Methods of treating anaemia

• US 9,428,578 B2
• Filed: 02/11/2016
• Issued: 08/30/2016
• Est. Priority Date: 07/15/2014
• Status: Active Grant

• Current Assignee: Kymab Limited (Sanofi )
• Original Assignee: Kymab Limited (Sanofi )
• Inventors: Clube, Jasper Rupert
• Primary Examiner(s): WEN, SHARON X
• Application Number:
  US15/041,514
• Publication Number:
  US 20160159896A1
• Time in Patent Office: 201 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

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

Claims

1. A method of treating or reducing the risk of anaemia in a human haemodialysis patient, the method comprising administering a trap, an antibody or an antibody fragment that binds specifically to BMP6 to the human haemodialysis patient,

wherein the trap, antibody or antibody fragment comprises a human kappa chain constant region comprising a Val at position 84 shown in SEQ ID NO:

93 or a Cys at position 87 shown in SEQ ID NO;

9; and

wherein

(i) the human comprises a TMPRSS6 nucleotide sequence comprising a SNP rs855791;

rs2543519;

rs2235324;

or rs1421312; and

(ii) the human comprises and expresses an IGKC1*01 human kappa chain constant region gene segment, or the human expresses antibodies comprising human kappa chain constant regions comprising a Val corresponding to position 84 shown in SEQ ID NO;

93 or a Cys at position 87 shown in SEQ ID NO;

93.

2. The method of claim 1, wherein the human haemodialysis patient is homozygous for said selected SNP.

3. The method of claim 1, wherein the trap, antibody or antibody fragment comprises an IGKC1*01 human kappa chain constant region.

4. The method of claim 1, comprising, before said administering, selecting a human haemodialysis patient comprising said TMPRSS6 nucleotide sequence, wherein the human is the human of claim 1.

5. The method of claim 1, wherein the human haemodialysis patient has been determined to comprise said TMPRSS6 nucleotide sequence.

6. The method of claim 1, comprising the step of determining that the human haemodialysis patient comprises said TMPRSS6 nucleotide sequence, optionally, wherein the determining step is performed before administration of the trap, antibody, or antibody fragment to the human.

7. The method of claim 6, wherein the step of determining comprises assaying a biological sample from the human haemodialysis patient for a nucleotide sequence encoding said SNP.

8. The method of claim 7, 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 comprises a nucleotide sequence encoding TMPRSS6 and comprising said SNP.

9. The method of claim 7, 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.

10. The method of claim 1, wherein said human haemodialysis patient is or has been further determined to be substantially resistant to an anaemia treatment.

11. The method of claim 1, wherein said human haemodialysis patient is receiving or has received an anaemia treatment or has reduced responsiveness to an anaemia treatment.

12. The method of claim 7, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine or saliva of said human.

13. 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.

14. The method of claim 1, wherein the trap, antibody or antibody fragment is a human trap, antibody, or antibody fragment.

15. The method of claim 1, wherein said human haemodialysis patient is or has been further determined to be substantially resistant to an EPO anaemia treatment.

16. The method of claim 1, wherein said human haemodialysis patient is receiving or has received an EPO anaemia treatment or has reduced responsiveness to an EPO anaemia treatment.

17. A method of treating or reducing the risk of anaemia in a human haemodialysis patient in need thereof, the improvement comprising:

administering to said patient an anti-BMP6 trap, antibody or antibody fragment to specifically bind in the patient a BMP6;

wherein the trap, antibody, or antibody fragment comprises a human kappa chain constant region comprising a Val at position 84 shown in SEQ ID NO;

93 or a Cys at position 87 shown in SEQ ID NO;

93, and

wherein said patient comprises;

(i) TMPRSS6 nucleotide sequence comprising a SNP rs855791;

rs2543519;

rs2235324;

or rs1421312; and

(ii) a constant region gene segment encoding said selected constant region;

or wherein said patient expresses antibodies comprising said selected constant region.

18. The method of claim 17, wherein the human haemodialysis patient is homozygous for said selected SNP.

19. The method of claim 17, wherein the trap, antibody, or antibody fragment comprises an IGKC1*01 human kappa chain constant region.

20. The method of claim 17, comprising, before said administering, selecting a human haemodialysis patient comprising said TMPRSS6 nucleotide sequence, wherein the human is the human of claim 17.

21. The method of claim 17, wherein the human haemodialysis patient has been determined to comprise said TMPRSS6 nucleotide sequence.

22. The method of claim 17, comprising the step of determining that the human haemodialysis patient comprises said TMPRSS6 nucleotide sequence, optionally, wherein the determining step is performed before administration of the trap, antibody, or antibody fragment to the human.

23. The method of claim 17, wherein the step of determining comprises assaying a biological sample from the human haemodialysis patient for a nucleotide sequence encoding said SNP.

24. The method of claim 23, 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 comprises a nucleotide sequence encoding TMPRSS6 and comprising said SNP.

25. The method of claim 23, 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.

26. The method of claim 17, wherein said human haemodialysis patient is or has been further determined to be substantially resistant to an anaemia treatment.

27. The method of claim 17, wherein said human haemodialysis patient is receiving or has received an anaemia treatment or has reduced responsiveness to an anaemia treatment.

28. The method of claim 23, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine or saliva of said human.

29. The method of claim 17, wherein said trap, antibody, or antibody fragment is administered by intravenous or subcutaneous injection or is comprised in an injectable preparation.

30. The method of claim 17, wherein the trap, antibody, or antibody fragment is a human trap, antibody, or antibody fragment.