Fusion protein of Exendin-4 and its analog, preparation method and use thereof

• US 8,889,619 B2
• Filed: 06/10/2011
• Issued: 11/18/2014
• Est. Priority Date: 06/11/2010
• Status: Active Grant

• Current Assignee: Beijing Dongfang Biotech Co., Ltd.
• Original Assignee: Beijing Dongfang Biotech Co., Ltd.
• Inventors: Bai, Xianhong, Tu, Hua, Li, Xianzhong
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US13/635,236
• Publication Number:
  US 20130142795A1
• Time in Patent Office: 1,257 Days
• Field of Search: None
• US Class Current: 514/7.2
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/46 from vertebrates
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

Provided are a fusion protein of Exendin-4 and its analog, the preparation method and use thereof. The fusion protein is obtained by fusing of Exendin-4 or its analog to Fc region of human IgG2 via a linking peptide, which has the better stability and prolonged serum half-life, and can be used for treating diabetes and obesity.

Claims

1. A fusion protein obtained by fusing a peptide hormone to a transport protein via a linker, wherein the peptide hormone is capable of lowering the blood glucose, the transport protein is the Fc fragment of the immunoglobulin IgG2, and the fusion protein is capable of lowering the blood glucose;

the peptide hormone is exendin-4, which has the amino acid sequence set forth in SEQ ID NO;

1, and the linker is a peptide consisting of the sequence of (Gly)_m-Xaa-(Gly)_n, in which m is an integer between 3 and 8, n is an integer between 3 and 8, and Xaa is any one selected from the group consisting of Gly, Ser, Ala and Thr.

2. The fusion protein according to claim 1, wherein m is an integer between 4 and 6;

and n is an integer between 4 and 6.

3. The fusion protein according to claim 2, wherein the linker has the amino acid sequence set forth in SEQ ID NO:

3.

4. The fusion protein according to claim 1, wherein the Fc fragment of IgG2 originates from human.

5. The fusion protein according to claim 1, wherein the fusion protein has the amino acid sequence set forth in SEQ ID NO:

4.

6. A pharmaceutical composition, wherein the pharmaceutical composition comprises the fusion protein according to claim 1 and pharmacologically acceptable excipient.

7. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition is administered as local administration, aerosol or injection.

8. The pharmaceutical composition according to claim 7, wherein the injection is administered through at least one of intraperitoneal injection, subcutaneous injection, intramuscular injection or intravenous injection.

9. A method of treating diabetes or obesity, wherein the method comprises the step of administering the fusion protein according to claim 1 to subjects.