Angiopoietin 2, VEGF dual antagonists
The present disclosure relates to fusion molecules and chimeric molecules which comprise two components: an Ang-2 antagonist peptide linked to a VEGF-binding moiety. Further disclosed are methods of using said chimeric molecules to treat a patient cancer, proliferative retinopathy, neovascular glaucoma, macular edema, wet age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR).
1. A method of treating a human patient with proliferative retinopathy, wet age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR) comprising administering to the patient a pharmaceutical composition comprising a chimeric molecule comprising:
a) a variable light chain (VL) polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence set forth in SEQ ID NO: 4, wherein the VL polypeptide comprises complementary-determining region (CDR) sequences having the amino acid sequences of SASQDISNYLN (SEQ ID NO: 65), FTSSLHS (SEQ ID NO: 66), and QQYSTVPWT (SEQ ID NO: 67); and
b) a variable heavy chain (VH) polypeptide comprising an amino acid sequence that is at least 99% identical to the amino acid sequence set forth in SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 34, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 49, or SEQ ID NO: 51, wherein the VH polypeptide comprises CDR sequences having the amino acid sequences of GYDFTHYG (SEQ ID NO: 68), INTYTGEP (SEQ ID NO: 69), and YCAKYPYYYGTSHWYFDV (SEQ ID NO: 70).
2. A method of treating a human patient with proliferative retinopathy, wet age-related macular degeneration (wAMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), or diabetic retinopathy (DR) comprising administering to the patient a pharmaceutical composition comprising a chimeric molecule comprising:
a) a variable light chain (VL) polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 4; and
b) a variable heavy chain (VH) polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 31.