Claims for Patent: 9,012,606

Summary for Patent: 9,012,606

Title:	In vivo half life increased fusion protein or peptide maintained by sustained in vivo release, and method for increasng in vivo half-life using same
Abstract:	The present invention relates to a fusion protein or peptide, the in vivo half-life of which is increased by maintaining in vivo sustained release, and to a method for increasing in vivo half-life using same. A fusion protein or peptide according to the present invention has excellent in vivo stability by binding a physiologically active protein or physiologically active peptide to an alpha-1 antitrypsin or alpha-1 antitrypsin mutant with one or more amino acids mutated to maintain the in vivo sustained release and to significantly increase the half-life thereof in blood (T1/2) compared to an inherent physiologically active protein or physiologically active peptide. Thus, a fusion protein or peptide according to the present invention can be useful in developing a sustained-release preparation of a protein or peptide drug.
Inventor(s):	Chung; Hye-Shin (Daejeon, KR), Yoo; Seung Bum (Daejeon, KR), Lee; Sang Mee (Daejeon, KR)
Assignee:	Alteogen, Inc. (Daejeon, KR)
Application Number:	13/265,775
Patent Claims:	1. A fusion protein or peptide, comprising a physiologically active protein or peptide fused to alpha-1 antitrypsin variant having at least one mutated amino acid residue, whereby the physiologically active protein or peptide has an increased in vivo half-life by maintenance in a sustained circulation, and the alpha-1 antitrypsin variant has a reduced protease inhibitor activity, wherein the alpha-1 antitrypsin variant is selected from the group consisting of alpha-1 antitrypsin monovariant [.alpha.1AT(P357N)] set forth as SEQ ID NO:28, alpha-1 antitrypsin divariant [.alpha.1AT(P357N, S359T)] set forth as SEQ ID NO:29, alpha-1 antitrypsin divariant [.alpha.1AT(P357N, C232S)] set forth as SEQ ID NO:30, and alpha-1 antitrypsin trivariant .alpha.1AT(P357N, C232S, S359T) set forth as SEQ ID NO:31. 2. The fusion protein or peptide of claim 1, wherein the physiologically active protein or peptide is fused directly or via a linker consisting of amino acids to alpha-1 antitrypsin variant having at least one mutated amino acid residue. 3. The fusion protein or peptide of claim 1, wherein the physiologically active protein is selected from the group consisting of hormones and their receptors, biological response modifiers and their receptors, cytokines and their receptors, enzymes, antibodies, and antibody fragments. 4. The fusion protein or peptide of claim 3, wherein the physiologically active protein is selected from the group consisting of human growth hormone (hGH), insulin, follicle-stimulating hormone (FSH), human chorionic gonadotropin, parathyroid hormone (PTH), erythropoietin (EPO), thrombopoietin (TPO), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon alpha, interferon beta, interferon gamma, interleukins, macrophage activating factor, tumor necrosis factor, tissue plasminogen activator, coagulation factor VII, VIIa, VIII and IX, human bone morphogenic protein 2 (hBMP2), keratinocyte growth factor (KGF), platelet-derived growth factor (PDGF), glucocerebrosidase, .alpha.-galactosidase A, .alpha.-L-iduronidase, iduronate-2-sulfatase, lactase, adenosine deaminase, butyrylcholinesterase, chitinase, glutamate decarboxylase, imiglucerase, lipase, uricase, platelet-activating factor acetylhydrolase, neutral endopeptidase, urokinase, streptokinase, myeloperoxidase, superoxide dismutase, botulinum toxin, collagenase, hyaluronidase, L-asparaginase, monoclonal antibodies, polyclonal antibodies, scFv, Fab, Fab', F(ab').sub.2 and Fd, and a combination thereof. 5. The fusion protein or peptide of claim 1, being selected from the group consisting of a human growth hormone/alpha-1 antitrypsin monovariant fusion [T109: .alpha.1AT(P357N)/hGH](SEQ ID NO: 2), a human growth hormone/alpha-1 antitrypsin divariant fusion [T109T: .alpha.1AT(P357N, S359T)/hGH](SEQ ID NO: 3), a human interferon alpha/alpha-1 antitrypsin monovariant fusion [T502: .alpha.1AT(P357N)/IFN-.alpha.](SEQ ID NO: 4), a granulocyte colony-stimulating factor/alpha-1 antitrypsin divariant fusion [T602S: .alpha.1AT(P357N, C232S)/G-CSF] (SEQ ID NO: 5), a granulocyte colony-stimulating factor/alpha-1 antitrypsin trivariant fusion [T602ST: .alpha.1AT(P357N, C232S, S359T)/G-CSF] (SEQ ID NO: 6), and an exendin-4/alpha-1 antitrypsin monovariant fusion [T304: Exendin-4/.alpha.1AT(P357N)](SEQ ID NO: 7).

Details for Patent 9,012,606

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	01/15/1974		2029-04-22
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	12/27/1984		2029-04-22
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/15/1985		2029-04-22
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/16/1990		2029-04-22
Bel-mar Laboratories, Inc.	CHORIONIC GONADOTROPIN	chorionic gonadotropin	Injection	017054	03/26/1974		2029-04-22
Fresenius Kabi Usa, Llc	CHORIONIC GONADOTROPIN	chorionic gonadotropin	For Injection	017067	03/05/1973		2029-04-22