Methods of treating patients with compositions comprising Anti-CD19 antibodies

Abstract

The invention provides novel methods for treatment of patients with membranous nephropathy by administration of compositions comprising a therapeutic agent for the treatment of membranous nephropathy. According to the invention, the therapeutic agent for the treatment of membranous nephropathy may be an anti-CD19 antibody.

Description

[0001]Patent Application CLIMB-005 / 01WO 40193 / 24 METHODS OF TREATING PATIENTS WITH COMPOSITIONS COMPRISING ANTI- CD19 ANTIBODIES I. FIELD OF THE INVENTION The invention provides novel methods for treatment of patients by administration of compositions comprising anti-CD19 antibodies. II. SEQUENCE LISTING The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file named CLIMB-005-01WO-Seq-Listing.xml, created on October 10, 2025, which is 55 KB in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety. III. BACKGROUND Membranous nephropathy (MN) Membranous nephropathy (MN) is an immune-mediated glomerular disease and is the leading cause of non-diabetic nephrotic syndrome (NS) in Caucasian adults. The most prominent clinical feature of MN is NS and its associated manifestations, including various degrees of edema, fatigue, hypoalbuminemia, and hyperlipidemia. Approximately 60% of patients with MN presentwith nephrotic-UDQJH^ SURWHLQXULD^ ^^^^^^ J^GD\^^ DQG^ WKH^ UHPDLQLQJ^ ^^^^ KDYH^ VXE-nephroticproteinuria, but two-thirds of these latter patients later become nephrotic usually within the first year. Immune thrombocytopenia (ITP) Immune thrombocytopenia (ITP) is an autoimmune disease. ITP is an illness that can lead to bruising and bleeding. In particular, antiplatelet autoantibodies lead to accelerated removal of platelets by macrophages with bone marrow compensation. Low levels of the cells that help blood clot, also known as platelets, most often cause the bleeding. Once known as idiopathic thrombocytopenic purpura, ITP can cause purple bruises. It also can cause tiny reddish-purple dots on the skin that look like a rash. Children can get ITP after a virus. They most often get better without treatment. In adults, the illness often lasts months or years. People with ITP who aren't bleeding and whose platelet count isn't too low might not need treatment. For worse symptoms, treatment might include medicines to raise platelet count or surgery to remove the spleen. Glomerulonephropathy Patent Application CLIMB-005 / 01WO 40193 / 24 The functioning of kidneys depends on the glomeruli — the mass of tiny, semipermeable tubes deep in the kidneys through which the blood passes, filtering out water and soluble wastes, which then travel to the bladder and out of the body through the ureters and urethra. These tubes are subject to injury from several sources including viruses, bacteria, certain immune diseases such as lupus, and other conditions such as hypertension. Symptoms of such kidney problems include fatigue, nausea, hematuria (pink or dark-colored urine due to red blood cells), proteinuria (bubbly urine from excess protein), hypertension (high blood pressure) and edema (fluid retention) causing swelling of face, hands and feet. Glomerulonephropathy is a disease that damages the glomeruli, or filters, in the kidneys. This damage can cause protein and red blood cells to leak into the urine, which can lead to kidney failure. Glomerulonephropathy may also result from other conditions including, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN). Systemic lupus erythematosus (SLE) Systemic lupus erythematosus (SLE), also known as lupus, is a chronic autoimmune disease that causes the body's immune system to attack healthy tissues and organs. This attack can lead to inflammation and damage in many parts of the body, including the skin, joints, heart, lungs, kidneys, and brain. The symptoms of SLE can vary from mild to severe. SLE can affect almost any organ in the body, but the kidneys and central nervous system are most commonly affected. The severity of the disease can range from mild to life threatening, and the outcome can range from lasting remission to death. IV. SUMMARY OF THE INVENTION Treatment of MN: The invention provides a method for treatment of patients with MN. In certain preferred embodiments, the invention provides methods for treatment of patients with primary membranous nephropathy (PMN). The method of the invention provides for administration of compositions comprising anti-CD19 antibodies for the treatment of MN and / or PMN. B-cell depletion therapy with the anti-CD20 mAb, rituximab, has shown clinical benefit in patients with MN by reducing proteinuria, presumably by limiting the maturation of B-cells into auto-reactive, antibody- secreting plasmablasts and plasma cells (PCs). However, it was beneficially recognized that CD19 is expressed at an earlier stage in B-cell development, appearing on early pro B-cells, and also Patent Application CLIMB-005 / 01WO 40193 / 24 persists throughout B-cell maturation on the surface of plasmablasts and some PCs. Accordingly, the methods of the invention provide the administration of anti-CD19 antibodies for elimination of CD19+ plasmablasts. Thus, the methods of the invention are directed to a method for treatment of MN and / or PMN by the administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. The impact of the administration of anti-CD19 antibody for treatment of MN and / or PMN was not previously explored. The methods of the invention beneficially provide that MN and / or PMN patients expressing anti-phospholipase A2 receptor (PLA2R) antibody have a higher response rate for the administration of anti-CD19 antibodies. This correlation of expression of anti-PLA2R antibody on the efficacy of a treatment with anti-CD19 antibodies was surprising and unexpected. Accordingly, in certain aspects, the methods of the invention provide a method for treatment of MN and / or PMN patients by administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody could be any anti-CD19 antibody that binds to the CD19 on the surface of B-cells. In certain aspects, the invention provides a method of treating a subject having membranous nephropathy (MN), the method comprising: providing a composition comprising a therapeutically effective amount an anti-CD19 antibody to the subject having an anti- phospholipase A2 receptor (PLA2R) antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and a light chain variable region comprising SEQ ID NO: 29. In certain preferred embodiments, the anti-CD19 antibody is budoprutug (also referred to as VB119 or TNT119 through the application). In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition is administered subcutaneously. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition comprises about 600 mg budoprutug. In certain embodiments, the composition comprises about 1000 mg budoprutug. In certain embodiments, the composition comprises 100 mg budoprutug. In certain embodiments, the composition comprises 200 mg budoprutug. In certain embodiments, the composition comprises 600 mg budoprutug. In certain embodiments, the composition comprises 1000 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the composition is administered in treatment cycles, wherein each treatment cycle comprises administering the composition comprising budoprutug once every two weeks, with a 24-week interval between each treatment cycle. In certain embodiments, the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15, and wherein there is a 24-week interval between each treatment cycle. In certain embodiments, the administration of composition results in remission of proteinuria in the patients. In certain aspects, the invention provides a method for treating a subject having membranous nephropathy (MN), wherein the method comprises testing the subject for the presence of anti-PLA2R antibody in serum. If the subject tests positive for anti-PLA2R antibody, administering a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the administration of composition results in remission of proteinuria in the patients. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain aspects, the invention method of determining whether a subject having membranous nephropathy (MN) will respond to treatment with an anti-CD19 antibody, the method comprising: conducting an assay on a sample from the subject that MN in order to determine the presence of anti- PLA2R antibody in the sample; providing results of the assay to the physician such that physician prescribes or provides the subject with a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the administration of composition results in remission of proteinuria in the patients. In certain aspects, the invention provides use of anti-CD19 antibody to in preparation of a medicament for treatment of membranous nephropathy (MN) in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody comprising a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, membranous nephropathy in the subject is primary membranous nephropathy (PMN). In certain embodiments, the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug. In certain embodiments, the medicament is administered parenterally. In certain embodiments, the medicament is administered via an intravenous (IV) infusion. In certain embodiments, the medicament is administered subcutaneously. In certain embodiments, the medicament comprises about 100 mg budoprutug, about 200 mg budoprutug, about 600 mg budoprutug, or about 1000 mg budoprutug. In certain embodiments, the medicament comprises 100 mg budoprutug, 200 mg budoprutug, 600 mg budoprutug, or 1000 mg budoprutug. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the medicament comprises 200 mg budoprutug. In certain embodiments, the medicament comprises 600 mg budoprutug. In certain embodiments, the medicament is administered once every two days. In certain embodiments, the medicament is administered at days 1, 15, 169, and 183. In certain embodiments, the medicament is administered in treatment cycles, wherein a treatment cycle comprises administering the composition once every two weeks, with a 24-week interval between each treatment cycle. In certain embodiments, the administration of the medicament results in remission of proteinuria in the patients. In certain embodiments, when it is determined that patient has an anti-phospholipase A2 receptor (PLA2R) antibody in serum, and administering medicament to said patient if the patient has an anti-phospholipase A2 receptor (PLA2R) antibody in serum. Treatment of ITP: The invention provides novel methods for treatment of immune thrombocytopenia (ITP). In certain aspects, the invention provides treating a subject having immune thrombocytopenia (ITP) comprising administering to the subject a composition comprising a therapeutically effective amount an anti-CD19 antibody. The anti-CD19 antibody may be a humanized anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. The invention beneficially provides that the anti-CD19 antibodies provide a good therapeutic response for patients with ITP. In particular, there are no previous therapies for ITP patients with compositions comprising anti-CD19 antibodies. The invention beneficially recognizes that the methods provided herein may provide a good response as compared to the previously known therapies because it targets CD-19+ plasma cells. The methods of the invention may be for patients who have had a previous therapy for treatment and / or management of ITP. In certain embodiments, the patient may have not benefited from the previous treatment regimen. Alternatively, the patient may have relapsed after the previous treatment regimen. In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprising the anti-CD19 antibody is administered in a dosing cycle. In certain embodiments, the dose cycle comprises administration Patent Application CLIMB-005 / 01WO 40193 / 24 of a single dose. In certain embodiments, the dose cycle comprises administration of more than one dose. In certain embodiments, the dose cycle comprises administration of two doses. In certain embodiments, the composition is administered at days 1 and 15 at the start of the treatment, wherein day 1 is the start of the treatment. In certain embodiments, the composition is further administered at days 169 and 183 after the start of the treatment. In certain embodiments, the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15 at start of each treatment cycle, wherein there is a 12 to 36-week interval between start of each said treatment cycle. In certain embodiments, interval between each treatment cycle is 12 weeks. In certain embodiments, said interval between each treatment cycle is 24 weeks. In certain embodiments, said interval between each treatment cycle is 36 weeks. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti- CD19 antibody is budoprutug. In certain embodiments, the composition comprises about 100 mg to about 1200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg to about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 600 mg to about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 250 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 600 mg of the anti-CD19 Patent Application CLIMB-005 / 01WO 40193 / 24 antibody. In certain embodiments, the composition comprises about 1000 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprises 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 250 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 600 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 1000 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain aspects, the method of the invention provides a novel “treat to target” approach for the treatment of ITP. This approach beneficially provides the measurement of the biological parameters associated with ITP after administration of the composition. The method of the invention provides the flexibility to alter the dosing regimen to provide additional doses of the anti-CD19 antibody after the initial dose to get optimal response for the treatment of ITP patients. In certain embodiments, the methods of the invention further comprise measuring concentration for markers or biological parameters of ITP progression in the subject after the administration of the initial dose. The method further provides that an additional dosing cycle of the anti-CD19 antibody may be administered. In certain embodiments, the additional dosing cycle is administered if there is below expected response after the administration of the initial dosing cycle of the anti-CD19 antibody. The markers or biological parameters for measurement of ITP progression could be measuring concentration of any marker or parameter associated to monitor the progression of ITP or symptoms thereof. The markers or parameters could be any parameters used to measure the efficacy of certain treatments. In certain embodiments, the methods of the invention provide that the markers are selected from the group consisting of platelet count and B cells. The concentration of B-cells measured could be circulating B cells. In certain embodiments, the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the composition. The timeline for measurement of markers or biological parameters could be determined based on the expected timeline for seeing a response after the administration of the initial dose of the composition comprising anti-CD19 antibody. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the measuring step is conducted about 8 to about 16 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. In certain embodiments, the measuring step is conducted about at least 12 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. In certain embodiments, the measuring step is conducted about at least 12 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. The invention recognizes that an additional dose of the treatment with anti-CD19 antibodies may be administered if an inadequate response is observed after the initial dose. The parameters or markers may be measured at the discretion of the physician treating the condition in the patient. The timeline for measurement of the markers of biological parameters may account for each patient’s physiological condition. For example, the parameters monitored are the platelet count and / or circulating B-cells in the patient. In certain embodiments, the additional dose is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle. In certain embodiments, the additional dosing cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle. In certain embodiments, the additional dosing cycle comprises administration of two doses of the composition comprising anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose of the composition comprising anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 50 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 200 mg of the anti-CD19 antibody. In Patent Application CLIMB-005 / 01WO 40193 / 24 certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 600 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 50 mg to about 500 mg of the anti- CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 600 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti- CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 1000 mg of the anti- CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 100 mg to about 1200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 200 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two Patent Application CLIMB-005 / 01WO 40193 / 24 doses, wherein at least one two doses comprises about 200 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 250 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 500 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 600 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 1000 mg of the anti-CD19 antibody. In certain embodiments, the invention provides pre-medication prior to each administration of the anti-CD19 antibody. In certain embodiments, the invention provides pre-medication prior to the infusion of budoprutug to reduce the frequency and severity of infusion-related reaction (IRRs). The premedication could be with a medical auxiliary product. In certain embodiments, the premedication is with a corticosteroid, antihistamine, or an antipyretic. In certain embodiments, the corticosteroid is administered intravenously. In certain embodiments, the antihistamine is administered orally. In certain embodiments, the antipyretic is administered orally. In certain preferred embodiments, the corticosteroid may be methylprednisone or an equivalent thereof. In certain preferred embodiments, the antihistamine may be diphenhydramine or an equivalent thereof. In certain preferred embodiments, the antipyretic may be acetaminophen / paracetamol or an equivalent thereof. In certain aspects, the invention provides a method of treating a subject having immune thrombocytopenia (ITP), the method comprising: administering a first cycle of a pharmaceutical composition comprising a therapeutically effective amount of a therapeutic agent; monitoring markers associated with ITP progression in the subject; and providing a second cycle of compositions comprising therapeutically effective amount of said anti-CD19 antibody if the biological parameters demonstrate an inadequate physiological response after the first cycle. In certain embodiments, the therapeutic agent is an anti-CD19 antibody. In certain embodiments, the second cycle is different from the first cycle. In certain embodiments, the first cycle comprises administration at days 1 and 15 at the start of the treatment. In certain Patent Application CLIMB-005 / 01WO 40193 / 24 embodiments, the markers are selected from the group consisting of platelet count and B cells. In certain embodiments, the monitoring step is conducted about 8 to about 16 weeks after start of the first cycle. In certain embodiments, the monitoring step is conducted about 12 weeks after start of the first cycle. In certain embodiments, the second cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after start of the first cycle. In certain embodiments, the second cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after start of the first cycle. In certain embodiments, the subject has insufficient response to at least one prior therapy for treatment of ITP. The invention beneficially recognizes that the methods provided herein demonstrate treatment of orphan conditions, such as ITP, in a personalized medicine approach. CD19 B cell depletion has the potential to reshape the treatment in immune mediated diseases, and the unique treat to target approach provided herein enables the treatment of patients throughout their journey and provide a tailored approach for each patient. In certain aspects, the invention provides use of an anti-CD19 antibody to in preparation of a medicament for treatment of immune thrombocytopenia (ITP) in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody comprising a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti- CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug. In certain embodiments, the medicament is administered parenterally. In certain embodiments, the medicament is administered via an intravenous (IV) infusion. In certain embodiments, the medicament is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to about 1000 mg, or about 500 mg to about 1000 mg the anti-CD19 antibody. In certain embodiments, the medicament comprises 100 mg to 500 mg, 100 mg to 400 mg, 100 mg to 300 mg about, 100 mg to 1000 mg, 250 mg to 1000 mg, or 500 mg to 1000 mg the anti-CD19 antibody. In certain embodiments, the medicament comprises about 100 mg, about 200 mg, about 500 mg, or about 1000 mg of the anti-CD19 antibody. In certain embodiments, the medicament comprises 100 mg, 200 mg, 500 mg, or 1000 mg of the anti-CD19 antibody. In certain embodiments, the use Patent Application CLIMB-005 / 01WO 40193 / 24 further comprises measuring concentration for markers of ITP progression in the subject; and optionally administering an additional dosing cycle of the composition to the subject. In certain embodiments, the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the medicament. In certain embodiments, the markers are selected from the group consisting of platelet count and B cells. In certain embodiments, the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the medicament. In certain embodiments, the measuring step is conducted about 8 to about 16 weeks, about at least 12 weeks, or about 12 weeks after administration of initial dose of the medicament. In certain embodiments, the additional dosing cycle comprises administration of a single dose of the medicament or at least two additional doses of the medicament. In certain embodiments, the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to about 1000 mg, about 500 mg to about 1000 mg, about 200 mg, about 250 mg, about 500 mg, or about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle, or if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle. In certain embodiments, the patient has insufficient response to at least one prior therapy for treatment of ITP. In certain aspects, the invention provides use of an anti-CD19 antibody to in preparation of a medicament for treatment of immune thrombocytopenia (ITP) in a patient in need thereof, wherein the use comprises: administering a first cycle of said medicament comprising a therapeutically effective amount of an anti-CD19 antibody; monitoring markers associated with ITP progression in the subject; and providing a second cycle of medicament comprising therapeutically effective amount of said anti-CD19 antibody if the biological parameters demonstrate an inadequate physiological response after the first cycle. In certain embodiments, the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug. In certain embodiments, the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion. In certain embodiments, the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to Patent Application CLIMB-005 / 01WO 40193 / 24 about 1000 mg, about 500 mg to about 1000 mg, about 200 mg, about 250 mg, about 500 mg or about 1000 mg of the anti-CD19 antibody. In certain embodiment, the second cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle, or if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle. Treatment of Glomerulonephropathy: In certain aspects, the invention provides novel methods for treatment of glomerulonephropathy. The patients may be suffering from glomerulonephropathy associated with autoantibodies. The patients may have glomerulonephropathy due to other underlying pathology. For example, glomerulonephropathy may be due to MCD or FSGS. There is an unmet need for improved therapies for steroid-dependent and frequently relapsing MCD and FSGS, and there are currently no Food and Drug Administration-approved treatments specifically indicated for primary MCD or primary FSGS. Patients with MCD and FSGS suffer frequent disease flares and complications from long-term corticosteroid exposure. The invention provides a novel therapeutic approach for reducing inflammation and injury to kidney through depletion of CD19+ cells through compositions comprising anti-CD19 antibodies. The invention provides methods of treatment of glomerulonephropathy associated with MCD and FSGS. In certain beneficial aspects, the methods provided herein reduce proteinuria and maintain remission in MCD / FSGS patients. A significant challenge in the treatment of patients with MCD is that a significant number of patients have become steroid dependent, which is the current standard of care for the treatment of MCD patients. These patients are unable to taper steroids without a relapse. In addition, this is a frequently relapsing disease. In certain aspects, the invention provides a method of treating a subject having glomerulonephropathy, wherein the method comprises administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, glomerulonephropathy is associated with the generation of autoantibodies. In certain embodiments, glomerulonephropathy is selected from the group consisting of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN). In certain embodiments, the invention provides that immunomodulation by anti-CD19 antibody and reduction in number of CD19+ B-cells. