1VSTAVA (SEQ ID NO:
- 4), wherein X1 is Asp or Arg;
- (e) an HVR-L2 comprising the amino acid sequence of X1ASFLYS (SEQ ID NO:
- 5), wherein X1 is Ser or Met;
- and
- (f) an HVR-L3 comprising the amino acid sequence of X1QGYGX2PFT (SEQ ID NO:
- 6), wherein X1 is Gln, Asn, or Thr and X2 is Ala, Gln, or Arg.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 1 MDa or lower, and wherein the antibody comprises (a) a VH domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO:
- 11;
- (b) a VL domain comprising an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO:
- 12;
- or (c) a VH domain as in (a) and a VL domain as in (b).
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 1 MDa or lower, and wherein the antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 11 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 12.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 1 MDa or lower, and wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 48 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:
- 50.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 1 MDa or lower, and wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 49 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:
- 50.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of 1 MDa or lower.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 200 kDa and is not cross-linked, wherein the antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 11 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 12.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 200 kDa and is not cross-linked, wherein the antibody comprises (a) a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 48 or SEQ ID NO:
- 49 and (b) a light chain comprising the amino acid sequence of SEQ ID NO:
- 50.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 100 kDa and is not cross-linked, wherein the antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 11 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 12.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 150 kDa and is not cross-linked, wherein the antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 11 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 12.
An antibody conjugate comprising (i) an antibody that specifically binds VEGF and (ii) an HA polymer covalently attached to the antibody, wherein the HA polymer has a molecular weight of about 250 kDa and is not cross-linked, wherein the antibody comprises (a) a VH domain comprising the amino acid sequence of SEQ ID NO:
- 11 and (b) a VL domain comprising the amino acid sequence of SEQ ID NO:
- 12.
Dependencies are inferred from the claim text.