IP Library › Granted Patent US 12,595,299
Granted Patent B2
US 12,595,299 · App. 17/494,199 · Granted Apr 7, 2026

FC variants

Inventors: Tomoyuki Igawa (Shizuoka, JP); Atsuhiko Maeda (Shizuoka, JP); Kenta Haraya (Shizuoka, JP); Tatsuhiko Tachibana (Shizuoka, JP); Yuki Iwayanagi (Shizuoka, JP)
Assignee: Chugai Seiyaku Kabushiki Kaisha
C07K16/244C07K16/18C07K16/2866C07K16/36C07K16/40C07K16/4291G01N33/6854A61K2039/505C07K2317/14C07K2317/24C07K2317/31C07K2317/51C07K2317/515C07K2317/52C07K2317/55C07K2317/56C07K2317/76C07K2317/77C07K2317/90C07K2317/92C07K2317/94G01N2500/04
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Quick Facts
Patent No.
US 12,595,299
App. No.
17/494,199
Granted
Apr 7, 2026
Kind
B2
Abstract

One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.

Claims (36)

1 . A human Fc region variant comprising

a heavy chain constant region that comprises SEQ ID NO:18 with only amino acid substitutions selected from:

(a) N434A/Q438R/S440E in the EU numbering system;

(b) N434A/Y436T/Q438R/S440E in the EU numbering system;

(c) N434A/Y436V/Q438R/S440E in the EU numbering system;

(d) M428L/N434A/Q438R/S440E in the EU numbering system;

(e) M428L/N434A/Y436T/Q438R/S440E in the EU numbering system; and

(f) M428L/N434A/Y436V/Q438R/S440E in the EU numbering system; or

a heavy chain constant region that comprises SEQ ID NO:21 with only amino acid substitutions selected from:

(g) N434A/Q438R/S440E in the EU numbering system;

(h) N434A/Y436T/Q438R/S440E in the EU numbering system;

(i) N434A/Y436V/Q438R/S440E in the EU numbering system;

(j) M428L/N434A/Q438R/S440E in the EU numbering system;

(k) M428L/N434A/Y436T/Q438R/S440E in the EU numbering system; and

(l) M428L/N434A/Y436V/Q438R/S440E in the EU numbering system.

2 . The Fc region variant of claim 1 , wherein the Fc region variant has one or more features selected from:

(a) enhanced FcRn-binding activity under an acidic pH condition compared to that of an Fc region of a native IgG;

(b) not enhanced binding activity to an anti-drug antibody (ADA) under a neutral pH condition compared to that of an Fc region of a native IgG, wherein the ADA is optionally rheumatoid factor (RF);

(c) decreased plasma clearance (CL), increased plasma retention time, or increased plasma half-life (t½), compared to that of an Fc region of a native IgG;

(d) increased plasma retention compared to a reference Fc region variant comprising a heavy chain constant region that comprises SEQ ID NO:18 with only the amino acid substitutions N434Y/Y436V/Q438R/S440E in the EU numbering system; and

(e) increased plasma retention compared to a reference Fc region variant comprising a heavy chain constant region that comprises SEQ ID NO:21 with only the amino acid substitutions N434Y/Y436V/Q438R/S440E in the EU numbering system.

3 . An antibody comprising the Fc region variant of claim 1 .

4 . The antibody of claim 3 , wherein the antibody is an IgG antibody.

5 . A pharmaceutical composition comprising the antibody of claim 3 .

6 . The Fc region variant of claim 1 , wherein the Fc region variant comprises SEQ ID NO:18 with only the amino acid substitutions M428L/N434A/Q438R/S440E in the EU numbering system.

7 . An antibody comprising the Fc region variant of claim 6 .

8 . The antibody of claim 7 , wherein the antibody is an IgG antibody.

9 . A pharmaceutical composition comprising the antibody of claim 7 .

10 . The Fc region variant of claim 1 , wherein the Fc region variant comprises SEQ ID NO:21 with only the amino acid substitutions M428L/N434A/Y436T/Q438R/S440E in the EU numbering system or M428L/N434A/Y436V/Q438R/S440E in the EU numbering system.

11 . The Fc region variant of claim 1 , wherein the Fc region variant comprises SEQ ID NO:21 with only the amino acid substitutions M428L/N434A/Q438R/S440E in the numbering system.

12 . An antibody comprising the Fc region variant of claim 10 .

13 . The antibody of claim 12 , wherein the antibody is an IgG antibody.

14 . A pharmaceutical composition comprising the antibody of claim 12 .

15 . An antibody comprising the Fc region variant of claim 11 .

16 . The antibody of claim 15 , wherein the antibody is an IgG antibody.

17 . A pharmaceutical composition comprising the antibody of claim 15 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 5, 2025
From: IGAWA, TOMOYUKI; MAEDA, ATSUHIKO; HARAYA, KENTA; TACHIBANA, TATSUHIKO; IWAYANAGI, YUKI; HORI, YUJI; NAKAMURA, GENKI; MURAOKA, MASARU
To: CHUGAI SEIYAKU KABUSHIKI KAISHA
Reel/Frame 073128/0336 →
Priority Claims (2)
JP 2015-021371 · Feb 5, 2015 · national
JP 2015-185254 · Sep 18, 2015 · national
Continuity (4)
Division 16697310 · Nov 27, 2019
Division 15976288 · May 10, 2018
Division 15015287 · Feb 4, 2016
Related Publication 20220089715A1 · Mar 24, 2022
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