IP Library › Granted Patent US 12,043,666

Granted Patent B2

US 12,043,666 · App. 17/836,457 · Granted Jul 23, 2024

Anti-IL1RAP antibody

Inventors: David Liberg (Lomma, SE); Camilla Rydberg Millrud (Limhamn, SE); Gabriel Svensson Birkedal (Höör, SE); Sara Rattik (Åkarp, SE); Kjell Sjöström (Lund, SE); Karin von Wachenfeldt (Lund, SE); Caitriona Grönberg (Torna-Hällestad, SE)

Assignee: Cantargia AB

C07K16/283 A61P35/00 C12N15/63 A61K2039/505 C07K2317/565 C07K2317/732 C07K2317/76

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Quick Facts

Patent No.: US 12,043,666
App. No.: 17/836,457
Granted: Jul 23, 2024
Kind: B2

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Abstract

The present invention relates to an antibody or antigen-binding fragment thereof with binding specificity for interleukin-1 receptor accessory protein (IL1RAP). Furthermore, it relates to a polynucleotide encoding said antibody, a vector comprising said polynucleotide and a recombinant host cell comprising said polynucleotide or said vector. Further, it relates to a method for producing said antibody or antigen-binding fragment. Further, it relates to a composition comprising said antibody or antigen-binding fragment, said polynucleotide, said vector and/or said host cell. Further, it relates to the said antibody or antigen-binding fragment, said polynucleotide, said vector, said host cell and/or said composition for use in medicine and/or for use in the prevention and/or treatment and/or alleviation and/or detection and/or diagnosis of a disease or disorder susceptible to treatment with an inhibitor of IL-1α, IL-1β, IL-33, IL-36α, IL-36β and/or IL-36γ signaling, and/or wherein the disease or disorder is associated with cells expressing IL1RAP.

Claims (136)

1. A method for reducing inflammation and/or fibrosis in a subject, the method comprising the step of administering to the subject an effective amount of an antibody or antigen-binding fragment that binds to interleukin-1 receptor accessory protein (IL1RAP), wherein the antibody or antigen-binding fragment comprises:

(a)(i) a CDR-L1 comprising the amino acid sequence of ESISTA (SEQ ID NO: 1); a CDR-L2 comprising the amino acid sequence of KAS; and a CDR-L3 comprising the amino acid sequence of QQGFSSGNVHNA (SEQ ID NO: 3); and

(ii) a CDR-H1 comprising the amino acid sequence of GPSLSHFD (SEQ ID NO: 4); a CDR-H2 comprising the amino acid sequence of ISPGVST (SEQ ID NO: 5); and a CDR-H3 comprising the amino acid sequence of ARGGVGSSWKAFDL (SEQ ID NO: 6); or

(b)(i) a CDR-L1 comprising the amino acid sequence of QASESISTALA (SEQ ID NO: 7); a CDR-L2 comprising the amino acid sequence of KASTLPS (SEQ ID NO: 8); and a CDR-L3 comprising the amino acid sequence of QQGFSSGNVHNA (SEQ ID NO: 9); and

(ii) a CDR-H1 comprising the amino acid sequence of HFDIT (SEQ ID NO: 10); a CDR-H2 comprising the amino acid sequence of TISPGVSTYYASWAKS (SEQ ID NO: 11); and a CDR-H3 comprising the amino acid sequence of GGVGSSWKAFDL (SEQ ID NO: 12); or

(c)(i) a CDR-L1 comprising the amino acid sequence of QASESISTALA (SEQ ID NO: 13); a CDR-L2 comprising the amino acid sequence of KASTLPS (SEQ ID NO: 14); and a CDR-L3 comprising the amino acid sequence of QQGFSSGNVHNA (SEQ ID NO: 15); and

(ii) a CDR-H1 comprising the amino acid sequence of GPSLSHFDIT (SEQ ID NO: 16); a CDR-H2 comprising the amino acid sequence of TISPGVSTYYASWAKS (SEQ ID NO: 17); and a CDR-H3 comprising the amino acid sequence of ARGGVGSSWKAFDL (SEQ ID NO: 18).

2. The method of claim 1 , wherein the subject has myocarditis.

3. The method of claim 2 , wherein the myocarditis is autoimmune myocarditis.

4. A method for reducing fibrosis in a subject, the method comprising the step of administering to the subject an effective amount of an antibody or antigen-binding fragment that binds to interleukin-1 receptor accessory protein (IL1RAP), wherein the antibody or antigen-binding fragment comprises:

5. The method of claim 4 , wherein the subject has systemic sclerosis.

6. The method of claim 4 , wherein the fibrosis is pulmonary fibrosis, and wherein the method comprises reducing the Ashcroft score and/or the amount of collagen in the lungs of the subject.

