# US 4,399,124 A · Peptides having immunostimulating properties and pharmaceutical compositions containing them > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,399,124 A - Document ID: US4399124A - Status: Granted - Kind: A - Application number: 06/268,991 - Filed: 1981-06-01 - Granted: 1983-08-16 - Earliest claimed: 1979-10-01 - Assignees: Institut Pasteur - Inventors: Robert M. Fauve - Web page: https://patentgrep.com/patent/US4399124A ## CPC - C07K 7/18: Kallidins; Bradykinins; Related peptides - A61K 38/00: 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) - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - Y10S 930/14: Lymphokine; related peptides - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE - Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS ## Abstract Peptides having immunostimulating properties making them applicable to pharmaceutical compositions for the treatment or prevention of infections. They contain the sequence prolyl glycyl. ## Claims ### Claim 1 A method of stimulating macrophages in vivo in a host which comprises administering to said host an immunostimulant effective amount of a biologically active composition which comprises a biologically acceptable carrier and a peptide which is effective for stimulating macrophages in vivo having a prolyl.fwdarw.prolyl.fwdarw.glycyl sequence and a maximum of seven aminoacyl residues. ### Claim 2 (depends on 1) The method of claim 1 wherein said peptide has a prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl sequence. ### Claim 3 (depends on 2) The method of claim 2 wherein the phenylalanyl residue carries the C-terminal end of said peptide. ### Claim 4 (depends on 1) The method of claim 1 wherein the amino group of the first prolyl residue of said prolyl.fwdarw.prolyl.fwdarw.glycyl sequence is linked through a peptide linkage with another aminoacyl residue. ### Claim 5 (depends on 4) The method of claim 4 wherein said aminoacyl residue is selected from the group consisting of arginyl, lysyl or histidyl. ### Claim 6 (depends on 1, 2, 3, 4, 5) The method of any one of claims 1, 2, 3, 4 or 5 in which all the aminoacyl residues of said peptide, with the exception of glycine, are levorotatory. ### Claim 7 (depends on 1) The method of claim 1 wherein the peptide is a pentapeptide selected from the group consisting of: Arginyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanine; lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanine; and histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanine. ### Claim 8 (depends on 7) The method of claim 7 wherein from 1 to 2 additional aminoacyl residues are linked to the N-terminal aminoacyl residue of said peptides, said additional aminoacyl residue being selected from the group consisting of lysyl and methionyl. ### Claim 9 (depends on 1) The method of claim 1 wherein the carboxylic acid group of the glycyl residue is linked through a peptide linkage with another aminoacyl residue. ### Claim 10 An immunostimulant peptide which peptide has not more than seven amino acid residues, which peptide has the following amino acid sequence: X.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw.Y, wherein X is an amino acid residue selected from the group consisting of lysyl and histidyl, and Y is at least one amino acid residue selected from the amino acids consisting of proline and serine, but both residues not being the same, or hydroxyl. ### Claim 11 (depends on 10) The immunostimulant of claim 10 wherein the peptide is selected from the group consisting of: Lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .serine; lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .seryl.fwdarw.proline; histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.serine; and histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.seryl.fwdarw.proline. ### Claim 12 (depends on 10) The peptide of claim 10 which is a pentapeptide having the following amino acid sequence: Lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl. ### Claim 13 (depends on 10) The peptide of claim 10 which is a pentapeptide having the following amino acid sequence: Histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl. ### Claim 14 (depends on 10, 11, 12, 13) The peptide of any of claims 10, 11, 12 or 13 wherein, with the exception of glycine, all the aminoacyl residues are levorotatory. ### Claim 15 A composition for stimulating an immune response in a host which comprises a biologically acceptable carrier and an immunostimulant effective amount of a pharmacologically active peptide, said peptide having a maximum of seven amino acid residues, which peptide has the following acid sequence: x.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw.Y, wherein X is an amino acid residue selected from the group consisting of lysyl and histidyl, and Y is at least one amino acid residue selected from the amino acids consisting of proline and serine but both residues not being the same, or hydroxyl. ### Claim 16 (depends on 15) The composition of claim 15 wherein the peptide is selected from the group consisting of: Lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .serine; lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .seryl.fwdarw.proline; histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.serine; and histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.seryl.fwdarw.proline. ### Claim 17 (depends on 15) The composition of claim 15 wherein the peptide is a pentapeptide having the formula: Lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl. ### Claim 18 (depends on 15) The composition of claim 15 wherein the peptide is a pentapeptide having the formula: Histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl. ### Claim 19 (depends on 17) The composition of claim 17 wherein, with the exception of glycine, all the aminoacyl residues are levorotatory. ### Claim 20 A method for stimulating an immunal response in a host which comprises a administering biologically acceptable carrier and an immunostimulant effective amount of a pharmacologically active peptide, said peptide having a maximum of seven amino acid residues, which peptide has the following acid sequence: X.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw.Y, wherein X is an amino acid residue selected from the group consisting of lysyl and histidyl, and Y is at least one amino acid residue selected from the amino acids consisting of proline and serine, but both residues not being the same, or hydroxyl. ### Claim 21 A method of stimulating macrophages in vivo in a host which comprises administering to said host an immunostimulant effective amount of a biologically active composition which comprises a biologically acceptable carrier and a hexa or hepta peptide selected from the group consisting of: lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .serine; lysyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwdarw .seryl.fwdarw.proline; Histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.serine; Histidyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwd arw.seryl.fwdarw.proline; arginyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwda rw.serine; and arginyl.fwdarw.prolyl.fwdarw.prolyl.fwdarw.glycyl.fwdarw.phenylalanyl.fwda rw.seryl.fwdarw.proline. ### Claim 22 (depends on 20) The method of claim 20 wherein all of the aminoacyl residues forming the peptide, with the exception of glycine, are levoratory. ### Claim 23 (depends on 20) The method of claim 20 wherein the administration is parenterally in an amount which ranges from about 10.sup.-5 to about 10.sup.-3 mole. ### Claim 24 (depends on 23) The method of claim 23 wherein the dosage administered ranges from 0.25.multidot.10.sup.-4 to 1.10.sup.-4 mole. ### Claim 25 (depends on 24) The method of claim 24 wherein the administration is parenterally in an amount of from about 10.sup.-5 to about 10.sup.-3 mole. ### Claim 26 (depends on 25) The method of claim 25 wherein the dosage administered ranges from about 0.25.multidot.10.sup.-4 to about 1.10.sup.-4 mole.