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the patients are corticosteroid-dependent or frequently relapsing. In certain embodiments, the subject has previously received corticosteroid therapy and / or any additional therapy for treatment of nephrotic syndromes. In certain embodiments, the patients are responsive to corticosteroids. Accordingly, in certain embodiments, the patients receiving the anti- CD19 therapy are responsive to therapy with corticosteroids or steroids. In certain embodiments, the additional therapies are selected from the group consisting of calcineurin inhibitors, mycophenolic acid analogues, azathioprine, and cyclophosphamide. In certain embodiments, the subject has received the corticosteroid therapy for at least 8 weeks before start of administration of the composition comprising a therapeutically effective amount of anti- CD19 antibody. In certain embodiments, the corticosteroid therapy is administration of prednisone. In certain embodiments, the prednisone is administered at a dose higher than 20 mg / day, the subject is tapered off to a dose of 20 mg / day of prednisone. In certain embodiments, tapering is done from at least eight weeks to about 2 weeks before starting administration of the composition. In certain embodiments, prednisone is administered at a dose of less than about 20 mg / day for at least two weeks before starting administration of the composition. In certain embodiments, the anti-CD19 antibody of the invention could be any anti-CD19 antibody provided herein. In certain embodiments, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, wherein the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising a therapeutically effective amount of anti-CD19 antibody is administered parenterally. In certain embodiments, the composition comprising a therapeutically effective amount of anti-CD19 antibody is administered via intravenous (IV) infusion. In certain preferred embodiments, the anti-CD19 antibody administered to the subject is budoprutug. In certain embodiments, the composition comprising a therapeutic effective amount of anti- CD19 antibody is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of Patent Application CLIMB-005 / 01WO 40193 / 24 the anti-CD19 antibody. In certain embodiments, composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, composition comprises about 100 mg to about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, composition comprises about 100 mg of the anti-CD19 antibody. In certain preferred embodiments, composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the method further comprises administration of an additional cycle to the subject, wherein the additional cycle comprises administration of a first additional dose of the composition and a second additional dose of the composition. In certain embodiments, the concentration of B cells is measured to decide if the additional cycle is administered. A high B cell count indicates that the administration of the composition of the invention did not have the desired effect. In certain embodiments, the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 155 after first administration of the composition to the subject. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 141 after first administration of the composition to the subject. In certain embodiments, the second additional dose is administered 14 days after administration of the first additional dose. In certain embodiments, the first additional dose of the additional cycle is administered between day 169 and day 183 after first administration of the composition to the subject. In certain embodiments, the first additional dose and the second additional dose are administered if the subject has not previously received the first additional dose and the second additional dose between days 113 and 115 after first administration of the composition to the subject. In certain embodiments, the first additional dose and the second additional dose comprise about 100 mg of the anti-CD19 antibody. In certain embodiments, the first additional dose and the second additional dose comprise about 200 mg of the anti-CD19 antibody. In certain embodiments, the invention provides use of an anti-CD19 antibody to in preparation of a medicament for treatment of glomerulonephropathy in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region Patent Application CLIMB-005 / 01WO 40193 / 24 comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug. In certain embodiments, the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion. In certain embodiments, glomerulonephropathy is associated with autoantibodies. In certain embodiments, the glomerulonephropathy is selected from the group consisting of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN). In certain embodiments, the patient is corticosteroid-dependent or frequently relapsing. In certain embodiments, the patient has previously received corticosteroid therapy and / or any additional therapy for treatment of nephrotic syndromes, and preferably the additional therapies are selected from the group consisting of calcineurin inhibitors, mycophenolic acid analogues, azathioprine, and cyclophosphamide. In certain embodiments, the medicament is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg, about 100 mg, or about 200 mg of the anti-CD19 antibody. In certain embodiments, the patient has received the corticosteroid therapy for at least 8 weeks before start of administration of the medicament. In certain embodiments, the corticosteroid therapy is administration of prednisone, and preferably the prednisone is administered at a dose higher than 20 mg / day, the patient is tapered off to a dose of 20 mg / day of prednisone, and tapering is done from at least eight weeks to about 2 weeks before starting administration of the composition. In certain embodiments, prednisone is administered at a dose of less than about 20 mg / day for at least two weeks before starting administration of the composition. In certain embodiments, the corticosteroid therapy is gradually tapered off in about 12 weeks or about 16 weeks after starting the administration of the composition. In certain embodiments, the use further comprises administration of an additional cycle to the patient, wherein the additional cycle comprises administration of a first additional dose of the composition and a second additional dose of the medicament. In certain embodiments, the additional cycle is administered if B cell count in the patient is greater than 10 cells / µL. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 155 after first administration of the medicament to the patient. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 141 after first administration of the medicament to the patient. In certain embodiments, the second additional dose is administered 14 days after administration of the first additional dose. In certain embodiments, the first additional Patent Application CLIMB-005 / 01WO 40193 / 24 dose of the additional cycle is administered between day 169 and day 183 after first administration of the medicament to the patient. In certain embodiments, the first additional dose and the second additional dose are administered if the patient has not previously received the first additional dose and the second additional dose between days 113 and 115 after first administration of the medicament to the subject; and preferably the first additional dose and the second additional dose comprise about 200 mg of the anti-CD19 antibody. Treatment of SLE: The invention provides novel methods for treatment of systemic lupus erythematosus (SLE). The methods of the invention provide safe and efficacious treatment of SLE. Specifically, the invention recognizes that there is an unmet need for treatment of patients with refractory SLE. The current standard of care also involves the use belimumab (C cell activating factor blockade), anifrolumab (type 1 receptor blockade) for refractory disease. In certain instances, rituximab is also used for treatment or management of symptoms of SLE patients. In the current standard of care, there is a substantial population of patients that are refractory to the current therapies. Indeed, the current standard of care lead to a lot of patients being dependent on corticosteroids. There are also frequent relapses, especially of nephritis, vasculitis, thrombosis, and lead to cumulative damage and organ failure. In addition, there is also fatigue and cognitive dysfunction in patients with current standard of care. This leads to poor responses, impaired participation, and reduced quality of life. In addition, there treatment- associated burden of cardiovascular mortality, infection, and neoplasm risk. The invention beneficially recognizes that targeting B cell depletion by anti-CD19 antibodies will provide a novel method for treatment of SLE. The methods of the invention overcome the drawbacks of conventional therapies for treatment by SLE by targeting CD19 positive B cells. In certain aspects, the invention provides a method of treating a subject having systemic lupus erythematosus (SLE), wherein the method comprises administration of a composition comprising a therapeutically effective amount an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody may be any anti-CD19 antibody provided herein. In certain embodiments, the anti-CD19 antibody, wherein the anti-CD19 antibody Patent Application CLIMB-005 / 01WO 40193 / 24 comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti- CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition of the invention is administered parenterally. In certain embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 4. In certain embodiments, the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 6. In certain embodiments, the subject has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid. In certain embodiments, the subject is receiving equal to or less than 20 mg prednisone at least 28 days before start of the treatment. In certain embodiments, the composition is administered only on the first day after start of treatment. Thus, in certain embodiments, the methods of the invention provide a single dose administration of the compositions of the invention. In certain embodiments, the composition is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the composition comprises about 100 mg to about 600 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 600 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises 600 mg of the anti-CD19 antibody. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain aspects, the patient has previously received therapy for treatment of SLE. IN certain embodiments, the subject has previously received at least two therapies for SLE. In certain embodiments, at least one of the prior therapy is corticosteroid therapy. In certain embodiments, the corticosteroid therapy is treatment of prednisone. In certain embodiments, biological parameters associated with SLE are monitored to gauge the efficacy of the treatment. In certain embodiments, the method provides that the B-cell concentration is monitored during the course of the treatment. In certain embodiments, B-cell count is monitored after administration of the composition. In certain embodiments, the method further comprises administration of an additional cycle to the subject if B-cell count is high. In certain embodiments, the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL. In certain aspects, the invention provides use of an anti-CD19 antibody to in preparation of a medicament for treatment of systemic lupus erythematosus (SLE) in a patient in need thereof, wherein the medicament comprises a therapeutically effective amount an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug. In certain embodiments, the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion. In certain embodiments, the patient has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 4, or preferably SLEDAI of greater than 6. In certain embodiments, the patient has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid, and preferably the patient is receiving equal to or less than 20 mg prednisone at least 28 days before start of the treatment. In certain embodiments, the medicament is administered only on first day after start of treatment or wherein the medicament is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the medicament comprises about 100 mg to about 600 mg, about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg, about 300 mg to about 600 mg, about 100 mg, about 200 mg, about 300 mg, or about 600 mg of the anti-CD19 antibody. In certain embodiments, the medicament comprises 100 mg to 600 mg, 100 mg to 500 mg, 100 mg to 400 mg, 100 mg to 300 mg, 300 mg Patent Application CLIMB-005 / 01WO 40193 / 24 to 600 mg, 100 mg, 200 mg, 300 mg, or 600 mg of the anti-CD19 antibody. In certain embodiments, the patient has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid; and the corticosteroid therapy is administration of prednisone. In certain embodiments, B-cell count is monitored after administration of the composition. In certain embodiments, the use further comprises administration of an additional cycle to the subject if B- cell count is high; and preferably the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL. V. BRIEF DESCRIPTION OF THE FIGURES FIG.1 provides B-cell count of a patient after administration of budoprutug. FIG.2 provides an overview of the participants in the trial. FIG.3 provides individual peripheral CD20+ B-cell count versus time following first budoprutug administration for participants with MN. FIG.4 provides individual proteinuria (UPCR) versus time following first budoprutug administration for participants with MN. FIG.5 provides Sensitivity Analysis: Individual Proteinuria (UPCR) Versus Time Following First Budoprutug Administration for Participants with MN. FIG. 6 provides collated data for the CD20+ cell count, anti-PLA2R antibodies, and UPCR at various time points after the administration of budoprutug. FIG.7, FIG.8, and FIG.9 show the IgA, IgG, and IgM versus time following first budoprutug administration for participants with MN for the FAS, respectively. FIG.10 provides average anti-PLA2R antibodies over time after the administration of budoprutug. FIG.11 shows plasma budoprutug concentration versus time for the PK population. FIG.12 and FIG.13 provide an overview of the clinical trials for Phase 1b clinical trials. FIG.14 and FIG.15 provide an overview of the Phase 2 trial. FIG.16 provides an overview of the current methods of management and administered therapies to patients with ITP. Patent Application CLIMB-005 / 01WO 40193 / 24 FIG.17 provides the data pertaining to plasma cells in spleen after treatment with rituximab. FIG.18 provides a schematic of the mechanism for the B cell population growth after treatment with rituximab. FIG.19 and FIG.20 provide overview of Phase 2 trial design for treatment of ITP. FIG.21 provides the schematic of the design of Phase II trials for glomerulonephropathy. FIG.22 provides an overview of the therapies for treatment of SLE. FIG.23 provides an overview of CD19 CAR-T therapy. FIG.24 provides an overview of autoantibodies in B cells. FIG.25 provide an overview of design of Phase Ib / 2a clinical trials. FIG.26 provides viability of PBMC subsets following incubation with budoprutug. FIG.27 provides distribution of PBMC subsets following incubation with budoprutug. FIG.28, FIG.29, FIG.30, FIG.31, FIG.32, FIG.33, FIG.34, FIG.35, FIG.36, and FIG. 37 provide the data from multiplex cytokine analysis using MSD following stimulation with plate-bound or soluble antibodies. FIG.38 provides the data of TNT119 binding assays, as compared to rituximab and isotype. FIG.39 and FIG.40 provide a comparison of ADCC with PBMCs from healthy donors and SLE donors respectively. VI. DETAILED DESCRIPTION The invention provides a method for treatment of patients with MN. In certain preferred embodiments, the invention provides methods for treatment of patients with primary membranous nephropathy (PMN). The method of the invention provides for administration of compositions comprising anti-CD19 antibodies for the treatment of MN and / or PMN. B-cell depletion therapy with the anti-CD20 mAb, rituximab, has shown clinical benefit in patients with MN by reducing proteinuria, presumably by limiting the maturation of B-cells into auto-reactive, antibody- secreting plasmablasts and plasma cells (PCs). However, it was beneficially recognized that CD19 is expressed at an earlier stage in B-cell development, appearing on early pro B-cells, and also Patent Application CLIMB-005 / 01WO 40193 / 24 persists throughout B-cell maturation on the surface of plasmablasts and some PCs. Accordingly, the methods of the invention provide the administration of anti-CD19 antibodies for elimination of CD19+ plasmablasts. Anti-CD19 antibodies of the invention: In certain aspects, the invention provides anti-CD19 antibodies which feature an amino acid sequence defining a modified immunoglobulin heavy chain framework region comprising amino acid residues 1-30 of SEQ ID NO:22, wherein one or more of the amino acid residues at positions X5, X12, X19, X20, X23, and X24 are as follows: X5 is Q or E, X12 is V or K, X19 is R or K, X20 is L or V, X23 is K, E or D, or X24 is T or A. In certain embodiments, at least one of the amino acid residues at positions X5, X12, X19, X20, X23, or X24 is not the same amino acid residue as the amino acid at the corresponding position in the unmodified immunoglobulin heavy chain framework region as set forth in amino acid residues 1-30 of SEQ ID NO:13. In one embodiment, X23 is E or D. In certain embodiments, the anti-CD19 antibodies feature an amino acid sequence defining a modified immunoglobulin heavy chain framework region comprising amino acid residues 1-14 of SEQ ID NO:23, wherein one or more of the amino acid residues at positions X3, X5, X7, and X8, are as follows: X3 is K or R, X5 is R, T, or A, X7 is G, D, or E, or X8 is Q or K. According to this aspect of the invention, at least one of the amino acid residues at positions X3, X5, X7, or X8 is not the same as the amino acid at the corresponding position in the unmodified immunoglobulin heavy chain framework region as set forth in amino acid residues 36-49 of SEQ ID NO:13. In one embodiment, X7 is E or D. In certain embodiments, the anti-CD19 antibodies feature an amino acid sequence defining a modified immunoglobulin heavy chain framework region comprising amino acid residues 1-39 of SEQ ID NO:24, wherein one or more of the amino acid residues at positions X6, X10, X26, X29, and X34 are as follows: X6 is K, D, or E, X10 is K, E, or D, X26 is S, D, or E, X29 is S or A, or X34 is V or T. According to this aspect of the invention, at least one of the amino acid residues at positions X6, X10, X26, X29, or X34 is not the same as the amino acid at the corresponding position in the unmodified immunoglobulin heavy chain framework region as set forth in amino acid residues 60-98 of SEQ ID NO:13. In one embodiment, X10 is E or D. In certain embodiments, the anti-CD19 antibodies feature an amino acid sequence defining a modified immunoglobulin light chain framework region comprising amino acid residues 1-23 of Patent Application CLIMB-005 / 01WO 40193 / 24 SEQ ID NO:32, wherein one or more of the amino acid residues at positions X1, X3, X7, X10, X11, and X19 are as follows: X1 is Q or D, X3 is V or A, X7 is S or E, X10 is I or T, X11 is M or L, or X19 is V or A. According to this aspect of the invention, at least one of the amino acid residues at positions X1, X3, X7, X10, X11, or X19 is not the same as the amino acid at the corresponding position in the unmodified immunoglobulin light chain framework region as set forth in amino acid residues 1-23 of SEQ ID NO:25. In one embodiment, X3 is A and X7 is E. In another embodiment, X1 is D, X10 is I, and X11 is L. In certain embodiments, the invention features an amino acid sequence defining a modified immunoglobulin light chain complementarity determining region comprising amino acid residues 24-33 of SEQ ID NO:28. In certain embodiments, the invention features an amino acid sequence defining a modified immunoglobulin light chain framework region comprising amino acid residues 56-87 of SEQ ID NO:28. According to another aspect, the invention features an antibody variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, or SEQ ID NO: 31, wherein the antibody variable region specifically binds to CD19. In certain embodiments, the invention features a polypeptide at least 90% or at least 95% identical to a B4 antibody heavy chain variable region, the polypeptide comprising an amino acid substitution at one or more residues corresponding to Val12, Leu20, Lys23, Thr24, Lys38, Gly42, Gln43, Lys65, Lys69, Ser85, Ser88, or Val93. In one embodiment, the polypeptide comprises one or more of substitutions Gln5Glu, Val12Lys, Arg19Lys, Leu20Val, Lys23Glu, Lys23Asp, Thr24Ala, Lys38Arg, Arg40Thr, Gly42Asp, Gly42Glu, Gln43Lys, Lys65Asp, Lys65Glu, Lys69Glu, Lys69Asp, Ser85Asp, Ser85Glu, Ser88Ala, or Val93Thr. According to another aspect, the invention features a polypeptide at least 90% or at least 95% identical to a B4 antibody light chain variable region, the polypeptide comprising an amino acid substitution at one or more residues corresponding to Val3, Ser7, Ile10, Met11, Val19, Val29, Ser51, Leu53, Ala54, or Ser75. In one embodiment, the polypeptide comprises one or more of substitutions Gln1Asp, Val3Ala, Ser7Glu, Ile10Thr, Met11Leu, Val19Ala, Val29Ala, Ser51Asp, Leu53Thr, Ala54Asp, or Ser75Glu. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain aspects, the invention provides a process for preparation of anti-CD19 antibody, wherein the anti-CD19 antibody comprises variable domain comprising a light chain variable region that is at least 90% identical to SEQ ID NO: 25 and has an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53; and the process comprises production of the anti-CD19 antibody in Chinese Hamster Ovary (CHO) cells. In certain aspects, the invention provides a process for preparation of an anti-CD19 antibody, wherein: the anti-CD19 antibody comprises SEQ ID NO: 13 with an amino acid substitution at one or more residues corresponding to Gln5, Arg19, Leu20, Arg40, Gln43, Lys65, Ser85, Ser88, and Val93, and SEQ ID NO: 25 with an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53; and the process comprises production of the anti-CD19 antibody in Chinese Hamster Ovary (CHO) cells. In certain embodiments, the anti-CD19 antibody variable domain comprises a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody is provided in U.S. Patent No. 8,691,952, which is incorporated by reference in its entirety. In certain embodiments, the anti-CD19 antibody variable domain comprises a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 29 are provided in U.S. Patent No.8,691,952. In certain embodiments, the heavy chain variable region of the anti-CD19 antibody has, compared to SEQ ID NO:13, one or more amino acid substitutions selected from the group consisting of Gln5Glu, Arg19Lys, Leu20Val, Arg40Thr, Gln43Lys, Lys65Asp, Ser85Asp, Ser88Ala, and Val93Thr. In certain embodiments, the heavy chain variable region of the anti-CD19 antibody is SEQ ID NO: 13 comprising an amino acid substitution at one or more residues corresponding to Gln5, Arg19, Leu20, Arg40, Gln43, Lys65, Ser85, Ser88, and Val93. In certain embodiments, the heavy chain variable region of the anti-CD19 antibody has one or more amino acid substitutions selected from the group consisting of Gln5Glu, Arg19Lys, Leu20Val, Arg40Thr, Gln43Lys, Lys65Asp, Ser85Asp, Ser88Ala, and Val93Thr. In certain embodiments, wherein the heavy chain variable region of the anti-CD19 antibody has one or more amino acid substitutions selected from the group consisting of Gln5Glu, Arg19Lys, Leu20Val, Arg40Thr, Gln43Lys, Lys65Asp, Ser85Asp, Ser88Ala, and Val93Thr. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, wherein the heavy chain variable region of the anti-CD19 antibody is the amino acid sequence of SEQ ID NO: 17. In certain embodiments, the anti-CD19 antibody variable domain of the anti-CD19 antibody further comprises a light chain variable region that is at least 90% identical to SEQ ID NO: 25 and has an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53. In certain embodiments, wherein the light chain variable region the anti-CD19 antibody has one or more amino acid substitutions selected from the group consisting of Ile10Thr, Met11Leu, Val19Ala, Ser51Asp, and Leu53Thr. In certain embodiments, the light chain variable region is at least 95% identical to SEQ ID NO: 25. In certain embodiments, the light chain variable region has one or more amino acid substitutions selected from the group consisting of Ile10Thr, Met11Leu, Val19Ala, Ser51Asp, and Leu53Thr. In certain embodiments, the light chain variable region is SEQ ID NO: 25 comprising an amino acid substitution at one or more residues corresponding to Ile10, Met11, Val19, Ser51, and Leu53. In certain embodiments, the light chain variable region has one or more amino acid substitutions selected from the group consisting of Ile10Thr, Met11Leu, Val19Ala, Ser51Asp, and Leu53Thr. In certain embodiments, the light chain variable region is the amino acid sequence of SEQ ID NO: 29. In certain embodiments, the heavy chain variable region comprises one or more of substitutions Gln5Glu, Arg19Lys, Leu20Val, Arg40Thr, Gln43Lys, Lys65Asp, Ser85Asp, Ser88Ala, and Val93Thr. In certain embodiments, wherein the light chain variable region comprises one or more of substitutions Ile10Thr, Met11Leu, Val19Ala, Ser51Asp, and Leu53Thr. In certain embodiments, the anti-CD19 antibody is VB119 (budoprutug). In certain embodiments, VB119 is an anti-CD19, IgG1 monoclonal antibody. VB119 demonstrates antibody- dependent cell mediated toxicity (ADCC) with minimal to no complement dependent cytotoxicity (CDC). Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the anti-CD19 antibody comprises one or more of the below listed subunits in the anti-CD19 antibody: Subunit 1 (SEQ ID NO: 50): QVQLEQPGAEVVKPGASVKVSCKTSGYTFTSNWMHWVKQTPGKGLEWIGEIDP SDSYTNYNQKFDGKAKLTVDKSSSTAYMEVSDLTAEDSATYYCARGSNPYYYAMDYW GQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Subunit 2 (SEQ ID NO: 51): QVQLEQPGAEVVKPGASVKVSCKTSGYTFTSNWMHWVKQTPGKGLEWIGEIDP SDSYTNYNQKFDGKAKLTVDKSSSTAYMEVSDLTAEDSATYYCARGSNPYYYAMDYW GQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNA KTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Subunit 3 (SEQ ID NO: 52): QIVLTQSPATLSASPGEKATMTCSASSGVNYMHWYQQKPGTSPKRWIYDTDKTAS GVPARFSGSGSGTSYSLTISSMEAEDAATYYCHQRGSYTFGGGTKLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Subunit 4 (SEQ ID NO: 53): QIVLTQSPATLSASPGEKATMTCSASSGVNYMHWYQQKPGTSPKRWIYDTDKTAS GVPARFSGSGSGTSYSLTISSMEAEDAATYYCHQRGSYTFGGGTKLEIKRTVAAPSVFIFP PSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the heavy chain sequence of the anti-CD19 antibody is provided below (SEQ ID NO: 54): QVQLEQPGAEVVKPGASVKVSCKTSGYTFTSNWMHWVKQTPGKGLEWIGEIDPSDSYT NYNQKFDGKAKLTVDKSSSTAYMEVSDLTAEDSATYYCARGSNPYYYAMDYWGQGTS VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTL PPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK In certain embodiments, the light chain sequence of the anti-CD19 antibody is provided below (SEQ ID NO: 55): QIVLTQSPATLSASPGEKATMTCSASSGVNYMHWYQQKPGTSPKRWIYDTDKTASGVPA RFSGSGSGTSYSLTISSMEAEDAATYYCHQRGSYTFGGGTKLEIKRTVAAPSVFIFPPSDE QLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, budoprutug comprises a heavy chain and a light chain. In certain embodiments, budoprutug comprises heavy chain and light chain provided in SEQ ID NO: 54 and SEQ ID NO: 55 respectively. In certain embodiments, the heavy chain of anti-CD19 antibody is at least 90% identical to SEQ ID NO: 54. In certain embodiments, the heavy chain of anti-CD19 antibody is at least 95% identical to SEQ ID NO: 54. In certain embodiments, the heavy chain of anti-CD19 antibody is at least 98% identical to SEQ ID NO: 54. In certain embodiments, the heavy chain of anti-CD19 antibody is identical to SEQ ID NO: 54. In certain embodiments, the light chain of anti-CD19 antibody is at least 90% identical to SEQ ID NO: 55. In certain embodiments, the light chain of anti-CD19 antibody is at least 95% identical to SEQ ID NO: 55. In certain embodiments, the light chain of anti-CD19 antibody is at least 98% identical to SEQ ID NO: 55. In certain embodiments, the light chain of anti-CD19 antibody is identical to SEQ ID NO: 55. Fc Portion Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the antibody variable domains of the antibodies prepared using the methods of the invention are optionally fused to an Fc portion. As used herein, the Fc portion encompasses domains derived from the heavy chain constant region of an immunoglobulin, preferably a human immunoglobulin, including a fragment, analog, variant, mutant or derivative of the constant region. The constant region of an immunoglobulin heavy chain is defined as a naturally-occurring or synthetically produced polypeptide homologous to at least a portion of the C-terminal region of the heavy chain, including the CH1, hinge, CH2, CH3, and, for some heavy chain classes, CH4 domains. The “hinge” region joins the CH1 domain to the CH2-CH3 region of an Fc portion. The constant region of the heavy chains of all mammalian immunoglobulins exhibit extensive amino acid sequence similarity. In the present invention, the Fc portion typically includes at least a CH2 domain. For example, the Fc portion can include the entire immunoglobulin heavy chain constant region (CH1- hinge-CH2-CH3). Alternatively, the Fc portion can include all or a portion of the hinge region, the CH2 domain and the CH3 domain. The constant region of an immunoglobulin is responsible for many important antibody effector functions, including those mediated by Fc receptor (FcR) binding and by complement binding. There are five major classes of the heavy chain constant region, classified as IgA, IgG, IgD, IgE, and IgM, each with characteristic effector functions designated by isotype. IgG, for example, is separated into four Ȗ^isotypes: Ȗ^^^Ȗ^^^Ȗ^^^and Ȗ^^^also known as IgG1, IgG2, IgG3, and IgG4, respectively. IgG molecules can interact with multiple classes of cellular receptors including three classes of FcȖ^receptors (FcȖR) specific for the IgG class of antibody, namely FcȖRI, FcȖRII, and FcȖRIII. The sequences important for the binding of IgG to the FcȖR receptors have been reported to be in the CH2 and CH3 domains. It is also often useful to alter the serum half-life of the antibody. The serum half-life of an antibody, as of an immunoglobulin fusion protein, is influenced by the ability of that antibody to bind to an Fc receptor (FcR) (Gillies et al., Cancer Research (1999) 59:2159-66). The CH2 and CH3 domains of IgG2 and IgG4 have undetectable or reduced binding affinity to Fc receptors compared to those of IgG1. Accordingly, the serum half-life of the featured antibody can be increased by using the CH2 and / or CH3 domain from IgG2 or IgG4 isotypes. Alternatively, the antibody can include a CH2 and / or CH3 domain from IgG1 or IgG3 with modification in one or more amino acids in these domains to reduce the binding affinity for Fc receptors (see, e.g., U.S. Patent Application CLIMB-005 / 01WO 40193 / 24 patent application Ser. No. 09 / 256,156, published as U.S. patent application publication 2003- 0105294, which is incorporated by reference in its entirety). In certain embodiments, an Fc portion fused to an antibody variable region of the invention can contain CH2 and / or CH3 domains and a hinge region that are derived from different antibody isotypes. For example, the Fc portion can contain CH2 and / or CH3 domains of IgG2 or IgG4 and a hinge region of IgG1. Assembly of such hybrid Fc portions has been described in U.S. patent application publication 2003-0044423, which is incorporated by reference in its entirety. When fused to an antibody variable region of the invention, the Fc portion may contain one or more amino acid modifications that generally extend the serum half-life of an Fc fusion protein. Such amino acid modifications include mutations substantially decreasing or eliminating Fc receptor binding or complement fixing activity. For example, one type of such mutation removes the glycosylation site of the Fc portion of an immunoglobulin heavy chain. In IgG1, the glycosylation site is Asn297 (see, for example, U.S. patent application Ser. No. 10 / 310,719, published as U.S. patent application publication 2003-0166163). The term “about,” when used in the context of describing the dose of the anti-CD19 antibody means ± 5% of the recited dose. The term “shelf-stable pharmaceutical composition” as used herein means a pharmaceutical composition which is stable for at least the period which is required by regulatory agencies in connection with therapeutic proteins. Preferably, a shelf-stable pharmaceutical composition is stable for at least one year at 5° C. Stability includes chemical stability as well as physical stability. The term “effective amount” as used herein means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment. The term “composition” or “pharmaceutical composition” as used herein means a product comprising an active compound or a salt thereof together with pharmaceutical excipients such as buffer, preservative and tonicity modifier, said pharmaceutical composition being useful for treating, preventing or reducing the severity of a disease or disorder by administration of said pharmaceutical composition to a person. Thus, a pharmaceutical composition is also known in the art as a pharmaceutical formulation. It is to be understood that pH of a pharmaceutical composition which is to be reconstituted is the pH value which is measured on the reconstituted composition produced by reconstitution in the prescribed reconstitution liquid at room temperature. Patent Application CLIMB-005 / 01WO 40193 / 24 The term “pharmaceutically acceptable” as used herein means suited for normal pharmaceutical applications, i.e. giving rise to no adverse events in patients etc. The term “buffer” as used herein refers to a chemical compound in a pharmaceutical composition that reduces the tendency of pH of the composition to change over time as would otherwise occur due to chemical reactions. Buffers include chemicals such as sodium phosphate, TRIS, glycine and sodium citrate. Membranous Nephropathy: The majority of patients present nephrotic syndrome. The complications associated with nephrotic syndrome include edema, hyperlipidemia, thrombosis, and infections. Remission of nephrotic patients with MN increases the chances of survival. Kidney Int. 2004 Sep;66(3):1199- 205. Rituximab, a monoclonal antibody against the cell surface antigen CD20 of B cells, was reported to safely reduce proteinuria and ameliorate nephrotic syndrome (NS) in eight patients with primary membranous nephropathy (MN) and severe NS unresponsive to prolonged angiotensin-converting-enzyme (ACE) inhibitor therapy. J Am Soc Nephrol. 2015 Oct;26(10):2545-58. N Engl J Med.2019 Jul 4;381(1):36-46. In approximately 70% of adult patients with primary MN autoantibodies against an antigen normally expressed on the podocyte cell, the M-type phospholipase A2 receptor (PLA2R) circulates and binds to conformational epitopes present on PLA2R, producing in situ deposits characteristic of the disease. Circulating anti-PLA22R autoantibodies are almost exclusively specific to patients with primary MN offered clinicians and scientists a powerful tool to differentiate primary from secondary forms and monitor disease activity and response to therapy. Combination therapies for MN have been previously explored. For example, rituximab and Cytoxan were utilized for treatment of MN with prednisone. Cortazar, Frank B. et al. KI Reports 2018; 3(2):94 – 402. Am J Kidney Dis.2021 Dec;78(6):793-803. FIG.12 and FIG.13 provide an overview of the clinical trials for Phase 1b clinical trials. Methods of Treatment of MN: Thus, the methods of the invention are directed to a method for treatment of MN and / or PMN by the administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. The impact of the administration of anti-CD19 antibody for treatment of MN and / or PMN was not previously explored. The methods of the invention beneficially provide that Patent Application CLIMB-005 / 01WO 40193 / 24 MN and / or PMN patients expressing anti-phospholipase A2 receptor (PLA2R) antibody have a higher response rate for the administration of anti-CD19 antibodies. This correlation of expression of anti-PLA2R antibody on the efficacy of a treatment with anti-CD19 antibodies was surprising and unexpected. Accordingly, in certain aspects, the methods of the invention provide a method for treatment of MN and / or PMN patients by administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody could be any anti-CD19 antibody that binds to the CD19 on the surface of B-cells. In certain aspects, the invention provides a method of treating a subject having membranous nephropathy (MN), the method comprising: providing a composition comprising a therapeutically effective amount an anti-CD19 antibody to the subject having an anti- phospholipase A2 receptor (PLA2R) antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition is administered subcutaneously. In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition comprises about 600 mg budoprutug. In certain embodiments, the composition comprises about 1000 mg budoprutug. In certain embodiments, the composition comprises 100 mg budoprutug. In certain embodiments, the composition comprises 200 mg budoprutug. In certain embodiments, the composition comprises 600 mg budoprutug. In certain embodiments, the composition comprises 1000 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the composition is administered in treatment cycles, wherein each treatment cycle comprises administering the composition comprising budoprutug once every Patent Application CLIMB-005 / 01WO 40193 / 24 two weeks, with a 24-week interval between each treatment cycle. In certain embodiments, the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15, and wherein there is a 24-week interval between each treatment cycle. In certain aspects, the invention provides a method for treating a subject having membranous nephropathy (MN), wherein the method comprises testing the subject for the presence of anti-PLA2R antibody in serum. If the subject tests positive for anti-PLA2R antibody, administering a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the administration of composition results in remission of proteinuria in the patients. In certain aspects, the invention method of determining whether a subject having membranous nephropathy (MN) will respond to treatment with an anti-CD19 antibody, the method comprising: conducting an assay on a sample from the subject that MN in order to determine the presence of anti- PLA2R antibody in the sample; providing results of the assay to the physician such that physician prescribes or provides the subject with a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody comprises a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the patient is suffering from primary membranous nephropathy (PMN). In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti- CD19 antibody is administered parenterally. In certain preferred embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprises about 100 mg budoprutug. In certain embodiments, the composition comprises about 200 mg budoprutug. In certain embodiments, the composition is administered once every two weeks. In Patent Application CLIMB-005 / 01WO 40193 / 24 certain embodiments, the composition is administered at days 1, 15, 169, and 183 after the start of the treatment. In certain embodiments, the administration of composition results in remission of proteinuria in the patients. Budoprutug: Budoprutug (VB119) is a humanized, low-fucosylated, anti-Cluster of Differentiation (CD) 19, immunoglobulin (Ig) G1, monoclonal antibody (mAb) with potent antibody-dependent cellular toxicity as determined by cell-based assays. The target antigen, CD19, is expressed on many Ig- producing B-cells, making it an attractive target for Ig-mediated diseases. Budoprutug has been shown to inhibit proliferation of a wide range of B-cell lines at lower effective concentrations of rituximab. Budoprutug was also found to deplete B-cells in severe combined immunodeficient (SCID) mice injected with human primary peripheral blood mononuclear cells (PBMCs). Unlike rituximab, budoprutug has been shown to have minimal complement-dependent cytotoxicity (CDC) in preclinical models. Complement-dependent cytotoxicity is a likely cause of the infusion- related reactions (IRRs) of antibody therapies. In a Phase 1 clinical study in patients with B-cell malignancies, a total of 28 patients were treated with budoprutug doses ranging from 0.02 mg to 1000 mg weekly for up to 4 weeks. By :HHN^^^^^^^^^%-cell depletion was observed in 25 out of 28 patients. Of the 20 patients with evaluable data who received at least 250 mg of budoprutug, 17 out of 20 (85%) patients experienced complete B-cell depletion, defined as >90% reduction in CD20+ B-cells compared to baseline during at least 1 timepoint during the study period, with some responses lasting beyond 6 months from the last dose. No human anti-human antibodies (HAHA) were detected, and budoprutug was tolerated at all doses studied. The majority of adverse events (AEs; such as IRRs and Grade 3 or higher neutropenia) and the 3 study withdrawals all occurred in patients in the highest dose cohort (1000 mg). Importantly, because the 1000 mg cohort was expanded, two-thirds of the total study population was treated at this dose level, which provides additional safety experience at the highest dose, but also limits the ability to compare frequencies of uncommon AEs. Serum immunoglobulins (IgA, IgM, and IgG) were assessed at baseline, during the study, and at the End of Therapy and follow-up visits. Twenty-seven (96.4%) patients had a value that was outside the normal range, but none of these abnormalities were considered clinically significant. Phase Ib trial of budoprutug in adult subjects with PMN: Patent Application CLIMB-005 / 01WO 40193 / 24 Membranous nephropathy (MN) is an immune-mediated glomerular disease and is the leading cause of non-diabetic nephrotic syndrome (NS) in Caucasian adults. The most prominent clinical feature of MN is NS and its associated manifestations, including various degrees of edema, fatigue, hypoalbuminemia, and hyperlipidemia. Approximately 60% of patients with MN presentwith nephrotic-UDQJH^ SURWHLQXULD^ ^^^^^^ J^GD\^^ DQG^ WKH^ UHPDLQLQJ^ ^^^^ KDYH^ VXE-nephroticproteinuria, but two-thirds of these latter patients later become nephrotic usually within the first year. The most consequential long-term manifestation of MN is progressive loss of renal function, which occurs in 60% of untreated patients with about 35% eventually developing end- stage renal disease (ESRD) within 10 years. The long-term outcomes correlate with the degree of proteinuria, and thus, proteinuria is an established surrogate marker for disease control andprogression. Patients presenting with nephrotic-UDQJH^ SURWHLQXULD^ ^L^H^^^ ^^^^^ J^GD\^^ KDYH^ZRUVH^outcomes than those presenting with sub-nephrotic proteinuria, but even those presenting with sub- nephrotic proteinuria remain at risk for the disease consequences over time. Treatment for MN is aimed specifically at reducing proteinuria. More recently, a robust correlation of proteinuria and serum anti-phospholipase A2 receptor (PLA2R) antibody levels has been observed, with anti-PLA2R antibody levels being a leading indicator of proteinuria. Serum anti-PLA2R antibody levels are increasingly gaining acceptance as a predictive surrogate marker of disease and response to treatment. It is common for anti-PLA2R antibody levels to decrease weeks to months following the initiation of treatment, and for proteinuria to decrease in the weeks to months following anti-PLA2R antibody reduction. Rationale: B-cell depletion therapy with the anti-CD20 mAb, rituximab, has shown clinical benefit in patients with MN by reducing proteinuria, presumably by limiting the maturation of B-cells into auto-reactive, antibody-secreting plasmablasts and plasma cells (PCs). CD19 is expressed at an earlier stage in B-cell development, appearing on early pro B-cells, and also persists throughout B-cell maturation on the surface of plasmablasts and some PCs. The clinical implications of this differential expression of CD19 are not yet fully understood. Preclinical data suggest that the elimination of CD19+ plasmablasts and PCs could provide a greater clinical effect in B-cell-driven autoimmune diseases than targeting CD20+ B-cells. Patent Application CLIMB-005 / 01WO 40193 / 24 Patients with autoimmune disease, including multiple sclerosis, have been shown to have greater numbers of CD19+ B-cells in serum when compared to healthy controls. Plasmablasts and PCs have been suggested to be a primary effector B-cell population involved in the secretion of immunoglobulins leading to autoantibody mediated inflammation, and CD19+ B-cell niches persist following treatment with rituximab. In MN specifically, circulating PCs are elevated in diseased patients compared to controls, and plasmablasts from patients have been shown to produce pathogenic anti-PLA2R autoantibodies. Therefore, there is a scientific rationale for depleting CD19+ B-cells in patients with autoimmune diseases, including glomerular diseases such as primary MN (pMN). Though rituximab has provided encouraging clinical data in managing proteinuria in MN, non-responder rates remain high. Experts believe that the duration of time until patient relapse tends to shorten following subsequent rounds of rituximab therapy. Rituximab’s ability to deplete B-cells is restricted to cells expressing CD20 antigen, which is typically absent on plasmablasts and PCs. Furthermore, rituximab remains an unapproved, off-label option for patients with MN, which often limits access and lacks clear prescribing guidelines. Thus, targeting CD19 with a cell- depleting antibody has the potential to provide safe and effective elimination of B-cells, including pathologically relevant plasmablasts and PCs. Risk Benefit: Anti-CD19 mAb therapy is expected to deplete B-lymphocytes. Budoprutug has been shown to reduce B-cell populations in a Phase 1 clinical trial (CRUKD / 12 / 003) in patients with advanced CD19-positive indolent B-cell malignancies. The duration of this intended drug effect is anticipated to be temporary, lasting weeks to months, and may increase the risk of serious and opportunistic infections. To reduce the infection risk, participants with acute infections were not enrolled, and all participants were pre-screened and excluded if they tested positive for certain opportunistic pathogens, such as tuberculosis and hepatitis. Participants reporting signs or symptoms of infection following administration of budoprutug therapy were promptly evaluated and treated appropriately. Budoprutug may also induce neutropenia, which was observed in some patients with B- cell lymphomas and chronic lymphocytic leukemia after administration of the drug. Hematological oncology patients are more susceptible to neutropenia, and experience with the B-cell depleting agent rituximab shows the risk of neutropenia is greater in patients with hematological Patent Application CLIMB-005 / 01WO 40193 / 24 malignancies compared to autoimmune populations. Nevertheless, the protocol excluded participants with abnormal neutrophil counts at baseline and regularly monitored neutrophil levels. The primary acute risk of budoprutug administration was the possibility of an IRR, including cytokine release syndrome (CRS), which can occur from the administration of any therapeutic antibody. This is a well-recognized aspect of clinical practice with chimeric, humanized, or fully human antibodies, regardless of their mode of action. There is no supportive data from other clinical trials to suggest that anti-CD19 antibodies are more prone to this effect than other types of antibodies; however, in order to minimize the risk of reactions, participants who had experienced prior IRRs to rituximab were excluded from the study. Participants who received budoprutug received premedication prior to each infusion. This premedication was in line with standard practice for administration of other mAbs, including the recently approved anti- CD19 antibody Uplizna™. Participants were carefully monitored for signs of CRS or IRRs during and after each infusion. If participants developed any signs, such as urticaria, wheezing, hypotension, tachycardia, or dyspnea, the infusion was stopped immediately, and additional treatment administered. Primary Objective The primary objective of this study was to define the safety and tolerability of ascending doses of budoprutug in participants with PMN. Secondary Objectives: The secondary objectives of this study included the following: To investigate a range of dose levels for budoprutug in participants with MN; To characterize the pharmacokinetic (PK) profile of budoprutug in participants with MN; To evaluate the effects of budoprutug on B-cell depletion (pharmacodynamic [PD] response); To evaluate the effects of budoprutug on serum anti-PLA2R antibodies (immunologic response); To evaluate the effects of budoprutug on proteinuria (clinical response); To evaluate the effects of budoprutug on albuminuria and albuminemia; To evaluate the effects of budoprutug on NS; To evaluate the effects of budoprutug on serum IgG, IgM, and IgA levels; and To evaluate the development of anti-drug antibodies (ADAs) to budoprutug. Patent Application CLIMB-005 / 01WO 40193 / 24 Exploratory Objectives: The exploratory objectives of this study included the following: To evaluate participant reported outcomes / Quality of Life (QOL) measures, including edema; and To evaluate the PK and PK / PD (dose relationship) profile overall and as they relate to proteinuria levels. Overall Study Design and Plan: 7KLV^VWXG\^ZDV^D^3KDVH^^E^^RSHQ^ODEHO^^VHTXHQWLDO-cohort, dose escalation study to evaluate the safety, tolerability, PK, and PD of budoprutug in participants with PMN. Participants received 2 or 4 doses of budoprutug, 14 days apart (1 dose on Day 1 and 1 dose on Day 15 [protocol Versions 1.0-6.0] and 1 dose on Day 168 and 1 dose on Day 182 [protocol Versions 1.0-5.0]) at the specified dose level, administered via intravenous (IV) infusion. For all participants enrolled, retrospective data was collected from medical records for up to 2 years prior to Screening to document the participant’s pre-treatment disease history. These data included any available renal biopsy, estimated glomerular filtration rate (eGFR), anti-PLA2R antibody titers, proteinuria, and B-cell / lymphocyte levels, as well as MN treatments received. To minimize bias, these data was only collected following signing of informed consent and confirmation that the participant met all study eligibility criteria. Participants were screened for study eligibility at Visit 1 (Visit 1a or Visit 1b, as applicable, for participants who required tapering of immunosuppressive medications, including calcineurin inhibitors [CNIs] and / or glucocorticoids). After Screening, participants were reassessed at Visit 2 / Day 1 and all participants who met the eligibility criteria were enrolled into the study. The study used a starting dose based on the results of the completed first-in-human Phase 1 study. Dose escalation based on safety and B-cell depletion was conducted using a flexible sample size (3 to 6 participants) for each cohort. The first dose cohort was 100 mg administered IV on Day 1 and on Day 15 for 2 doses (200 mg cumulative dose). The planned dose cohort that followed was 200 mg administered IV on Day 1 and on Day 15 for 2 doses (400 mg cumulative dose). The dose escalation cohort would have been enrolled sequentially. The overall goal was to demonstrate PD effects with 2 bi-weekly doses. Escalation in dose between the cohorts would not exceed more than double the previous cohort’s cumulative dose. Following the first dosing cohort, the plan was flexible