Method of treating rheumatoid arthritis using antibody to IL6R

• US 8,945,560 B1
• Filed: 08/12/2014
• Issued: 02/03/2015
• 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:
  US14/457,566
• Time in Patent Office: 175 Days
• US Class Current: 424/143.1
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/40 against enzymes

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 rheumatoid arthritis in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds an IL6R protein that comprises a mutation Asp358Ala or Val385Ile in SEQ ID NO:

78,

wherein the antibody or antibody fragment comprises a human gamma-1 heavy chain constant region that comprises an amino acid selected from the group consisting of;

an Asp at position 204 shown in SEQ ID NO;

81 and a Leu at position 206 shown in SEQ ID NO;

81;

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 nucleotide sequence encoding said IL6R protein comprising said Asp358Ala or Val385Ile in SEQ ID NO;

78.

2. The method of claim 1, wherein the antibody or antibody fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp at position 204 shown in SEQ ID NO:

81 and a Leu at position 206 shown in SEQ ID NO;

81.

3. The method of any claim 1, wherein the antibody or antibody fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp at position 204 shown in SEQ ID NO:

81 and a Leu at position 206 shown in SEQ ID NO;

81 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said IL6R protein comprising said mutation Asp358Ala or Val385Ile in SEQ ID NO;

78.

4. The method of claim 1, wherein the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.

5. The method of claim 1 comprising, before said administering, selecting a human comprising said nucleotide sequence of (ii), wherein the human is the human of claim 1.

6. The method of claim 1, wherein the human has been determined to comprise the nucleotide sequence that encodes an IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO:

78 and/or an IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO;

78.

7. The method of claim 1, comprising the step of determining that the human comprises the nucleotide sequence that encodes an IL6R protein comprising said mutation Asp358Ala and/or Val385Ile and/or an IL6R protein comprising said mutation Asp358Ala and/or Val385Ile, optionally, wherein the determining step is performed before administration of the antibody to the human.

8. The method of claim 7, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding a IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO:

78.

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 of a nucleotide sequence encoding an IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO:

78 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises a nucleotide sequence encoding said mutation Asp358Ala and/or Val385Ile in SEQ ID NO;

78, thereby forming a complex when at least one nucleotide sequence encoding the IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO;

78 is present; and

detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the IL6R protein comprising said mutation Asp358Ala and/or Val385Ile in SEQ ID NO;

78.

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 and/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 and/or saliva of said human.

12. The method of claim 1, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the IL6R protein comprising said mutation Asp358Ala or Val385Ile in SEQ ID NO:

78, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO;

79, or said human is indicated as homozygous for a nucleotide sequence encoding the IL6R protein comprising said mutation Asp358Ala or Val385Ile in SEQ ID NO;

78.

13. The method of claim 1, wherein said human is or has been further determined to be substantially resistant to an anti-TNF alpha treatment.

14. The method of claim 1, wherein said human is receiving or has received an anti-TNF alpha treatment or has reduced responsiveness to an anti-TNF alpha treatment.

15. The method of claim 1, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with methotrexate or an anti-TNF alpha treatment.

16. The method of claim 1, wherein said human has been diagnosed with rheumatoid arthritis.

17. The method of claim 1, wherein the nucleotide sequence comprises SNP rs2228145 and/or SNP rs28730736.

18. The method of claim 1, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.

19. The method of claim 1, wherein the antibody is a human antibody.