Bibliographic Details
| Title: |
GENETIC POLYMORPHISMS IN AGE-RELATED MACULAR DEGENERATION |
| Document Number: |
20120003641 |
| Publication Date: |
January 5, 2012 |
| Appl. No: |
13/127433 |
| Application Filed: |
November 05, 2009 |
| Abstract: |
Methods for determining whether a patient is at increased risk of developing wet AMD or whether a patient has an increased likelihood of benefiting from treatment with a high-affinity anti-VEGF antibody. |
| Inventors: |
Graham, Robert R. (San Francisco, CA, US); Behrens, Timothy W. (Burlingame, CA, US); Lanchulev, Tsontcho (San Francisco, CA, US); Shapiro, Howard (Denver, CO, US) |
| Claim: |
1. A method of predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with a high-affinity anti-VEGF antibody, comprising screening a sample isolated from said patient for a genomic polymorphism in the complement factor H gene (CFH) Y402H allele corresponding to rs1061170, wherein the patient has an increased likelihood of benefiting from said treatment if the corresponding genotype comprises CC or CT. |
| Claim: |
2. A method of predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with an anti-VEGF antibody, comprising screening a sample isolated from said patient for a genomic polymorphism in the C5 complement component gene (C5) I802V allele corresponding to rs17611, wherein the patient has an increased likelihood of benefiting from said treatment if the corresponding genotype comprises AA or AG. |
| Claim: |
3. A method of predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with an anti-VEGF antibody, comprising screening a sample isolated from said patient for a genomic polymorphism in the HTRA1 A69S allele corresponding to rs10490924, wherein the patient has an increased likelihood of benefiting from said treatment if the corresponding genotype comprises GT. |
| Claim: |
4. The method of any one of claims 1 to 3, wherein said anti-VEGF antibody binds the same epitope as the monoclonal anti-VEGF antibody A4.6.1 produced by hybridoma ATCC® HB 10709. |
| Claim: |
5. The method of claim 4, wherein said anti-VEGF antibody has a heavy chain variable domain comprising the following heavy chain complementarity determining region (CDR) amino acid sequences: CDRH1 (GYDFTHYGMN; SEQ ID NO: 1), CDRH2 (WINTYTGEPTYAADFKR; SEQ ID NO: 2) and CDRH3 (YPYYYGTSHWYFDV; SEQ ID NO: 3) and a light chain variable domain comprising the following light chain CDR amino acid sequences: CDRL1 (SASQDISNYLN; SEQ ID NO: 4), CDRL2 (FTSSLHS; SEQ ID NO: 5) and CDRL3 (QQYSTVPWT; SEQ ID NO: 6). |
| Claim: |
6. The method of claim 5, wherein said anti-VEGF antibody has the heavy chain variable domain and light chain variable domain of Y0317. |
| Claim: |
7. The method of any one of claims 1 to 3, wherein said anti-VEGF antibody is ranibizumab. |
| Claim: |
8. The method of claim 1, wherein the corresponding genotype comprises CC. |
| Claim: |
9. The method of claim 1, wherein the corresponding genotype comprises CT. |
| Claim: |
10. The method of claim 2, wherein the corresponding genotype comprises AA. |
| Claim: |
11. The method of claim 2, wherein the corresponding genotype comprises AG. |
| Claim: |
12. A kit for predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with ranibizumab comprising a first oligonucleotide and a second oligonucleotides specific for a C/T polymorphism in the CFH Y402H allele corresponding to rs1061170. |
| Claim: |
13. The kit of claim 12, wherein said first oligonucleotide and said second oligonucleotide may be used to amplify a part of the CFH gene comprising a C/T polymorphism in the CFH Y402H allele. |
| Claim: |
14. A kit for predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with an anti-VEGF antibody comprising a first oligonucleotide and a second oligonucleotide specific for a A/G polymorphism in the C5 I802V allele corresponding to rs17216529. |
| Claim: |
15. The kit of claim 14, wherein said first oligonucleotide and said second oligonucleotide may be used to amplify a part of the CFH gene comprising a A/G polymorphism in the I802V C5 allele. |
| Claim: |
16. A kit for predicting whether a wet AMD patient has an increased likelihood of benefiting from treatment with an anti-VEGF antibody comprising a first oligonucleotide and a second oligonucleotide specific for a G/T polymorphism in the HTRA1 A69S allele corresponding to rs10490924. |
| Claim: |
17. The kit of claim 16, wherein said first oligonucleotide and said second oligonucleotide may be used to amplify a part of the CFH gene comprising a A/G polymorphism in the HTRA1 A69S allele. |
| Claim: |
18. A method of predicting whether an individual has an increased likelihood of developing AMD, comprising screening a sample isolated from said patient for a genomic polymorphism in the C5 I145V allele corresponding to rs17216529, wherein the patient has an increased likelihood of developing AMD if the corresponding genotype comprises GG or AG. |
| Claim: |
19. The method of claim 18, wherein the corresponding genotype comprises GG. |
| Claim: |
20. The method of claim 18, wherein the corresponding genotype comprises AG. |
| Claim: |
21. A method of predicting whether an individual has an increased likelihood of developing wet AMD or dry with GA AMD, comprising screening a sample isolated from said patient for a genomic polymorphism in the C5 I802V allele corresponding to rs17611, wherein the patient has an increased likelihood of developing AMD if the corresponding genotype comprises allele T (ile). |
| Current U.S. Class: |
435/611 |
| Current International Class: |
12 |
| Accession Number: |
edspap.20120003641 |
| Database: |
USPTO Patent Applications |