based on decisions of the Data Review Committee (DRC), focusing primarily Patent Application CLIMB-005 / 01WO 40193 / 24 on safety and PD effects of B-cell depletion. Following initiation of the first study cohort, the subsequent cohort would have been opened for enrolment following review of the data and determinations of the DRC. The study collected data on safety and tolerability, PK, B-cell depletion, serum anti-PLA2R antibody levels, and proteinuria. Four sites in the United States opened for this study. Study Duration The total study duration for each individual participant was up to 88 weeks, including Screening (up to 18 weeks), Treatment Period (initially 2 bi-weekly and 2 possible bi-weekly maintenance doses starting at 6 months [Week 24]), and a Follow-up Visit. The total study duration following the first dose was up to 72 weeks. Data Review: Each cohort in the dose escalation phase were followed for at least 5 weeks after dose initiation in at least 3 participants prior to escalation decisions. The following data was reviewed by the DRC to determine the addition of participants within a cohort and escalation to the next dose cohort: Relevant information on participants’ demographics, characteristics, medical history, physical examinations, and concomitant medications; Available PD data (e.g., B-cell subsets [including CD20+ B-cell counts]); List of all AEs, including severity, time of onset related to study drug administration, duration, relatedness, and causality, including serious adverse events (SAEs), adverse events of special interest (AESIs), and all potential dose-limiting toxicities (DLTs); Any clinically significant, out of range safety clinical laboratory test results; Electrocardiogram (ECG) and vital sign results, including clinically significant abnormal values; Available PK data; and Any available anti-PLA2R antibody and proteinuria data from the current cohort or prior cohort. Within the planned dose range, a dose lower than the next planned dose may have been tested, depending on review of available safety, efficacy, tolerability, PK, and PD data. If the Patent Application CLIMB-005 / 01WO 40193 / 24 highest planned dose level was found to be safe and tolerable, also considering the PK and PD data, additional higher doses may have been added through a protocol amendment. Dose Escalation: Participants with PMN were assigned to the open cohort, per the Table below. The dose escalation cohort was enrolled sequentially. Three participants were enrolled into the first cohort initially, with an option of enrolling up to 6 participants total in a cohort based on the DRC recommendation of additional participants for safety assessments or more complete assessment of B-cell depletion. As the participant follow-up data were generated over time, anti-PLA2R antibody levels and proteinuria were also factored into the evaluation of cohort size. During and following each cohort, the DRC reviewed the available safety, efficacy, tolerability, PK, and PD data to determine the addition of participants within a cohort and escalation from Cohort 1 to Cohort 2. Escalation from Cohort 1 to Cohort 2 only took place after DRC review. The next dosing cohort began at Visit 2 / Day 1. Doses of Budoprutug Dose Level Dose (mg) Frequency (Cumulative Dose) Level 1 100 Every 14 days for 2 doses (200 mg cumulative dose) For safety, if none of the initial 3 participants experienced a DLT during the initial treatment period, then enrolment into the next dose cohort could begin. If 1 of the first 3 participants experienced a DLT, then dosing was stopped. If study enrolment was stopped due to a DLT, the DRC reviewed all available safety data to determine if the study could resume at the current dose, resume at a lower dose, proceed to a study amendment to address safety concerns, or terminate. For PD effects, if the data from 3 participants did not demonstrate consistent effects, then up to 3 more participants could be enrolled at that dose level to better understand the PD effects prior to escalation to the next higher dose cohort. The PD respoQVH^WDUJHW^ZDV^^^^^^UHGXFWLRQ^LQ^SHULSKHUDO^CD20+ B-cell counts and / or B-FHOO^ FRXQWV^ ^^^^ FHOOV^^L, and optimally this response occurredwithin 2 weeks of dose initiation. Participants who withdrew from the study for reasons other than a DLT prior to completing the 1-month follow-up after the second bi-weekly dose could be replaced to ensure an adequate safety and PD assessment for each cohort. Replacement participants were enrolled to the same dose cohort as the participant being replaced. Patent Application CLIMB-005 / 01WO 40193 / 24 Definition of dose-limiting toxicities: Dose-limiting toxicities due to a study drug were generally defined as a toxicity that prevents further administration of the study drug at that dose level. Based on preclinical and human-dosing in B-cell malignancies with budoprutug, fatigue, nausea, vomiting, neutropenia, and IRRs were the most common AEs. The reported DLTs in that experience included IRR and hypoxemia. Study recruitment would stopped and a DRC meeting would occur if any participant experienced any of the following toxicities which were considered possibly, probably, or definitely related to study drug: 1. Any SAE; 2. Severely decreased neutrophil count (i.e., absolute neutrophil count <500 / mm); 3. Moderately decreased neutrophil count of prolonged duration (i.e., absolute neutrophil count 500 to 1000 / mm3IRU^^^^GD\V^^ 4. Severe infection, defined as requiring IV antibiotics, antifungal, and / or antiviral treatment and / or hospital admission for >24 hours and / or is considered life-threatening; 5. 6HUXP^,J*^OHYHOV^^^^^^PJ^G / ^IRU^^^^PRQWKV^ 6. IRR of any severity that requires stopping of study drug infusion or requires treatment with additional medications or interventions to address the signs and symptoms; 7. Hypoxia (hypoxemia, hypoxaemia, hypoxic) with or without IRR; 8. 1DXVHD^RI^GXUDWLRQ^^^^GD\V^ 9. 9RPLWLQJ^RI^GXUDWLRQ^^^^GD\V^ 10. )DWLJXH^RI^GXUDWLRQ^^^^GD\V^^RU Any AE or toxicity, at the discretion of the Investigator, that is thought to warrant withholding the study drug. Study recruitment would be stopped and a DRC meeting would occur if any participant experienced any of the following events: 1. Acute kidney injury (AKI) stage 1 or higher, defined by the Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, and does not demonstrate immediate reversibility as suggested by a serum creatinine level that does not improve below the level of the AKI definition or worsens with repeat confirmation of the serum creatinine within 7 days upon notification; Patent Application CLIMB-005 / 01WO 40193 / 24 2. Thromboembolic events (e.g., deep-venous thrombosis, renal vein thrombosis, pulmonary embolism); 3. Worsening of proteinuria by >50% from baseline; or 4. Worsening of measures of the NS which, in the opinion of the Investigator, may preclude ongoing participation. For example, new onset anasarca or severe hypoalbuminemia. If study enrolment was stopped due to DLTs or disease-specific AEs / conditions as noted above, the DRC reviewed all available safety data to determine if the study could resume at the current dose, resume at a lower dose, proceed to a study amendment to address safety concerns, or terminate. Note that any amendments to address stopping rules was considered substantial amendments of the protocol. If the study was stopped after reaching a stopping rule, health authorities were to be notified, as required, and a substantial amendment was to be filed to request study restart. Throughout the study, participants were seen at protocol-defined timepoints to assess safety, B-cell depletion, serum anti-PLA2R antibodies, proteinuria, albuminemia, and eGFR. This enabled detection of change from baseline, the time to effect, and duration of effect. In addition, the patterns of each parameter were evaluated; it was anticipated that B-cell depletion would be followed by anti-PLA2R antibody reduction, and then proteinuria reduction. Proteinuria was measured as urine protein-to-creatinine ratio (UPCR) from either a 24 hour collection or spot urine collections. Other measures of proteinuria were also measured, including urinary albumin excretion and total daily protein excretion. All participants had a follow-up End of Study (EOS) Visit at either Week 72 or when the study was terminated. This duration of follow up allowed the collection of additional safety data and data on the persistence of B-cell depletion, anti-PLA2R antibody reduction, proteinuria reduction, and overall MN disease activity over time. Inclusion Criteria: Participants who met all the following criteria were eligible to participate in the study: 1. :DV^^^^^\HDUV^RI^DJH^DW^WKH^WLPH^RI^LQIRUPHG^FRQVHQW^ 2. Had a kidney biopsy-proven diagnosis of pMN within the past 10 years; Note: It was preferable that participants enrolled have kidney biopsy tissue samples that were positive for anti-PLA2R antibody staining. Participants with kidney biopsy-proven diagnosis of Patent Application CLIMB-005 / 01WO 40193 / 24 S01^!^^^\HDUV^DQG^^^^^\HDUV^WKDW^PHW^DOO^RWKHU^HOLJLELOLW\^FULWHULD^FRXOG^EH^HQUROOHG^DIWHU^ discussion with the Medical Monitor. 3. Had a documented laboratory history of nephrotic range proteinuria (defined as either ^^^^^J^WRWDO^SURWHLQ^SHU^^^-KRXU^XULQH^FROOHFWLRQ^RU^^^^^^J^J^83&5^E\^VSRW^FROOHFWLRQ^^ $1'^KDG^SURWHLQXULD^ZLWK^D^83&5^^^^^^J^J^EDVHG^RQ^^^FRQVHFXWLYH^VSRW^XULQH^^ILUVW^ morning void) sample collections obtained within 14 days of each other during the Screening Period. Both samples must have qualified; 4. Was on maximum allowable or maximum tolerated anti-proteinuric therapy with a renin angiotensin system inhibitor (RASi; i.e., angiotensin converting enzyme inhibitor or DQJLRWHQVLQ^,,^UHFHSWRU^EORFNHU^^ZKRVH^GRVH^PXVW^KDYH^EHHQ^VWDEOH^IRU^^^^PRQWKV^SULRU^Wo Screening (as well as anticipated to be stable during the study). A stable dose of RASi ZDV^GHILQHG^DV^GRVHV^WKDW^ZHUH^ZLWKLQ^^^^^RI^WKH^SODQQHG^GRVH^IRU^^^^PRQWKV^SULRU^WR^ Screening. Participants with short-term interruptions of RASi therapy (e.g., for volume- depleting illness or medication refills) and those who were intolerant to or contraindicated for RASi therapy may have been enrolled upon discussion with the Medical Monitor; 5. Had systolic blood pressure (BP) <160 mmHg and diastolic BP <100 mmHg after 5 minutes of rest at Screening; 6. Was considered by the Investigator to be an appropriate candidate for immunosuppressive therapy according to international guidelines (KDIGO 2012 / 2020); 7. Was willing and able to provide written informed consent prior to Screening; 8. Female participants of non-childbearing potential must have been either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and / or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone in the postmenopausal range at Screening, based on the central laboratory’s ranges; 9. Female participants of childbearing potential (i.e., ovulating, premenopausal, or not surgically sterile) and all male participants were to use a medically accepted, highly effective contraceptive regimen during their participation in the study and for 125 days after the last administration of study drug. Highly effective contraceptive methods were defined as those with 99% or greater efficacy; Patent Application CLIMB-005 / 01WO 40193 / 24 a. Acceptable methods of contraception for male participants enrolled in the study included the following: i. Condoms with spermicide; or ii. Surgical sterilization of participant at least 26 weeks before Screening (vasectomy); b. Acceptable methods of contraception for female participants of childbearing potential enrolled in the study included the following: i. Intrauterine device for at least 12 weeks before Screening; ii. Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before Screening. Hormonal contraceptives were only acceptable if the contraceptive prevented ovulation; or iii. True abstinence; True abstinence: When this was in line with the preferred and usual lifestyle of the participant. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. 10. Male participants agreed to abstain from sperm donation through 125 days after administration of the last dose of study drug; and Had recovered from a previous SARS-CoV-2 infection or received a SARS-CoV-2 vaccination at least 2 weeks prior to Screening. Exclusion criteria: Participants who met any of the following criteria were excluded from participating in the study: 1. Had received treatment with rituximab or other B-cell depleting agents within 6 months prior to Screening; 2. Had a CD19+ B-cell count <80 cells / ^L at Screening or <40 cells / ^L if B-cell depleting treatment was received 6 months to 2 years prior to Screening; 3. Had an eGFR <45 mL / min / 1.73 m2 at Screening utilizing the Chronic Kidney Disease Epidemiology Collaboration formula confirmed by the central laboratory; 4. Had a known AKI event in the last 3 months. If a participant’s recent decline in eGFR was thought to be attributable to MN, they could have been enrolled upon discussion with the Medical Monitor; Patent Application CLIMB-005 / 01WO 40193 / 24 5. Had achieved a >50% reduction in proteinuria over the previous 6 months; 6. Had an absolute neutrophil count <1.5 × 109 / L; 7. Had a white blood cell count <3.0 × 109 / L; 8. Had an aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) >2 × upper limit of normal (ULN); Note: Participants with AST and / or ALT >2 × ULN at Screening could have repeat laboratory samples drawn approximately 1 week later. Participants were considered eligible after repeat ODERUDWRU\^VDPSOHV^LI^UHSHDW^YDOXH^ZDV^^8 / 1^DQG^WKH^SDUWLFLSDQW^KDG^QR^NQown liver disease. 9. Had a total bilirubin >1.5 × ULN, unless due to Gilbert’s syndrome; Note: Participants with total bilirubin >1.5 × ULN at Screening could have repeat laboratory samples drawn approximately 1 week later. Participants were considered eligible after repeat ODERUDWRU\^VDPSOHV^LI^UHSHDW^YDOXH^ZDV^^8 / 1^DQG^WKH^SDUWLFLSDQW^KDG^QR^NQRZQ^OLYHU^GLVHDVH^ 10. Had a history of serious or significant infusion reaction associated with rituximab or other B-cell depleting therapy; 11. Had secondary causes of MN (e.g., malignancy, hepatitis B or C, human immunodeficiency virus [HIV], systemic lupus erythematosus [SLE], or other autoimmune diseases [e.g., thyroiditis, sarcoidosis], or drug-induced); 12. Had a diagnosis or history of SLE (including non-renal disease); 13. Had type 1 or type 2 diabetes mellitus; 14. Had concomitant or overlapping glomerulopathies on renal biopsy or known by the participant’s clinical history (e.g., diabetic nephropathy, IgA nephropathy, or primary or genetic variant focal segmental glomerulosclerosis [FSGS]). Those with secondary or adaptive FSGS could be enrolled upon discussion with the Medical Monitor; 15. Had an acute, chronic, or latent infection, including tuberculosis, hepatitis, HIV, or chronic urinary tract infections; 16. Had a live vaccine within 28 days prior to the first scheduled day of budoprutug administration or planned to obtain a live vaccine during the study; 17. Had used glucocorticoids or mycophenolate mofetil within 14 days prior to Screening; Note: The Screening Period could be extended to allow for the tapering of glucocorticoids or mycophenolate mofetil over approximately 90 days, provided that the participant was off the medication for at least 14 days prior to the first dose of budoprutug. Patent Application CLIMB-005 / 01WO 40193 / 24 18. Had used alkylating agents (e.g., cyclophosphamide) within 2 months prior to Screening; 19. Had used azathioprine within 14 days prior to Screening; Note: The Screening Period could be extended to allow for the tapering of azathioprine over approximately 90 days, provided that the participant was off the medication for at least 14 days prior to the first dose of budoprutug. 20. Had used or was using CNIs at the time of enrolment: a. Participants that had used CNIs, including cyclosporine and tacrolimus, within 14 days of the first dose of budoprutug; b. The Screening Period could be extended to allow for the tapering of CNIs over approximately 90 days, provided that the participant was off the medication for at least 14 days prior to the first dose of budoprutug. 21. Had undergone stem cell, bone marrow, or solid organ transplant; 22. Had a history of malignancy within the past 5 years, or was likely to require chemotherapeutic or surgical treatment during the study, with the exception of successfully treated non-melanoma skin cancer, cervical carcinoma in situ, or ductal carcinoma in situ; 23. Was pregnant or lactating female; 24. Had received any investigational drug within 30 days prior to the first scheduled day of budoprutug administration, or at least 5 times the elimination half-life of the investigational drug, whichever was longer; 25. Had a history of drug or alcohol abuse within 5 years prior to Screening; 26. Had a planned surgery during the 6 weeks following the first scheduled day of budoprutug administration; 27. Had a known sensitivity to any components (i.e., sodium citrate, citric acid, or L- arginine) in the budoprutug formulation; or 28. Had any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with participant safety, study evaluations, and / or study procedures. Removal criteria: Participation of a participant in this clinical study could be discontinued for any of the following reasons: Patent Application CLIMB-005 / 01WO 40193 / 24 The participant withdrew consent or requested discontinuation from the study for any reason; Occurrence of any medical condition or circumstance that exposed the participant to substantial risk and / or did not allow the participant to adhere to the requirements of the protocol; Any SAE, DLT, clinically significant AE, severe laboratory abnormality, intercurrent illness, or other medical condition which indicated to the Investigator that continued participation was not in the best interest of the participant; Pregnancy; The participant failed to comply with protocol requirements or study-related procedures; or Termination of the study by the Sponsor or the regulatory authority. If a participant withdrew prematurely from the study due to the above criteria or any other reason, study staff should make every effort to complete the full panel of assessments scheduled for the Early Termination (ET) Visit. The reason for participant withdrawal was documented in the electronic case report form (eCRF). In the case of participants lost to follow-up, attempts to contact the participant were made and documented in the participant’s medical records. Participants who withdrew from the study for reasons other than a DLT prior to completing the 1-month follow-up after the second bi-weekly dose could be replaced to ensure an adequate safety and PD assessment for each cohort. Replacement participants were enrolled to the same dose cohort as the participant being replaced. Treatment: Participants with pMN were enrolled to the open cohort as described previously (100 mg or 200 mg). The dose escalation cohort was enrolled sequentially. Three participants were enrolled into the first cohort initially, with an option of enrolling up to 6 participants total in a cohort based on the DRC recommendation of additional participants for safety assessments or more to complete assessment of B-cell depletion. As participant follow- up data was generated over time, anti-PLA2R antibody levels and proteinuria could also be factored into the evaluation of cohort size. Patent Application CLIMB-005 / 01WO 40193 / 24 For safety, if none of the initial 3 participants experienced a DLT during the initial treatment period, then enrolment into the next dose cohort could begin. If 1 of the first 3 participants experienced a DLT, then dosing would stop. If study enrolment was stopped due to a DLT, the DRC reviewed all available safety data to determine if the study could resume at the current dose, resume at a lower dose, proceed to a study amendment to address safety concerns, or terminate. For PD effects, if the data from 3 participants did not demonstrate consistent effects, then up to 3 more participants could be enrolled at that dose level to better understand the PD effects prior to escalation to the next higher dose cohort. The PD respoQVH^WDUJHW^ZDV^^^^^^UHGXFWLRQ^LQ^SHULSKHUDO^ CD20+ B-cell counts and / or B-FHOO^FRXQWV^^^^^FHOOV^^L, and optimally this response would occur within 2 weeks of dose initiation. Rationale for dosing: The proposed starting dose of budoprutug was 100 mg administered IV on Day 1 and on Day 15 for 2 doses (200 mg cumulative dose, Cohort 1, Table below). This dose level was informed by safety and PD data from a previous Phase 1 clinical study in patients with B-cell malignancies. The proposed starting dose was anticipated to be well tolerated and result in partial, transient B-cell depletion. Cohort 2 received 200 mg administered IV on Day 1 and on Day 15 for 2 doses (400 mg cumulative dose). Cohort Dosing Cohort Dose Level Dose Frequency Total No. of Doses Cumulative Dose st- in-human safety and tolerability data for budoprutug. In this study, participants were administered cumulative doses of budoprutug ranging from 0.87 mg to 4000 mg, and single doses ranging from 0.02 mg to 1000 mg administered once weekly for 4 weeks; the first 3 participants underwent intra-participant dose escalation. Twenty-seven participants in the safety population (n = 28) experienced at least 1 treatment-emergent adverse event (TEAE) during the study and 26 participants had a TEAE that was considered related (possibly, probably, or highly probably) to budoprutug. The majority of TEAEs reported were classified as Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or Grade 2. A total of 11 participants reported 29 TEAEsWKDW^ ZHUH^ *UDGH^ ^^^^ WKH^ PDMRULW\^ RI^ ZKLFK^ ZHUH^ HYHQWV^ RI^ P\HORVXSSUHVVLRQ^ (e.g., low Patent Application CLIMB-005 / 01WO 40193 / 24 lymphocytes, platelets, neutrophils, and white blood cells) and occurred in participants who were in the 1000 mg dose once weekly cohort. Detailed safety data are available in Section 7.3.1.1 of the Investigator’s Brochure. Six of the 28 participants (21%) had treatment-emergent SAEs reported. Four participants experienced 5 SAEs that were considered related to budoprutug (neutropenic sepsis, two events of IRR [1 of which was classified as a DLT], and 2 events of urinary tract infection in 1 participant, who withdrew from the study). Three of these participants were in 1000 mg once weekly cohorts and 1 participant (neutropenic sepsis) was in the 250 mg once weekly cohort. Infusion-related reactions were an event of interest during the study, and participants were carefully monitored for signs of CRS or acute infusion reaction during and following each infusion. Pretreatment in most participants consisted of administration of paracetamol, chlorphenamine, and hydrocortisone prior to administration of budoprutug. Five TEAEs of IRR were reported by 4 participants, all in 1000 mg once weekly dose cohorts. All of the IRRs were deemed probably or highly probably related to budoprutug. Sixteen participants in the study did not experience any treatment-emergent SAEs orGrade ^^^$(V^^ LQFOXGLQJ^DOO^^^SDUWLFLSDQWV^ LQ^WKH^ILUVW^^^GRVH^FRKRUWV^^2QH^RI^ WKHVH^SDUWLFLSDQWV^(Participant 36 / 003 of the third dose cohort) received a cumulative dose (225 mg) most similar to the newly proposed starting dose in the MN study. Following single doses of 15, 30, 60, and 120 mg budoprutug, the cumulative area under the concentration-time curve (AUC; 253 ^g / mL × day) in this participant was within 10% of the predicted cumulative AUC (277 ^g / mL × day) of the proposed starting dose of 100 mg administered IV every 14 days for 2 doses (200 mg cumulative dose) over the 4-week period. Based on PD data from the Phase 1 study in oncology patients, B-cell depletion occurred following 2 of 4 weekly doses in most participants. Participant 46 / 002 of the second cohort received a cumulative dose of 15 mg and transient reductions in B-cells were noted; peripheral B-cell counts initially dropped below 10 cells / ^L but were above the lower limit of normal (>80 cells / ^L) within 4 weeks following the last dose. Participant 36 / 003 of the third cohort received 4 escalating doses of budoprutug at 15, 30, 60, and 120 mg (225 mg cumulative dose). Prior to Week 4 dosing, and after a cumulative dose of 105 mg administered, B-cell counts were reduced ~60% from the earliest available timepoint (FIG.1). The last dose of 120 mg resulted in ~80% depletion from the earliest available timepoint. B-cell reduction in this participant persisted Patent Application CLIMB-005 / 01WO 40193 / 24 through Week 12, although B-cells increased above Week 12 levels by the 6-month follow-up. Based on these data the proposed starting dose of 100 mg administered IV on Day 1 and on Day 15 for 2 doses (200 mg cumulative dose) is anticipated to lead to partial and transient reductions in B-cell counts. The proposed cumulative dose range of 200 mg to 400 mg in the MN study was below the 1000 mg cumulative dose of the first multi-participant (n = 3) cohort (250 mg once weekly) in the previous Phase 1 study in cancer patients. Although the 1000 mg cumulative dose was considered to be tolerated in the oncology study, lower doses could be adequate to achieve clinically meaningful B-cell depletion in participants eligible for the proposed MN study. The treatment goal in participants with autoimmune diseases, including MN, when given other B-cell depleting antibodies (i.e., rituximab, inebilizumab) was typically >90% B-cell depletion from baseline for ^^ months. Pharmacokinetic modelling indicates that plasma concentrations of budoprutug would continue to increase during the 2 bi-weekly doses as the drug remains within its distribution phase. Following the final dose of the initial treatment period, budoprutug plasma concentrations were expected to remain detectable for weeks, but fall more rapidly in participants with proteinuria, based on budoprutug PK modelling and data from other antibodies that have been tested in participants with proteinuria, including rituximab, adalimumab, eculizumab, and belimumab. The