IP Library › Granted Patent US 12,304,959
Granted Patent B2
US 12,304,959 · App. 17/486,864 · Granted May 20, 2025

Method of treating asthma with anti-IL1RAP antibodies

Inventors: Davide Foletti (Menlo Park, CA); Erik Karrer (Los Altos, CA); Germaine Fuh-Kelly (Pacifica, CA); Kristie Ibarra (San Jose, CA); Quan Zheng (Fremont, CA); Yao-ming Huang (San Mateo, CA); Lindsay Deis (San Bruno, CA); Christine Wolak (Burlingame, CA); Dominic Samuel Berns (Redwood City, CA)
Assignee: 23andMe, Inc.
C07K16/2866C12N5/16A61K2039/505C07K2317/30C07K2317/33C07K2317/56C07K2317/71C07K2317/75C07K2317/92
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Quick Facts
Patent No.
US 12,304,959
App. No.
17/486,864
Granted
May 20, 2025
Kind
B2
Abstract

The present invention provides binding proteins, such as antibodies and antigen-binding fragments, which specifically bind to human interleukin-1 receptor accessory protein (hu-IL1RAP) and fully block the IL-1, IL-33, and IL-36 intracellular signaling pathways. Compositions comprising such binding proteins and methods of making and using such binding proteins are also provided.

Claims (54)

1. A method of treating an IL1RAP mediated disease in a subject, wherein the IL1RAP mediated disease is asthma, comprising administering to the subject a therapeutically effective amount of an antibody, wherein the antibody comprises: (i) a first light chain hypervariable region (HVR-L1), a second light chain hypervariable region (HVR-L2), and a third light chain hypervariable region (HVR-L3), and (ii) a first heavy chain hypervariable region (HVR-H1), a second heavy chain hypervariable region (HVR-H2), and a third heavy chain hypervariable region (HVR-H3); wherein:

(a) HVR-L1 comprises an amino acid sequence of SEQ ID NO: 11;

(b) HVR-L2 comprises an amino acid sequence selected from SEQ ID NO: 37, and 54;

(c) HVR-L3 comprises an amino acid sequence selected from SEQ ID NO: 63, 69, and 70;

(d) HVR-H1 comprises an amino acid sequence of SEQ ID NO: 78;

(e) HVR-H2 comprises an amino acid sequence selected from SEQ ID NO: 191, and 195;

(f) HVR-H3 comprises an amino acid sequence selected from SEQ ID NO: 203 and 215.

2. The method of claim 1 , wherein the antibody comprises:

a first light chain framework region (FR-L1) comprising an amino acid sequence of SEQ ID NO: 244;

a second light chain framework region (FR-L2) comprising an amino acid sequence of SEQ ID NO: 246;

a third light chain framework region (FR-L3) comprising an amino acid sequence of SEQ ID NO: 247; and

a fourth light chain framework region (FR-L4) comprising an amino acid sequence of SEQ ID NO: 248; or

a first heavy chain framework region (FR-H1) comprising an amino acid sequence of SEQ ID NO: 253;

a second heavy chain framework region (FR-H2) comprising an amino acid sequence of SEQ ID NO: 254;

a third heavy chain framework region (FR-H3) comprising an amino acid sequence of SEQ ID NO: 255; and

a fourth heavy chain framework region (FR-H4) comprising an amino acid of SEQ ID NO: 256.

3. The method of claim 1 , wherein the antibody comprises a light chain variable domain (V L ) amino acid sequence having at least 90% identity to SEQ ID NO: 259; and/or a heavy chain variable domain (V H ) amino acid sequence having at least 90% identity to SEQ ID NO: 290.

4. The method of claim 3 , wherein the antibody comprises:

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 259, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 290;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 268, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 307;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 268, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 298;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 269, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 307;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 269, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 298;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 269, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 297;

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 270, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 307; or

the light chain variable domain (V L ) amino acid sequence of SEQ ID NO: 270, and the heavy chain variable domain (V H ) amino acid sequence of SEQ ID NO: 298.

