Method and pharmaceutical composition for treating Crohn's disease

Patent metadata

Field	Value
Publication number	US-11052150-B2
Application number	US-201815951321-A
Country	US
Kind code	B2
Filing date	Apr 12, 2018
Priority date	Apr 14, 2017
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

It is an object of the present invention to provide a pharmaceutical composition comprising an anti-fractalkine antibody that provides therapeutically effective improvement to Crohn's disease, after the administration thereof to a human subject, and a method for treating Crohn's disease. Provided is a pharmaceutical composition for treating Crohn's disease. The present pharmaceutical composition comprises an anti-fractalkine antibody and a pharmaceutically acceptable excipient, and is used, such that the anti-fractalkine antibody is intravenously administered to a human at a dose of at least 10 mg/kg of human body weight in a method for treating Crohn's disease.

First claim

What is claimed is:

1. A method for treating Crohn's disease, comprising intravenously administering to a human in need thereof multiple doses of an anti-fractalkine antibody, wherein each dose of the anti-fractalkine antibody is 10 to 15 mg/kg of human body weight, wherein the mean trough concentration of the anti-fractalkine antibody is 80 μg/mL or more, wherein the human is a Crohn's disease patient in whom prior treatment with at least one of 5-aminosalicylic acid (5-ASA), salazosulfapyridine, a corticosteroid, an immunomodulator, or an anti-TNF antibody was not effective, was initially effective but the effect became attenuated or disappeared, or could not be continued due to side effects, wherein the anti-fractalkine antibody comprises:
a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO: 13

(QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYIHWVKQAPGQGLEWIGW

IYPGDGSPKFNERFKGRTTLTADKSTNTAYMLLSSLRSEDTAVYFCATGPT

DGDYFDYWGQGTTVTVSS);

a light chain variable region comprising the amino acid sequence shown in SEQ ID NO: 14

(DIQMTQSPSSLSASVGDRVTITCRASGNIHNFLAWYQQKPGKAPKLLIYN

EKTLADGVPSRFSGSGSGTDYTLTISSLQPEDFATYFCQQFWSTPYTFGGG

TKVEIK);

and
a constant region of human IgG2 isotype, wherein
a Fc region of the constant region comprises mutations V234A and G237A.

2. The method according to claim 1 , wherein the anti-fractalkine antibody is intravenously administered to the human at a dose of 10 mg/kg of human body weight or 15 mg/kg of human body weight.

3. The method according to claim 1 , wherein the anti-fractalkine antibody is administered in a pharmaceutical composition that provides a mean C max of the anti-fractalkine antibody at a dose of 1 mg/kg of human body weight in single-dose intravenous administration with a value of 21 to 25 μg/mL.

4. The method according to claim 1 , wherein the anti-fractalkine antibody is administered in a pharmaceutical composition that provides a mean C max of the anti-fractalkine antibody of a value included in the numerical range of 80% to 125% of 2.4×10 2 μg/mL when the anti-fractalkine antibody is administered to the human by single-dose intravenous administration at a dose of 10 mg/kg of human body weight.

5. The method according to claim 1 , wherein the anti-fractalkine antibody is administered in a pharmaceutical composition that provides a mean AUC (0-t) of the anti-fractalkine antibody of a value included in the numerical range of 80% to 125% of 7.0×10 4 μg·h/mL when the anti-fractalkine antibody is administered to the human by single-dose intravenous administration at a dose of 10 mg/kg of human body weight.

6. The method according to claim 1 , wherein the anti-fractalkine antibody is administered in a pharmaceutical composition that provides a mean AUC (0-336h) of the anti-fractalkine antibody of a value included in the numerical range of 80% to 125% of 3.8×10 4 μg·h/mL when the anti-fractalkine antibody is administered to the human by single-dose intravenous administration at a dose of 10 mg/kg of human body weight.

7. The method according to claim 1 , which comprises multiple-dose intravenous administration of the anti-fractalkine antibody at dosing intervals from once every week to once every two weeks.

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Yasuda Nobuyuki
• Oketani Kiyoshi
• Baba Hiroko
• Nakano Tomohisa
• Mori Masahiko

Classifications

• A61P1/00 Primary

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• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/52

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