Methods and compositions for treating subjects having rheumatoid arthritis

Patent metadata

Field	Value
Publication number	US-11319375-B2
Application number	US-201916553338-A
Country	US
Kind code	B2
Filing date	Aug 28, 2019
Priority date	Aug 29, 2018
Publication date	May 3, 2022
Grant date	May 3, 2022

Abstract

Disclosed herein are methods for treating subjects having rheumatoid arthritis (RA) with a human anti-interleukin 6 (IL-6) antibody, or antigen-binding portion thereof.

First claim

The invention claimed is:

1. A method for treating a subject having rheumatoid arthritis (RA), comprising
determining the level of interleukin 6 (IL-6) in a serum sample(s) obtained from the subject having RA, and
administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody or antigen-binding portion thereof if the level of IL-6 in the subject sample(s) is determined to be a high IL-6 level,
wherein the high IL-6 level is about ≥3 times the upper limit of normal (≥3×ULN),
wherein the anti-IL-6R antibody, or antigen-binding portion thereof, comprises three heavy chain complementarity determining region (HCDR) sequences HCDR1, HCDR2, and HCDR3 comprising SEQ ID NOs:21, 23, 25, respectively, and three light chain complementarity determining (LCDR) sequences LCDR1, LCDR2, and LCDR3 comprising SEQ ID NOs: 29, 31, 33, respectively, and
wherein the therapeutically effective amount of the human anti-IL-6R antibody or antigen-binding portion thereof is administered to the subject as a dose of about 200 mg about once every two weeks (q2w), thereby treating the subject.

2. The method of claim 1 , wherein the subject was previously diagnosed as having RA.

3. The method of claim 1 , wherein the subject is a treatment naïve RA subject or has previously been administered one or more therapeutic agents for treating RA.

4. A method for treating subjects having rheumatoid arthritis, the method comprising the steps of:
determining the level of interleukin 6 (IL-6) in serum samples from the subjects so that each subject is determined to belong to either a first category of rheumatoid arthritis disease severity or a second category of rheumatoid arthritis disease severity;
wherein the first category of rheumatoid arthritis disease severity corresponds to a high level of IL-6 and the second category of rheumatoid arthritis disease severity corresponds to a moderate level of IL-6 and/or a low level of IL-6,
wherein a high level of IL-6 is about ≥3 times the upper limit of normal (≥3×ULN);
assigning a therapy to the subjects in the first category of rheumatoid arthritis disease severity, wherein the therapy is administration of a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof; and
administering the human IL-6R antibody, or antigen-binding portion thereof, to the subjects in the first category of rheumatoid arthritis disease severity,
wherein the anti-IL-6R antibody, or antigen-binding portion thereof, comprises three heavy chain complementarity determining region (HCDR) sequences HCDR1, HCDR2, and HCDR3 comprising SEQ ID NOs:21, 23, 25, respectively, and three light chain complementarity determining (LCDR) sequences LCDR1, LCDR2, and LCDR3 comprising SEQ ID NOs: 29, 31, 33, respectively, and
wherein the therapeutically effective amount of the human anti-IL-6R antibody or antigen-binding portion thereof is administered to the subject as a dose of about 200 mg about once every two weeks (q2w), thereby treating the subjects having rheumatoid arthritis.

5. A method for treating a subject having high interleukin 6 rheumatoid arthritis (high IL-6RA), comprising
selecting a subject having high IL-6RA,
wherein the subject having high IL-6RA has a serum level of IL-6 that is about ≥3 times the upper limit of normal (≥3×ULN), and
administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof,
wherein the anti-IL-6R antibody, or antigen-binding portion thereof, comprises three heavy chain complementarity determining region (HCDR) sequences HCDR1, HCDR2, and HCDR3 comprising SEQ ID NOs:21, 23, 25, respectively, and three light chain complementarity determining (LCDR) sequences LCDR1, LCDR2, and LCDR3 comprising SEQ ID NOs: 29, 31, 33, respectively, and
wherein the therapeutically effective amount of the human anti-IL-6R antibody or antigen-binding portion thereof is administered to the subject as a dose of about 200 mg about once every two weeks (q2w), thereby treating the subject.

6. A method for inhibiting joint damage in a subject, comprising
selecting a treatment naïve subject having high interleukin 6 rheumatoid arthritis (high IL-6RA),
wherein the subject having high IL-6RA has a serum level of IL-6 that is about ≥3 times the upper limit of normal (≥3×ULN), and
administering to the subject a therapeutically effective amount of a human anti-interleukin 6 receptor (IL-6R) antibody, or antigen-binding portion thereof, as a monotherapy,
wherein the anti-IL-6R antibody, or antigen-binding portion thereof, comprises three heavy chain complementarity determining region (HCDR) sequences HCDR1, HCDR2, and HCDR3 comprising SEQ ID NOs:21, 23, 25, respectively, and three light chain complementarity determining (LCDR) sequences LCDR1, LCDR2, and LCDR3 comprising SEQ ID NOs: 29, 31, 33, respectively,
wherein the therapeutically effective amount of the human anti-IL-6R antibody or antigen-binding portion thereof is administered to the subject as a dose of about 200 mg about once every two weeks (q2w), thereby inhibiting joint damage in the subject.

7. The method of any one of claims 1 , 4 , 5 , and 6 , wherein the anti-IL-6R antibody, or antigen-binding portion thereof, is a fully human anti-IL-6R antibody, or antigen-binding portion thereof.

8. The method of any one of claims 1 , 4 , 5 , and 6 , wherein the anti-IL-6R antibody, or antigen-binding portion thereof, is administered to the subject in a pharmaceutical composition.

9. The method of claim 8 , wherein the pharmaceutical composition is present in a pre-filled syringe.

10. The method of any one of claims 1 , 4 , 5 , and 6 , wherein the anti-IL-6R antibody, or antigen-binding portion thereof, comprises an HCVR having the amino acid sequence of SEQ ID NO: 19 and an LCVR having the amino acid sequence of SEQ ID NO: 27.

11. The method of claim 10 , wherein the anti-IL-6R antibody, or antigen-binding portion thereof, is sarilumab, or a biosimilar thereof.

12. A method for treating a subject having rheumatoid arthritis, the method comprising:
selecting a subject previously treated with adalimumab or a biosimilar of adalimumab, who has or presented with high IL-6 serum levels, and had an inadequate response to adalimumab or a biosimilar of adalimumab,
wherein the high IL-6 level is about ≥3 times the upper limit of normal (≥3×ULN),
discontinuing adalimumab treatment for the subject, and
initiating a therapeutic regimen comprising about 200 mg about once every two weeks (q2w) of sarilumab for the subject,
thereby treating the subject.

13. The method of any one of claims 1 , 4 , and 5 - 12 , wherein the high IL-6RA level that is ≥3×ULN is ≥30 pg/mL serum IL-6.

Assignees

• Regeneran Pharmaceuticals Inc
• Sanofi Biotechnology
• Regeneron Pharma

Inventors

• Boyapati Anita
• Graham Neil
• Kimura Toshio
• Msihid Jérôme

Classifications

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• G01N33/564

  for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title