7. The method of claim 4 , wherein the fibrosis is dermal fibrosis, and wherein the method comprises reducing dermal thickness, reducing the number of myofibroblasts and/or reducing the amount of collagen in the skin of the subject.

8. The method of claim 4 , wherein the method comprises altering the IL-1 gene expression profile in the skin of the subject.

9. The method of claim 1 , wherein the antibody or antigen-binding fragment comprises a light chain variable region and a heavy chain variable region, wherein:

a) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 19 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 20; or

b) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 26; or

c) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 27; or

d) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 28; or

e) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 29; or

f) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 21 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30; or

g) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 26; or

h) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 27; or

i) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 28; or

j) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 29; or

k) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 22 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30; or

l) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 23 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 26; or

m) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 23 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 27; or

n) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 23 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 28; or

o) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 23 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 29; or

p) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 23 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30; or

q) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 26; or

r) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 27; or

s) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 28; or

t) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 29; or

u) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30; or

v) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 26; or

w) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 27; or

x) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 28; or

y) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 29; or

z) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30, or

aa) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 32; or

bb) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 33; or

cc) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 24 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 34; or

dd) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 32; or

ee) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 33; or

ff) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 25 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 34; or

gg) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 31 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 30; or

hh) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 31 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 32; or

ii) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 31 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 33; or

jj) the light chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 31 and the heavy chain variable region comprises or consists of the amino acid sequence of SEQ ID NO: 34.

10. The method of claim 1 , wherein the antibody or antigen-binding fragment comprises:

a) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

b) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 21, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

c) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 22, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

d) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

e) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 24, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

f) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 25, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

g) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 31, and the CDRs of claim 1 (a)(i), (b)(i), and (c)(i); or

h) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 20 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

i) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

j) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

k) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 28 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

l) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 29 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

m) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 30 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

n) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 32 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

o) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 33 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii); or

p) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 34 and the CDRs of claim 1 (a)(ii), (b)(ii), and (c)(ii).

11. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain constant region comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 35, and a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 36 or SEQ ID NO: 2.

12. The method of claim 1 , wherein the antibody or antigen-binding fragment is not capable of inducing ADCC of cells expressing IL1RAP.

13. The method of claim 1 , wherein the antibody or antigen-binding fragment comprises a moiety for increasing the in vivo half-life of the agent.

14. The method of claim 1 , wherein the antibody or antigen-binding fragment comprises a cytotoxic moiety or a detectable moiety.

15. The method of claim 4 , wherein the antibody or antigen-binding fragment comprises a light chain variable region and a heavy chain variable region, wherein:

16. The method of claim 4 , wherein the antibody or antigen-binding fragment comprises:

a) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

b) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 21, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

c) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 22, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

d) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 23, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

e) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 24, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

f) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 25, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

g) a light chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 31, and the CDRs of claim 4 (a)(i), (b)(i), and (c)(i); or

h) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 20 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

i) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

j) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

k) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 28 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

l) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 29 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

m) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 30 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

n) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 32 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

o) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 33 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii); or

p) a heavy chain variable region comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 34 and the CDRs of claim 4 (a)(ii), (b)(ii), and (c)(ii).

17. The method of claim 4 , wherein the antibody or antigen-binding fragment thereof comprises a light chain constant region comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 35, and a heavy chain constant region comprising an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 36 or SEQ ID NO: 2.

18. The method of claim 4 , wherein the antibody or antigen-binding fragment is not capable of inducing ADCC of cells expressing IL1RAP.

19. The method of claim 4 , wherein the antibody or antigen-binding fragment comprises a moiety for increasing the in vivo half-life of the agent.

20. The method of claim 4 , wherein the antibody or antigen-binding fragment comprises a cytotoxic moiety or a detectable moiety.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 14, 2025

From: CANTARGIA AB

To: OTSUKA PHARMACEUTICAL CO., LTD.

Reel/Frame 072557/0236 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 20, 2022

From: LIBERG, DAVID; MILLRUD, CAMILLA RYDBERG; BIRKEDAL, GABRIEL SVENSSON; RATTIK, SARA; SJÖSTRÖM, KJELL; VON WACHENFELDT, KARIN; GRÖNBERG, CAITRÍONA

To: CANTARGIA AB

Reel/Frame 062153/0204 →

Priority Claims (3)

EP 20216926 · Dec 23, 2020 · regional

GB 2105933 · Apr 26, 2021 · national

EP 21212368 · Dec 3, 2021 · regional

Continuity (2)

Continuation 17559227 · Dec 22, 2021

Related Publication 20230108007A1 · Apr 6, 2023