Claims for Patent: 8,956,611

Summary for Patent: 8,956,611

Title:	Combination of BLyS inhibition and anti-CD 20 agents for treatment of autoimmune disease
Abstract:	The invention relates to novel combination therapies involving BLyS or BLyS/APRIL inhibition and anti-CD20 agents for the treatment of autoimmune diseases. One preferred method is where the BLyS antagonist is a Fc-fusion protein which can be a TACI-Fc-fusion protein comprising the extracellular domain of TACI or a functional fragment thereof, a BAFF--R-Fc-fusion protein comprising the extracellular domain of BAFF--R or a functional fragment thereof, or a BCMA-Fc-fusion protein comprising the extracellular domain of BCMA or a functional fragment thereof. In the methods of the present invention some of anti-CD20 agents contemplated include RITUXAN.RTM., (rituximab),ocrelizumab, ofatumumab (HuMax-CD20.RTM.), TRU-015, and DXL625, although any agent that binds to CD 20 may be suitable. The methods of the present invention reduce the levels of B cells in patients in need of such reduction, such as those suffering from autoimmune diseases.
Inventor(s):	Ponce, Jr.; Rafael A. (Seattle, WA), Peano; Sergio (Ivrea, IT), Broly; Herve (Saint Selve, FR), Graffner; Hans Otto Lennart (Helsingborg, SE)
Assignee:	ZymoGenetics, Inc. (Seattle, WA) Ares Trading S.A. (Aubonne, CH)
Application Number:	12/252,955
Patent Claims:	1. A method of reducing memory B cell numbers in a mammal comprising administering a therapeutically effective amount of an extracellular domain of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) polypeptide comprising a secreted form of SEQ ID NO:23 having the modified tissue plasminogen activation signal sequence (SEQ ID NO:41) removed and an anti-CD-20 agent comprising rituximab, wherein said therapeutically effective amount results in a synergistic reduction in the number of memory B cells. 2. A method of alleviating a B-cell regulated autoimmune disease comprising administering to a patient suffering from the disorder a therapeutically effective amount of an extracellular domain of a transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI) polypeptide comprising a secreted form of SEQ ID NQ:23 having the modified tissue plasminogen activation signal sequence (SEQ ID NO:41) removed and an anti-CD20 agent comprising rituximab, wherein said therapeutically effective amount results in a synergistic reduction in the number of memory B cells. 3. The method of claim 2 wherein the autoimmune disease is selected from the group consisting systemic lupus erythematosus (SLE) and lupus nephritis (LN). 4. The method of claim 3 wherein the autoimmune disease is systemic lupus erythmatosus (SLE). 5. The method of claim 2 wherein the TACI polypeptide is administered at a dosage of about 1 to about 25 mg/kg and the anti-CD20 agent is administered at a dosage of about 1 to about 25 mg/kg. 6. The method of claim 5 wherein the TACT polypeptide is administered at a dosage of about 20 mg/kg and the anti-CD20 agent is administered at a dosage of about 20 mg/kg. 7. The method of claim 2 wherein the TACI polypeptide and the rituximab is administered in conjunction with therapy using an immunosuppressive drug selected from the group consisting of cyclophosphamide (CYC), azathioprine (AZA), cyclosporine A (CSA), mycophenolate mofetil (MMF), nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, prednisone, and disease-modifying antirheumatic drugs (DMARDs). 8. The method of claim 1 wherein the TACI polypeptide is administered at a dosage of about 1 to about 25 mg/kg and the anti-CD20 agent is administered at a dosage of about 1 to about 25 mg/kg. 9. The method of claim 1 wherein the TACI polypeptide is administered at a dosage of about 20 mg/kg and the anti-CD20 agent is administered at a dosage of about 20 mg/kg. 10. The method of claim 1 wherein the TALI polypeptide and the rituximab is administered in conjunction with therapy using an immunosuppressive drug selected from the group consisting of cyclophosphamide (CYC), azathioprine (AZA), cyclosporine A (CSA), mycophenolate mofetil (MMF), nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, prednisone, and disease-modifying antirheumatic drugs (DMARDs).

Details for Patent 8,956,611

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2027-10-16
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2027-10-16
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2027-10-16