Il-17a binding peptides and medical uses thereof

Patent metadata

Field	Value
Publication number	US-2022112244-A1
Application number	US-202117555154-A
Country	US
Kind code	A1
Filing date	Dec 17, 2021
Priority date	Jul 27, 2018
Publication date	Apr 14, 2022
Grant date	—

Abstract

The invention relates to IL-17A binding peptides, inhibitors of the interaction of IL-17A with the receptor IL-17RA, and to bioconjugates, dimers, pharmaceutical compositions and medical use thereof.

First claim

1 .- 17 . (canceled)

18 . A peptide that specifically inhibits IL-17 Å binding to ILRA, comprising the amino acid sequence of Formula (I), wherein Formula (I) comprises:

(SEQ ID NO: 258)

X 1 -X 2 -X 3 -X 4  X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 1 I-X 12 -X 13 -X 14 -X 15 ,

wherein, independently from each other:
X 1 is I, V, D, K, W, A, G, L or P;
X 2 is H, M, K, N, R, E, Q, W or Y;
X 3 is V, F, A, G, L, P, I, Y or W;
X 4 is T, Q, H, S, N or Y;
X 5 is I, F, A, G, L, P, V or Y;
X 6 is P, G, A, L, V, I or N;
X 7 is A, Q, G, L, P, V, I, N or E;
X 8 is D, E, N, Q or Y;
X 9 is L, V, F, W, A, G, P, I or H;
X 10 is W, Y, F or Q or it is absent;
X 11 is D, E or N or it is absent;
X 12 is W, F, V, H or Y or it is absent;
X 13 is I, V, F, E, K, A, G, L, P or Y or its absent;
X 14 is N, R, E, F, Q or D or it is absent; and
X 15 is K, R, E, F, V, W, H or D or it is absent;

with the proviso that said sequence is not IHVTIPADLWDWINK (SEQ ID NO: 1) or HVTIPADLWDWIN (SEQ ID NO: 259), IHVTIPADLWDWI (SEQ ID NO: 260) or IHVTIPADLWDW (SEQ ID NO: 261).

19 . The peptide of claim 18 , wherein the peptide consists of a 15 amino acid sequence.

20 . The peptide of claim 18 , wherein X 1 is V or I.

21 . The peptide of claim 18 , comprising an amino acid sequence selected from SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 169, SEQ ID NO: 181, SEQ ID NO: 192, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 197, SEQ ID NO: 214, SEQ ID NO: 219, SEQ ID NO: 221, or SEQ ID NO: 223.

22 . The peptide of claim 18 , comprising an amino acid sequence selected from

(SEQ ID NO: 262)

KHVTIPADLWDWINK

or

(SEQ ID NO: 263)

VHVTIPNELWEWVRR.

23 . The peptide of claim 18 , further comprising, at the C- and/or N-terminal of the peptide, a sequence comprising the amino acid sequence of formula (III):

(III)

(SEQ ID NO: 264)

Y 1 -Y 2 -Y 3 -Y 4 -Y 5 -Y 6 -Y 7 -Y 8 -Y 9 -Y 10 -Y 11 -Y 12 -Y 13 -Y 14 -Y 15 -Y 16 ,

wherein:
Y 1 is A, T, V, K, R, I, L, X, or G;
Y 2 is R, W, P, E, Q, or A;
Y 3 is K, W, G, T, I, R, or P;
Y 4 is K, T, E, W, A, R, D, G, X, or F;
Y 5 is A, E, T, G, W, I, R, P, or V;
Y 6 is A, W, E, R, G, P, or absent;
Y 7 is K, S, W, T, F, R, V, G, or absent;
Y 8 is A, Q, W, R, G, or absent;
Y 9 is N, G or absent;
Y 10 is R or absent;
Y 11 is R or absent;
Y 12 is M or absent;
Y 13 is K or absent.
Y 14 is W or absent;
Y 15 is K or absent; and
Y 16 is K or absent.

24 . The peptide of claim 23 , wherein formula (III) comprises SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

25 . The peptide of claim 23 , wherein, at the N-terminal of the peptide, formula (III) comprises SEQ ID NO: 44, SEQ ID NO: 47, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 52, or SEQ ID NO: 53.

26 . The peptide of claim 23 , wherein, at the C-terminal of the peptide, formula (III) comprises SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

27 . The peptide of claim 23 , wherein, at the C-terminal of the peptide, formula (III) comprises RRRRRR (SEQ ID NO: 265).

28 . The peptide of claim 23 , wherein the peptide comprises the sequence, in order, selected from:

(a)

(SEQ ID NO: 53)

VPGDG

(SEQ ID NO: 12)

--IHVTIPADLWDWINE,

(b)

(SEQ ID NO: 12)

IHVTIPADLWDWINE

(SEQ ID NO: 53)

--VPGDG,

or

(c)

(SEQ ID NO: 53)

VPGDG

(SEQ ID NO: 12)

--IHVTIPADLWDWINE

(SEQ ID NO: 53)

--VPGDG.

29 . The peptide of claim 23 , wherein the peptide comprises the sequence, in order, selected from:

(a)

(SEQ ID NO: 53)

VPGDG

(SEQ ID NO: 266)

--IHVTIPADLWEWIEK,

(b)

(SEQ ID NO: 53)

VPGDG

Assignees

• Dompe Farm Spa

Inventors

• Allegretti Marcello
• Aramini Andrea
• Beccari Andrea
• Gemei Marica
• Mantelli Flavio

Classifications

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K7/08 Primary

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K38/04

  Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof ({enzyme inhibitors A61K38/005;} gastrins {A61K38/2207}, somatostatins A61K38/31, melanotropins A61K38/34 {; protease inhibitors A61K38/55}) · CPC title

• A61P19/02

  for joint disorders, e.g. arthritis, arthrosis · CPC title