effect of proteinuria on the PK and PD of budoprutug will be explored in the current study. Of note, the Phase 1 oncology study evaluated 4 weekly doses. While 4 weekly doses may be necessary for complete and durable B-cell depletion, participant-level data show that, in the majority of participants, B-cell depletion occurs after the first 1 or 2 doses. The drug half-life (approximately 25 days) supports less frequent dosing, and other B-cell depleting therapies (i.e., rituximab and inebilizumab) are administered once every 2 weeks for a total of 2 doses. Accordingly, this study design for budoprutug in MN participants commenced with a low-dose cohort at 2 bi-weekly doses. In summary, based on available data from the oncology study, 100 mg administered IV on Day 1 and on Day 15 for 2 doses (200 mg cumulative dose) was anticipated to be a well-tolerated starting dose in moderate-to-high risk MN patients and could induce transient B-cell reductions for several weeks. Higher and potentially more frequent doses could be required to induce greater, Patent Application CLIMB-005 / 01WO 40193 / 24 sustained B-cell depletion and, in turn, disease control (improvement in proteinuria and NS) in moderate-to-high risk patients with MN. Formulation: drug product was provided as a colourless to slightly opalescent liquid budoprutug antibody formulated in 10 mM citrate, and 30 g / L L-arginine- HCl. It had a pH of 6.0 and was presented in a 5 mL glass vial with a 5 mL fill. Administration of the drug: Study drug was administered by site staff during site visits. Budoprutug was administered IV on Day 1 and on Day 15 for 2 doses at the 100 mg dose level (200 mg cumulative dose). Dosing occurred no less than 14 days and no more than 16 days from the previous dose at Visit 4. Budoprutug was diluted in 0.9% saline at a concentration of no more than 1.7 mg / mL for administration as an IV infusion. For standardization in this study, budoprutug was diluted in 250 mL prefilled saline bags prior to administration. During the first dosing cohort (100 mg bi- weekly) the infusion administered to each participant was initiated at a rate of 40 mg / hour (100 mL / hour). In the absence of infusion toxicity, the infusion rate could be increased by 20 mg / hour (50 mL / hour) increments every 30 minutes. The infusion rate could be the same or higher for the other dosing cohort, based upon DRC review of available safety data. Participants were observed for at least 1 hour following each infusion to monitor for potential infusion reactions. A Study Pharmacy Manual provided more specific information on budoprutug preparation and administration. Participants were required to receive premedication prior to each infusion of budoprutug to reduce the frequency and severity of infusion reactions. Acceptable types of premedication are shown in the Table below. Participants with minor symptoms that settled quickly after treatment interruption could restart budoprutug administration with a reduction in the infusion rate. Participants who experienced severe, life-threatening reactions to budoprutug did not receive any further infusions of budoprutug and were withdrawn from study treatment but were followed for required safety follow-up. Patent Application CLIMB-005 / 01WO 40193 / 24 Table: Premedication Required Prior to Each Budoprutug Infusion Administration Type of Route of Examples (or Equivalent) Time prior to ed fic participant records of study drug dispensed and administered, including dosage and date and time of study drug administration, in the participant’s source documents and the eCRF. Storage: All vials were stored upright and refrigerated (between 2°C to 8°C [36°F to 46°F]) at the study site. All study drugs were stored in a secure, temperature-controlled refrigerator, with access limited to site staff involved in the study. Prior and concomitant medications: All participants who did not require tapering of medications could proceed to enrolment following confirmation of all inclusion and exclusion criteria. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. Excluded medications: Participants who had received treatment with the following within the specified timeframe were excluded from the study: Rituximab or other B-cell depleting agents within 6 months prior to Screening; Glucocorticoids or mycophenolate mofetil within 14 days prior to Screening; Note: The Screening Period could be extended to allow for the tapering of glucocorticoids or mycophenolate mofetil over approximately 90 days, provided that the Patent Application CLIMB-005 / 01WO 40193 / 24 participant was off the medication for at least 14 days prior to the first dose of budoprutug. Alkylating agents within 2 months prior to Screening; Azathioprine within 14 days prior to Screening; Note: The Screening Period could be extended to allow for the tapering of azathioprine over approximately 90 days, provided that the participant was off the medication for at least 14 days prior to the first dose of budoprutug. CNIs, including cyclosporine and tacrolimus, within 14 days of the first dose of budoprutug; or Note: The Screening Period could be extended to allow for the tapering of CNIs over approximately 90 days, provided that the participant was off the medication for at least 14 days prior to the first dose of budoprutug. For all participants who underwent tapering of their immunosuppressive medication(s), an additional Qualifying Visit occurred once the taper had been completed and within 7 days of completion of the taper. Live vaccines within 28 days prior to the first dose of budoprutug. Rescue Therapy: During the study, the Investigator could administer or prescribe rescue therapy (e.g., glucocorticoids with additional concomitant immunosuppressive agents) for participants with recurring or persistent nephrotic-range proteinuria, worsening symptomatology, and / or declining kidney function. The Medical Monitor was consulted for advice prior to initiation. When rescue therapy was required, the Investigator tapered the rescue medications as soon as clinically appropriate to avoid risk of over-immunosuppression and to better assess the effects of budoprutug. Participants who received rescue medication were evaluated for continuation in the study by the Investigator, who could consult with the Medical Monitor and the Sponsor. Participants who discontinued complete all ET procedures as indicated in the schedule of study procedures (refer to the Table below). Table: Schedule of Screening Procedures: Patent Application CLIMB-005 / 01WO 40193 / 24 Screening Period Follow- EOT Qualifying Treatment PeriodaUp visitETit S Patent Application CLIMB-005 / 01WO 40193 / 24 Screening Period Follow- EOT Qualifying Treatment PeriodaUp visitETit S o era y, , an a a o e erm ne e a on o par c pan s w n a co or an escalation to the next dose cohort. Escalation to the next higher dose only took place after DRC review. The next dosing cohort began at Visit 2 / Day 1. b. All participants who did not require tapering of CNIs and / or glucocorticoids could proceed to enrollment following confirmation of all I / E criteria. For participants who did not require tapering of their current medications, two spot urine (first morning void) collections were completed within 14 days of each other during the Screening Period, butwas initiated within 1 week of the Screening Visit, to confirm eligibility. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. c. For participants who used restricted medications as outlined in the I / E criteria (i.e., glucocorticoids, mycophenolate, azathioprine, CNIs [Phase 1b]) within 14 days prior to Screening, the Screening Period were extended to allow for their tapering over approximately 90 days, provided that the participant was off the medication(s) for at least 14 days prior to the first dose of budoprutug. Participants in Phase 2a also could taper CNIs during the study (e.g., if complete remission of proteinuria is achieved), though it was not required. For participants required to taper their current medications, a Qualifying Visit occurred within 7 days of completion of the taper, and the first of two spot urine (first morning void) collections occurred within 7 days of completion of the taper. The two spot urine sample collections were completed Patent Application CLIMB-005 / 01WO 40193 / 24 within 14 days of each other. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. d. All assessments were completed pre-infusion on days where study drug was administered, with the exception of applicable PK samples. e. Eligibility criteria were reviewed at Screening and the Qualifying Visit (as applicable) and Visit 2 / Day 1. Participants were required to meet all criteria prior to the first dose of budoprutug. f. For all participants enrolled, retrospective data were collected from medical records for up to 2 years prior to Screening to document the participants’ pre-treatment disease history. These data included any available renal biopsy, eGFR, anti-PLA2R antibody titers, proteinuria, and B-cell / lymphocyte levels, as well as MN treatments received. g. Height was measured at Screening only. Weight was collected at each specified visit. BMI was calculated at Screening. h. Vital signs measured included heart rate, temperature, systolic and diastolic BP, and respirations. i. FSH was only performed in postmenopausal females, defined as spontaneous amenorrhea for at least 2 years, who were not surgically sterile. j. A serum hCG was drawn at Screening. A urine hCG test was performed during the Treatment Period (Visits 2 through 5), Follow-up Visit 6, and at ET. k. Budoprutug was administered IV on Day 1 and on Day 15 for 2 doses at the 100 mg dose level (200 mg cumulative dose) and subsequent bi-weekly dosing schedules at Visit 2 and Visit 4. Dosing occurred no less than 14 days and no more than 16 days from the previous dose at Visit 4. Participants were required to receive premedication prior to each infusion of budoprutug to reduce the frequency and severity of infusion reactions. Participants were observed for at least 1 hour following each infusion to monitor for potential infusion reactions. l. PK samples collected before the infusion were collected within 5 minutes of the start of the infusion. Samples collected at the end of infusion had a collection window of ±3 minutes. Samples collected 4 hours post the end of the infusion had a window of ±30 minutes. Samples collected 24 hours post the end of the infusion had a window of ±1 hour. Samples collected >24 hours post the end of the infusion had a window of ±2 hours. Urine PK samples were collected at the Week 7 visit from the spot urine collection. Patent Application CLIMB-005 / 01WO 40193 / 24 m. Urine testing included albumin, UPCR, UACR, total creatinine, and urine total protein, based on a spot urine (first morning void) sample collection. Supplies for at-home spot urine sample collection were provided to all participants at the visit prior to when the next collection was due. A spot urine collection was repeated if the Investigator, Medical Monitor, or Sponsor suspects that the sampling was insufficient or inadequate. If a repeat sample was required, the timeline for returning the sample could be extended by 1 week (7 days). If a repeat sample was required during the Screening Period, the sample collection occurred no more than 14 days prior to the first dose of budoprutug. n. Supplies for spot urine sample collection were provided to participants at this visit. Participants were instructed to begin collecting spot urine samples within 5 days of the next scheduled visit and to return all samples to the study site no more than 4 days prior to the next scheduled visit or at the next scheduled visit. o. In order to ensure collections were returned in a timely manner during the Screening and Qualifying Visit, participants were to return the spot urine collections within 5 days of each completion. For participants who did not require tapering of their current medications, two spot urine (first morning void) collections were completed within 14 days of each other during the Screening Period, but initiated within 1 week of the Screening Visit, to confirm eligibility. For participants who required to taper their current medications, the first of two spot urine (first morning void) collections occurred within 7 days after completion of the taper. The two spot urine sample collections was completed within 14 days of each other. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. ADA = anti-drug antibody; AE = adverse event; anti-PLA2R = anti-phospholipase A2 receptor; BMI = body mass index; BP = blood pressure; CNI = calcineurin inhibitor; DRC = Data Review Committee; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EOS = End of Study; ET = Early Termination; FSH = follicle-simulating hormone; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; hCG = human chorionic gonadotropin; HCV = hepatitis C virus; HIV = human immunodeficiency virus; I / E = inclusion and exclusion; IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M; IV = intravenous(ly); MN = membranous nephropathy; PD = pharmacodynamic(s); PK = pharmacokinetic(s); QOL = Quality of Life; TB = tuberculosis; Patent Application CLIMB-005 / 01WO 40193 / 24 UACR = urine albumin-to-creatinine ratio; UNS = unscheduled; UPCR = urine protein-to- creatinine ratio. Documentation of prior and concomitant medication use: All prior and concomitant medications were documented in the source documents and applicable eCRFs. Concomitant medications were assessed and recorded at every study visit from the time of informed consent until study participation was complete. For all participants enrolled, retrospective data was collected from medical records for up to 2 years prior to Screening, to document the participant’s pre-treatment disease history. These data included any available renal biopsy, eGFR, anti-PLA2R antibody titers, proteinuria, and B- cell / lymphocyte levels, as well as MN treatments received. To minimize bias, these data were only collected following signing of informed consent and confirmation that the participant met all study eligibility criteria. Study Procedures: All assessments were to be completed pre-infusion on days where study drug was administered, with the exception of applicable PK samples. Efficacy Measurements: There were no primary efficacy endpoints. The secondary efficacy endpoints included the following: Budoprutug PK parameters (including area under the maximum observed concentration, time to maximum observed concentration, terminal half-life, apparent clearance, and volume of distribution); The change from baseline in absolute peripheral CD20+ B-cell count; 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^%-cell depletion and / or B-FHOO^FRXQW^^^^^ cells / ^L; The change from baseline in proteinuria (via UPCR) by spot urine collection measurements; The proportion of participants achieving complete remission of proteinuria (i.e., UPCR ^^^^^J^J^^ The proportion of participants achieving a reduction from their baseline proteinuria (i.e., 83&5^!^^^^J^J^EXW^^^^^^J^J^DQG^^^^^^UHGXFWLRQ^RI^SURWHLQXULD^IURP^EDVHOLQH^^ 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^SURWHLQXULD^IURP^EDVHOLQH^ Patent Application CLIMB-005 / 01WO 40193 / 24 The change from baseline in albuminuria by spot urine collection measurements or albuminemia; 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^DOEXPLQXULD^RU^^^^^^ increase in albuminemia from baseline; The proportion of participants who develop NS on-study and / or proportion of participants whose NS resolves on-VWXG\^^16^LV^GHILQHG^DV^XULQDU\^SURWHLQ^H[FUHWLRQ^^^^^^J^J^^ hypoalbuminemia, and edema); The change in serum IgA, IgG, and IgM from baseline over time; and The incidence of participants who develop ADAs at any time after study drug administration. For the subset of participants who are anti-PLA2R antibody positive at baseline, additional secondary efficacy endpoints include the following: The change from baseline in anti-PLA2R antibody levels; The proportion of anti-PLA2R antibody-negative participants (defined as <2 RU / mL) over time; 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time; and 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time. The exploratory endpoints included the following: The change in participant reported outcomes / QOL measures, including edema (Patient- Reported Outcomes Measurement Information System [PROMIS]); PK and its relationship to B-cell depletion and clinical response (e.g., anti-PLA2R antibody levels and proteinuria); and Dose and its relationship to B-cell depletion and clinical response. B-cell subset evaluation: Samples were collected for B-cell subset evaluation at visits specified in the Table above. For B-cell evaluations during Month 1 (Visits 2 through 4), samples were collected weekly. B-cell subset evaluations included CD19+ and CD20+ B-cell counts. All B-cell subset evaluation samples were collected pre-infusion at visits where participants received study drug. Immunoglobulin assessment: Patent Application CLIMB-005 / 01WO 40193 / 24 Samples for Ig assessment (including IgA, IgG, and IgM) were collected at visits specified in the Table above. All samples for Ig assessment were collected pre-infusion at visits where participants received study drug. Anti-Drug Antibody Evaluation: Samples for ADA evaluation were collected at visits specified in the Table above. At visits where study drug was administered, samples for ADA evaluation were collected pre-infusion. Pharmacokinetic assessment: Serum PK samples were collected per the Table below. Samples collected before the infusion were collected within 5 minutes of the start of the infusion. Samples collected at the end of infusion had a collection window of ±3 minutes. Samples collected 4 hours post the end of the infusion had a window of ±30 minutes. Samples collected 24 hours post the end of the infusion had a window of ±1 hour. Samples collected >24 hours post the end of the infusion had a window of ±2 hours. Table: Serum PK Sampling Time Points Initial Treatment Period Serum PK Sampling Times in Relation to Infusion Urine-Testing: Urine testing was performed at visits specified in the Table for Scheduling procedures above. Urine testing included albumin, UPCR, urine albumin-to-creatinine ratio (UACR), total creatinine, and urine total protein, based on a spot urine (first morning void) sample collection at each specified measurement timepoint. For participants who did not require tapering of their current medications, two spot urine (first morning void) collections was completed within 14 days of each other during the Screening Period, but must have been initiated within 1 week of the Screening Visit, to confirm eligibility. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. Baseline was defined as the average of the Screening or Qualifying Visit (if applicable) UPCR values. Patent Application CLIMB-005 / 01WO 40193 / 24 For participants who required to taper their current medications, a Qualifying Visit occurred within 7 days of completion of the taper, and the first of two spot urine (first morning void) collections occurred within 7 days of completion of the taper. The two spot urine sample collections was completed within 14 days of each other. Participants received the first dose of budoprutug within 14 days of completion of the second spot urine sample after eligibility was confirmed. Supplies for at-home spot urine sample collection was provided to all participants at the visit prior to when the next collection was due. A spot urine collection could be repeated if the Investigator, Medical Monitor, or Sponsor suspects that the sampling was insufficient or inadequate. If a repeat sample was required, the timeline for returning the sample could be extended by 1 week (7 days). If a repeat sample was required during the Screening Period, the sample collection occurred no more than 14 days prior to the first dose of budoprutug. Supplies for spot urine sample collection was provided to participants at visits specified in the Table for Scheduling procedures above. All participants received instructions in order to increase compliance and accurate data collection for the spot urine sample collections. Participants were instructed to begin collecting spot urine samples within 5 days of the next scheduled visit and to return all samples to the study site no more than 4 days prior to the next scheduled visit or at the next scheduled visit. In order to ensure collections were returned in a timely manner during the Screening and Qualifying Visit, participants were to return the spot urine collections within 5 days of each completion. Anti-PLA2R Antibody-testing: Anti-PLA2R antibody testing was performed at visits specified in the Table for Scheduling procedures above. All samples for anti-PLA2R antibody testing were collected pre-infusion at visits where participants received the study drug. The EUROIMMUN anti-PLA2R (IgG) test kit was fully CE-marked for this purpose and met the requirements of relevant European product directives. Quality of Life Assessment: Quality of life was assessed at visits specified in the Table for Scheduling procedures above. The PROMIS was used to assess participant QOL. Edema was also measured as part of the QOL assessment using an edema self-assessment tool. All QOL assessments was collected pre- infusion at visits where participants were to receive the study drug. Patent Application CLIMB-005 / 01WO 40193 / 24 Safety Assessments: The primary safety endpoint was the incidence of TEAEs. A TEAE was defined as any AE with an onset at any time after the first study drug administration. The secondary safety endpoints included the following: DLTs; and The change from baseline in safety assessments (including clinical laboratory assessments, ECGs, vital signs, and physical examinations). Adverse Events: An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and / or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product, whether or not related to the investigational medicinal product. All AEs, including observed or volunteered problems, complaints, or symptoms, were recorded on the appropriate eCRF. AEs, which included clinical laboratory test variables, were monitored and documented from the time of informed consent until study participation was complete. Participants were instructed to report any AE that they experienced to the Investigator, whether or not they thought the event was due to study drug. Following informed consent, Investigators made an assessment for AEs at each visit and recorded the event on the appropriate AE eCRF. Wherever possible, a specific disease or syndrome rather than individual associated signs and symptoms were identified by the Investigator and recorded on the eCRF. However, if an observed or reported sign or symptom was not considered a component of a specific disease or syndrome by the Investigator, it was recorded as a separate AE on the appropriate eCRF. Additionally, the condition that led to a medical or surgical procedure (e.g., surgery, endoscopy, tooth extraction, or transfusion) was recorded as an AE, not the procedure itself. Any medical condition already present prior to informed consent was recorded as medical history and not reported as an AE unless the medical condition or signs or symptoms present at baseline worsened in severity, frequency, or seriousness at any time during the study. In this case, it was reported as an AE. Patent Application CLIMB-005 / 01WO 40193 / 24 Clinically significant abnormal laboratory or other examination (e.g., ECG, vital sign, and physical examination) findings that were detected during the study or are present after informed consent was obtained and significantly worsen during the study were reported as AEs, as described below. The Investigator exercised his or her medical and scientific judgment in deciding whether an abnormal laboratory finding or other abnormal assessment was clinically significant. Clinically significant abnormal laboratory values occurring during the clinical study were followed until repeat tests returned to normal, stabilize, or were no longer clinically significant. Abnormal test results that were determined to be an error were not reported as an AE. Laboratory abnormalities or other abnormal clinical findings (e.g., ECG, vital sign, or physical examination abnormalities) were reported as an AE if any of the following were applicable: If an intervention was required as a result of the abnormality; If action taken with the study drug was required as a result of the abnormality; or Based on the clinical judgment of the Investigator. Adverse Drug Reaction All noxious and unintended responses to a medicinal product related to any dose were considered an adverse drug reaction (ADR). “Responses” to a medicinal product meant that a causal relationship between a medicinal product and an AE was at least a reasonable possibility, i.e., the relationship could not be ruled out. Unexpected Adverse Drug Reaction: An Unexpected ADR was defined as an adverse reaction, the nature or severity of which was not consistent with the applicable product information. For budoprutug, the reference safety information was included in the Investigator’s Brochure in force at the time of the study. The reference safety information was reviewed annually and the periodicity of the review was harmonized with the reporting period of the Development Safety Update Report. Assessment of Adverse Events by the Investigator: AEs, including those in the context of DLTs, were graded per National Cancer Institute (NCI) CTCAE version 5.0. For those AE terms not listed in the NCI CTCAE, the following grading system was used: CTCAE Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Patent Application CLIMB-005 / 01WO 40193 / 24 CTCAE Grade 2: Moderate; minimal local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living; CTCAE Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; CTCAE Grade 4: Life-threatening consequences; urgent intervention indicated; and CTCAE Grade 5: Death related to the AE. Causality assessment The relationship of an AE to the administration of the study drug was assessed according to the