# US 9,518,088 B2 · Peptide-phospholipid conjugates > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,518,088 B2 - Document ID: US9518088B2 - Status: Granted - Kind: B2 - Application number: 13/983,435 - Filed: 2012-01-19 - Published: 2013-12-26 - Granted: 2016-12-13 - Earliest claimed: 2011-02-07 - Assignees: Indiana University Research and Technology Corporation - Applicants: Michael S. Van Nieuwenhze; William W. Turner; Joseph L. Witztum; Karsten Hartvigsen - Inventors: Michael S. Van Nieuwenhze; William W. Turner; Joseph L. Witztum; Karsten Hartvigsen - Web page: https://patentgrep.com/patent/US9518088B2 ## CPC - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - A61K 47/544: {Phospholipids} - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - C07K 5/0806: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala} - C07K 5/1008: {the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala} - C07K 7/06: having 5 to 11 amino acids - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention provides a peptide-phospholipid conjugate of Formula 1: wherein: X is selected from the group consisting of —CR1R2—, —R3—, —O—, —S—, and S+(R3)—; Y is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; Z is a peptide comprising 1 to 50 amino acids; R1 and R2 each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; and R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl. ## Claims ### Claim 1 A peptide-phospholipid conjugate of Formula 1: wherein: X is selected from the group consisting of —CR1R2—, —NR3—, —O—, —S—, and —S+(R3)—; Y is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; Z is a peptide comprising 1 to 50 amino acids; R1 and R2 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; and R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl. ### Claim 2 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein X is an —NR3— group, wherein R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, and ether. ### Claim 3 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein X is an —NR3— group, wherein R3 is selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, and aminoalkyl. ### Claim 4 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein Y is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, and hydroxyalkyl. ### Claim 5 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein Y is selected from the group consisting of a bond and alkyl. ### Claim 6 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein Z is a peptide comprising 1 to 25 amino acids. ### Claim 7 (depends on 1) The peptide-phospholipid conjugate of claim 1, wherein Z is a peptide comprising 1 to 15 amino acids. ### Claim 8 A method of manufacturing a peptide-phospholipid conjugate of Formula 2: the method comprising forming a mixture comprising an acid of Formula 3 and lyso-PC: wherein: R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; and Z is a peptide comprising 1 to 50 amino acids. ### Claim 9 (depends on 8) The method of claim 8, wherein R3 is selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, and aminoalkyl. ### Claim 10 (depends on 8) The method of claim 8, wherein R3 is alkyl. ### Claim 11 (depends on 8) The method of claim 8, wherein Z is a peptide comprising 1 to 25 amino acids. ### Claim 12 (depends on 8) The method of claim 8, wherein Z is a peptide comprising 1 to 15 amino acids. ### Claim 13 (depends on 8) The method of claim 8, wherein the mixture further comprises a coupling reagent. ### Claim 14 (depends on 13) The method of claim 13, wherein the coupling reagent is a carbodiimide. ### Claim 15 (depends on 13) The method of claim 13, wherein the coupling reagent is selected from the group consisting of dicyclohexylcarbodiimide, diisopropylcarbodiimide, and combinations thereof. ### Claim 16 (depends on 13) The method of claim 13, wherein the mixture further comprises a solvent selected from the group consisting of CHCl3, CH2Cl2, tetrahydrofuran, acetonitrile, dimethylformamide, and mixtures thereof. ### Claim 17 A pharmaceutical formulation for treating atherosclerosis, the formulation comprising: a peptide-phospholipid conjugate of Formula 1 or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or a combination thereof, and a pharmaceutically acceptable excipient: wherein: X is selected from the group consisting of —CR1R2—, —NR3—, —O—, —S—, and —S+(R3)—; Y is selected from the group consisting of a bond, alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; Z is a peptide comprising 1 to 50 amino acids; R1 and R2 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl; and R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, aminoalkyl, amino, ether, cycloamino, cycloether, aryl, heteroaryl, arylalkyl, heteroarylalkyl, hydroxyaryl, arylether, cycloalkyl, heterocycloalkyl, hydroxycycloalkyl, halocycloalkyl, and aminocycloalkyl. ### Claim 18 (depends on 17) The pharmaceutical formulation of claim 17, wherein moiety X is an —NR3— group, wherein R3 is selected from the group consisting of alkyl, haloalkyl, alkoxyalkyl, hydroxyalkyl, and aminoalkyl. ### Claim 19 (depends on 18) The pharmaceutical formulation of claim 18, wherein R3 is alkyl. ### Claim 20 (depends on 17) The pharmaceutical formulation of claim 17, wherein moiety Y is selected from the group consisting of a bond and alkyl.