Use of peptide-drug conjugation to reduce inter-subject variability of drug serum levels

• US 20050065086A1
• Filed: 08/23/2004
• Published: 03/24/2005
• Est. Priority Date: 02/22/2002
• Status: Abandoned Application

• Current Assignee: Shire LLC (Shire plc)
• Original Assignee: New River Pharmaceuticals Inc. (Shire plc)
• Inventors: Piccariello, Thomas, Kirk, Randal
• Application Number:
  US10/923,089
• Publication Number:
  US 20050065086A1
• Time in Patent Office: Days
• US Class Current: 435/400
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

The present invention provides compositions and methods to decrease inter-patient variability particularly with respect to the systemic concentration of a drug. More particularly the invention relates to oral drugs which are conjugated to peptides or related carriers which alter release characteristics as compared to the analogous free drug.

Claims

1. A method for altering bioavailability of a patient population to produce a serum profile described in FIG. 1 as compare to reference drug.

3. The method of claim 1, wherein the composition improves AUC.

4. The method of claim 1, wherein the composition improves an active agent'"'"'s facilitated diffusion rate as compared to the reference drug delivered alone.

5. The method of claim 1, wherein the composition improves an active agent'"'"'s active transport as compared to the reference drug delivered alone.

6. The method of claim 1, wherein the composition improves an active agent'"'"'s absorption as compared to the reference drug delivered alone.

7. The method of claim 1, wherein the composition improves an active agent'"'"'s peak values as compared to the reference drug delivered alone.

10. A method for controlling release of a pharmaceutically active agent to reduce inter-subject variability among a group of patients, comprising administering to said group of patients the composition according to claim 1.

2. A method of reducing patient to patient variability through administering an orally active peptide-active agent composition.

8. A composition which provides the serum profile in FIG. 1.

9. A method of formulating a drug to reduce inter-subject variability comprising:

(i) a pharmaceutically effective agent; and

(ii) a peptide covalently bonded to said pharmaceutically active agent wherein said pharmaceutically effective agent is released according to a serum profile substantially identical to that of FIG. 1.

11. A composition comprising:

(i) a pharmaceutically effective agent; and

(ii) a peptide covalently bonded to said pharmaceutically active agent wherein said pharmaceutically effective agent is released according to a serum profile substantially identical to that of FIG. 1.