following definitions: No (not related, unlikely to be related) – The time course between the administration of study drug and the occurrence or worsening of the AE ruled out a causal relationship and another cause (concomitant drugs, therapies, complications, etc.) was suspected. Yes (possibly, probably, or definitely related) – The time course between the administration of study drug and the occurrence or worsening of the AE was consistent with a causal relationship and no other cause (concomitant drugs, therapies, complications, etc.) could be identified. The definition implied a reasonable possibility of a causal relationship between the event and the study drug. This meant that there were facts (evidence) or arguments to suggest a causal relationship. The following factors were also considered: The temporal sequence from study drug administration- The event occurred after the study drug was given. The length of time from study drug exposure to event was evaluated in the clinical context of the event. Underlying, concomitant, intercurrent diseases- Each report was evaluated in the context of the natural history and course of the disease being treated and any other disease the participant may have had. Concomitant drug- other drugs the participant was taking or the treatment the participant received were examined to determine whether any of them might have been recognized to cause the event in question. Patent Application CLIMB-005 / 01WO 40193 / 24 Known response pattern for this class of study drug- Clinical and / or preclinical data indicated whether a particular response was likely to be a class effect. Exposure to physical and / or mental stresses- The exposure to stress induced adverse changes in the recipient and provided a logical and better explanation for the event. The pharmacology and PK of the study drug- The known pharmacologic properties (absorption, distribution, metabolism, and excretion) of the study drug were considered. Adverse Events of Special Interest The Investigator monitored each participant for clinical and laboratory evidence for pre- defined AESIs throughout the participant’s participation in this study. AESIs were chosen on the basis of drug-specific factors as well as disease-specific factors. The Investigator assessed and recorded any additional information on the AESI in detail on an AE form which was submitted within 24 hours of awareness of the event. For this study, AESIs included the following: IRR (any grade); Severely decreased neutrophil count (i.e., absolute neutrophil count <500 / mm3); Serious infection (i.e., CTCAE Grade 3 or higher); AKI; and Thromboembolic events. During the course of the study, additional AESIs could have been identified by the Sponsor. AESIs were recorded in the eCRF. Serious Adverse Events An AE or adverse reaction was considered serious if, in the view of either the Investigator or Sponsor, it resulted in any of the following outcomes: Death; A life-threatening AE; Note: An AE or adverse reaction was considered “life-threatening” if, in view of either the Investigator or Sponsor, its occurrence places the participant at immediate risk of Patent Application CLIMB-005 / 01WO 40193 / 24 death. It did not include an event that, had it occurred in a more severe form, might have caused death. Required hospitalization or prolongation of existing hospitalizations; Note: Any hospital admission with at least 1 overnight stay was considered an inpatient hospitalization. An emergency room or urgent care visit without hospital admission was not recorded as an SAE under this criterion, nor was hospitalization for a procedure scheduled or planned before signing of informed consent, or elective treatment of a pre- existing condition that did not worsen from baseline. However, unexpected complications and / or prolongation of hospitalization that occurred during elective surgery were recorded as AEs and assessed for seriousness. Admission to the hospital for social or situational reasons (i.e., no place to stay, live too far away to come for hospital visits, respite care) were not considered inpatient hospitalizations. A persistent or significant disability / incapacity or substantial disruption of the ability to conduct normal life functions; A congenital anomaly / birth defect; or An important medical event. Note: Important medical events that did not meet any of the above criteria were considered an SAE when, based upon appropriate medical judgment, they may have jeopardize the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events included allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that did not result in inpatient hospitalizations, or the development of drug dependency. Analysis Populations: All treated population (ATP) was defined as the set of participants who received at least 1 dose of study drug. The ATP was the primary analysis population for summaries of participant characteristics and safety analyses. Full-Analysis Set: The full analysis set (FAS) contained all participants in the ATP, excluding participants who met any of the following conditions: Patent Application CLIMB-005 / 01WO 40193 / 24 Participant did not provide informed consent. Participant did not receive all eligible doses of budoprutug : o If the participant was recruited under Protocol Versions 1.0 to 5.0. which assigned 4 doses of budoprutug, and the participant did not receive all 4 doses. o If the participant was recruited under Protocol Version 6.0 (dated 23 JUN 2023), which assigned 2 doses of budoprutug, and the participant did not receive both doses. The FAS was the primary analysis population for the analysis of B-cell depletion and other PD endpoints. Pharmacokinetic Analysis Set: The PK population consisted of all participants in the ATP who had sufficient blood samples taken for at least 1 of the PK variables to be calculated. The PK analysis set was the primary population for all PK analyses. Analysis of Subgroups: Multiple secondary efficacy measures were planned to include participants who were anti- PLA2R antibody positive at baseline only. The following analyses were performed involving this subgroup only: The change from baseline in anti-PLA2R antibody levels. The proportion of anti-PLA2R antibody-negative participants (defined as <2 RU / mL) over time. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time. Determination of Sample Size The sample size was determined empirically to meet the objectives of the study while recognizing the low prevalence of MN that precludes a larger study. Each cohort size was designed to be informative and flexible enough to add participants to a dose cohort if determined necessary by the DRC. Following participants longitudinally for safety, persistence of B-cell depletion, anti- PLA2R antibody reduction, and proteinuria reduction further determined the clinical profile of budoprutug and optimize the learnings from the selected sample size. Patent Application CLIMB-005 / 01WO 40193 / 24 The total number of participants depended upon the number of participants accrued to each dose level and the number of dose levels evaluated. It was anticipated that 2 dose cohorts would be evaluated (3 to 6 participants per cohort). Participant Disposition Participant Disposition was summarised using a table and listing. Percentages were calculated using the ATP. Analysis populations was also summarised using a table and a listing. Percentages were calculated using the ATP. Protocol Violations Protocol Violations were summarised using a table and listing. Percentages were calculated using the number of participants screened. Demographics Demographics were be summarised using a table and listing. Percentages were calculated using the ATP. Baseline Disease Characteristics Baseline disease characteristics were be summarised using a table and listing. Percentages were calculated using the ATP. Medical History Medical history was summarised using a table and listing. Percentages were calculated using the ATP. Prior and Concomitant Medications Prior and concomitant medications were summarised using a table and listing. Percentages were calculated using the ATP. Efficacy Measures The efficacy endpoints included collected and derived continuous and categorical variables. Primary Efficacy Analysis There were no primary efficacy analyses planned for this study. Secondary Efficacy Analysis: Budoprutug PK parameters Patent Application CLIMB-005 / 01WO 40193 / 24 All bioanalytical and PK data generated were summarised by analyte and treatment using a table and listing. Percentages calculated using the PK population. Arithmetic mean plasma concentration (± standard deviation [SD]) was presented over time on linear / linear and log10 / linear scales using figures. Spaghetti plots were used to display individual plasma concentrations over time for individual treatment groups using linear / linear scales. Plots were created using the PK population. Absolute Peripheral CD20+ B-Cell Count (cells / ^L) Absolute peripheral CD20+ B-cell count was summarised by visit using a listing. Percentages were calculated using the FAS. Changes in CD20+ B-cell count from baseline and over time (by visit) were summarised using a table and a patient profiles plot. For both the table and the figure, data were grouped by treatment dose and contained participants in the FAS only. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^D^3'^UHVSRQVH^^ZLWK^^^^^^%-cell depletion and / or B-cell count <25 cells / ^L were summarised using a table. In addition, the proportion of participants with B-cell count <5.02 cells / ^L were also summarised on the same table. Proportions were calculated and displayed for all post-baseline visits. Percentages were calculated using the FAS. Proteinuria (UCPR in g / g) Proteinuria via UCPR were summarised using a listing. Percentages were calculated using the FAS. Changes in proteinuria from baseline and over time (by visit) were summarised using a table and a patient profiles plot. For both the table and the figure, data were grouped by treatment dose and contained participants in the FAS only. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^FRPSOHWH^UHPLVVLRQ^^SDUWLDO^UHPLVVLRQ^^DQG^D^^^^^^ reduction in proteinuria when compared to baseline were summarised using a table. Percentages were calculated using the FAS. Albuminuria (UACR in g / g) and Albuminemia (g / dL) Albuminuria (via UACR) and albuminemia (via blood albumin) were summarised using a listing. Percentages were calculated using the FAS. Patent Application CLIMB-005 / 01WO 40193 / 24 Changes in albuminuria and albuminemia from baseline and over time (by visit) were summarised using a table. Data were grouped by treatment dose and contained participants in the FAS only. 7KH^ SURSRUWLRQ^ RI^ SDUWLFLSDQWV^ DFKLHYLQJ^ D^ ^^^^^ UHGXFWLRQ^ LQ^ DOEXPLQXULD^ RU^ ^^^^^increase in albuminemia when compared to baseline were summarised using a table. Percentages were calculated using the FAS. Nephrotic Syndrome (NS) Both NS (without edema) and NS (with edema) developing and / or being resolved on-study were summarised using a listing. Percentages were calculated using the FAS. The proportion of participants developing NS (without edema and with edema) on-study and / or the proportion whose NS resolves on-study were summarised using a table. Percentages were calculated using the FAS. Serum IgA, IgG, and IgM (mg / dL or g / L) Samples for immunoglobulin assessment (Serum IgA, IgG and IgM) were summarised using a listing. Percentages were calculated using the FAS. The change in serum IgA, IgG and IgM from baseline and over time were summarised using a table and a patient profiles plot. For both the table and the figure, data were grouped by treatment dose and contained participants in the FAS only. ADA Development Any Time After Study Drug Administration ADA development was summarised using a listing. Percentages was calculated using the FAS. The incidence of participants who developed ADAs following drug administration were summarised using a table. Percentages were calculated using the FAS. Anti-PLA2R Antibody Levels (RU / mL) Anti-PLA2R antibody levels were summarised using a listing. Percentages were calculated using the FAS. The anti-PLA2R change from baseline and over time were summarised using a table and a patient profiles plot. For both the table and the figure, data were grouped by treatment dose and will contain participants in the FAS who were anti-PLA2R positive at baseline only. Patent Application CLIMB-005 / 01WO 40193 / 24 The proportion of anti-PLA2R antibody negative participants over time (by visit), as wellDV^ WKH^ SURSRUWLRQ^ RI^ SDUWLFLSDQWV^ DFKLHYLQJ^ D^ ^^^^^ DQG^RU^ ^^^^^ UHGXFWLRQ^ LQ^ DQWL-PLA2Rantibodies were summarised using tables. Proportions were presented for each of the visits. Percentages were calculated using participants in FAS who were anti-PLA2R positive at baseline. Exploratory Efficacy Analyses: Change in Participant Reported QOL and Edema Outcomes Self-reported outcomes relating to QOL and edema were summarised using a listing. Percentages were calculated using participants in the FAS. Changes in self-reported outcomes over time were summarised using a table. Percentages were calculated using participants in the FAS. The Relationship Between PK, B-cell Depletion and Clinical Response The relationship between PK vs B-cell depletion and clinical response were presented using a time series plot (by visit). The figure were created using the FAS. The Relationship Between Treatment Dose, B-cell Depletion and Clinical Response The relationship between PK vs B-cell depletion and clinical response were presented using a time series plot (by visit). The figure was created using the FAS. Adverse Events: Adverse Events were summarised using tables and listings. Percentages were calculated using the ATP. The following types of AEs were summarised: Overview of all AEs. Treatment-Emergent Adverse Events. Adverse Events Related to Study Treatment. Serious Adverse Events. Adverse Events by CTCAE Grading. Adverse Events Leading to Dose Interruption / Reduction. Adverse Events Leading to Treatment Discontinuation. Adverse Events of Special Interest. Changes to the planned analysis: Patent Application CLIMB-005 / 01WO 40193 / 24 The most recent study protocol available at the time of writing the Statistical Analysis Plan (SAP) was Protocol Version 6.0.0 (dated 23 June 2023). However, this protocol amendment was made late into the lifespan of the study, by which point the majority of the data had already been collected. Differences between Protocol were mostly visit-related and treatment dose-related. Following discussion with the sponsor, it was decided to write the SAP based on Protocol Version 6.0, but following the visit schedule and treatment doses described in the previous Protocol, which allowed for analysis of all data collected during the study. The following changes to planned analysis were made: For Visit 3 and Visit 5 no actual sample collection times were available and therefore a nominal time of 168 h was assumed and used in the PK analysis Exposure accumulation ratios (maximum observed plasma drug concentration [Cmax] and AUClast) were also calculated where possible Participants were dosed either a cumulative 200 mg or 400 mg IV dose of budoprutug. Study Participants: Of the 38 participants who were screened, 8 participants were enrolled in the study. All enrolled participants received budoprutug (4 in the budoprutug 100 mg Cohort and 4 in the budoprutug 200 mg Cohort). Overall, 5 (62.5%) participants received at least 4 doses of budoprutug and had at least 48 weeks of data. Three participants completed the study (2 [50%] in the budoprutug 100 mg Cohort and 1 [25%] in the budoprutug 200 mg Cohort). FIG.2 provides a summary of the participants in the study. Protocol deviations: Summary of protocol violations for screened participants are provided in the table below. Total a Patent Application CLIMB-005 / 01WO 40193 / 24 Total (N=38)a Data Sets Analyzed All 8 treated participants were included in the ATP and PK populations. The FAS included 5 (62.5%). The Table belowsummarizes analysis sets by treatment group. 100 mg 200 mg Total (N=4) (N=4) (N=8) ) ) ) ) Demographics: The mean (SD) age was 49.8 years old (14.68) with a mean (SD) body mass index of 30.6 kg / m2(10.2). The majority of participants were male and White. The demographic data were similar across treatment groups. The Table below summarizes demography and baseline characteristics by treatment group for the ATP. Table: Summary of Demography and Baseline Characteristics: All Treated Population 100 mg 200 mg Total N 4 N 4 N 8 Patent Application CLIMB-005 / 01WO 40193 / 24 100 mg 200 mg Total (N=4) (N=4) (N=8) The Table below provides the baseline disease characteristics: Summary of Prior Disease History: All Treated Population 100 mg 200 mg Total (N=4) (N=4) (N=8) Patent Application CLIMB-005 / 01WO 40193 / 24 100 mg 200 mg Total (N=4) (N=4) (N=8) Patent Application CLIMB-005 / 01WO 40193 / 24 100 mg 200 mg Total (N=4) (N=4) (N=8) N / n CR = urine protein-to-creatinine ratio. Previous and Concomitant Medication: All participants were at least on 1 prior and / or concomitant medication. The most commonly reported prior medications were lisinopril reported by 5 (63.0%) participants and atorvastatin reported by 4 (50.0%) participants. The most commonly reported concomitant medications were paracetamol reported by 8 (100%) participants and diphenhydramine, cetirizine, and methylprednisolone reported by 4 (50.0%) participants each. Extent of Exposure: The entire dose was administered in 8 (100%), 7 (87.5%), 5 (62.5%), and 5 (62.5%) participants at Week 1, Week 3, Week 24, and Week 26 visits, respectively. Overall, 5 (62.5%) participants received at least 4 doses of budoprutug and had at least 48 weeks of data. Efficacy, Pharmacokinetic, Pharmacodynamic, and other Evaluations: Mean (SD) percentage change from baseline at the EOS was -78.4 (22.3; -74.6 [26.3] for participants in budoprutug 100 mg group and -84.2 [22.3] for participants in budoprutug 200 mg Patent Application CLIMB-005 / 01WO 40193 / 24JURXS^^^7KH^ SURSRUWLRQ^ ^^^^^ FRQILGHQFH^ LQWHUYDO^ >&,@^^ RI^ SDUWLFLSDQWV^ DFKLHYLQJ^ ^^^^^%-celldepletion was 0.4 (0.118, 0.769). The proportion (95% CI) of participants achieving B-cell count of <5.02 cells / µL was 0.2 (0.036, 0.624). FIG. 3 shows the average peripheral CD20+ B-cell count over time following first budoprutug administration for participants with MN for the FAS. Average peripheral CD20+ B- cell count overtime following first budoprutug administration for participants with MN for the FAS are also measured. Proteinuria (UPCR), Albuminuria (UACR), and Albuminemia (g / dL) Proteinuria (UPCR assessments) Mean (SD) change from baseline in UPCR at the end of the study was -2.8 (0.48) g / g. All participants achieved complete remission. Thus the proportion (95% CI) of participants achieving ^^^^^UHGXFWLRQ^RI^SURWHLQXULD^IURP^EDVHOLQH^ZDV^DOVR^^^^^^^^^^^^^^ FIG. 4 shows the average proteinuria (UPCR) over time following first budoprutug administration for participants with MN for the FAS and FIG.5 shows the sensitivity analysis. The baseline value at Day 0 is defined as the mean of Screening Visit and Qualifying Visit. Complete5HPLVVLRQ^ZDV^GHILQHG^DV^83&5^^^^^^J^J^^$GGLWLRQDOO\^ LQFOXGLQJ^SDUWLFLSDQWV^ZKR^REWDLQHG^^^FRQVHFXWLYH^83&5^PHDVXUHPHQWV^^^^^^ZLWKLQ^^^^GD\V^GXULQJ^WKH^6FUHHQLQJ^3HULRG^ FIG.6 provides collated data for the CD20+ cell count, anti-PLA2R antibodies, and UPCR at various time points after the administration of budoprutug. The data provided in FIG. 6 demonstrates that complete remission was achieved in 60% (3 / 5) of patients at Week 48. Partial remission (>50% reduction in UPCR + UPCR < 3.5 g / g) achieved in all (5 / 5) subjects. Complete B-cell depletion (CD20+count <5 cells / µL) achieved in all (5 / 5) subjects Anti-PLA2R Ab negativity (<14 RU / mL) achieved in all (3 / 3) evaluable subjects 2 subjects on study that have not entered complete remission have achieved PLA2R negativity (serological remission) In effect, budoprutug in MN was well-tolerated and demonstrated clinical and immunological remission rates superior to rituximab based on historical data. Immunoglobulin assessments: Mean (SD) change in serum IgA, IgG, and IgM from baseline over time were -56.8 mg / dL (42.19), 154.2 mg / dL (114.84), and -13.6 mg / dL (5.98), respectively. Patent Application CLIMB-005 / 01WO 40193 / 24 FIG. 7, FIG. 8, and FIG. 9 show the IgA, IgG, and IgM versus time following first budoprutug administration for participants with MN for the FAS, respectively. Anti-PLA2R Antibodies: Participant anti-PLA2R antibody levels following budoprutug administration. Mean (SD) change from baseline in anti-PLA2R antibody levels at EOS was -62.1 RU / mL (24.9). FIG. 10 shows average anti-PLA2R antibodies over time. The proportion (95% CI) of anti-PLA2R negative participants was 0.7 (0.2, 0.9) at the end of the study. The proportion (95% CI) of SDUWLFLSDQWV^DFKLHYLQJ^D^^^^^^DQG^D^^^^^^UHGXFWLRQ^LQ^DQWL-PLA2R antibodies were 1 (0.4, 1) and 0.7 (0.2, 0.9), respectively. Examination of subgroups: Multiple secondary efficacy measures included participants who were anti-PLA2R antibody positive at baseline only. The following analyses were performed involving this subgroup only: The change from baseline in anti-PLA2R antibody levels. The proportion of anti-PLA2R antibody-negative participants (defined as <2 RU / mL) over time. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time. 7KH^SURSRUWLRQ^RI^SDUWLFLSDQWV^DFKLHYLQJ^^^^^^UHGXFWLRQ^RI^VHUXP^DQWL-PLA2R antibody levels from baseline over time. Plasma Concentration Over Time: FIG.11 shows plasma budoprutug concentration versus time for the PK population. Efficacy: A decrease in absolute peripheral CD20+ B-Cell was observed from baseline for both treatment groups. The decrease was greater for the budoprutug 200 mg group. There was a sustained decrease in proteinuria as measured by UPCR throughout the treatment period with all SDUWLFLSDQWV^DFKLHYLQJ^FRPSOHWH^UHPLVVLRQ^^SURWHLQXULD^^^^^^J^J^^ There was a reduction in serum IgA and IgM from baseline. The reduction was greater with budoprutug 200 mg. Pharmacokinetics: Patent Application CLIMB-005 / 01WO 40193 / 24 Following IV infusion of 100 or 200 mg (cumulative 200 mg or 400 mg) of budoprutug to adult participants with primary membranous nephropathy the exposure appeared less than proportional upon doubling the dose. The serum half-life was considered long at 405.80 h and 219.97 h following dosing of 100 mg and 200 mg budoprutug, respectively after the Day 15 dose. The serum clearance was considered low at <0.99 L / day. No considerable accumulation (as determined by Cmax) was observed following dosing at 100 mg and 200 mg budoprutug (0.90 and 1.10, respectively). Overall, there was a considerable amount of variability observed in the determined PK parameters across 2 doses and dosing periods. Safety: Summary of AEs Following budoprutug administration for participants with MN for ATP is presented in the Table below. Overall, 7 (87.5%) participants reported at least one TEAE. Of these, 4 (50.0%) participants had at least 1 treatment-related TEAE. There were 3 (37.5%) participants with at least one SAE, 1 (12.5%) participant with an ADR, and 3 (37.5%) participants with an AESI. There were no study discontinuations due to an AE. No DLTs were reported during the conduct of this study. Table: Overview of AEs Following Budoprutug Administration for Participants with MN: All Treated Population 100 mg 200 mg Total Patent Application CLIMB-005 / 01WO 40193 / 24 100 mg 200 mg Total (N=4) (N=4) (N=8) Terminology Criteria for Adverse Events; TEAE = treatment-emergent adverse event. Display of Adverse events: The most commonly reported SOC was general disorders and administration site conditions reported by 4 (50.0%) participants followed by infections and infestations reported by 4 (50.0%) participants. The most commonly reported TEAEs by PT were COVID-19 reported by 3 (37.5%) participants and chills reported by 2 (25.0%) participants. The pattern and incidence of TEAEs (by SOC and PT) were similar between treatment groups. Patent Application CLIMB-005 / 01WO 40193 / 24 Summary of TEAEs following budoprutug administration for participants with MN by SOC and PT for the ATP is presented in the Table below. Table: Summary of TEAEs Following Budoprutug Administration for Participants with MN by SOC and PT: All Treated Population SOC 100 mg 200 mg Total PT (N=4) (N=4) (N=8) Patent Application CLIMB-005 / 01WO 40193 / 24 SOC 100 mg 200 mg Total PT (N=4) (N=4) (N=8) ac par c pan s coun e on y once w n eac an . Percentages are calculated using the number of participants in the corresponding treatment group as the denominator. Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; N = number of participants; MN = membranous neuropathy; N = number of participants; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent adverse event. Analysis of Adverse Events: Treatment-Related Treatment-Emergent Adverse Events There were 4 (50.0%) participants with at least one treatment-related TEAE. The most commonly reported treatment-related TEAE was COVID-19 reported by 2 (25.0%) participants. Summary of TEAEs following budoprutug administration for participants with MN by relationship to study drug for the ATP is presented in the Table below. Summary of TEAEs Following Budoprutug Administration for Participants with MN by Relationship to Study Drug: All Treated Population System Organ Class 100 mg (N=4) 200 mg (N=4) Total (N=8) d %) Patent Application CLIMB-005 / 01WO 40193 / 24 System Organ Class 100 mg (N=4) 200 mg (N=4) Total (N=8) Preferred Term Related Not- Related Not- Related Not- d %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) %) Patent Application CLIMB-005 / 01WO 40193 / 24 System Organ Class 100 mg (N=4) 200 mg (N=4) Total (N=8) Preferred Term Related Not- Related Not- Related Not- d %) %) ng the event that falls into the most severe 'Related' category. An AE is defined as 'Related', if it is recorded as 'Possibly', 'Probably' or 'Definitely' related to the study treatment. Percentages are calculated using the number of participants in the corresponding treatment group as the denominator.MN: Membranous Neuropathy; AE: Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; N = number of participants; MN = membranous neuropathy; N = number of participants; TEAE = treatment-emergent adverse event. Serious Adverse Events: There were 3 (37.5%) participants with treatment-emergent SAEs (pneumonia bacterial, rhabdomyolysis, and chronic obstructive pulmonary disease [COPD]). Summary of serious TEAEs following budoprutug administration for participants with MN by SOC and PT for the ATP is presented in the Table below. Table: Summary of Serious TEAEs Following Budoprutug Administration for Participants with MN by SOC and PT: All Treated Population System Organ Class 100 mg 200 mg Total Patent Application CLIMB-005 / 01WO 40193 / 24 All TEAEs are coded using MedDRA Version 24.0. Each participant is counted only once within each system organ class and preferred term. Percentages are calculated using the number of participants in the corresponding treatment group as the denominator. Abbreviations: MedDRA = Medical Dictionary for Regulatory Activities; MN = membranous neuropathy; N = number of participants; PT = Preferred Term; SOC = System Organ Class; TEAE = treatment-emergent adverse event. Other Adverse Events of Special Interest: Overall, 7 (87.5%) participants reported an AESI. The most commonly reported AESIs by PT were COVID-19 reported by 3 (37.5%) participants and chills reported by 2 (25.0%) participants. Summary of AESI following budoprutug administration for participants with MN by SOC and PT for the ATP is presented in the Table below. Table: Summary of AESI Following Budoprutug Administration for Participants with MN by SOC and PT: All Treated Population System Organ Class 100 mg 200 mg Total Preferred Term (N=4) (N=4) (N=8) Patent Application CLIMB-005 / 01WO 40193 / 24 System Organ Class 100 mg 200 mg Total Preferred Term (N=4) (N=4) (N=8) Each participant is counted only once within each system organ class and preferred term. Percentages are calculated using the number of participants in the corresponding treatment group as the denominator. Abbreviations: AESI = adverse event of special interest; MedDRA = Medical Dictionary for Regulatory Activities; MN = membranous neuropathy; N = number of participants; PT = Preferred Term; SOC = System Organ Class Safety Conclusions: The pattern and incidence of TEAEs were similar between treatment groups. Overall, 7 (87.5%) participants reported at least one TEAE. Of these, 4 (50.0%) participants had at least 1 treatment-related TEAE. There were 3 (37.5%) participants with at least one SAE, 1 (12.5%) participant with an ADR, and 3 (37.5%) participants with an AESI. There were no study discontinuations due to an AE. Patent Application CLIMB-005 / 01WO 40193 / 24 The most commonly reported SOC was general disorders and administration site conditions reported followed by infections and infestations. The most commonly reported TEAEs by PT were COVID-19 and chills. No DLTs or deaths were reported during the conduct of this study. Budoprutug was generally well tolerated and no major safety concerns were observed. Discussion and overall conclusion: Overall, 7 (87.5%) participants reported at least one TEAE with 4 (50.0%) participants experiencing at least 1 treatment-related TEAE. Three (3 [37.5%]) participants reported SAEs, 1 (12.5%) participant reported an ADR, and 3 (37.5%) participants reported an AESI during the conduct of this study. Neither of the SAEs were deemed related to the study drug. The most commonly reported SOC was general disorders and administration site conditions reported followed by infections and infestations. The most commonly reported TEAEs by PT were COVID-19 and chills. No DLTs or deaths were reported during the conduct of this study. Following IV infusion of 100 or 200 mg (cumulative 200 mg or 400 mg) of budoprutug to adult participants with primary membranous nephropathy the exposure appeared less than proportional upon doubling the dose. The serum half-life was considered long at 405.80 h and 219.97 h following dosing of 100 mg and 200 mg budoprutug, respectively after the Day 15 dose. The serum clearance was considered low at <0.99 L / day. No considerable accumulation (as determined by Cmax) was observed following dosing at 100 mg and 200 mg budoprutug (0.90 and 1.10 respectively). Mean (SD) percentage change from baseline at the EOS was -78.4 (22.3; -74.6 [26.3] for participants in budoprutug 100 mg group and -84.2 [22.3] for participants in budoprutug 200 mggroup). 7KH^ SURSRUWLRQ^ ^^^^^ &,^^ RI^ SDUWLFLSDQWV^ DFKLHYLQJ^ ^^^^^B-cell depletion demonstrated a sharp decrease towards the middle of the study (proportion of 1 [0.566, 1] during Visits 8, 11, 12; 1 [0.510, 1] during visit 13; 1 [0.439, 1] during visit 14), and was then demonstrated to increase again, with a final proportion of 0.4 (0.118, 0.769) at EOS / ET. The proportion (95% CI) of participants achieving complete remission of proteinuria^83&5^ ^^^^^ J^J^^ZDV^ ^^ ^^^^^^^^ ^^^^7KH^ SURSRUWLRQ^ ^^^^^&,^^ RI^ SDUWLFLSDQWV^ DFKLHYLQJ^ ^^^^^reduction of proteinuria from baseline was 1 (0.342, 1). Patent Application CLIMB-005 / 01WO 40193 / 24 The proportion (95% CI; sensitivity analysis) of participants with NS (with and without edema) resolving on-study was 1 (0.207, 1) in the budoprutug 200 mg group. Mean (SD) change in serum IgA, IgG, and IgM from baseline over time were -56.8 mg / dL (42.19), 154.2 mg / dL (114.84), and -13.6 mg / dL (5.98), respectively. Mean (SD) change from baseline in anti-PLA2R antibody levels at EOS was -62.1 RU / mL (24.9). The proportion (95% CI) of anti-PLA2R negative participants was 0.7 (0.2, ^^^^^DW^WKH^HQG^RI^WKH^VWXG\^^7KH^SURSRUWLRQ^^^^^^&,^^RI^SDUWLFLSDQWV^DFKLHYLQJ^D^^^^^^DQG^D^^^^^^ reduction in anti-PLA2R antibodies were 1 (0.4, 1) and 0.7 (0.2, 0.9), respectively. Budoprutug was generally well tolerated and no major safety concerns were observed. The pattern and incidence of TEAEs were similar between treatment groups. Overall, there was a considerable amount of variability observed in the determined PK parameters across 2 doses and dosing periods. A sustained decrease in absolute peripheral CD20+ B-Cell, proteinuria as measured by UPCR, serum IgA and IgM, and anti-PLA2R antibodies was observed from baseline for both treatment JURXSV^^$OO^SDUWLFLSDQWV^DFKLHYHG^FRPSOHWH^UHPLVVLRQ^^SURWHLQXULD^^^^^ g / g). Summary of Phase Ib trial: Introduction: Membranous nephropathy (MN) is characterized by a histologic pattern of injury caused by autoantibodies directed against podocyte antigens. Targeting B lymphocytes with anti-CD20 monoclonal antibodies has become a preferred therapy for primary MN, but this strategy fails to induce complete remission (CR) in most patients. Budoprutug is an anti-CD19 monoclonal antibody with a broader spectrum of B-cell depletion, including activity against CD19- positive plasmablasts. Here, we present the results of a Phase 1b, open label, dose escalation study of budoprutug in patients with primary MN. Methods: Eligible patients had primary MN with a history of nephrotic syndrome, received maximally tolerated therapy with a renin-angiotensin system inhibitor for 6 months, and had a urine protein to creatinine ratio (UPCR) of > 2 g / g on two measurements during screening. Budoprutug was administered as 2 bi-weekly doses of 100 or 200 mg six months apart on Days 1,15,169, and 183. The primary objective was safety. Secondary objectives included B-cell levels, anti-phospholipase A2 receptor (anti-PLA2R) antibody (Ab) levels, and changes in proteinuria. The analysis was restricted to patients with at least 48 weeks of follow-up. Patent Application CLIMB-005 / 01WO 40193 / 24 Results: Five patients met inclusion criteria, 3 of which were PLA2R Ab positive. All patients achieved complete B cell depletion, with 2 patients reconstituting B-cells before Week 24. Serologic remission was achieved in all anti-PLA2R Ab positive patients over a range of 5 to 18 weeks. Median baseline proteinuria was 4.2 g / g. Three patients achieved complete remission ^83&5^^^^^^^J^J^^UDQJH^^^^^WR^^^^ZHHNV^^^ZLWK^D^IRXUWK^SDWLHQW^DFKLHYLQJ^D^83&5^RI^^^^^^DW^ZHHN^ 48. All patients achieved a UPCR < 1 g / g and partial remission. Two patients with 72 week follow up achieved durable CRs ~18 months from initial dosing. Budoprutug was well tolerated with no VHULRXV^DGYHUVH^HYHQWV^RU^*UDGH^^^^GUXJ-related AEs. Conclusions: Treatment with budoprutug resulted in high rates of serologic and clinical remission, suggesting that CD19-targeted B-cell depletion may be a promising approach to the treatment of primary MN. These findings warrant larger studies to confirm the efficacy of budoprutug in MN. Phase 2 Study: A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of Budoprutug in Subjects with Primary Membranous Nephropathy Number of subjects planned: Up to 45 subjects Objectives Endpoints t Patent Application CLIMB-005 / 01WO 40193 / 24 Objectives Endpoints Change from Baseline in proteinuria Methodology: This Phase 2, open-label study evaluates the safety and efficacy of 3 dose regimens of budoprutug, as outlined below: Dose (mg) Frequency All subjects will be administered 2 cycles of treatment with budoprutug IV infusions. In Cycle 1, the infusions will occur at Baseline (Day 1) and at Week 2 (Day 15). In Cycle 2, the infusions will be administered at Week 24 (Day 169) and Week 26 (Day 183). At each dose- administration visit, subjects will remain at the study site for at least 4 hours after the infusion is completed to monitor for AEs and for blood sample collections for PK and laboratory assessments. Subjects will return at prespecified intervals for assessment of safety, PK and PD. All subjects will be followed through Week 48. Subjects who have not repopulated B cells by Week 48 will return Patent Application CLIMB-005 / 01WO 40193 / 24 to the clinic for safety and PD assessments until B cell levels return to the subject’s Baseline value or are within normal limits. FIG.14 and FIG.15 provide an overview of the Phase 2 trial. The subjects are enrolled sequentially into one of the 3 dose cohorts (budoprutug 200 mg, 600 mg, and 1000 mg). After at least 6 subjects in a cohort continue for at least 8 weeks of treatment and assessments in this study, the Safety Review Committee will meet and review all available data to decide on dose escalation. In FIG. 15, the down arrow indicates the budoprutug dose administration days. The primary endpoint may be incidence of treatment-emergent adverse events (TEAEs). Study Duration: The study duration for each individual subject in this Phase 2 study will be up to 52 weeks, including up to 4 weeks for screening and a 48-week open-label treatment period. Study Population: This study will enroll adult subjects who meet all the inclusion criteria and none of the exclusion criteria. Subjects will be eligible for enrollment in this study regardless of race / ethnicity. Inclusion Criteria: Subjects who meet all the following criteria will be eligible for enrollment. 1. Willing and able to provide written informed consent 2. $JHG^^^^^\HDUV^WR^^^^^\HDUV^ROG^DW^WKH^WLPH^RI^LQIRUPHG^FRQVHQW^ 3. 6XEMHFW^KDV^&'^^^^%^FHOO^FRXQW^^^^^FHOOV^^L at Screening and Baseline 4. Confirmed diagnosis of PMN (e.g., based on a kidney biopsy result, a positive serum anti- PLA2R antibody titer). 5. Subjects must have positive anti-PLA2R antibody titer levels at Screening 6. Subjects with persistent evidence of disease activity despite an adequate trial of ACEi / ARB treatment at maximum tolerated doses, with a stable dose for at least 4 weeks prior to Screening, and no planned or anticipated dose adjustment during the study 7. 83&5^^^^^^^J^J^GXULQJ^^^FRQVHFXWLYH^XULQH^VDPSOH^FROOHFWLRQV^REWDLQHG^ZLWKLQ^^^^GD\V^ during the Screening period 8. 6XEMHFWV^PXVW^KDYH^DQ^HVWLPDWHG^JORPHUXODU^ILOWUDWLRQ^UDWH^^H*)5^^^^^^P / ^PLQ^^^^^^P^^ (by 2021 CKD-EPI creatinine equation) 9. Blood pressure below 160 / 100 mmHg at Screening and below 150 / 90 mmHg at Baseline Patent Application CLIMB-005 / 01WO 40193 / 24 10. Adequate hematologic, hepatic, and renal function within the Screening period and prior to the first dose of study drug. 11. Willingness to use effective contraception. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in the study: 1. Rapidly progressive glomerulonephritis, or other concomitant or overlapping glomerulopathies based on previous renal biopsy, or glomerulopathies known by the subject’s medical history (e.g., diabetic nephropathy, IgA nephropathy, or primary or genetic variant of focal segmental glomerulosclerosis [FSGS]) 2. Secondary causes of MN (e.g., malignancy, hepatitis B or C, human immunodeficiency virus [HIV], systemic lupus erythematosus [SLE], or other autoimmune diseases [e.g., thyroiditis, sarcoidosis], or drug-induced). (Note: Potential secondary causes of MN must be ruled out by the investigator, following local guidelines and standard of care.) 3. Prior treatment with any other B cell depleting agent (e.g., rituximab, ocrelizumab, obinutuzumab, ofatumumab, inebilizumab) within 24 weeks prior to the first dose of study drug 4. Prior treatment with corticosteroids or mycophenolate mofetil within 30 days prior to Screening; permitted exceptions include topical corticosteroids, inhaled corticosteroids, or low dose oral corticosteroids (10 mg or less prednisone or equivalent) for non-renal conditions. 5. Treatment with any investigational drug within 30 days or at least 5 times the elimination half-life of the drug (whichever is longer) prior to the first dose of study drug, or subject is currently enrolled in another clinical study or plans to use an investigational device or drug during the 6. Pregnant or lactating females or females who are considering becoming pregnant during the study and for 6 months after the last administration of study drug. 7. History of malignancy (active or suspected) within the past 5 years, except for non- melanoma skin cancer or cervical carcinoma in-situ. 8. Acute, chronic, or latent infection, including SARS-CoV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, or splenectomy that predisposes subject to infections. 9. Subjects with active tuberculosis (TB) or considered at high risk for active TB. 10. Active systemic infection (except common cold) within 4 weeks prior to the Screening visit that requires treatment with anti-infectives, hospitalization, or represents additional risk to the subject as assessed by the investigator. Patent Application CLIMB-005 / 01WO 40193 / 24 11. Recent hospitalization for any reason within 14 days prior to Screening, unless approved by the Medical Monitor. 12. Major surgery (e.g., hip replacement, aneurysm removal, stomach ligation) performed within 12 weeks prior to the Screening visit or planned during the conduct of the study. 13. Any other clinically significant disease, condition, or medical history that, in the Investigator's opinion, would compromise safety, interfere with study evaluations or procedures, or make subject unsuitable candidates for the study drug. This includes individuals who are permanently wheelchair-bound, bedridden, or have a very poor functional status that prevents self- care. Dosage Form and route of administration: Budoprutug drug product will be provided as a colorless to slightly opalescent for administration as an IV infusion. Immune Thrombocytopenia Immune thrombocytopenia (ITP) is an autoimmune disease. ITP is an illness that can lead to bruising and bleeding. In particular, antiplatelet autoantibodies lead to accelerated removal of platelets by macrophages with bone marrow compensation. The symptoms of ITP include bruising, bleeding episodes, and fatigue. The diagnosis relies on low platelet count, and is further supported by additional blood tests, i.e., CBC and blood smear, and antiplatelet antibody test. The diagnosis may further rely on bone marrow aspiration, if needed. ITP is a predominantly an IgG1 immune mediated disorder with antiplatelet antibodies. These autoantibodies attach themselves to the platelet surface marking the cells for the immune system, targeting both their production and circulation. This results in shorter platelet lifespan with splenic destruction as a hallmark feature. The bone marrow attempts to compensate by increasing cell production, but the cascading immune disorders leaves patients vulnerable to the effects of thrombocytopenia. For patients this low platelet count results in bruising or petechiae and purpura, hemorrhagic episodes or extensive bleeding, and chronic fatigue. Children fare better than adults with the natural history of the disease taking a more benign course. Conversely, adults rarely have spontaneous remission; they are reliant on a number of treatments which contribute to higher mortality than is observed in aged-matched controls. In the US alone over 80,000 adults live with chronic ITP and they face a complex treatment journey. In fact, the majority of these patients relapse after receiving first line therapy with subsequent lines of therapy only partially addressing patient needs. Patent Application CLIMB-005 / 01WO 40193 / 24 In general, most of the children have spontaneous remission within a few weeks or months. While adults often stabilize after the first line therapy, the majority eventually relapse or become refractory, necessitating treatment with second and often third line therapies. In certain hard to treat situations, splenectomy is also considered as an option for treatment. An overview of the current methods of management of ITP is provided in FIG. 16. For example, the current treatment includes treatment with corticosteroid, intravenous immunoglobulin (IVIG), and anti-RhD immunoglobulin. The International Working Group (IWG) on ITP and the American Society of Hematology (ASH) 2019 guidelines. Based on the current treatment recommendations of the American Society of Hematology, it is clear that the there is no efficacious treatment for ITP patients. There is a clear significant unmet need for treatment of these patients. Even if a patient is fortunate enough to stabilize on first line therapy, upwards of 80% relapse and move to 2ndline treatments, namely Rituximab or thrombopoietin receptor agonists. Many of those necessitate a 3rdline treatment with additional doses of Rituximab and thrombopoietin receptor agonists, or a trial of Fostamatinib or other ISTs. If unsuccessful, combination therapy and even splenectomy are considered. A more detailed examination of the current treatments and their mechanism of action reveals modalities that attempt to intervene down stream in disease pathogenesis. Anti-RhD IG a first line therapy and Fostamatinib a third line therapy attempt to evade the already cascading immune mediated platelet destruction. Other treatments like TPO-RA try to boost bone marrow production of platelets. Few current treatments target upstream disease pathogenesis with Rituximab attempting to target pathological B-cells but falling short. Certainly, rituximab or CD20 B cell depleters are effective, but they can only address a limited B cell lineage. Most importantly, plasma cells, the autoantibody producing cells implicated in ITP, are not addressed by rituximab or CD 20 depleters, a key feature that Steven already highlighted. This fundamental shortfall may be overcome by the methods of the current invention. The invention beneficially realizes that anti-CD19 antibodies may provide an impact by targeting plasma cells and plasmablasts in addition to other cells across the B cell lineage. ITP patients are unlikely to respond to therapies with anti-CD20 agents, such as rituximab, because ITP patients have CD19+ / CD20- cells. The data provided in FIG. 17 demonstrates that CD19+ / CD20- plasma cells expand within B-cell niches post anti-CD20 treatment. Moreover, FIG.18 provides the mechanisms for primary failure of anti-CD19 antibodies. The primary failure Patent Application CLIMB-005 / 01WO 40193 / 24 could be due to pre-existing CD20- plasma cells. In other mechanisms, there may also be a relapse after the initial response. This includes pre-existing CD20- B-cells and de novo CD20- B-cells. Rituximab depletes peripheral B cells but its limited effect leaves tissues vulnerable and the underlying disease only partially treated as evidenced by primary failures and more commonly high relapse rates. FIG.17 and FIG.18 demonstrate that CD20 negative B cells continue to drive disease through expansion and formation of germinal centers. The splenic plasma cells are also a big driver of the disease progression. In the pre Rituximab treated patient only 2.4% plasma cells are found in the spleen, which is in dramatic contrast to the post rituximab treated patient with nearly 75% plasma cells in the spleen. These pathogenic plasma cells, which are CD 20 negative and CD19 positive, continue to wreak havoc with persistent immune mediated destruction likely from tissue level expansion. Thus, the methods of the invention, which require administration of anti-CD19 antibody, target plasma cells as well as a number of cells across the B cell linage can potentially address this gap in the current treatment paradigm, not only serving as a more complete B cell depleter but addressing the rituximab failure population. Methods of the Invention: The invention provides novel methods for treatment of immune thrombocytopenia (ITP). In certain aspects, the invention provides treating a subject having immune thrombocytopenia (ITP) comprising administering to the subject a composition comprising a therapeutically effective amount an anti-CD19 antibody. The anti-CD19 antibody may be a humanized anti-CD19 antibody. In certain embodiments, the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. The invention beneficially provides that the anti-CD19 antibodies provide a good therapeutic response for patients with ITP. In particular, there are no previous therapies for ITP patients with compositions comprising anti-CD19 antibodies. The invention beneficially recognizes that the methods provided herein may provide a good response as compared to the previously known therapies because it targets CD-19+ plasma cells. The methods of the invention may be for patients who have had a previous therapy for treatment and / or management of ITP. In certain embodiments, the patient may have not benefited from the previous treatment regimen. Alternatively, the patient may have relapsed after the previous treatment regimen. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising the anti-CD19 antibody is administered parenterally. In certain embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the composition comprising the anti-CD19 antibody is administered in a dosing cycle. In certain embodiments, the dose cycle comprises administration of a single dose. In certain embodiments, the dose cycle comprises administration of more than one dose. In certain embodiments, the dose cycle comprises administration of two doses. In certain embodiments, the composition is administered at days 1 and 15 at the start of the treatment, wherein day 1 is the start of the treatment. In certain embodiments, the composition is further administered at days 169 and 183 after the start of the treatment. In certain embodiments, the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15 at start of each treatment cycle, wherein there is a 12 to 36-week interval between start of each said treatment cycle. In certain embodiments, interval between each treatment cycle is 12 weeks. In certain embodiments, said interval between each treatment cycle is 24 weeks. In certain embodiments, said interval between each treatment cycle is 36 weeks. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti- CD19 antibody is budoprutug. In certain embodiments, the composition comprises about 100 mg to about 1200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about Patent Application CLIMB-005 / 01WO 40193 / 24 1000 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg to about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 600 mg to about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 250 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 600 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 1000 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain aspects, the method of the invention provides a novel “treat to target” approach for the treatment of ITP. This approach beneficially provides the measurement of the biological parameters associated with ITP after administration of the composition. The method of the invention provides the flexibility to alter the dosing regimen to provide additional doses of the anti-CD19 antibody after the initial dose to get optimal response for the treatment of ITP patients. In certain embodiments, the methods of the invention further comprise measuring concentration for markers or biological parameters of ITP progression in the subject after the administration of the initial dose. The method further provides that an additional dosing cycle of the anti-CD19 antibody may be administered. In certain embodiments, the additional dosing cycle is administered if there is below expected response after the administration of the initial dosing cycle of the anti-CD19 antibody. The markers or biological parameters for measurement of ITP progression could be measuring concentration of any marker or parameter associated to monitor the progression of ITP or symptoms thereof. The markers or parameters could be any parameters used to measure the efficacy of certain treatments. In certain embodiments, the methods of the invention provide that the markers are selected from the group consisting of platelet count and B cells. The concentration of B-cells measured could be circulating B cells. