Pharmaceutical composition comprising an immunoglobulin fc region as a carrier

• US 20060275254A1
• Filed: 11/13/2004
• Published: 12/07/2006
• Est. Priority Date: 11/13/2003
• Status: Active Grant

• Current Assignee: Hanmi Science Co., Ltd
• Original Assignee: Hanmi Pharm Company Limited
• Inventors: Song, Dae Hae, Kwon, Se Chang, Kim, Young Min, Lee, Gwan Sun, Choi, In Young, Jung, Sung Youb, Kim, Chang Hwan
• Granted Patent: US 7,736,653 B2
• Time in Patent Office: Days
• US Class Current: 424/85.100
• CPC Class Codes: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6813 the drug being a peptidic cytokine, e.g. an interleukin or interferon
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/535 Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C07K 14/56 IFN-alpha
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 16/46 Hybrid immunoglobulins hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00
• CPC Class Codes: C07K 19/00 : Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]
• 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

Disclosed is a novel use of an immunoglobulin Fe fragment, and more particularly, a pharmaceutical composition comprising an immunoglobulin Fe fragment as a carrier. The pharmaceutical composition comprising an immunoglobulin Fe fragment as a carrier remarkably extends the serum half-life of a drug while maintaining the in vivo activity of the drug at relatively high levels. Also, when the drug is a polypeptide drug, the pharmaceutical composition has less risk of inducing immune responses compared to a fusion protein of the immunoglobulin Fe fragment and a target protein, and is thus useful for developing long-acting formulations of various polypeptide drugs.

Claims

1. A pharmaceutical composition comprising an immunoglobulin Fc fragment as a carrier.

2. The pharmaceutical composition according to claim 1, wherein the immunoglobulin Fc fragment is aglycosylated.

3. The pharmaceutical composition according to claim 1, wherein the immunoglobulin Fc fragment is composed of one to four domains selected from the group consisting of C_H1, C_H2, C_H3 and C_H4 domains.

4. The pharmaceutical composition according to claim 3, wherein the immunoglobulin Fc fragment further includes a hinge region.

5. The pharmaceutical composition according to claim 1, wherein the immunoglobulin Fc fragment is selected from the group consisting of Fc fragments from IgG, IgA, IgD, IgE, IgM, and combinations and hybrids thereof.

6. The pharmaceutical composition according to claim 5, wherein the immunoglobulin Fc fragment is selected from the group consisting of Fc fragments from IgG1, IgG2, IgG3, IgG4, and combinations and hybrids thereof.

7. The pharmaceutical composition according to claim 6, wherein the immunoglobulin Fc fragment is an IgG4 Fc fragment.

8. The pharmaceutical composition according to claim 7, wherein the immunoglobulin Fc fragment is a human aglycosylated IgG4 Fc fragment.

9. The pharmaceutical composition according to claim 1, wherein the immunoglobulin Fc fragment is linked to a drug that is a physiologically active polypeptide.

10. The pharmaceutical composition according to claim 9, wherein the physiologically active polypeptide is selected from the group consisting of hormones, cytokines, enzymes, antibodies, growth factors, transcription regulatory factors, coagulation factors, vaccines, structural proteins, ligand proteins and receptors.

11. The pharmaceutical composition according to claim 10, wherein the physiologically active polypeptide is selected from the group consisting of human growth hormone, growth hormone releasing hormone, growth hormone releasing peptide, interferons, interferon receptors, colony stimulating factors, glucagon-like peptides, G-protein-coupled receptor, interleukins, interleukin receptors, enzymes, interleukin binding proteins, cytokine binding proteins, macrophage activating factor, macrophage peptide, B cell factor, T cell factor, protein A, allergy inhibitor, cell necrosis glycoproteins, immunotoxin, lymphotoxin, tumor necrosis factor, tumor suppressors, metastasis growth factor, alpha-1 antitrypsin, albumin, alpha-lactalbumin, apolipoprotein-E, erythropoietin, highly glycosylated erythropoietin, angiopoietins, hemoglobin, thrombin, thrombin receptor activating peptide, thrombomodulin, factor VII, factor VIIa, factor VIII, factor IX, factor XIII, plasminogen activating factor, fibrin-binding peptide, urokinase, streptokinase, hirudin, protein C, C-reactive protein, renin inhibitor, collagenase inhibitor, superoxide dismutase, leptin, platelet-derived growth factor, epithelial growth factor, epidermal growth factor, angiostatin, angiotensin, bone growth factor, bone stimulating protein, calcitonin, insulin, atriopeptin, cartilage inducing factor, elcatonin, connective tissue activating factor, tissue factor pathway inhibitor, follicle stimulating hormone, luteinizing hormone, luteinizing hormone releasing hormone, nerve growth factors, parathyroid hormone, relaxin, secretin, somatomedin, insulin-like growth factor, adrenocortical hormone, glucagon, cholecystokinin, pancreatic polypeptide, gastrin releasing peptide, corticotropin releasing factor, thyroid stimulating hormone, autotaxin, lactoferrin, myostatin, receptors, receptor antagonists, cell surface antigens, virus derived vaccine antigens, monoclonal antibodies, polyclonal antibodies, and antibody fragments.

12. The pharmaceutical composition according to claim 11, wherein the physiologically active polypeptide is selected from the group consisting of human growth hormone, colony stimulating factor, interferon-alpha, human erythropoietin and Fab′

antibody fragment.

13. The pharmaceutical composition according to claim 1, wherein the immunoglobulin Fc fragment is linked to a drug through a peptide or non-peptide linker.

14. A method of improving in vivo duration of action of a drug, which is characterized by using an immunoglobulin Fc fragment as a carrier.

15. The method according to claim 14, wherein the immunoglobulin Fc fragment is aglycosylated.

16. The method according to claim 14, wherein the immunoglobulin. Fc fragment is composed of one to four domains selected from the group consisting of C_H1, C_H2, C_H3 and C_H4 domains.

17. The method according to claim 16, wherein the immunoglobulin Fc fragment further includes a hinge region.

18. The method according to claim 14, wherein the immunoglobulin Fc fragment is selected from the group consisting of Fc fragments from IgG, IgA, IgD, IgE, IgM, and combinations and hybrids thereof.

19. The method according to claim 18, wherein the immunoglobulin Fc fragment is selected from the group consisting of Fc fragments from IgG1, IgG2, IgG3, IgG4, and combinations and hybrids thereof.

20. The method according to claim 19, wherein the immunoglobulin Fc fragment is an IgG4 Fc fragment.

21. The method according to claim 20, wherein the immunoglobulin Fc fragment is a human aglycosylated IgG4 Fc fragment.

22. The method according to claim 14, wherein the immunoglobulin Fc fragment is linked to a drug that is a physiologically active polypeptide.

23. The method according to claim 22, wherein the physiologically active polypeptide is selected from the group consisting of hormones, cytokines, enzymes, antibodies, growth factors, transcription regulatory factors, coagulation factors, vaccines, structural proteins, ligand proteins and receptors.

24. The method according to claim 23, wherein the physiologically active polypeptide is selected from the group consisting of human growth hormone, growth hormone releasing hormone, growth hormone releasing peptide, interferons, interferon receptors, colony stimulating factors, glucagon-like peptides, G-protein-coupled receptor, interleukins, interleukin receptors, enzymes, interleukih binding proteins, cytokine binding proteins, macrophage activating factor, macrophage peptide, B cell factor, T cell factor, protein A, allergy inhibitor, cell necrosis glycoproteins, immunotoxin, lymphotoxin, tumor necrosis factor, tumor suppressors, metastasis growth factor, alpha-1 antitrypsin, albumin, alpha-lactalbumin, apolipoprotein-E, erythropoietin, highly glycosylated erythropoietin, angiopoietins, hemoglobin, thrombin, thrombin receptor activating peptide, thrombomodulin, factor VII, factor VIIa, factor VIII, factor IX, factor XIII, plasminogen activating factor, fibrin-binding peptide, urokinase, streptokinase, hirudin, protein C, C-reactive protein, renin inhibitor, collagenase inhibitor, superoxide dismutase, leptin, platelet-derived growth factor, epithelial growth factor, epidermal growth factor, angiostatin, angiotensin, bone growth factor, bone stimulating protein, calcitonin, insulin, atriopeptin, cartilage inducing factor, elcatonin, connective tissue activating factor, tissue factor pathway inhibitor, follicle stimulating hormone, luteinizing hormone, luteinizing hormone releasing hormone, nerve growth factors, parathyroid hormone, relaxin, secretin, somatomedin, insulin-like growth factor, adrenocortical hormone, glucagon, cholecystokinin, pancreatic polypeptide, gastrin releasing peptide, corticotropin releasing factor, thyroid stimulating hormone, autotaxin, lactoferrin, myostatin, receptors, receptor antagonists, cell surface antigens, virus derived vaccine antigens, monoclonal antibodies, polyclonal antibodies, and antibody fragments.

25. The method according to claim 24, wherein the physiologically active polypeptide is selected from the group consisting of human growth hormone, colony stimulating factor, interferon-alpha, human erythropoietin and a Fab′

antibody fragment.

26. The method according to claim 14, wherein the immunoglobulin Fc fragment is linked to a drug through a peptide or non-peptide linker.