Claims for Patent: 10,301,376

Summary for Patent: 10,301,376

Title:	Combinations and methods for subcutaneous administration of immune globulin and hyaluronidase
Abstract:	Provided are combinations, compositions and kits containing a immune globulin (IG) composition and a soluble hyaluronidase composition formulated for subcutaneous administration. Such products can be used in methods of treating IG-treatable diseases or conditions. Also provided are methods for subcutaneous administration of immune globulin whereby the dosing regimen is substantially the same as for intravenous administration of the same dosage for treatment of the same IG-treatable disease or condition.
Inventor(s):	Schiff; Richard (Santa Rosa Valley, CA), Leibl; Heinz (Vienna, AT)
Assignee:	Baxalta GmbH (Zug, CH) Baxalta Incorporated (Bannockburn, IL)
Application Number:	12/381,844
Patent Claims:	1. A method for treating an IG-treatable disease or condition in a subject, comprising subcutaneously administering to the subject no more than once monthly a soluble hyaluronidase and an immune globulin (IG) composition for treating the disease or condition, wherein: the IG is from human plasma; the IG and hyaluronidase are administered separately; the hyaluronidase is administered prior to administration of the IG; the IG composition has a protein concentration that is 5 to 25% w/v IG; the IG is administered at a dosage of 100 mg per kg body weight (100 mg/kg BW) to 2 g/kg BW; and the hyaluronidase is administered at a ratio of Units hyaluronidase per gram of IG that is the range of about 10 to 500 Units hyaluronidase per gram of the IG, whereby the dose of IG administered is a full monthly dose. 2. The method of claim 1, wherein the soluble hyaluronidase is an ovine PH20, bovine PH20 or a soluble human PH20, wherein the soluble human PH20 is a C-terminally truncated PH20 that lacks all or a portion of the glycosylphosphatidylinositol (GPI) anchor attachment sequence. 3. The method of claim 1, wherein the soluble hyaluronidase is selected from among a polypeptide having a sequence of amino acids set forth in any of SEQ ID NOS:4-9. 4. The method of claim 1, wherein: the IG is administered in a volume of 50 mL to 700 mL; and the hyaluronidase is administered in a volume of less than 50 mL. 5. The method of claim 1, wherein the IG is administered as a liquid solution in a volume of 50 mL to 700 mL. 6. The method of claim 1, wherein the pH of the IG preparation is at or about 4.8 to 5.0. 7. The method of claim 1, wherein the pH of the IG preparation is at or about 4.6 to 5.1. 8. The method of claim 1, wherein the pH of the IG preparation is at or about 4.2 to 5.4. 9. The method of claim 1, wherein 20-30 grams (g) IG is administered. 10. The method of claim 1, wherein about or 5 grams (g), 10 g, 15 g, 20 g, 21 g, 22 g, 23 g, 24 g, 25 g, 26 g, 27 g, 28 g, 29 g, 30 g, 31 g, 32 g, 33 g, 34 g, 35 g, 36 g, 37 g, 38 g, 39 g or 40 g of IG is administered. 11. The method of claim 1, wherein at least 5 grams (g) of IG is administered. 12. The method of claim 1, wherein the IG is administered at a dosage of at least 200 mg/kg BW, 300 mg/kg BW, 400 mg/kg BW, 500 mg/kg BW or 600 mg/kg BW. 13. The method of claim 1, wherein the IG is administered at 600 mg/kg body weight (BW) and the soluble hyaluronidase is administered at a ratio of 50 units hyaluronidase/gram of IG. 14. The method of claim 1, wherein the hyaluronidase is administered in a volume of less than 50 mL. 15. The method of claim 1, wherein the hyaluronidase is administered in a volume of 5-30 mL. 16. The method of claim 1, wherein bioavailability of the subcutaneously administered IG is at least about 90% of the bioavailability of the same dosage administered via IV administration. 17. The method of claim 1, wherein the soluble hyaluronidase is a PH20, or a truncated form thereof. 18. The method of claim 17, wherein the PH20 is selected from an ovine, bovine or truncated human PH20. 19. The method of claim 18, wherein the PH20 is a truncated human PH20 selected from among a polypeptide having a sequence of amino acids set forth in any of SEQ ID NOS:4-9, or a variant thereof that has at least 95% sequence identity with any of SEQ ID NOS:4-9, is soluble and exhibits hyaluronidase activity. 20. The method of claim 18, wherein the truncated human PH20 is selected from among a polypeptide having a sequence of amino acids set forth in any of SEQ ID NOS:4-9. 21. The method of claim 1, wherein the soluble hyaluronidase is designated rHuPH20. 22. The method of claim 1, wherein the IG is purified from human plasma. 23. The method of claim 22, wherein the IG purified from human plasma is purified by alcohol fractionation. 24. The method of claim 23, wherein the IG is further purified by any one or more of a chemical modification, incubation at pH 4.0 with or without pepsin, polyethylene glycol (PEG) precipitation, ion-exchange chromatography, enzymatic cleavage, solvent detergent treatment, diafiltration or ultrafiltration. 25. The method of claim 1, wherein the IG contains IgG, IgA and IgM. 26. The method of claim 25, wherein the IG contains greater than 95% IgG. 27. The method of claim 26, wherein the IgG is monomeric. 28. The method of claim 1, wherein the IG further contains protein-stabilizing excipients. 29. The method of claim 28, wherein the protein-stabilizing excipient is selected from among one or more of glycine, maltose, a polyol, human serum albumin, mannitol, and non-ionic detergent. 