Targeting vector-phospholipid conjugates

Patent metadata

Field	Value
Publication number	US-9295737-B2
Application number	US-201414190860-A
Country	US
Kind code	B2
Filing date	Feb 26, 2014
Priority date	Mar 1, 2002
Publication date	Mar 29, 2016
Grant date	Mar 29, 2016

Abstract

Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

First claim

What is claimed is:

1. A method of making a peptide phospholipid conjugate having less than or equal to 0.3% trifluoroacetic acid (TFA) comprising the steps of:
converting a peptide TFA salt to an acetate salt via anion exchange; and
conjugating the peptide to a phospholipid, wherein said phospholipid at the time of conjugation is not included in a gas-filled ultrasound contrast agent.

2. The method of claim 1 , wherein the peptide comprises a peptide dimer.

3. The method of claim 1 , wherein the peptide dimer comprises Ac-AGPTWCEDDWYYCWLFGTGGGK[Ac-VCWEDSWGGEVCFRYDPGGGK(-Adoa-Adoa-Glut-K)-NH 2 cyclic (2-12) disulfide]-NH 2 cyclic (6-13) disulfide.

4. The method of claim 1 , wherein the anion exchange chromatography comprises a step gradient of ammonium acetate.

5. The method of claim 1 , wherein the phospholipid is pegylated.

6. The method of claim 1 , wherein the pegylated phospholipid is DSPE-PEG2000-NH 2 .

Assignees

• Bracco Suisse Sa

Inventors

• Bussat Philippe
• Cherkaoui Samir
• Fan Hong Helen
• Lamy Bernard
• Nanjappan Palaniappa
• Pillai Radhakrishna K
• Pochon Sibylle
• Song Bo
• Swenson Rolf E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K14/71

  for growth factors; for growth regulators · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K14/52

  Cytokines; Lymphokines; Interferons · CPC title