Variants of vegfr and their use in the diagnosis and treatment of pregnancy associated medical conditions

Abstract

An isolated polypeptide variant of VEGFR comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 and an isolated polynucleotide encoding same are disclosed. A polynucleotide comprising a nucleic acid sequence capable of specifically hybridizing to the isolated polynucleotide and an isolated antibody comprising an antigen recognition domain which specifically binds the isolated polypeptide are also disclosed. Pharmaceutical compositions, methods of diagnosing and treating comprising same are also disclosed.

1 - 13 . (canceled) 
     
     
         14 . An isolated polynucleotide comprising a nucleic acid sequence capable of specifically hybridizing to a polynucleotide encoding a polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi), and not hybridizing to a polynucleotide as set forth in SEQ ID NO: 9. 
     
     
         15 . An isolated antibody comprising an antigen recognition domain which specifically binds a polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi) and does not bind to a polypeptide as set forth in SEQ ID NO: 10. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . A pharmaceutical composition comprising an antibody and a pharmaceutically acceptable carrier, the antibody comprising an antigen recognition domain which specifically binds a polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi) and does not bind to a polypeptide as set forth in SEQ ID NO: 10. 
     
     
         19 . A pharmaceutical composition comprising an isolated polynucleotide of and a pharmaceutically acceptable carrier, the isolated polynucleotide comprising a nucleic acid sequence capable of specifically hybridizing to a polynucleotide encoding a polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi), and not hybridizing to a polynucleotide as set forth in SEQ ID NO: 9. 
     
     
         20 . A method of treating a VEGF-associated medical condition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an agent capable of regulating an activity and/or expression of sFlt-14 (SEQ ID NO: 1 or 2) and not sFlt-1 (SEQ ID NO: 9 or 10), thereby treating the VEGF-associated medical condition. 
     
     
         21 . The method of  claim 20 , wherein said VEGF-associated medical condition is associated with reduced activity and/or expression of VEGF and whereas said regulating comprises downregulating said sFlt-14. 
     
     
         22 . The method of  claim 20 , wherein said VEGF-associated medical condition is associated with excessive activity and/or expression of VEGF and whereas said regulating comprises upregulating said sFlt-14. 
     
     
         23 . The method of  claim 20 , wherein said VEGF-associated medical condition is selected from the group consisting of preeclampsia, gestational diabetes, gestational hypertension, fetal growth restriction (FGR), fetal alcohol syndrome (FAS), cancer, corneal neovascularization and hypertension. 
     
     
         24 - 27 . (canceled) 
     
     
         28 . A method of detecting sFlt-14 (SEQ ID NO: 2) in a biological sample, the method comprising:
 (a) contacting the biological sample with an antibody comprising an antigen recognition domain which specifically binds a polypeptide comprising an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi) and not to a polypeptide as set forth in SEQ ID NO: 10 such that the sFlt-14 and the antibody form a complex; and   (b) measuring a presence or a level of said complex to thereby detect sFlt-14 in the biological sample.   
     
     
         29 . A method of detecting sFlt-14 (SEQ ID NO: 1) in a biological sample, the method comprising:
 (a) contacting the biological sample with an isolated polynucleotide capable of specifically hybridizing to polynucleotide encoding an amino acid sequence at least 70% homologous to SEQ ID NO: 4 as determined by protein BLAST algorithm (http://wwwdotncbidotnlmdotnihdotgov/blast/Blastdotcgi), and not to a polynucleotide as set forth in SEQ ID NO: 9 so as to form a hybridization complex; and   (b) measuring a presence or a level of said complex to thereby detect sFlt-14 in the biological sample.   
     
     
         30 . The method of  claim 29 , wherein said measuring is effected by a method selected from the group consisting of PCR, Real Time PCR, RT PCR, nucleic acid sequence-based amplification (NASBA), Northern blot and in situ hybridization. 
     
     
         31 . A method of diagnosing a pregnancy-associated medical condition associated with maternal or fetal stress in a subject in need thereof, the method comprising detecting expression level of sFlt-14 (SEQ ID NO: 1 or 2) in a biological sample of the subject using an agent capable of recognizing sFlt-14 (SEQ ID NO: 1 or 2) and not sFlt-1 (SEQ ID NO: 9 or 10), wherein an expression level of said sFlt-14 above a predetermined threshold is indicative of the pregnancy-associated medical condition associated with maternal or fetal stress. 
     
     
         32 . A method of diagnosing a pregnancy-associated medical condition associated with maternal or fetal stress in a subject in need thereof, the method comprising detecting expression level of sFlt-14 (SEQ ID NO: 1 or 2) in a biological sample, wherein said biological sample is of a gestation week 13 and on, and wherein an expression level of said sFlt-14 above a predetermined threshold is indicative of the pregnancy-associated medical condition associated with maternal or fetal stress. 
     
     
         33 . The method of  claim 31  wherein said condition is selected from the group consisting of preeclampsia, gestational diabetes, gestational hypertension, fetal growth restriction (FGR), and fetal alcohol syndrome (FAS). 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 32  wherein said condition is selected from the group consisting of preeclampsia, gestational diabetes, gestational hypertension, fetal growth restriction (FGR), and fetal alcohol syndrome (FAS).