Targeting constructs

Patent metadata

Field	Value
Publication number	US-9333273-B2
Application number	US-201514927865-A
Country	US
Kind code	B2
Filing date	Oct 30, 2015
Priority date	Aug 9, 2010
Publication date	May 10, 2016
Grant date	May 10, 2016

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.

First claim

The invention claimed is:

1. A targeting construct comprising:
a) an amphiphilic compound; and
b) a homodimeric polypeptide consisting of two polypeptide monomers, wherein each polypetide monomer consists of at most 200 amino acid residues, comprises a single lysine amino acid residue, at least amino acids 5-16 as set forth in SEQ ID NO:1 and at least one cysteine residue;
wherein the peptide monomers form a disulfide bond with the respective cysteine residues;

said homodimeric polypeptide being covalently associated with said amphiphilic compound.

2. The targeting construct according to claim 1 wherein said polypeptide monomers comprise at least amino acids 1-19 as set forth in SEQ ID NO: 1.

3. The targeting construct according to claim 1 wherein said polypeptide monomers comprise at least amino acids 5-41 as set forth in SEQ ID NO: 1.

4. The targeting construct according to claim 1 wherein said polypeptide monomers comprise at least amino acids 1-47 as set forth in SEQ ID NO: 1.

5. The targeting construct according to claim 1 wherein said polypeptide monomers comprise at most 100 amino acid residues.

6. The targeting construct according to claim 1 wherein said polypeptide monomers comprise at most 75 amino acid residues.

7. The targeting construct according to claim 1 wherein said polypeptide monomers consist of the amino acid sequence as set forth in SEQ ID NO: 3.

8. The targeting construct according to claim 1 wherein said polypeptide monomers consist of the amino acid sequence of formula (I):
(X A ) n —Y—(X B ) m   (I)

where:
(X A ) n represents a sequence of n amino acids X A where:
n is an integer of from 12 to 199;
X A is any amino acid with the exclusion of lysine; and
(X A ) n further comprises at least amino acids 5-16 as set forth in SEQ NO:1 and at least one cysteine;

(X B ) m represents a sequence of m amino acids X B , where:
m is an integer from 0 to 10, with the proviso that the sum m+n is at most 199; and
X B is any amino acid with the exclusion of lysine and cysteine; and

Y is lysine.

9. The targeting construct according to claim 8 wherein (X A ) n comprises at least amino acids 1-19 as set forth in SEQ ID NO:1.

10. The targeting construct according to claim 8 wherein (X A ) n comprises at least amino acids 5-41 as set forth in SEQ ID NO:1.

11. The targeting construct according to claim 8 wherein (X A ) n comprises at least amino acids 1-47 as set forth in SEQ ID NO:1.

12. The targeting construct according to claim 8 wherein n is an integer of from 12 to 99 and m+n is at most 99.

13. The targeting construct according to claim 8 wherein n is an integer of from 12 to 74 and m+n is at most 74.

14. The targeting construct according to claim 8 wherein X A comprises two cysteine residues.

15. The targeting construct according to claim 1 wherein said polypeptide monomers are glycosylated comprising an O-glycan moiety.

16. The targeting construct according to claim 15 wherein said O-glycan moiety comprises a sialyl Lewis x structure.

17. The targeting construct according to claim 15 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.

18. The targeting construct according to claim 4 wherein said polypeptide monomers are glycosylated comprising an O-glycan moiety.

19. The targeting construct according to claim 18 wherein said O-glycan moiety comprises a sialyl Lewis x structure.

20. The targeting construct according to claim 18 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.

21. The targeting construct according to claim 8 wherein said polypeptide monomers are glycosylated comprising an O-glycan moiety.

22. The targeting construct according to claim 21 wherein said O-glycan moiety comprises a sialyl Lewis x structure.

23. The targeting construct according to claim 21 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.

24. The targeting construct according to claim 1 wherein said polypeptide monomers further comprise a sulfate group bound to a tyrosine.

25. The targeting construct according to claim 4 wherein said polypeptide monomers further comprise a sulfate group bound to a tyrosine.

26. The targeting construct according to claim 1 wherein said amphiphilic compound is a phospholipid.

27. The targeting construct according to claim 4 wherein said amphiphilic compound is a phospholipid.

Assignees

• Bracco Suisse Sa

Inventors

• Bettinger Thierry
• Bussat Philippe
• Cherkaoui Samir
• Guilbert-Brigger Irene
• Lamy Bernard

Classifications

• A61K38/178

  Lectin superfamily, e.g. selectins · CPC title

• A61K49/227

  Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric · CPC title

• A61K49/222

  characterised by a special physical form, e.g. emulsions, liposomes · CPC title

• A61K49/223 Primary

  Microbubbles, hollow microspheres, free gas bubbles, gas microspheres · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title