Crystalline insulin-conjugates

• US 9,463,249 B2
• Filed: 05/19/2014
• Issued: 10/11/2016
• Est. Priority Date: 01/28/2009
• Status: Active Grant

• Current Assignee: SmartCells, Inc. (Merck & Co., Inc.)
• Original Assignee: SmartCells, Inc. (Merck & Co., Inc.)
• Inventors: Lancaster, Thomas M., Zion, Todd C.
• Primary Examiner(s): Lukton, David
• Application Number:
  US14/280,793
• Publication Number:
  US 20140275476A1
• Time in Patent Office: 876 Days
• Field of Search: 530/303, 514/5.9
• US Class Current: 1/1
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/62 Insulins

Abstract

The present disclosure provides crystalline insulin-conjugates. The present disclosure also provides formulations, methods of treatment, methods of administering, and methods of making that encompass these crystalline insulin-conjugates.

Claims

1. A crystalline insulin-conjugate of formula (I):

2. The crystalline insulin-conjugate of claim 1, wherein the conjugate is of formula

3. The crystalline insulin-conjugate of claim 2, wherein the conjugate is of formula

4. The crystalline insulin-conjugate of claim 1, wherein the conjugate is of formula

5. The crystalline insulin-conjugate of claim 4, wherein the conjugate is of the formula

6. The crystalline insulin-conjugate of claim 1, wherein the conjugate is of formula

7. The crystalline insulin-conjugate of claim 6, wherein the conjugate is of formula

8. The crystalline insulin-conjugate of claim 1, wherein the insulin molecule is selected from the group consisting of insulin lispro, insulin aspart and insulin glulisine.

9. The crystalline insulin-conjugate of claim 1, wherein the insulin molecule is insulin glargine or insulin detemir.

10. The crystalline insulin-conjugate of claim 1, wherein the insulin molecule is conjugated via the epsilon-amino group of Lys^B29.

11. The crystalline insulin-conjugate of claim 1, wherein each occurrence of X is independently a ligand that includes aminoethylmannose (AEM), or aminoethyltrimannose (AETM).

12. A crystalline insulin-conjugate of formula

13. A crystalline insulin-conjugate comprising a formula selected from the group consisting of: