IL-17F and IL-17A-specific capture agents, compositions, and methods of using and making

Patent metadata

Field	Value
Publication number	US-12546785-B2
Application number	US-202318335819-A
Country	US
Kind code	B2
Filing date	Jun 15, 2023
Priority date	Jun 15, 2017
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

The present application provides stable peptide-based IL-17F and IL-17A capture agents and methods of use as detection agents. The application further provides methods of manufacturing IL-17F capture agents.

First claim

We claim:

1 . A capture agent for a heterodimer of IL-17A and IL-17F, wherein the capture agent comprises a first ligand having specific binding affinity for a first epitope on IL-17A, a second ligand having specific binding affinity for a second epitope on IL-17F, and a linker covalently connecting the first ligand to the second ligand,
wherein the first ligand is cyclic and comprises a first peptide having an amino acid sequence selected from the group consisting of rhfrl (SEQ ID NO:44), nrfff (SEQ ID NO:45), and rkhyh (SEQ ID NO:46), and wherein the second ligand is cyclic and comprises a second peptide having an amino acid sequence selected from the group consisting of KYGEV (SEQ ID NO:11), LYGEV (SEQ ID NO: 12), VHKSG (SEQ ID NO:13), VHLSG (SEQ ID NO:14), QKHGP (SEQ ID NO:15), TKHGP (SEQ ID NO:16), QLHGP (SEQ ID NO:17), TLHGP (SEQ ID NO:18), YDLQR (SEQ ID NO: 19), YDLTR (SEQ ID NO:20), YDKQR (SEQ ID NO:21), YDKTR (SEQ ID NO:22), KKGWP (SEQ ID NO:23), KLGWP (SEQ ID NO:24), LKFWP (SEQ ID NO:25), LLGWP (SEQ ID NO: 26), RSYNL (SEQ ID NO:27), RSYNK (SEQ ID NO:28), Kygev (SEQ ID NO:51), VHkSG (SEQ ID NO:52), QkHGP (SEQ ID NO:53), TkHGP (SEQ ID NO:54), YDLQr (SEQ ID NO: 55), YDLTr (SEQ ID NO:56), YDkQr (SEQ ID NO:57), YDkTr (SEQ ID NO:58), kkGWP (SEQ ID NO:59), kLGQP (SEQ ID NO:60), LkGWP (SEQ ID NO:61), rSYNL (SEQ ID NO: 62), rSYNk (SEQ ID NO:63), kygev (SEQ ID NO:64), vhksg (SEQ ID NO:65), qkhgp (SEQ ID NO:66), tkhgp (SEQ ID NO:67), ydlqr (SEQ ID NO:68), ydltr (SEQ ID NO:69), ydkqr (SEQ ID NO:70), ydktr (SEQ ID NO:71), kkgwp (SEQ ID NO:72), klgwp (SEQ ID NO:73), lkgwp (SEQ ID NO:74), rsynl (SEQ ID NO:75), and rsynk (SEQ ID NO:76).

2 . The capture agent of claim 1 , wherein the first ligand has the structure:

wherein X represents the rest of the capture agent.

3 . The capture agent of claim 1 , wherein the capture agent specifically binds IL-17A/F heterodimer and/or is selective for IL-17A/F heterodimer over IL-17F and over IL-17A.

4 . The capture agent of claim 3 , wherein the second epitope comprises the amino acid sequence NENQRVS (SEQ ID NO:3).

5 . The capture agent of claim 4 , wherein the second ligand comprises an amino acid sequence selected from the group consisting of:
a. YDkQr (SEQ ID NO:57); b. YDkTr (SEQ ID NO:58); c. kkGWP (SEQ ID NO:59); d. rSYNk (SEQ ID NO:63); e. kygev (SEQ ID NO:64); f. vhksg (SEQ ID NO:65); g. qkhgp (SEQ ID NO:66); h. tkhgp (SEQ ID NO:67); i. ydlqr (SEQ ID NO:68); j. ydltr (SEQ ID NO:69); k. ydkqr (SEQ ID NO:70); l. ydktr (SEQ ID NO:71); m. kkgwp (SEQ ID NO:72); n. klgwp (SEQ ID NO:73); o. lkgwp (SEQ ID NO:74); p. rsynl (SEQ ID NO:75); and q. rsynk (SEQ ID NO:76).

