Methods of treating asthma with polypeptides targeting IL-13 and TSLP

Patent metadata

Field	Value
Publication number	US-11840566-B2
Application number	US-202117530800-A
Country	US
Kind code	B2
Filing date	Nov 19, 2021
Priority date	Dec 9, 2019
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

Abstract

The present technology aims at providing a novel type of drug for treating a subject suffering from an inflammatory disease. Specifically, the present technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that at least two ISVDs bind to IL-13 and at least two ISVDs binds to TSLP. The present technology also provides nucleic acids, vectors and compositions.

First claim

The invention claimed is:

1. A method of treating asthma, wherein said method comprises administering, to a subject in need thereof, an effective amount of a polypeptide that comprises at least one immunoglobulin single variable domain (ISVD) that specifically binds to IL13 or TSLP, wherein said ISVD comprises three complementarity determining regions (CDR1 to CDR3, respectively); and wherein the at least one ISVD comprises:
a) a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7;
a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12; and
a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17,

b) a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8;
a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13; and
a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18,

c) a CDR1 that comprises the amino acid sequence of SEQ ID NO: 9;
a CDR2 that comprises the amino acid sequence of SEQ ID NO: 14; and
a CDR3 that comprises the amino acid sequence of SEQ ID NO: 19, or

d) a CDR1 that comprises the amino acid sequence of SEQ ID NO: 11;
a CDR2 that comprises the amino acid sequence of SEQ ID NO: 16; and
a CDR3 that comprises the amino acid sequence of SEQ ID NO: 21.

2. The method according to claim 1 , wherein said at least one IS VD that specifically binds to IL-13 or TSLP comprises:
a) the amino acid sequence of SEQ ID NO: 2,
b) the amino acid sequence of SEQ ID NO: 3,
c) the amino acid sequence of SEQ ID NO: 4, or
d) the amino acid sequence of SEQ ID NO: 6.

3. The method according to claim 1 , wherein the polypeptide comprises at least two ISVDs, wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), and wherein:
a) a first and a second ISVD specifically binds to IL-13 and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17,

b) a first and a second ISVD specifically binds to IL-13 and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18,

c) a first ISVD specifically binds to IL-13 and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17, and
a second ISVD specifically binds to IL-13 and comprises
iv. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8;
v. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13; and
vi. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18,

d) a first ISVD specifically binds to IL-13 and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18, and
a second ISVD specifically binds to IL-13 and comprises
iv. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7;
v. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12; and
vi. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17,

e) a first ISVD specifically binds to TSLP and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 11;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 16; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 21, and
a second ISVD specifically binds to TSLP and comprises
iv. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 9;
v. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 14; and
vi. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 19, or

f) a first ISVD specifically binds to TSLP and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 9;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 14; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 19, and
a second ISVD specifically binds to TSLP and comprises
iv. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 11;
v. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 16; and
vi. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 21,

wherein the order of the ISVDs indicates their relative position to each other considered from the N-terminus to the C-terminus of said polypeptide.

4. The method according to claim 3 , wherein the polypeptide comprises:
a) the amino acid sequence of SEQ ID NO: 148,
b) the amino acid sequence of SEQ ID NO: 149,
c) the amino acid sequence of SEQ ID NO: 150,
d) the amino acid sequence of SEQ ID NO: 151,
e) the amino acid sequence of SEQ ID NO: 152,
f) the amino acid sequence of SEQ ID NO: 153,
g) the amino acid sequence of SEQ ID NO: 154,
h) the amino acid sequence of SEQ ID NO: 155,
i) the amino acid sequence of SEQ ID NO: 156,
j) the amino acid sequence of SEQ ID NO: 157,
k) the amino acid sequence of SEQ ID NO: 158, or
l) the amino acid sequence of SEQ ID NO: 159.

5. The method of claim 3 , wherein the at least two ISVDs are linked via one or more peptidic linkers.

6. The method according to claim 1 , wherein the polypeptide comprises at least four ISVDs, wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), and wherein:
a) a first ISVD specifically binds to IL-13 and comprises
i. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7;
ii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12; and
iii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17,

b) a second ISVD specifically binds to IL-13 and comprises
iv. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8;
v. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13; and
vi. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18,

c) a third ISVD specifically binds to TSLP and comprises
vii. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 9;
viii. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 14; and
ix. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 19, and

d) a fourth ISVD specifically binds to TSLP and comprises
x. a CDR1 that comprises the amino acid sequence of SEQ ID NO: 11;
xi. a CDR2 that comprises the amino acid sequence of SEQ ID NO: 16; and
xii. a CDR3 that comprises the amino acid sequence of SEQ ID NO: 21,

wherein the order of the ISVDs indicates their relative position to each other considered from the N-terminus to the C-terminus of said polypeptide.

7. The method according to claim 6 , wherein:
a) said first ISVD comprises the amino acid sequence of SEQ ID NO: 2;
b) said second ISVD comprises the amino acid sequence of SEQ ID NO: 3;
c) said third ISVD comprises the amino acid sequence of SEQ ID NO: 4; and
d) said fourth ISVD comprises the amino acid sequence of SEQ ID NO: 6.

8. The method according to claim 6 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 1.

9. The method according to claim 8 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 1.

10. The method of claim 6 , wherein the at least four ISVDs are linked via one or more peptidic linkers.

11. The method according to claim 1 , wherein said polypeptide further comprises one or more other groups, residues, moieties or binding units, in which said one or more other groups, r

Assignees

• Ablynx Nv
• Sanofi Sa

Inventors

• Rommelaere Heidi
• Brigé Ann
• Cornelis Sigrid
• Dombrecht Bruno
• Lorent Eric
• Rieger Melanie
• Soos Timothy
• Park John
• Weigle Bernd
• Erb Klaus

Classifications

• C07K16/244 Primary

  Interleukins [IL] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/18

  against material from animals or humans · CPC title