Methods of treating anaemia

Abstract

The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.

We claim: 
     
         1 . A method of increasing erythopoiesis in a human subject, the method comprising administering a trap, and antibody or an antibody fragment that binds a human TMPRSS6 encoded by a TMPRSS6 nucleotide sequence comprising a SNP selected from the group consisting of:
 rs855791, rs2543519, rs2235324 and rs1421312;   
       wherein the trap, antibody or antibody fragment comprises a constant region selected from the group consisting of:
 (a) a human gamma-4 heavy chain constant region that comprises a Leu at position 189 shown in SEQ ID NO: 73 or an Arg at position 289 shown in SEQ ID NO: 73; and 
 (b) a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42; and 
 
       wherein
 (i) the human subject comprises a TMPRSS6 nucleotide sequence comprising said selected SNP; and 
 (ii) the human subject comprises a constant region gene segment encoding said selected constant region; or the human subject expresses antibodies comprising said selected constant region. 
 
     
     
         2 . The method of  claim 1 , wherein the human subject is homozygous for said selected SNP. 
     
     
         3 . The method of  claim 1 , wherein the trap, antibody or antibody fragment comprises an IGHG1*01 human heavy chain constant region. 
     
     
         4 . The method of  claim 1 , wherein the trap, antibody or antibody fragment comprises an IGHG4*01 human heavy chain constant region. 
     
     
         5 . The method of  claim 1 , comprising, before said administering, selecting a human subject comprising said TMPRSS6 nucleotide sequence, wherein the human is the human of  claim 1 . 
     
     
         6 . The method of  claim 1 , wherein the human subject has been determined to comprise said TMPRSS6 nucleotide sequence. 
     
     
         7 . The method of  claim 1 , comprising the step of determining that the human subject comprises said TMPRSS6 nucleotide sequence, optionally, wherein the determining step is performed before administration of the trap, antibody, or antibody fragment to the human. 
     
     
         8 . The method of  claim 7 , wherein the step of determining comprises assaying a biological sample from the human subject for a nucleotide sequence encoding said SNP. 
     
     
         9 . The method of  claim 8 , wherein the assaying comprises contacting the biological sample with
 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 SNP or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to said SNP or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence comprising said SNP is present; and/or   at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence comprising said SNP or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises said SNP thereby forming a complex when the nucleotide sequence comprising said SNP is present; and   detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human subject comprises a nucleotide sequence encoding TMPRSS6 and comprising said SNP.   
     
     
         10 . The method of  claim 8 , 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 or wherein the assaying is performed in a multiplex format. 
     
     
         11 . The method of  claim 8 , wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine or saliva of said human subject. 
     
     
         12 . The method of  claim 1 , wherein said human subject is or has been further determined to be substantially resistant to an anemia treatment. 
     
     
         13 . The method of  claim 1 , wherein said human subject is receiving or has received an anemia treatment or has reduced responsiveness to an anemia treatment. 
     
     
         14 . The method of  claim 1 , wherein said trap, antibody or antibody fragment is administered by intravenous or subcutaneous injection or is comprised in an injectable preparation. 
     
     
         15 . The method of  claim 1 , wherein the trap, antibody or antibody fragment is a human trap, antibody, or antibody fragment. 
     
     
         16 . The method of  claim 1 , wherein said human subject is or has been further determined to be substantially resistant to an EPO anemia treatment. 
     
     
         17 . The method of  claim 1 , wherein said human subject is receiving or has received an EPO anemia treatment or has reduced responsiveness to an EPO anemia treatment.