5. The method of claim 1 , wherein the antibody comprises a light chain (LC) amino acid sequence having at least 90% identity to SEQ ID NO: 328; and/or a heavy chain (HC) amino acid sequence having at least 90% identity to SEQ ID NO: 332.

6. The method of claim 5 , wherein the antibody comprises:

the light chain (LC) amino acid sequence of SEQ ID NO: 328, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 332;

the light chain (LC) amino acid sequence of SEQ ID NO: 329, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 335;

the light chain (LC) amino acid sequence of SEQ ID NO: 329, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 336;

the light chain (LC) amino acid sequence of SEQ ID NO: 329, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 333;

the light chain (LC) amino acid sequence of SEQ ID NO: 329, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 334;

the light chain (LC) amino acid sequence of SEQ ID NO: 330, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 335;

the light chain (LC) amino acid sequence of SEQ ID NO: 330, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 336;

the light chain (LC) amino acid sequence of SEQ ID NO: 330, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 333;

the light chain (LC) amino acid sequence of SEQ ID NO: 330, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 334;

the light chain (LC) amino acid sequence of SEQ ID NO: 331, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 335;

the light chain (LC) amino acid sequence of SEQ ID NO: 331, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 336;

the light chain (LC) amino acid sequence of SEQ ID NO: 331, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 333; or

the light chain (LC) amino acid sequence of SEQ ID NO: 331, and the heavy chain (HC) amino acid sequence of SEQ ID NO: 334.

7. The method of claim 1 , wherein an IL-1 stimulated signal, an IL-33 stimulated signal, or an IL-36 stimulated signal in the subject is decreased by at least 90%.

8. The method of claim 1 , wherein an intracellular signal initiated by one or more of IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ agonist binding to its cognate receptor in the subject is decreased by at least 90%.

9. The method of claim 1 , wherein the antibody specifically binds to one or more amino acid residues within domain 3 of human IL1RAP, wherein domain 3 comprises positions 238-367 of the amino acid sequence of SEQ ID NO: 1 or 3.

10. The method of claim 1 , wherein the antibody does not bind to amino acid residues within domain 1 or domain 2 of human IL1RAP; optionally, wherein domain 1 and domain 2 comprise positions 21-237 of the amino acid sequence of SEQ ID NO: 1 or 3.

11. The method of claim 1 , The antibody of claim 1 , wherein the antibody cross-reacts with a cynomolgus monkey IL1RAP polypeptide of SEQ ID NO: 8.

12. The method of claim 1 , wherein the antibody is a full-length antibody of class IgG; optionally, wherein the class IgG antibody has an isotype selected from IgG1, IgG2, IgG3, and IgG4.

13. The method of claim 1 , wherein the antibody is an Fc region variant; optionally wherein the Fc region variant alters effector function or alters half-life.

14. The method of claim 13 , wherein the Fc region variant comprises a set of YTE mutations.

15. The method of claim 13 , wherein the Fc region variant decreases effector function.

16. The method of claim 1 , wherein the antibody is formulated in a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier.

17. The method of claim 1 , wherein the antibody is administered systemically.

18. The method of claim 1 , wherein the antibody is administered at a dose of from about 1 pg/kg to about 15 mg/kg.

19. The method of claim 1 , wherein the method further comprises administering to the subject a dose of up to about 100 mg/kg.

Assignments (2)
CHANGE OF NAME Recorded Nov 4, 2025
From: 23ANDME PGS LLC
To: 23ANDME GENOMICS LLC
Reel/Frame 073465/0812 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2025
From: 23ANDME, INC.
To: 23ANDME PGS LLC
Reel/Frame 073079/0250 →
Continuity (3)
Division 16541990 · Aug 15, 2019
Provisional Application 62719397 · Aug 17, 2018
Related Publication 20220106395A1 · Apr 7, 2022
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