# US 2013/0156706 A1 · Targeted gas-filled microvesicles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156706 A1 - Document ID: US20130156706A1 - Status: Published application - Kind: A1 - Application number: 13/814,329 - Filed: 2011-08-09 - Published: 2013-06-20 - Earliest claimed: 2010-08-09 - Assignees: Bracco Suisse SA - Inventors: Thierry Bettinger; Philippe Bussat; Samir Cherkaoui; Irene Guilbert-Brigger; Bernard Lamy - Web page: https://patentgrep.com/patent/US20130156706A1 ## CPC - A61K 49/223: {Microbubbles, hollow microspheres, free gas bubbles, gas microspheres} - A61K 49/221: {characterised by the targeting agent or modifying agent linked to the acoustically-active agent} - A61K 49/222: {characterised by a special physical form, e.g. emulsions, liposomes} - A61K 49/227: {Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric} - A61K 38/178: {Lectin superfamily, e.g. selectins} - 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) ## Abstract Gas-filled microvesicles associated with a polypeptide comprising a sequence of amino acids, said sequence exhibiting binding affinity for selectins, particularly p-selectin. The gas-filled microvesicles can be used in ultrasound imaging. ## Claims ### Claim 1 An aqueous suspension comprising a gas-filled microvesicle, said microvesicle comprising a targeting construct comprising: a) an amphiphilic compound; and b) a polypeptide consisting of at most 200 amino acid residues and comprising at least amino acids 5-16 as set forth in SEQ ID NO:1; said polypeptide being in dimeric form and being covalently associated with said amphiphilic compound. ### Claim 2 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide comprises at least amino acids 1-19 as set forth in SEQ ID NO: 1. ### Claim 3 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide comprises at least amino acids 5-41 as set forth in SEQ ID NO: 1. ### Claim 4 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide comprises at least amino acids 1-47 as set forth in SEQ ID NO: 1. ### Claim 5 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide comprises at most 100 amino acid residues. ### Claim 6 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide comprises at most 75 amino acid residues. ### Claim 7 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide consists of the amino acid sequence as set forth in SEQ ID NO: 3. ### Claim 8 (depends on 1) An aqueous suspension according to claim 1 wherein said polypeptide consists of the amino acid sequence of formula (I): (XA)n—Y—(XB)m (I) wherein: (XA)n represents a sequence of n amino acids XA, comprising at least amino acids 5-16 as set forth in SEQ ID NO:1, where: n is an integer of from 12 to 199; and XA is any amino acid with the exclusion of lysine; (XB)m represents a sequence of m amino acids XB, where; m is an integer of from 0 to 10, with the proviso that the sum m+n is at most 199; and XB is any amino acid with the exclusion of lysine and cysteine; and Y is cysteine or lysine. ### Claim 9 (canceled) ### Claim 10 (depends on 8) An aqueous suspension according to claim 8 wherein (XA)n comprises at least amino acids 1-19 as set forth in SEQ ID NO: 1. ### Claim 11 (depends on 8) An aqueous suspension according to claim 8 wherein (XA)n comprises at least amino acids 5-41 as set forth in SEQ ID NO: 1. ### Claim 12 (depends on 8) An aqueous suspension according to claim 8 wherein (XA)n comprises at least amino acids 1-47 as set forth in SEQ ID NO: 1. ### Claim at position 13 13-14. (canceled) ### Claim 15 (depends on 8) An aqueous suspension according to claim 8 wherein Y is Lysine. ### Claim 16 (depends on 8) An aqueous suspension according to claim 8 wherein n is an integer of from 12 to 99 and m+n is at most 99. ### Claim 17 (depends on 8) An aqueous suspension according to claim 8 wherein n is an integer of from 12 to 74 and m+n is at most 74. ### Claim at position 17 18-19. (canceled) ### Claim 20 (depends on 8) An aqueous suspension according to claim 8 wherein XA comprises two Cysteine residues. ### Claim 21 (depends on 1) An aqueous suspension according to any one of claim 1 wherein said polypeptide is a glycosylated sequence of amino acids comprising an O-glycan moiety bound to an amino residue of the sequence. ### Claim 22 (depends on 21) An aqueous suspension according to claim 21 wherein said O-glycan moiety comprises a sialyl Lewis x structure. ### Claim 23 (depends on 12) An aqueous suspension according to claim 12 comprising one or more glycan residues bound to amino acids in positions 16, 24, 25, 26, 28, 29, 32, 36, 39, 40 and/or 41 of SEQ ID NO:1. ### Claim 24 (depends on 1, 8) An aqueous suspension according to any one of claim 1 or 8 wherein said amino acid sequence of the polypeptide further comprises a sulfate group bound to a tyrosine amino acid residue. ### Claim 25 (canceled) ### Claim 26 (depends on 1) An aqueous suspension according to claim 1 wherein said amphiphilic compound of said targeting construct is a phospholipid. ### Claim 27 (depends on 1, 8) An aqueous suspension according to any one of claim 1 or 8 wherein said microvesicle comprises a stabilizing amphiphilic material. ### Claim 28 (depends on 27) An aqueous suspension according to claim 27, wherein said amphiphilic material is a phospholipid. ### Claim 29 (depends on 1, 8) An aqueous suspension according to any one of claims 1 or 8 wherein the gas contained in the microvesicle is a fluorinated gas, optionally in admixture with air or nitrogen. ### Claim 30 (depends on 1, 8) A precursor of a gas-filled microvesicle as defined in any one of claims 1 or 8 said precursor being in dried powdered form and comprising a microvesicle-forming material in combination with a lyophilization additive, said precursor being reconstitutable to form an aqueous suspension comprising said gas-filled microvesicle upon contact and agitation with an aqueous carrier in the presence of a gas. ### Claim at position 29 31-32. (canceled) ### Claim 33 (depends on 30) A precursor according to claim 30, wherein the lyophilization additive is an amino acid, a sugar, a polysaccharide or polyaoxyalkyleneglycol. ### Claim 34 (depends on 30) A pharmaceutical kit comprising a precursor according to claim 30, and a physiologically acceptable aqueous carrier. ### Claim 35 (depends on 34) A pharmaceutical kit according to claim 34 wherein said precursor is in contact with a biocompatible gas. ### Claim 36 (depends on 35) A pharmaceutical kit according to claim 35 wherein said gas is a fluorinated gas, optionally in admixture with air or nitrogen. ### Claim 37 (depends on 1, 8) A method of diagnostic imaging which comprises: a) administering an effective amount of a suspension of gas-filled microvesicles according to any one of claims 1 or 8 to a patient; b) subjecting said patient to ultrasound imaging. ### Claim 38 (depends on 37) The method according to claim 37 wherein said imaging is performed on a patient suffering from an inflammatory disease or pathology during a treatment thereof. ### Claim 39 (depends on 1) An aqueous suspension according to claim 1, wherein the polypeptide comprises a cysteine and/or lysine residue. ### Claim 40 (depends on 1) An aqueous suspension according to claim 1, wherein said polypeptide is covalently associated with said amphiphilic compound through a lysine residue.