Fusion molecules targeting vegf and angiopoietin and uses thereof
AssigneeHangzhou Exegenesis Bio Ltd.
InventorsGuojie YE, Zhenhua WU, Lijun WANG, Li DAI
Life of this patent
Estimating the term…
Abstract
A polypeptide comprising two or three VEGF binding domains; and a domain that binds to an angiopoietin, and a gene therapy for delivering such a polypeptide.
Claims53
A polypeptide comprising:
- (i) a first domain that binds to VEGF;
- (ii) a second domain that binds to VEGF;
- and
- (iii) a third domain that binds to an angiopoietin,
- wherein optionally the third domain is at the N-terminus of the first domain and the second domain.
A polypeptide comprising:
- (i) a first domain that binds to VEGF, the first domain comprising an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identify to SEQ ID NO:
- 1;
- (ii) a second domain that binds to VEGF, the second domain comprising an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identify to SEQ ID NO:
- 2;
- and
- (iii) a third domain that binds to an angiopoietin, the third domain comprising two amino acid sequences each comprising an amino acid sequence having at least 80%, 85%, 90%, or 100% identify to SEQ ID NO:
- 3;
- two amino acid sequences each comprising an amino acid sequence having at least 80%, 85%, 90%, or 100% identify to SEQ ID NO:
- 51;
- or one amino acid sequence having at least 80%, 85%, 90%, or 100% identify to SEQ ID NO:
- 3 and one amino acid sequence having at least 80%, 85%, 90%, or 100% identify to SEQ ID NO:
- 51.
The polypeptide of any one of claims 1 to 17, further comprises one or more linkers.
A polypeptide comprising an amino acid sequence of SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, or SEQ ID NO:
- 10, or an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identify to SEQ ID NO:
- 7, SEQ ID NO:
- 8, SEQ ID NO:
- 9, or SEQ ID NO:
- 10.
A polypeptide comprising an amino acid sequence of SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65 or SEQ ID NO:
- 66, or an amino acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identify to SEQ ID NO:
- 58, SEQ ID NO:
- 59, SEQ ID NO:
- 60, SEQ ID NO:
- 61, SEQ ID NO:
- 62, SEQ ID NO:
- 63, SEQ ID NO:
- 64, SEQ ID NO:
- 65, or SEQ ID NO:
- 66.
A recombinant AAV (rAAV) vector comprising a nucleic acid encoding a polypeptide wherein the polypeptide comprises (i) a first domain derived from VEGFR-1;
- (ii) a second domain derived from VEGFR-2;
- and (iii) a third domain that is capable of binding to an angiopoietin, wherein the rAAV vector comprises an inverted terminal repeat (ITR) from AAV1, AAV2, AAV2i8, AAV3, AAV3-B, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV13, AAV-DJ, AAV LK03, AAVrh74, or AAV44-9.
A recombinant AAV (rAAV) vector comprising a nucleic acid encoding a polypeptide wherein the polypeptide comprises (i) a first domain derived from VEGFR-1;
- (ii) a second domain derived from VEGFR-2;
- (iii) a third domain that is capable of binding to an angiopoietin;
- and (iv) a fourth domain that is capable of binding to VEGFC, wherein the rAAV vector comprises an inverted terminal repeat (ITR) from AAV1, AAV2, AAV2i8, AAV3, AAV3-B, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV13, AAV-DJ, AAV LK03, AAVrh74, or AAV44-9.
A vector comprising a nucleic acid sequence of SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 13, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 20, SEQ ID NO:
- 21, SEQ ID NO:
- 22 or SEQ ID NO:
- 23, or a nucleic acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identify to SEQ ID NO:
- 11, SEQ ID NO:
- 12, SEQ ID NO:
- 13, SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 18, SEQ ID NO:
- 19, SEQ ID NO:
- 20, SEQ ID NO:
- 21, SEQ ID NO:
- 22 or SEQ ID NO:
- 23.
A vector comprising a nucleic acid sequence of SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, SEQ ID NO:
- 73, SEQ ID NO:
- 74, or SEQ ID NO:
- 75, or a nucleic acid sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identify to SEQ ID NO:
- 67, SEQ ID NO:
- 68, SEQ ID NO:
- 69, SEQ ID NO:
- 70, SEQ ID NO:
- 71, SEQ ID NO:
- 72, SEQ ID NO:
- 73, SEQ ID NO:
- 74, or SEQ ID NO:
- 75.
A recombinant AAV (rAAV) particle comprising
- (a) a nucleic acid encoding a polypeptide wherein the polypeptide comprises (i) a first domain derived from VEGFR-1;
- (ii) a second domain derived from VEGFR-2;
- and (iii) a third domain that is capable of binding to an angiopoietin;
- and
- (b) a capsid protein of AAV1, AAV2, AAV2i8, AAV3, AAV3-B, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV13, AAV-DJ, AAV LK03, AAVrh74, AAV44-9, or a variant thereof.
A recombinant AAV (rAAV) particle comprising
- (a) a nucleic acid encoding a polypeptide wherein the polypeptide comprises (i) a first domain derived from VEGFR-1;
- (ii) a second domain derived from VEGFR-2;
- and (iii) a third domain that is capable of binding to an angiopoietin;
- and (iv) a fourth domain capable of binding to VEGFC;
- and
- (b) a capsid protein of AAV1, AAV2, AAV2i8, AAV3, AAV3-B, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV13, AAV-DJ, AAV LK03, AAVrh74, AAV44-9, or a variant thereof.
The method of any one of 46 to 52, wherein the method comprises administering by intravitreal or subretinal injection into an eye of the subject.
Dependencies are inferred from the claim text.