IP Library › Granted Patent US 12,365,738
Granted Patent B2
US 12,365,738 · App. 18/896,799 · Granted Jul 22, 2025

Method of treating an interleukin-11-associated or -mediated fibrotic disease or condition by administering an anti-interleukin-11 receptor subunit alpha (IL-11RA) antibody

Inventors: Robert A. Horlick (San Diego, CA); Helen Toni Jun (San Diego, CA); David J. King (Encinitas, CA)
Assignee: Lassen Therapeutics, Inc.
C07K16/2866A61P11/00A61P43/00C07K2317/24C07K2317/52C07K2317/565C07K2317/71C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,365,738
App. No.
18/896,799
Granted
Jul 22, 2025
Kind
B2
Abstract

Provided are antibodies and antigen binding fragments thereof that bind to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions, which may be used in any of a variety of therapeutic or diagnostic methods, including the treatment or diagnosis of cancers, inflammatory diseases, autoimmune diseases, and others.

Claims (52)

1. A method of treating an IL-11-associated or IL-11-mediated fibrotic disease or condition in a subject in need thereof, comprising administering to the subject an antibody, or antigen binding fragment thereof, which binds to interleukin-11 receptor subunit α (IL-11Rα), wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region (V H ) and a light chain variable region (V L ), wherein the V H comprises complementary determining region V H CDR1, V H CDR2, and V H CDR3 sequences and the V L comprises complementary determining region V L CDR1, V L CDR2, and V L CDR3 sequences, and wherein:

a. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 25-27, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 28-30, respectively;

b. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 91-93, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 94-96, respectively;

c. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 97-99, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 100-102, respectively;

d. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 103-105, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 106-108, respectively;

e. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 109-111, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 112-114, respectively;

f. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 115-117, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 118-120, respectively;

g. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 121-123, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 124-126, respectively;

h. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 127-129, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 130-132, respectively;

i. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 133-135, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 136-138, respectively;

j. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 139-141, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 142-144, respectively;

k. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 145-147, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 148-150, respectively;

l. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 151-153, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 154-156, respectively;

m. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 157-159, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 160-162, respectively;

n. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 163-165, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 166-168, respectively;

o. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 169-171, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 172-174, respectively;

p. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 175-177, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 178-180, respectively;

q. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 181-183, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 184-186, respectively; or

r. the V H CDR1, V H CDR2, and V H CDR3 sequences comprise SEQ ID NOs: 187-189, respectively, and the V L CDR1, V L CDR2, and V L CDR3 sequences comprise SEQ ID NOs: 190-192, respectively.

2. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, binds to a fibronectin domain III of human IL-11Rα, or approximately residues 112-219 of SEQ ID NO: 257.

3. The method of claim 1 , wherein:

a. the VH comprises a sequence of SEQ ID NO: 201, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 202, or a sequence comprising at least 80% sequence identity thereto;

b. the VH comprises a sequence of SEQ ID NO: 223, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 224, or a sequence comprising at least 80% sequence identity thereto;

c. the VH comprises a sequence of SEQ ID NO: 225, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 226, or a sequence comprising at least 80% sequence identity thereto;

d. the VH comprises a sequence of SEQ ID NO: 227, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 228, or a sequence comprising at least 80% sequence identity thereto;

e. the VH comprises a sequence of SEQ ID NO: 229, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 230, or a sequence comprising at least 80% sequence identity thereto;

f. the VH comprises a sequence of SEQ ID NO: 231, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 232, or a sequence comprising at least 80% sequence identity thereto;

g. the VH comprises a sequence of SEQ ID NO: 233, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 234, or a sequence comprising at least 80% sequence identity thereto;

h. the VH comprises a sequence of SEQ ID NO: 235, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 236, or a sequence comprising at least 80% sequence identity thereto;

i. the VH comprises a sequence of SEQ ID NO: 237, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 238, or a sequence comprising at least 80% sequence identity thereto;

j. the VH comprises a sequence of SEQ ID NO: 239, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 240, or a sequence comprising at least 80% sequence identity thereto;

k. the VH comprises a sequence of SEQ ID NO: 241, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 242, or a sequence comprising at least 80% sequence identity thereto;

l. the VH comprises a sequence of SEQ ID NO: 243, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 244, or a sequence comprising at least 80% sequence identity thereto;

m. the VH comprises a sequence of SEQ ID NO: 245, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 246, or a sequence comprising at least 80% sequence identity thereto;

