Apo-AI/AII peptide derivatives

• US 6,743,778 B2
• Filed: 04/23/2001
• Issued: 06/01/2004
• Est. Priority Date: 04/21/2000
• Status: Expired due to Fees

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Kohno, Tadahiko
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): KAM, CHIH MIN
• Application Number:
  US09/840,669
• Publication Number:
  US 20030040470A1
• Time in Patent Office: 1,135 Days
• Field of Search: 514/12, 514/2, 514/13, 530/324, 530/325, 530/326, 530/344, 530/350, 350/387.1, 435/69.7, 435/69.1, 930/10, 930/30
• US Class Current: 424/130.1
• CPC Class Codes: 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
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: C07K 14/775 Apolipopeptides

Abstract

The present invention concerns therapeutic agents that mimic the activity of Apo-AI amphipathic helix peptide. In accordance with the present invention, the compounds of the invention comprise:

a. a Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain, preferably the amino acid sequence of SEQ ID NO: 7, or sequences derived therefrom by phage display, RNA-peptide screening, or the other techniques mentioned above; and

b. a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred;

wherein the vehicle, preferably an Fc domain, is covalently attached to the Apo-AI amphipathic helix peptide or Apo-AL amphipathic helix peptide-mimetic domain. The vehicle and the Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain may be linked through the N- or C-terminus of the Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domains comprise the amino acid sequences described in Table 2. Other Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein.

Claims

1. A composition of matter of the formula

2. The composition of matter of claim 1 of the formulae

3. The composition of matter of claim 1 of the formula

4. The composition of matter of claim 1 of the formula

5. The composition of matter of claim 1 wherein F¹ is an IgG Fc domain.

6. The composition of matter of claim 1 wherein F¹ is an IgG1 Fc domain.

7. The composition of matter of claim 1 wherein F¹ comprises the sequence of SEQ ID NO:

2.

8. The composition of matter of claim 1 wherein the Apo-AI amphipathic helix peptide or Apo-AI amphipathic helix peptide-mimetic domain sequence is of the formula

9. The composition of matter of claim 8, wherein F¹ is an IgG Fc domain.

10. The composition of matter of claim 9, wherein F¹ is an IgG1 Fc domain.

11. The composition of matter of claim 1, having a sequence selected from the group consisting of SEQ ID Nos:

8, 9, 10 and 11.