IP Library › Granted Patent US 10,752,692

Granted Patent B2

US 10,752,692 · App. 16/358,459 · Granted Aug 25, 2020

Anti human interleukin-1 receptor accessory protein (IL1 RAP) antibodies and uses thereof

Inventors: Helena Ågerstam (Lund, SE); Thoas Fioretos (Lund, SE); Marcus Järås (Lund, SE); Cecilia Ann-Christin Malmborg Hager (Helsingborg, SE); Kjell Sjöström (Lund, SE); Agneta Svedberg (Lund, SE); Karin von Wachenfeldt (Lund, SE)

Assignee: Cantargia AB

C07K16/2866 C07K16/30 C07K16/303 C07K16/3015 C07K16/3023 C07K16/3038 C07K16/3053 C07K16/3069 G01N33/57492 A61K2039/505 C07K2317/24 C07K2317/32 C07K2317/33 C07K2317/41 C07K2317/55 C07K2317/56 C07K2317/565 C07K2317/72 C07K2317/732 C07K2317/76 C07K2317/77 C07K2317/92 G01N2333/7155

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Quick Facts

Patent No.: US 10,752,692
App. No.: 16/358,459
Granted: Aug 25, 2020
Kind: B2

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Abstract

The present invention provides an antibody or an antigen-binding fragment thereof with binding specificity for human interleukin-1 receptor accessory protein (IL1RAP) wherein the antibody or antigen-binding fragment is capable of inhibiting the binding of antibody ‘CAN04’ to human IL1RAP. The invention further provides the use of such antibodies or an antigen-binding fragments in the treatment and/or diagnosis of IL-1 associated diseases and conditions, including cancers such as acute myeloid leukemia and melanoma.

Claims (43)

1. A recombinant host cell comprising:

A) a nucleic acid molecule encoding an antibody or antigen-binding fragment thereof or a component polypeptide chain thereof; or

B) a vector comprising said nucleic acid molecule in A), wherein the antibody comprises:

a. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising: GYAFTSS (amino acids 26-32 of SEQ ID NO:9); (ii) Heavy chain CDR2 comprising: YPGDGN (SEQ ID NO: 4); and (iii) Heavy chain CDR3 comprising: GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising: (i) Light chain CDR 1 comprising: ASQGINNYLN (amino acids 25-34 of SEQ ID NO:16); (ii) Light chain CDR2 comprising: YTSGLHA (SEQ ID NO: 13); and (iii) Light chain CDR3 comprising: QQYSILPWT (SEQ ID NO: 14);

b. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising GYAFTSS (amino acids 26-32 of SEQ ID NO:9); (ii) heavy chain CDR2 comprising YPGDGN (SEQ ID NO: 4); and (iii) heavy chain CDR3 comprising GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising (i) light chain CDR 1 comprising SASQGINNYLN (SEQ ID NO:12); light chain CDR2 comprising YTSGLHA (SEQ ID NO: 13); and (iii) light chain CDR3 comprising QQYSILPWT (SEQ ID NO: 14);

c. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising GYAFSSS (SEQ ID NO:3); (ii) heavy chain CDR2 comprising YPGDGN (SEQ ID NO: 4); and (iii) heavy chain CDR3 comprising GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising (i) light chain CDR 1 comprising SASQGINNYLN (SEQ ID NO:12); light chain CDR2 comprising YTSGLHA (SEQ ID NO: 13); and (iii) light chain CDR3 comprising QQYSILPWT (SEQ ID NO: 14);

d. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising GYAFSSS (SEQ ID NO:3); (ii) heavy chain CDR2 comprising YPGDGN (SEQ ID NO: 4); and (iii) heavy chain CDR3 comprising GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising (i) light chain CDR 1 comprising ASQGINNYLN (amino acids 25-34 of SEQ ID NO:16); light chain CDR2 comprising YTSGLHA (SEQ ID NO: 13); and (iii) light chain CDR3 comprising QQYSILPWT (SEQ ID NO: 14);

e. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising GYTFTSS (amino acids 26-32 of SEQ ID NO:10); (ii) heavy chain CDR2 comprising YPGDGQ (amino acids 52-57 of SEQ ID NO:10); and (iii) heavy chain CDR3 comprising GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising (i) light chain CDR 1 comprising SASQGINNYLN (SEQ ID NO:12); light chain CDR2 comprising YTSGLHA (SEQ ID NO: 13); and (iii) light chain CDR3 comprising QQYSILPWT (SEQ ID NO: 14); or

f. A heavy chain variable region (VH) comprising (i) heavy chain CDR1 comprising GYTFTSS (amino acids 26-32 of SEQ ID NO:10); (ii) heavy chain CDR2 comprising YPGDGQ (amino acids 52-57 of SEQ ID NO:10); and (iii) heavy chain CDR3 comprising GYLDPMDY (SEQ ID NO: 5); and a light chain variable region (VL) comprising (i) light chain CDR 1 comprising ASQGINNYLN (amino acids 25-34 of SEQ ID NO:16); light chain CDR2 comprising YTSGLHA (SEQ ID NO: 13); and (iii) light chain CDR3 comprising QQYSILPWT (SEQ ID NO: 14).

2. The recombinant host cell of claim 1 wherein the antibody exhibits one or more of the following properties:

a) a binding affinity (K D ) for human IL1RAP of 200 pM or greater;

b) cross-reactivity with IL1RAP from Macaca fascicularis;

c) an inhibitory action on IL1 signalling;

d) capability of inducing ADCC in one or more cancer cell lines;

e) capability of inducing ADCC of cells expressing IL1RAP; and

f) capability of internalisation upon binding to one or more cancer cell lines.

3. The recombinant host cell of claim 1 , wherein the antibody is a Fv fragment or a Fab fragment.

4. The recombinant host cell of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising or consisting of the amino acids of SEQ ID NO: 9.

5. The recombinant host cell of claim 1 , wherein the antibody or antigen-binding fragment comprises a light chain variable region comprising or consisting of the amino acids of SEQ ID NO: 16.

6. The recombinant host cell of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising or consisting of the amino acids of SEQ ID NO: 9 and a light chain variable region comprising or consisting of the amino acids of SEQ ID NO: 16.

7. The recombinant host cell of claim 1 comprising:

a) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 15;

b) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 15;

c) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 15;

d) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 15;

e) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 16;

f) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 16;

g) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 16;

h) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 16;

i) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 8 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 17;

j) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 9 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 17;

k) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 10 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 17; or

l) a heavy chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 11 and a light chain variable region which comprises or consists of the amino acid sequence of SEQ ID NO: 17.

8. The recombinant host cell of claim 1 comprising a heavy and light chain constant region, or part thereof.

9. The recombinant host cell of claim 1 comprising Fc region.

10. The recombinant host cell of claim 1 further comprising a cytotoxic moiety.

11. The recombinant host cell of claim 1 further comprising a detectable moiety.

12. The recombinant host cell of claim 1 , wherein the antibody is humanized.

13. The recombinant host cell of claim 1 , wherein the antibody or antigen-binding fragment is capable of inducing ADCC of cells expressing IL1RAP.

14. The recombinant host cell of claim 1 , wherein the host cell is a bacterial cell.

15. The recombinant host cell of claim 1 , wherein the host cell is a mammalian cell.

16. The recombinant host cell of claim 1 , wherein the host cell is a human cell.

17. The recombinant host cell of claim 1 , wherein the vector is an expression vector.

Assignments (7)