n. the VH comprises a sequence of SEQ ID NO: 247, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 248, or a sequence comprising at least 80% sequence identity thereto;

o. the VH comprises a sequence of SEQ ID NO: 249, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 250, or a sequence comprising at least 80% sequence identity thereto;

p. the VH comprises a sequence of SEQ ID NO: 251, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 252, or a sequence comprising at least 80% sequence identity thereto;

q. the VH comprises a sequence of SEQ ID NO: 253, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 254, or a sequence comprising at least 80% sequence identity thereto; or

r. the VH comprises a sequence of SEQ ID NO: 255, or a sequence comprising at least 80% sequence identity thereto; and the VL comprises a sequence of SEQ ID NO: 256, or a sequence comprising at least 80% sequence identity thereto.

4. The method claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises an IgA (including subclasses IgA1 and IgA2), IgD, IgE, IgG (including subclasses IgG1, IgG2, IgG3, and IgG4), or IgM Fc domain, optionally a human Fc domain, a hybrid and/or variant thereof.

5. The method claim 1 , wherein the antibody, or antigen binding fragment thereof, comprises a human IgG1 or IgG4 Fc domain, or a hybrid, variant or modified Fc domain thereof, optionally wherein the human IgG4 Fc domain comprises SEQ ID NO: 258 or 259.

6. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is a monoclonal antibody.

7. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is a humanized antibody, optionally wherein the antibody, or antigen binding fragment thereof, is a humanized monoclonal antibody that comprises a human IgG4 Fc domain with an S228P mutation (EU numbering).

8. The method of claim 1 , wherein the antibody, or antigen binding fragment thereof, is selected from an Fv fragment, a single chain Fv (scFv) polypeptide, an adnectin, an anticalin, an aptamer, an avimer, a camelid antibody, a designed ankyrin repeat protein (DARPin), a minibody, a nanobody, and a unibody.

9. The method of claim 5 , wherein the antibody comprising the modified Fc domain exhibits an increased half-life relative to a corresponding wild-type Fc sequence.

10. The method of claim 9 , wherein the modified Fc domain comprises one or more of substitutions M252Y, S254T, and T256E or a residue corresponding thereto, relative to the wild-type Fc sequence, according to EU numbering.

11. The method of claim 5 , wherein the antibody comprising the modified Fc domain exhibits low effector function in humans.

12. The method of claim 11 , wherein the antibody comprising the modified Fc domain exhibits one or more of the following: decreased complement fixation or activation, decreased C1q binding affinity, decreased CDC-related activity, decreased FcR binding affinity, decreased ADCC-related activity, and decreased ADCP-related activity, relative to a corresponding wild-type Fc sequence.

13. The method of claim 11 , wherein the modified Fc domain comprises one or more of substitutions L234A, L235A, and P329S or a residue corresponding thereto, relative to the wild-type Fc sequence, according to EU numbering.

14. The method of claim 5 , wherein the antibody comprising the modified Fc domain exhibits an increased half-life relative to a corresponding wild-type Fc sequence and low effector function in humans.

15. The method of claim 14 , wherein the modified Fc domain exhibits one or more of the following: decreased complement fixation or activation, decreased C1q binding affinity, decreased CDC-related activity, decreased FcR binding affinity, decreased ADCC-related activity, and decreased ADCP-related activity, relative to a corresponding wild-type Fc sequence.

16. The method of claim 15 , wherein the modified Fc domain comprises one or more of substitutions M252Y, S254T, T256E, L234A, L235A, and P329S or a residue corresponding thereto, relative to the wild-type Fc sequence, according to EU numbering.

Assignments (3)
CHANGE OF NAME Recorded Jun 2, 2025
From: LASSEN THERAPEUTICS 1, INC.
To: LASSEN THERAPEUTICS, INC.
Reel/Frame 071468/0121 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2024
From: HORLICK, ROBERT A.; JUN, HELEN TONI; KING, DAVID J.
To: JUNIPER DISCOVERY, INC.
Reel/Frame 069832/0020 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2024
From: JUNIPER DISCOVERY, INC.
To: LASSEN THERAPEUTICS 1, INC.
Reel/Frame 069832/0429 →
Continuity (5)
Division 18590853 · Feb 28, 2024
Continuation PCTUS2022075680 · Aug 30, 2022
Provisional Application 63334923 · Apr 26, 2022
Provisional Application 63238443 · Aug 30, 2021
Related Publication 20250011444A1 · Jan 9, 2025
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