IP Library › Granted Patent US 12,509,511
Granted Patent B2
US 12,509,511 · App. 18/340,168 · Granted Dec 30, 2025

Method for predicting and evaluating therapeutic effect in diseases related to IL-6 and neutrophils

Inventors: Takako Matsuoka (Tokyo, JP); Manabu Araki (Tokyo, JP); Takashi Yamamura (Tokyo, JP)
Assignees: NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY; CHUGAI SEIYAKU KABUSHIKI KAISHA
C07K16/248A61K39/395A61K45/06
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Quick Facts
Patent No.
US 12,509,511
App. No.
18/340,168
Granted
Dec 30, 2025
Kind
B2
Abstract

It has become clear that the therapeutic effect of an IL-6 inhibitor for IL-6- and neutrophil-associated diseases can be predicted using the expression level of neutrophil-associated genes as an indicator. It has also become clear that an IL-6 inhibitor is effective for the treatment of IL-6- and neutrophil-associated diseases in patients with high expression levels of neutrophil-associated genes. The present invention provides a method for selecting cases of IL-6- and neutrophil-associated diseases in which treatment with an IL-6 inhibitor is effective, as well as a method for effectively treating patients with IL-6- and neutrophil-associated diseases and with high expression levels of neutrophil-associated genes.

Claims (22)

1 . A method for treating the IL-6 associated disease neuromyelitis optica, comprising administering an anti-IL-6 receptor antibody to a patient having neuromyelitis optica, wherein a sample obtained from the patient prior to the administration is determined to have a high expression level of DEFA4 (defensin alpha 4, corticostatin) compared to the expression level of DEFA4 in a sample obtained from a healthy individual, wherein the administered anti-IL-6 receptor antibody is selected from MR16-1, PM-1, humanized PM-1 (Tocilizumab), AUK-12-20, AUK64-7, AUK-146-15 and SA237, wherein the anti-IL-6 receptor antibody is administered to the patient via systemic administration, and further wherein the sample obtained from the patient is a peripheral blood sample.

2 . A method for treating the IL-6 associated disease neuromyelitis optica, comprising administering an anti-IL-6 receptor antibody selected from MR16-1, PM-1, humanized PM-1 (Tocilizumab), AUK-12-20, AUK64-7, AUK-146-15 and SA237IL 6 inhibitor to a patient for whom prior treatment of the IL-6 inhibitor has been determined to be highly effective, wherein the prior treatment is determined to be highly effective by:

(i) measuring the expression level of DEFA4 (defensin alpha 4, corticostatin) in a sample obtained from the patient with neuromyelitis optica who has been administered the anti-IL-6 receptor antibody, and

(ii) comparing the expression level measured in (i) with the expression level of DEFA4 in a sample obtained from the patient prior to administration of the anti-IL-6 receptor antibody, wherein the therapeutic effect of the IL-6 inhibitor is indicated to be high when the expression level of DEFA4 is lower than the expression level of DEFA4 in a sample obtained from the patient prior to administration of the anti-IL-6 receptor antibody, wherein the anti-IL-6 receptor antibody is administered to the patient via systemic administration, and further wherein the sample obtained from the patient is a peripheral blood sample.

3 . The method of claim 1 , wherein the IL-6 inhibitor is an anti-IL-6 receptor antibody.

4 . The method of claim 1 , wherein the anti-IL-6 receptor antibody is a chimeric antibody, a humanized antibody.

5 . The method of claim 1 , wherein the determined expression level of DEFA4 is five times or higher, or ten times or higher, than the expression level of DEFA4 in the sample obtained from a healthy individual.

6 . The method of claim 2 , wherein the anti-IL-6 receptor antibody is a chimeric antibody, a humanized antibody, or a human antibody.

7 . The method of claim 2 , wherein the measured expression level of DEFA4 in (i) is less than 0.5 times or less than 0.2 times the expression level of DEFA4 in the sample obtained from the patient before the prior administration of the anti-IL-6 receptor antibody.

8 . A method for treating the IL-6 associated disease neuromyelitis optica comprising administering an anti-IL-6 receptor antibody selected from MR16-1, PM-1, humanized PM-1 (Tocilizumab), AUK-12-20, AUK64-7, AUK-146-15 and SA237 to a patient for whom treatment with an IL-6 inhibitor is predicted to be highly effective, wherein the treatment is predicted to be highly effective by:

i) measuring the expression level of DEFA4 in a sample obtained from the patient with neuromyelitis optica, and

(ii) comparing the expression level measured in (i) with the expression level of DEFA4 in a sample obtained from a healthy individual,

wherein the therapeutic effect of the IL-6 inhibitor is indicated to be high when the expression level of DEFA4 is higher than the expression level of DEFA4 in a sample obtained from a healthy individual, wherein the anti-IL-6 receptor antibody is administered to the patient via systemic administration, and further wherein the sample obtained from the patient is a peripheral blood sample.

9 . The method of claim 8 , wherein the anti-IL-6 receptor antibody is a chimeric antibody, a humanized antibody, or a human antibody.

10 . The method of claim 8 , wherein the measured expression level of DEFA4 is five times or higher, or ten times or higher, than the expression level of DEFA4 in the sample obtained from the healthy individual.

11 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is MR16-1.

12 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is PM-1.

13 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is humanized PM-1 (Tocilizumab).

14 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is AUK-12-20.

15 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is AUK64-7.

16 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is AUK-146-15.

17 . The method of claim 1 , wherein the administered anti-IL-6 receptor antibody is SA237.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2025
From: MATSUOKA, TAKAKO; ARAKI, MANABU; YAMAMURA, TAKASHI
To: NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY
Reel/Frame 072740/0127 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 29, 2025
From: NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY
To: NATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY; CHUGAI SEIYAKU KABUSHIKI KAISHA
Reel/Frame 072740/0134 →
Priority Claims (1)
JP 2017-091600 · May 2, 2017 · national
Continuity (2)
Division 16609053
Related Publication 20240043526A1 · Feb 8, 2024
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