Claims for Patent: 9,062,105

Summary for Patent: 9,062,105

Title:	Precision Medicine by targeting VEGF-A variants for treatment of retinopathy
Abstract:	The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.
Inventor(s):	Clube; Jasper Rupert (Cambridge, GB)
Assignee:	Kymab Limited (Cambridge, GB)
Application Number:	14/536,129
Patent Claims:	1. A method of treating or reducing the risk of retinopathy in a human, the method comprising administering to said human an anti-VEGF-A ligand that specifically binds to a human VEGF-A that is expressed by a VEGF-A nucleotide sequence comprising a SNP selected from the group consisting of: rs699947; rs833061; rs2010963; rs3025039; rs699946; rs2146323; rs1413711; rs833068; rs833069; rs3025000 and rs1570360; wherein the ligand comprises a human gamma-1 heavy chain constant region that comprises an amino acid selected from the group consisting of: an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42; and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 heavy chain constant regions comprising said selected amino acid and (ii) a VEGF-A nucleotide sequence comprising said selected SNP. 2. The method of claim 1, wherein the ligand is an anti-VEGF-A trap; antibody; or antibody fragment. 3. The method of claim 1, wherein the retinopathy is diabetic retinopathy (DR) or retinopathy of prematurity (ROP). 4. The method of claim 1, wherein the SNP is selected from the group consisting of rs699947, rs833061, rs2010963, rs3025039 and rs699946; optionally wherein the human is homozygous for said SNP. 5. The method of claim 1, wherein the SNP is selected from the group consisting of rs699947, rs2146323, rs1413711, rs699946, rs833068, rs833069 and rs3025000; optionally wherein the human is homozygous for said SNP. 6. The method of claim 1, wherein the method further comprises treating the human with photodynamic therapy. 7. The method of claim 1, wherein the human comprises A: (a) a HTRA1 nucleotide sequence comprising SNP rs11200638; (b) an ARMS2 nucleotide sequence comprising SNP rs10490924; (c) a CFH nucleotide sequence comprising SNP rs800292, a T at the position of rs1061170 or an A at the position of rs3766404; (d) a complement component 2 (C2) nucleotide sequence comprising SNP rs547154; (e) a prothrombin nucleotide sequence comprising SNP rs1799963; (f) a MTHFR nucleotide sequence comprising SNP rs1801133; (g) a Factor V nucleotide sequence comprising SNP rs6025; or (h) a VEGFR2 nucleotide sequence comprising SNP rs4576072 or rs6828477; or B: (a') a HTRA1 nucleotide sequence comprising SNP rs11200638; (b') an ARMS2 nucleotide sequence comprising SNP rs10490924; (c') a CFH nucleotide sequence comprising SNP rs800292; or (d') a complement component 2 (C2) nucleotide sequence comprising SNP rs547154; or C: (i) an ARMS2 nucleotide sequence comprising a G at the position of SNP rs10490924; (ii) a CFH nucleotide sequence comprising a T at the position of SNP rs1061170 or rs3766404; (iii) a prothrombin nucleotide sequence comprising SNP rs1799963; (iv) a MTHFR nucleotide sequence comprising SNP rs1801133; (v) a Factor V nucleotide sequence comprising SNP rs6025; or (vi) a VEGFR2 nucleotide sequence comprising SNP rs4576072 or rs6828477. 8. The method of claim 1, wherein the ligand comprises an IGHG1*01 human heavy chain constant region. 9. The method of claim 1, comprising, before said administering, selecting a human comprising said VEGF-A nucleotide sequence of (ii), wherein the human is the human of claim 1. 10. The method of claim 1, wherein the human has been determined to comprise said VEGF-A nucleotide sequence of (ii). 11. The method of claim 1, comprising the step of determining that the human comprises the nucleotide sequence of (ii), optionally, wherein the determining step is performed before administration of the antibody to the human. 12. The method of claim 11, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence of (ii). 13. The method of claim 12, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence comprising said selected SNP or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to said selected SNP or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence comprising said selected SNP is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence comprising said selected SNP or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises said selected SNP thereby forming a complex when the nucleotide sequence comprising said selected SNP is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the nucleotide sequence of (ii). 14. The method of claim 12, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format. 15. The method of claim 1, wherein said human is or has been further determined to be substantially resistant to sunitinib, bevacizumab or ranizumab treatment. 16. The method of claim 1, wherein said human is receiving or has received sunitinib, bevacizumab or ranizumab treatment or has reduced responsiveness to sunitinib, bevacizumab or ranizumab treatment. 17. The method of claim 12, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human. 18. The method of claim 1, wherein said human has been diagnosed with an ocular condition, optionally DR or ROP. 19. The method of claim 1, wherein said ligand is administered by intraocular injection or by topical administration to the eye and/or is comprised in an injectable preparation or topical ocular preparation. 20. The method of claim 1, wherein the ligand is human. 21. The method of claim 2, wherein the ligand is human. 22. The method of claim 1, wherein the method comprises administering an anti-PDGF-B or anti-PDGFR-B ligand to the human simultaneously or sequentially with the anti-VEGF-A ligand. 23. The method of claim 22, wherein the anti-PDGF-B or PDGFR-B ligand is an anti-PDGF-B or PDGFR-B antibody or fragment, an anti-PDGF-B or PDGFR-B trap or an anti-PDGF-B or PDGFR-B aptamer. 24. The method of claim 1, wherein the method comprises administering an anti-Ang2 or anti-Tie2 ligand to the human simultaneously or sequentially with the anti-VEGF-A ligand. 25. The method of claim 1, wherein the human is greater than 60 years of age. 26. The method of claim 1, wherein the human is suffering from type I diabetes. 27. The method of claim 1, wherein the human is suffering from type II diabetes. 28. The method of claim 2, wherein the trap is a ligand comprising first and second VEGF-A receptor domain sequences fused to a human gamma 1 heavy chain constant region.

Details for Patent 9,062,105

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2039-02-26