TREATMENT OF MEMBRANOUS NEPHROPATHY, IGG4-RELATED DISEASE, AND ANTIPHOSPHOLIPID SYNDROME USING BTK INHIBITOR 2-[(3R)-3-[4-AMINO-3-(2-FLUORO-4-PHENOXY-PHENYL)PYRAZOLO[3,4-d]PYRIMIDIN-1-YL]PIPERIDINE-1-CARBONYL]-4-METHYL-4-[4-(OXETAN-3-YL)PIPERAZIN-1-YL]PENT-2-ENENITRILE

1 . A method of treating a disease chosen from membranous nephropathy (MN), IgG4-related diseases (IgG4-RD), and antiphospholipid syndrome (APS) in a mammal in need thereof, comprising administering to said mammal a pharmaceutical composition comprising:

a compound chosen from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomers of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile; and/or

a pharmaceutically acceptable salt of any of the foregoing compounds; and

a pharmaceutically acceptable carrier or excipient.

2 . The method of claim 1 , wherein the disease is acute.

3 . The method of claim 1 , wherein the disease is an IgG4-RD disease flare.

4 . The method of claim 1 , wherein the pharmaceutical composition is orally administered.

5 . (canceled)

6 . The method of claim 1 , wherein the pharmaceutical composition is orally administered daily.

7 . The method of claim 1 , wherein the pharmaceutical composition is administered in place of an immunosuppressive therapy and/or a corticosteroid therapy.

8 . (canceled)

9 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with an immunosuppressive therapy.

10 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with a corticosteroid therapy.

11 . The method of any of claim 1 , wherein the pharmaceutical composition is administered in combination with a noncorticosteroidal immunosuppressive and/or anti-inflammatory agent.

12 . The method of claim 1 , wherein the pharmaceutical composition is administered in place of an immunosuppressive maintenance therapy.

13 . The method of claim 1 , wherein the pharmaceutical composition is administered in place of a corticosteroid maintenance therapy.

14 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with an immunosuppressive maintenance therapy.

15 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with a corticosteroid maintenance therapy.

16 . The method of claim 13 , wherein the pharmaceutical composition is administered in combination with a noncorticosteroidal immunosuppressive and/or anti-inflammatory agent.

17 . The method of claim 1 , wherein the pharmaceutical composition comprises a compound which is a substantially pure (E) or (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile, and/or

a pharmaceutically acceptable salt of said compound; and

a pharmaceutically acceptable carrier or excipient.

18 . The method of claim 1 , wherein at least about 85% w/w of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile or at least about 85% w/w of a pharmaceutically acceptable salt of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile is the (E) isomer.

19 . The method of claim 1 , wherein the mammal is a human.

20 . The method of claim 1 , wherein the disease is an IgG4-related disease characterized by an IgG4-RD Responder Index (RI) greater than or equal to 2 in at least one organ system.

21 . The method of claim 1 , wherein the disease is an IgG4-related disease characterized by a serum IgG4 concentration greater than 1.5 times the upper limit of normal.

22 . The method of claim 1 , wherein the disease is chosen from IgG4-related sialadenitis, IgG4-related ophthalmic disease (IgG4-ROD), IgG4-related pharyngitis, IgG4-related thyroid disease, IgG4-related hypophysitis, IgG4-related pachymeningitis, IgG4-related leptomeningitis, IgG4-related pancreatitis, IgG4-related lung disease, IgG4-related pleuritis, IgG4-related hepatopathy, IgG4-related sclerosing cholangitis, IgG4-related cholecystitis, IgG4-related aortitis, IgG4-related periaortitis, IgG4-related periarteritis, IgG4-related pericarditis, IgG4-related mediastinitis, IgG4-related retroperitoneal fibrosis, IgG4-related mesenteritis, IgG4-related mastitis, IgG4-related kidney disease (IgG4-RKD), IgG4-related prostatitis, IgG4-related perivasal fibrosis, IgG4-related paratesticular pseudotumor, IgG4-related epididymo-orchitis, IgG4-related lymphadenopathy, IgG4-related skin disease, and IgG4-related perineural disease, or flares of any of the preceding IgG4-related diseases.

23 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with an active pharmaceutical ingredient chosen from interferon alpha, interferon gamma, cyclophosphamide, tacrolimus, mycophenolate mofetil, methotrexate, dapsone, sulfasalazine, azathioprine, an anti-CD20 agent, an anti-TNF alpha agent, an anti-IL-4 agent toward ligand or its receptors, an anti-IL-6 agent toward ligand or its receptors, an anti-IL-12 agent to ligand or its receptors, an anti-IL-17 agent to ligand or its receptors, an anti-IL-1 agent to ligand or its receptors, an anti-IL-2 agent to ligand or its receptors, an anti-IL-23 agent to ligand or its receptors, an anti-IL-12/23 agent to ligand or receptors, an anti-CD2 agent, an anti-CD3 agent, an anti-CD80/86 agent, an anti-sphingosine-1-phosphate receptor agent, an anti-05 agent, an anti-mTOR agent, an anti-calcineurin agent, an anti-BAFF/BlyS agent, leflunomide, and teriflunomide.

24 . The method of claim 1 , wherein the pharmaceutical composition is administered in combination with rituximab, dupilumab, ofatumumab, obinutuzumab, or veltuzumab, or a biosimilar version of any of the foregoing.

25 . The method of claim 1 , wherein the mammal is treatment naïve with respect to a immunosuppressive therapy.

26 . The method of claim 1 , wherein the mammal is treatment naïve with respect to any immunosuppressive therapy.

27 . The method of claim 1 , wherein the mammal has been previously treated with an immunosuppressive therapy.