Hydrochloride salts of C5a receptor agonist peptides

Patent metadata

Field	Value
Publication number	US-12552848-B2
Application number	US-201816621797-A
Country	US
Kind code	B2
Filing date	Jun 12, 2018
Priority date	Jun 12, 2017
Publication date	Feb 17, 2026
Grant date	Feb 17, 2026

Abstract

Hydrochloride salt forms of synthetic C-terminal peptide analogs of C5a, which are response selective agonists of C5aR-bearing antigen presenting cells. Methods of inducing an immune response in a subject by administering such peptide analogs alone or in combination with other active agents are also disclosed.

First claim

The invention claimed is:

1 . A hydrochloride (HCl) salt form of a C-terminal peptide analog of C5a, wherein the analog is a peptide comprising the formula:

(SEQ ID NO: 5)

A1-Ser-The-Lys-A2-A3-A4-A5-A6-A7

wherein:
A1 is Tyr, Trp, or N-acetyl derivatives of Tyr or Trp;
A2 is Asp, Gly, Pro or N-methyl derivatives of Asp or Gly;
A3 is Ala, Cys, Leu, Met or N-methyl derivatives of Ala, Cys, Leu or Met;
A4 is Gln, Leu, Pro or N-methyl derivatives of Gln or Leu;
A5 is Pro, Leu, α-methyl Leu or N-methyl Leu;
A6 is D-Ala, Gly, D-Pro, aminoisobutyric acid (Aib) or N-methyl derivatives of D-Ala or Gly; and
A7 is Arg or N-methyl Arg.

2 . The HCl salt form of said C-terminal peptide analog of C5a according to claim 1 , wherein said analog is selected from the group consisting of:

(SEQ ID NO: 6)

Tyr-Ser-Phe-Lys-Pro-Met-Pro-Leu-(D-Ala)-Arg;

(SEQ ID NO: 7)

Tyr-Ser-Phe-Lys-Asp-Ala-Pro-Leu-(D-Ala)-Arg;

(SEQ ID NO: 8)

Tyr-Ser-Phe-Lys-Asp-Met-Pro-Leu-(D-Ala)-Arg;

(SEQ ID NO: 9)

Tyr-Ser-Phe-Lys-Asp-Met-Pro-Leu-Gly-Arg;

(SEQ ID NO: 10)

Tyr-Ser-Phe-Lys-Asp-Ala-Pro-Leu-Gly-Arg ;

(SEQ ID NO: 11)

Tyr-Ser-Phe-Lys-Asp-Cys-Pro-Leu-Gly-Arg;

(SEQ ID NO: 12)

Tyr-Ser-Phe-Lys-Asp-Met-Pro-Leu-(D-Pro)-Arg;

(SEQ ID NO: 13)

Tyr-Ser-Phe-Lys-Asp-Met-Gln-Leu-(D-Ala)-Arg;

(SEQ ID NO: 14)

Tyr-Ser-Phe-Lys-Asp-Met-Gln-Leu-Gly-Arg;

(SEQ ID NO: 15)

Tyr-Ser-Phe-Lys-Asp-Met-Gln-Pro-Gly-Arg;

(SEQ ID NO: 16)

Tyr-Ser-Phe-Lys-Asp-Met-Pro-Leu-Aib-Arg;

(SEQ ID NO: 17)

Tyr-Ser-Phe-Lys-Gly-Met-Pro-Leu-Gly-Arg;

and

(SEQ ID NO: 18)

Tyr-Ser-Phe-Lys-Gly-Leu-Leu-Leu-Gly-Arg.

3 . The HCl salt form of said C-terminal peptide peptide analog of C5a according to claim 1 , wherein said analog is designated as EP67 having the formula: Tyr-Ser-Phe-Lys-Asp-Met-Pro-(MethylLeu)-D-Ala-Arg (SEQ ID NO:2).

4 . The HCl salt form of said C-terminal peptide analog of C5a according to claim 1 , wherein said analog is a conformationally-stable peptide having the formula:

(SEQ ID NO: 1)

Tyr-Ser-Phe-Lys-Asp-Met-Xaa-(Xaa2)-(D-Ala)-Arg,

wherein Xaa is Pro, and Xaa2 is leucine or N-methyl leucine.

5 . A composition comprising the HCl salt form of said C-terminal peptide analog of C5a according to claim 1 , dispersed in a pharmaceutically acceptable carrier.

6 . The composition of claim 5 , further comprising adjuvants, other active agents, preservatives, buffering agents, salts, and mixtures thereof.

7 . The composition of claim 6 , wherein said active agent is selected from the group consisting of killed virus, modified live virus, viral or bacterial proteins, viral or bacterial DNA, toxoids, protein subunits, peptide epitope, and tumor antigens.

8 . The composition of claim 7 , wherein said active agent is conjugated to said peptide analog.

9 . The composition of claim 7 , said composition comprising a plurality of different active agents, each of said active agents conjugated to a respective peptide analog in said composition.

10 . A kit comprising:
an HCl salt form of a C-terminal peptide analog of C5a according to claim 1 ; and instructions for administering said analog to a subject in need thereof.

11 . The kit of claim 10 , wherein said peptide analog is provided in unit dosage form.

12 . The kit of claim 10 , wherein said peptide analog is provided in a first container, said kit further comprising a carrier in a second container; and instructions for preparing said peptide analog for administration to said subject.

13 . A compound for enhancing an immune response to an immunogenic agent, said compound comprising an HCl salt form of a C-terminal peptide analog of C5a according to claim 1 covalently linked to an immunogenic agent.

14 . The compound of claim 13 , said immunogenic agent being selected from the group consisting of killed virus, modified live virus, viral or bacterial proteins, viral or bacterial DNA, toxoids, protein subunits, peptide epitopes, and tumor antigens.

15 . A therapeu

Assignees

• Univ Nebraska
• San Diego State Univ Research Foundation

Inventors

• Sanderson Sam D
• Morgan Edward Leroy

Classifications

• A61K38/1725

  Complement proteins, e.g. anaphylatoxin, C3a or C5a · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K14/472 Primary

  Complement proteins, e.g. anaphylatoxin, C3a, C5a · CPC title