6 . The capture agent of claim 4 , wherein the second epitope comprises the amino acid sequence GIINENQRVS (SEQ ID NO:4).

7 . The capture agent of claim 6 , wherein
(a) the first ligand comprises the sequence rhfrl (SEQ ID NO:44) and the second ligand comprises the sequence QKHGP (SEQ ID NO:15), (b) the first ligand comprises the sequence rhfrl (SEQ ID NO:44) and the second ligand comprises the sequence RSYNK (SEQ ID NO:28), (c) the first ligand comprises the sequence rhfrl (SEQ ID NO:44) and the second ligand comprises the sequence rSYNK (SEQ ID NO:63), or (d) the first ligand comprises the sequence rhfrl (SEQ ID NO:44) and the second ligand comprises the sequence rsynk (SEQ ID NO:76).

8 . The capture agent of claim 1 , wherein the first ligand comprises a 1,4-substituted-1,2,3-triazole residue (Tz4) or a 1,5-substituted-1,2,3-triazole residue (Tz5).

9 . The capture agent of claim 8 , wherein the second ligand comprises a 1,4-substituted-1,2,3-triazole residue (Tz4) or a 1,5-substituted-1,2,3-triazole residue (Tz5).

10 . The capture agent of claim 1 , wherein the capture agent is labeled with a detectable moiety.

11 . The capture agent of claim 10 , wherein the detectable moiety is selected from the group consisting of biotin, copper-DOTA, biotin-PEG3, aminooxyacetate, 19 FB, 18 FB, and FITC-PEG 3 .

12 . The capture agent of claim 10 , wherein the detectable moiety is selected from the group consisting of 64 Cu DOTA, 68 Ga DOTA, 68 Ga NOTA, 18 F, Al 18 F NOTA, 64 Cu, 68 Ga, 89 Zr, 124 I, 86 Y, 94m Tc, 110m In, 11 C, and 76 Br.

13 . The capture agent of claim 1 , wherein the linker is divalent and the length of the linker corresponds to the distance between the first epitope and the second epitope.

14 . The capture agent of claim 13 , wherein the length of the linker is from about 4.4 Å to about 26.4 Å, from about 8.8 Å to about 26.4 Å, or from about 7 Å to about 15 Å.

15 . The capture agent of claim 14 , wherein the length of the linker is about 15 Å.

16 . The capture agent of claim 1 , wherein the linker comprises (i) one or more repeat units of ethylene glycol or (ii) a peptide.

17 . The capture agent of claim 16 , wherein the linker is selected from the group consisting of PEG 1 , PEG 2 , PEG 3 , PEG 4 , PEG 5 , and glycine.

18 . A method for detecting IL-17A, IL-17F, or both IL-17A and IL-17F in a biological sample, the method comprising the steps of:
contacting the biological sample with one or more capture agents of claim 1 linked to a detectable moiety; binding the one or more capture agents to IL-17A, IL-17F, or both IL-17A and IL-17F; and detecting the detectable moiety linked to the one or more capture agents.

19 . The method of claim 18 , wherein the binding step comprises binding at least one of the one or more capture agents to IL-17A.

20 . The method of claim 19 , wherein IL-17A is detected.

21 . The method of claim 18 , wherein the binding step comprises binding at least one of the one or more capture agents to IL-17F.

22 . The method of claim 21 , wherein IL-17F is detected.

23 . The method of claim 18 , wherein the binding step comprises binding at least one of the one or more capture agents to IL-17A/F heterodimer.

24 . The method of claim 23 , wherein IL-17A/F heterodimer is detected.

25 . The method of claim 18 , wherein the IL-17A is in the form of a heterodimer with IL-17F or the IL-17F is in the form of a heterodimer with IL-17A.

Assignees

• Regeneron Pharma
• California Inst Of Techn

Inventors

• Agnew Heather
• Lai Bert Tsunyin
• Pitram Suresh Mark
• Farrow Blake
• Heath James R
• Bunck David
• Liang Jingxin
• Nag Arundhati
• Das Samir

Classifications

• C07K7/06

  having 5 to 11 amino acids · CPC title

• C07K14/54

  Interleukins [IL] · CPC title

• G01N33/6869 Primary

  Interleukin · CPC title