IL-17A binding peptides and medical uses thereof

Patent metadata

Field	Value
Publication number	US-11236129-B2
Application number	US-202117158728-A
Country	US
Kind code	B2
Filing date	Jan 26, 2021
Priority date	Jul 27, 2018
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

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

The invention claimed is:

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

(I)

(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 11 -X 12 -X 13 -X 14 -X 15

wherein in Formula (I):
(a) X 1 is I, V or L;
X 2 is H, M, R, K or E;
X 3 is V, F or I;
X 4 is T, Q, S, Y or N;
X 5 is I, F or V;
X 6 is P;
X 7 is A, Q, or L;
X 8 is D, E, or Q;
X 9 is L, W, F, V or I;
X 10 is W, Y or F;
X 11 is D, E or N;
X 12 is W or F;
X 13 is I, V, F or L;
X 14 is N, R, Q or E;
X 15 is K, R, H or E;

with the proviso that said sequence is not IHVTIPADLWDWINK (SEQ ID NO:1);
or
(b) X 1 is I or V,
X 2 is H, M or R,
X 3 is V or F;
X 4 is T or Q;
X 5 is I, F or V;
X 6 is P or G;
X 7 is A or Q;
X 8 is D or E;
X 9 is L;
X 10 is W or Y;
X 11 is D or E;
X 12 is W;
X 13 is I or V;
X 14 is N, R or E;
X 15 is K, R or E;

with the proviso that said sequence is not IHVTIPADLWDWINK (SEQ ID NO: 1)
or
(c) X 1 is I or V;
X 2 is H or M,
X 3 is V;
X 4 is T;
X 5 is I;
X 6 is P;
X 7 is A;
X 8 is D;
X 9 is L, W, F, V or I;
X 10 is W or Y;
X 11 is D or E;
X 12 is W;
X 13 is I or V;
X 14 is N, R or E;
X 15 is K, R or E;

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

2. The peptide of claim 1 , wherein in formula (I) X 1 is V.

3. The peptide of claim 1 , having an amino acid sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 42, SEQ ID SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 160, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 171, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 187, SEQ ID NO: 193, SEQ ID NO: 198, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 210, SEQ ID NO: 216, SEQ ID NO: 218, SEQ ID NO: 220, SEQ ID NO: 222, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 246, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 254, and SEQ ID NO: 256.

4. The peptide of claim 1 , further comprising sequence (A) m at the C- and/or N-terminal of the peptide, wherein A is an amino acid selected from the group consisting of R, K, G, E, Q and A, and m is an integer between 1 and 10.

5. A peptide as claimed in claim 4 , having sequence of SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 43.

6. The peptide of claim 1 , wherein a protective cap group is bound at the C- and/or N-terminal, wherein the protective cap group is selected from the group consisting of amides, aldehydes, esters, p-Nitroanilide, 7-Amino-4-methylcoumarin and the protective group cap bound to a N-terminal being selected from acetyl, formyl, pyroglutamyl, fatty acids, urea, carbamate sulfonamide, and alkylamine.

7. A dimer formed by two peptides, wherein each peptide is a peptide of claim 1 .

8. The dimer of claim 7 , wherein the peptides are linked by a polyethylene spacer.

9. A bioconjugate comprising the peptide of claim 1 and a biomolecule, wherein the biomolecule is bound to the N- and/or C-terminal of the peptide.

10. The bioconjugate of claim 9 , wherein the biomolecule is selected from the group consisting of capric acid, capronic acid, ascorbic acid, NAG-NAM, NAG, NAM, hyaluronic acid, alginic acid, chitin, (GaINAc)2, Ga1-alpha1,3-GaINAc and trigalacturonic acid.

11. A pharmaceutical composition comprising the peptide of claim 1 and at least one pharmaceutically acceptable excipient.

12. A method of treating a subject having an inflammatory and autoimmune disease comprising administering to the subject an effective amount of the peptide of claim 1 .

13. The method of claim 12 , wherein the inflammatory and autoimmune disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, Crohn's disease, systemic lupus erythematosus, asthma, Behçet's disease, hyper IgE syndrome, ankylosing spondylitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, keratoconjunctivitis sicca, vernal keratoconjunctivitis, stromal herpetic keratitis, corneal allograft rejection, corneal infections, herpes virus or Pseudomonas aeruginosa keratitis and dry eye disease, preferably psoriasis and dry eye disease.

14. A method of producing the peptide of claim 1 , comprising
(a) synthesizing the peptide; and
(b) purifying the peptide.

15. The peptide of claim 1 , comprising an amino acid sequence of SEQ ID NO: 2.

16. The peptide of claim 1 , having a 15 amino acid sequence.

Assignees

• Dompe Farm Spa

Inventors

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

Classifications

• C07K7/08 Primary

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

• A61P19/02

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

• A61P11/06

  Antiasthmatics · CPC title