30. The method of claim 1, wherein the pH of the IG preparation is at or about 4.2 to 5.4, 4.6 to 5.1 or 4.8 to 5.0. 31. The method of claim 30, wherein the IG has a protein concentration that is or is about 5 to 15% w/v, 6 to 15% w/v, or 8 to 12% w/v of IG composition. 32. The method of claim 30, wherein the IG has a protein concentration that is or is about 5 to 15% w/v of IG composition. 33. The method of claim 31, wherein the protein concentration is 10% w/v. 34. The method of claim 1, where the IG is administered as a liquid solution and the volume of liquid is or is about 100 ml, 150 ml, 200 ml, 300 ml, 400 ml, 500 ml, 600 ml or 700 ml. 35. The method of claim 1, wherein the IG is infused at a rate of 10 ml/hr to 300 ml/hr. 36. The method of claim 35, wherein the rate is selected from among at or about 10 ml/hr, 20 ml/hr, 30 ml/hr, 40 ml/hr, 50 ml/hr, 60 ml/hr, 70 ml/hr, 80 ml/hr, 90 ml/hr, 100 ml/hr, 150 ml/hr, 200 ml/hr, 250 ml/hr and 300 ml/hr. 37. The method of claim 35, wherein the rate is controlled by a pump. 38. The method of claim 35, wherein the rate is controlled by gravity. 39. The method of claim 1, wherein the hyaluronidase is administered 0.5 minutes, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 20 minutes or 30 minutes prior to administration of IG. 40. The method of claim 1, wherein the hyaluronidase is administered at a ratio (units hyaluronidase/grams of IG) at or about 10 U/gram (g), 20 U/g, 30 U/g, 35 U/g, 40 U/g, 50 U/g, 60 U/g, 70 U/g, 80 U/g, 90 U/g, 100 U/g, 150 U/g, or 300 U/g. 41. The method of claim 40, wherein the hyaluronidase is administered at a ratio of or about 50 U/gram IG. 42. The method of claim 1, wherein the hyaluronidase that is administered is at or about 10 Units to 500,000 Units, 100 Units to 100,000 Units, 500 Units to 50,000 Units, 1000 Units to 10,000 Units, 5000 Units to 7500 Units, 5000 Units to 50,000 Units, or 1,000 Units to 10,000 Units. 43. The method of claim 1, wherein the IG-treatable disease or condition is selected from among immunodeficiency; acquired hypogammaglobulinemia secondary to hematological malignancies; Kawasaki's disease; chronic inflammatory demyelinating polyneuropathy (CIDP); Guillain-Barre Syndrome; Idiopathic thrombocytopenic purpura; inflammatory myopathies; Lambert-Eaton myasthenic syndrome; multifocal motor neuropathy; Myasthenia Gravis; Moersch-Woltmann syndrome; secondary hypogammaglobulinaemia specific antibody deficiency; Acute disseminated encephalomyelitis; ANCA-positive systemic necrotizing vasculitis; Autoimmune haemolytic anaemia; Bullous pemphigoid; Cicatricial pemphigoid; Evans syndrome; Foeto-maternal/neonatal alloimmune thrombocytopenia (FMAIT/NAIT); Haemophagocytic syndrome; high-risk allogeneic haemopoietic stem cell transplantation; IgM paraproteinaemic neuropathy; kidney transplantation; multiple sclerosis; Opsoclonus myoclonus ataxia; Pemphigus foliaceus; Pemphigus vulgaris; Post-transfusion purpura; Toxic epidermal necrolysis/Steven Johnson syndrome (TEN/SJS); Toxic shock syndrome; Alzheimer's Disease; Systemic lupus erythematosus; multiple myeloma; sepsis; B cell tumors; trauma; and a bacterial, viral or fungal infection. 44. The method of claim 43, wherein the IG-treatable disease or condition is an immunodeficiency and the immunodeficiency is selected from among common variable immunodeficiency (CVID), congenital agammaglobulinemia, Wiskott-Aldrich syndrome, severe combined immunodeficiency (SCID), primary hypogammaglobulinemia, primary immunodeficiency diseases with antibody deficiency, X-linked agammaglobulinemia (XLA), hypogammaglobulinemia of infancy, and paraneoplastic cerebellar degeneration with no antibodies. 45. The method of claim 43, wherein the IG-treatable disease or condition is acquired hypogammaglobulinemia secondary to hematological malignancies and the hematological malignancy is selected from among chronic lymphocytic leukemia (CLL), multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). 46. The method of claim 43, wherein the IG-treatable disease or condition is an inflammatory myopathy and the inflammatory myopathy is selected from among polymyositis, dermatomyositis and inclusion body myositis. 47. The method of claim 43, wherein the IG-treatable disease or condition is a bacteria, viral or fungal condition and the bacterial viral or fungal condition is selected from among Haemophilus influenzae type B, Pseudomonas aeruginosa types A and B, Staphylococcus aureus, Group B Streptococcus, Streptococcus pneumoniae types 1, 3, 4, 6, 7, 8, 9, 12, 14, 18, 19, and 23, Adenovirus types 2 and 5, Cytomegalovirus, Epstein Barr virus VCA, Hepatitis A virus, Hepatitis B virus, Herpes simplex virus-1, Herpes simplex virus-2, Influenza A, Measles, Parainfluenza types 1, 2 and 3, Polio, Varicella zoster virus, Aspergillus and Candida albicans.

Details for Patent 10,301,376

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	05/05/2004		2028-03-17
Bausch & Lomb Incorporated	VITRASE	hyaluronidase	Injection	021640	12/02/2004		2028-03-17
Amphastar Pharmaceuticals, Inc.	AMPHADASE	hyaluronidase	Injection	021665	10/26/2004		2028-03-17
Akorn, Inc.	HYDASE	hyaluronidase	Injection	021716	10/25/2005		2028-03-17
Octapharma Pharmazeutika Produktionsges.m.b.h.	OCTAGAM	immune globulin intravenous (human)	Injection	125062	05/21/2004		2028-03-17