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the composition. The timeline for measurement of markers or biological parameters could be determined based on the expected timeline for seeing a response after the administration of the initial dose of the composition comprising anti-CD19 antibody. In certain embodiments, the measuring step is conducted about 8 to about 16 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. In certain embodiments, the measuring step is conducted about at least 12 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. In certain embodiments, the measuring step is conducted about at least 12 weeks after administration of initial dose of the composition comprising anti-CD19 antibody. The invention recognizes that an additional dose of the treatment with anti-CD19 antibodies may be administered if an inadequate response is observed after the initial dose. The parameters or markers may be measured at the discretion of the physician treating the condition in the patient. The timeline for measurement of the markers of biological parameters may account for each patient’s physiological condition. For example, the parameters monitored are the platelet count and / or circulating B-cells in the patient. In certain embodiments, the additional dose is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle. In certain embodiments, the additional dosing cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle. In certain embodiments, the additional dosing cycle comprises administration of two doses of the composition comprising anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose of the composition comprising anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 50 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 300 mg of the anti-CD19 Patent Application CLIMB-005 / 01WO 40193 / 24 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg to about 200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 100 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 600 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of a single dose comprising about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 50 mg to about 500 mg of the anti- CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg to about 200 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises from about 100 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 600 mg of the anti-CD19 antibody. In certain preferred embodiments, the anti- CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 1000 mg of the anti- CD19 antibody. In certain preferred embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 100 mg to about 1200 mg of the anti-CD19 Patent Application CLIMB-005 / 01WO 40193 / 24 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 100 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 200 mg to about 1000 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 200 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 250 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 500 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 600 mg of the anti-CD19 antibody. In certain embodiments, the additional dosing cycle comprises administration of two doses, wherein at least one two doses comprises about 1000 mg of the anti-CD19 antibody. In certain embodiments, the invention provides pre-medication prior to each administration of the anti-CD19 antibody. In certain embodiments, the invention provides pre-medication prior to the infusion of budoprutug to reduce the frequency and severity of infusion-related reaction (IRRs). The premedication could be with a medical auxiliary product. In certain embodiments, the premedication is with a corticosteroid, antihistamine, or a antipyretic. In certain embodiments, the corticosteroid is administered intravenously. In certain embodiments, the antihistamine is administered orally. In certain embodiments, the antipyretic is administered orally. In certain preferred embodiments, the corticosteroid may be methylprednisone or an equivalent thereof. In certain preferred embodiments, the antihistamine may be diphenhydramine or an equivalent thereof. In certain preferred embodiments, the antipyretic may be acetaminophen / paracetamol or an equivalent thereof. In certain aspects, the invention provides a method of treating a subject having immune thrombocytopenia (ITP), the method comprising: administering a first cycle of a pharmaceutical composition comprising a therapeutically effective amount of a therapeutic agent; monitoring markers associated with ITP progression in the subject; and Patent Application CLIMB-005 / 01WO 40193 / 24 providing a second cycle of compositions comprising therapeutically effective amount of said anti-CD19 antibody if the biological parameters demonstrate an inadequate physiological response after the first cycle. In certain embodiments, the therapeutic agent is an anti-CD19 antibody. In certain embodiments, the second cycle is different from the first cycle. In certain embodiments, the first cycle comprises administration at days 1 and 15 at the start of the treatment. In certain embodiments, the markers are selected from the group consisting of platelet count and B cells. In certain embodiments, the monitoring step is conducted about 8 to about 16 weeks after start of the first cycle. In certain embodiments, the monitoring step is conducted about 12 weeks after start of the first cycle. In certain embodiments, the second cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after start of the first cycle. In certain embodiments, the second cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after start of the first cycle. In certain embodiments, the subject has insufficient response to at least one prior therapy for treatment of ITP. The invention beneficially recognizes that the methods provided herein demonstrate treatment of orphan conditions, such as ITP, in a personalized medicine approach. CD19 B cell depletion has the potential to reshape the treatment in immune mediated diseases, and the unique treat to target approach provided herein enables the treatment of patients throughout their journey and provide a tailored approach for each patient. Phase 2 Trial ITP: An overview of the ITP is provided in FIG.19. The ITP phase 2 trial is a single arm open label study in adult patients with chronic disease evaluating the safety and efficacy of budoprutug. It leverages learnings from prior ITP phase 2 trials where placebo rates have been historically very low. The primary endpoint will measure platelet improvement along with other disease parameters. However, truly unique to this study design is a ‘treat to target’ approach that allows redosing based on individual patient needs. Patients will receive a treatment cycle at day 1 and day 15 for those who meet eligibility criteria. Investigators can elect for a second cycle of treatment if improvement wanes, guided by individual patient laboratory findings and clinical needs. These parameters include low or falling platelet counts, that are deemed clinically significant, coupled with B cell counts. ITP offers an ideal serological marker in platelet count that reflects clinical picture. Additionally, since B cells return at a variable rate in each patient Patent Application CLIMB-005 / 01WO 40193 / 24 these 2 parameters taken together will allow providers to create the ‘just right’ treatment regimen to meet patients where they are. This personalized approach aims to optimize treatment efficacy. Individualized medicine for the individual living with a rare disease. Examples: Phase 1b / 2a Open-Label Sequential-Cohort, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Effectiveness of Budoprutug (TNT119) in Subjects with Immune Thrombocytopenia (ITP) Synopsis: Study Objectives: Primary Objective: The primary objective of this study is: To evaluate the safety and tolerability of ascending doses of budoprutug in subjects with ITP. Secondary Objectives: The secondary objectives of this study include the following: To investigate potential doses for subsequent dose-finding studies in subjects with ITP. To characterize the pharmacokinetic (PK) profile of budoprutug in subjects with or ITP. To evaluate the effects of budoprutug on B-cell depletion (pharmacodynamic [PD] response). To evaluate the effects of budoprutug on platelet counts (ITP clinical response). Study Endpoints: The primary safety endpoints include the following: Incidence, relatedness, severity, and duration of treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs). The secondary endpoints include the following: Budoprutug PK parameters (including area under the concentration-time curve, time to maximum observed concentration, terminal half-life, apparent clearance, and volume of distribution). The change from baseline in absolute peripheral cluster of differentiation (CD)20+B-cell count. Patent Application CLIMB-005 / 01WO 40193 / 24 The change in platelet count observed with budoprutug over time in subjects with ITP. The percentage of subjects with ITP who achieve a stable, partial, and complete response by Week 12 The incidence of subjects who develop ADAs at any time after study drug administration. The percentage of subjects on a steroid at baseline who are able to stop steroid treatment. Study Population: This study will enroll adult male and female subjects who meet all of the inclusion criteria and none of the exclusion criteria. Subjects will be eligible for enrollment in this study regardless of race / ethnicity. Inclusion Criteria: 1. Willing and able to provide written informed consent. 2. Aged >18 years at the time of informed consent. 3. Diagnosed with primary ITP 4. Platelet count <30,000 / ^L despite an adequate trial of at least one prior therapeutic attempt. Platelet counts of <30,000 / ^L must be confirmed on 2 occasions at least 5 days apart, but no more than 14 days apart 5. Partial thromboplastin time <1.5 × upper limit of normal (ULN), prothrombin time <1.5 × ULN, total bilirubin <1.5 × ULN unless due to Gilbert’s syndrome, or an international normalized ratio <1.5 at screening. For subjects with Gilbert’s syndrome, the limit for GLUHFW^ELOLUXELQ^LV^^8 / 1^DQG^IRU^WRWDO^ELOLUXELQ^LV^^^^î^8 / 1^ Exclusion Criteria: 1. CD19+ B-cell count <80 cells / ^L at Screening or <40 cells / ^L if B-cell depleting treatment was received from 24 weeks to 2 years prior to Screening, or if the subject has received or is receiving other immunosuppressive or immunomodulatory agent that may reduce circulating B cell levels. 2. Pregnant or lactating females. 3. Diagnosis of paroxysmal nocturnal hemoglobinuria, Evan’s Syndrome, or any other bleeding disorder that could confound results and impact patient safety. 4. Prior treatment with rituximab or other B-cell depleting agents within 24 weeks prior to the first dose of study drug or plan to receive B-cell depleting agents during the study. Patent Application CLIMB-005 / 01WO 40193 / 24 5. Current or planned treatment with any chronic anticoagulants or platelet aggregation- inhibiting drugs such as aspirin, nonsteroidal anti-inflammatory drugs, or thienopyridines within 14 days of planned dosing through the end of follow-up. Symptom-based intermittent dosing of nonsteroidal anti-inflammatory drugs is permitted. 6. Prior treatment with immunosuppressants (other than corticosteroids) within 30 days or 5 times the elimination half-life (whichever is longer) of the Screening Visit (e.g., calcineurin inhibitors, mycophenolate mofetil, azathioprine), or alkylating agents within 180 days of the Screening Visit. 7. Prior treatment with intravenous (IV) Ig within the last 90 days of the Screening Visit. 8. Active treatment for ITP other than steroids or TPO agonists within 30 days or 5 times the elimination half-life (whichever is longer) prior to the first dose of study drug without discussion with the Medical Monitor. 9. Treatment with any investigational drug within 30 days prior to the first dose of study drug, or at least 5 times the elimination half-life of the drug (whichever is longer), or plan to use an investigational device during the study. 10. History of malignancy within the past 5 years and likely to require chemotherapeutic or surgical treatment during the study, with the exception of non-melanoma skin cancer, cervical carcinoma in-situ, or ductal carcinoma-in-situ. 11. History of stem cell, bone marrow, or solid organ transplant. 12. Acute, chronic, or latent infection, including hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 13. Evidence of active tuberculosis (TB) or being at high risk for TB based on: a. History of active TB or untreated / incompletely treated latent TB. Subjects with a history of active or latent TB who have documentation of completion of treatment according to local guidelines and no evidence of ongoing TB may be enrolled. b. +LVWRU\^RI^UHFHQW^^^^^^ZHHNV^RI^VFUHHQLQJ^^FORVH^FRQWDFW^ZLWK^VRPHRQH^ZLWK^DFWLYH^7%^ ^FORVH^FRQWDFW^LV^GHILQHG^DV^^^^KRXUV^ZHHN^25^OLYLQJ^LQ^WKH^VDPH^KRXVH^ 14. Active or uncontrolled infection at the time of informed consent or study drug initiation. 15. Recent hospitalization for any reason within 14 days prior to Screening, unless approved by the Medical Monitor. Patent Application CLIMB-005 / 01WO 40193 / 24 16. Receipt of a live vaccine within 28 days prior to the first dose of study drug or during the study. All other vaccines must be completed within 21 days prior to the first dose of study drug. Study Design and Duration: This study is a Phase 1b / 2a, open-label, sequential-cohort, dose escalation and expansion study to evaluate the safety, tolerability, PK, PD, and preliminary clinical effectiveness of budoprutug in subjects with ITP. The study consists of the Dose Escalation phase 1b, and Dose Expansion phase 2a (Note: the dose expansion phase 2a will not be conducted in Georgia). Subjects will be screened for study eligibility over 2 visits: the first visit on Days -21 to -14 (Screening) and the second visit on Days -13 to 0 (Qualifying Visit). The Qualifying Visit (Days -13 to 0) will occur at least 5 but no more than 14 days after the initial Screening Visit in order to confirm eligibility, particularly the platelet counts. After the Qualifying Visit, subjects who meet the eligibility criteria will be enrolled into the study to receive 2 doses of budoprutug on Day 1 and Day 15. Each subject may receive additional budoprutug doses between Weeks 12 and 36 if certain safety and PD criteria are met. All subjects will be followed for AEs and, if applicable, pregnancy, through 5 half-lives of budoprutug. In addition, subjects will be followed until there is evidence of recovery of circulating B cells. Specifically: 1. Subjects receiving a single cycle of budoprutug will undergo treatment and follow-up for a total of 52 weeks, including 2 weeks of treatment and 50 weeks of follow-up after the last budoprutug administration. 2. Subjects receiving a second cycle of budoprutug, initiated between Weeks 12 and 36, will undergo 50 weeks of follow-up after the last budoprutug administration. For example, subjects initiating the second treatment cycle at Week 12 (1 dose each at Weeks 12 and 14) will be followed until week 64, and subjects initiating the second cycle of budoprutug at Week 36 (2 doses at Weeks 36 and 38) will be followed until Week 88. 3. Subjects who have completed 50 weeks of follow-up after the last budoprutug administration but have not reached B cell recovery will continue to be followed for B cell recovery up to Week 104 of the study. Patent Application CLIMB-005 / 01WO 40193 / 24 The schematic for study is provided in FIG.20. 6 subjects enrolled sequentially in each cohort Safety review committee review Planned dose levels: 250, 500, 1000 mg biweekly (cumulative doses: 500, 1000, 2000 mg per dose cycle). Phase 2a: up to 6 subjects enrolled at dose identified in Phase 1b. Dose Escalation Phase During the Dose Escalation phase, subjects with ITP will be assigned to the currently open cohort in the study, per the table below. Each dosing cohort will be enrolled sequentially. Six subjects will be enrolled into each dosing cohort. The SRC will review all available data for the 6 subjects included in each cohort once the last dosed subject completes their Week 6 visit (4 weeks following the second dose of study drug in the initial dosing cycle). As the subject follow- up data are generated over time, platelet counts may also be factored into the evaluation. Dosing levels will continue sequentially to determine sufficient B-cell depletion and an acceptable safety and efficacy profile for subsequent trials. Doses of Budoprutug during the Dose Escalation Phase Dose Level Dose (mg) Frequency In the Dose Escalation phase (Phase 1b), subjects will receive 2 bi-weekly doses of budoprutug at the specified dose level, administered via IV infusion. Dose escalation will be conducted using an adaptive design for each cohort, based on safety and B-cell depletion data (and any available platelet count clinical data). The first dose cohort will be 250 mg administered IV every 14 days for 2 doses (500 mg cumulative dose). The planned dose cohorts that will follow are anticipated to be 500 mg and 1000 mg administered IV every 14 days for 2 doses (1000 mg and 2000 mg cumulative dose, respectively). Each Dose Escalation cohort will be enrolled Patent Application CLIMB-005 / 01WO 40193 / 24 sequentially. The protocol will allow for intermediate doses or lower doses, based on the data generated in the study and recommendation of the SRC. Escalation doses between successive cohorts will not exceed more than double a previous cohort’s cumulative dose. Following the first dosing cohort, the plan is flexible based on decisions of the SRC, focusing primarily on safety and PD effects of B-cell depletion. As the subject follow-up data are generated over time, platelet counts may also be factored into the evaluation. For safety, if none of the initial 6 subjects experience a protocol-defined DLT during the initial treatment period, then enrollment into the next dose cohort can begin. If any of the subjects experience a DLT, action taken will vary depending on the event and the number of occurrences and will be guided by SRC recommendations. Please refer to the study stopping rules for details. For PD effects, if the data from 6 subjects do not demonstrate consistent effects, then up to 3 additional subjects can be enrolled at that dose level to better understand the PD effects prior to escalation to the next higher dose cohort. Dose Expansion Phase The Dose Expansion phase (Phase 2a) will evaluate a cohort of subjects at the dose identified from Phase 1b. Up to 6 subjects in the expansion cohort will receive budoprutug at the dose identified for expansion and this cohort will also include subjects from the Dose Escalation phase treated with the expansion cohort dose. Both the Dose Escalation and Dose Expansion phases will collect data on tolerability, PK, B-cell depletion, and complete blood counts (CBCs), including platelet counts. Additional Budoprutug Doses Following the initial dosing cycle during the first 2 weeks of the study, the same subjects may receive additional budoprutug doses, i.e., 2 additional bi-weekly doses of budoprutug between Weeks 12 and 36. The additional dosing is intended for study subjects who have experienced some meaningful degree of clinical response but have not been able to maintain a complete remission and are therefore more likely to receive additional benefit. Subjects who achieve and maintain a complete remission and those who do not respond at all are unlikely to benefit from further dosing and therefore will not receive additional dosing. The additional dosing can be administered if criteria are met on the basis of immunologic or clinical response and the safety / tolerability profile as defined by the protocol. The additional budoprutug doses administered between Weeks 12 and 36 will match the dose level that is originally administered to each subject during the first cycle. Patent Application CLIMB-005 / 01WO 40193 / 24 The additional dosing can be administered between 12 and 36 weeks if subjects satisfy the following criteria and who have not experienced any DLTs: 1. Demonstration of a clinical response to therapy at any time during the first 12 to 36 weeks of the study (defined as a platelet count >30,000 / ^L and a >25% platelet count increase from Baseline). 2. Circulating B-cells levels show evidence of recovery from the nadir achieved following the initial dose cycle. 3. Demonstrated loss of improvement between Weeks 12 to 36 on any of the following: a. Platelet count has declined by 50% from the highest count following study drug administration; b. Platelet count <30,000 / ^L; c. Initiation or increase in corticosteroid rescue therapy to prevent further platelet decline and continuation of corticosteroids. The additional dosing with budoprutug should also be reviewed and approved by the medical monitor prior to administration and all activities listed in the schedule of procedures should be completed. The main goal of this study is to see how safe budoprutug is at different doses by monitoring the number and seriousness of side effects in participants. Other goals include understanding how the participant’s body deals with budoprutug by checking the amount of budoprutug in the blood over time (this is called pharmacokinetics) and to find out the safe and effective dose of budoprutug. The study doctors will also see how effective budoprutug is in participants with ITP by measuring the change in platelet count and B-cells observed with budoprutug over time. The participants are included in the stay if they: are at least 18 years old; have a specific platelet count; have certain blood test results within specific limits, like white blood cell count, liver function tests, and kidney function tests; and / or have taken corticosteroids or thrombopoietin (TPO) agonist, the dose must be stable for at least 14 days before starting budoprutug. Participants will not be included in the study if they: Patent Application CLIMB-005 / 01WO 40193 / 24 have B-cell count below certain levels; have specific blood disorders like paroxysmal nocturnal hemoglobinuria, Evan’s syndrome, or any other medical condition that may interfere with the study; and / or have taken certain treatments like rituximab within the last 24 weeks or currently use, or recently used, certain medications that may interfere with the study or have been hospitalized for reason in the last 14 days. The study has 2 parts. In Part 1, different sets of participants will receive increasing doses of budoprutug (dose escalation). Both the study doctor and participants will know the dose given. The first 6 participants will get the lowest dose. If no medical problems or side effects occur, the next 6 participants will receive the higher dose, and then again if the participants do not report any side effects, the next 6 participants will receive the highest dose. After finding a safe dose, this dose will be given to up to 6 more participants (dose expansion). Part 1 will be conducted in the following 3 periods over 23 clinic visits. In Part 2, the long-term safety and B-cell recovery follow-up with budoprutug will be done for up to 52 weeks after Part 1 is completed. Participants will come for clinic visits every 4 weeks to check their B-cell levels and overall health. Follow-up will end once their B-cells return to normal, which may happen before the 52 weeks are over. Overall, participants may be in the study for up to 2 years, including Part 1 and Part 2. They will answer some questions on how ITP affects their health and well-being. Blood and urine samples will be collected at most clinic visits. General health tests, physical exams, and electrocardiograms (tests that record the electrical activity of the heart) will be done. Certain substances called biomarkers in blood samples will be checked to see if budoprutug is effective in treating ITP. Participants will be asked to report any changes in their health to the study doctor or study staff. Participants received budoprutug via an infusion into the vein of the arm. Benefits / Risks of this study: Participants may or may not experience benefits from budoprutug. Like all medicines, budoprutug can cause unwanted effects called ‘side effects’. The potential safety risk of budoprutug to humans is not yet fully known. There is limited information about the possible side effects of budoprutug. Patent Application CLIMB-005 / 01WO 40193 / 24 The most common side effects seen in 37 participants who took budoprutug in earlier studies are pain and redness at the injection site, feeling sick to the stomach, diarrhea, abdominal pain, vomiting, tiredness, chills, swelling in hands and feet, headache, dizziness, rash, cough, skin turns red, joint stiffness, decrease in certain type of white blood cells that increases the chances of infection in the participants, urinary tract and respiratory tract infection. Drugs in the same category given in the vein are known to cause infusion-related reactions like delayed fever, rash, joint and muscle pain, blood or protein in urine, inflammation of body tissues, central nervous system complications, and a disorder in which red blood cells are destroyed faster than they can be made. Low oxygen levels may also occur. Other possible side effects are increased risk of serious infections, lower-than-normal levels of neutrophils (a type of white blood cell) in blood, and decrease in immunoglobulin (a protein in blood that help immune system fight off infections). Study Drug Dosing: Participants will be enrolled in groups of approximately 6 participants each. The first group will receive the study drug at the initial (lower) dose level. After 6 participants complete their first dosing cycle, a special committee of medical professionals will meet to review the information collected on side effects, laboratory and other medical examination results to determine if it is safe to continue to the next dose level. Three dose level groups are planned for this research study, but additional dose levels may be recommended by the medical committee. Once the optimal dose level is established, the corresponding group will be expanded, which means that additional participants will be enrolled at this dose level to enable better evaluation of the study drug safety, effects on B cells and other parameters. Approximately 30 to 60 minutes before the infusion the subjects will receive medications that will help prevent potential side effects of the study drug administration (called premedications). These medications will help reduce inflammation, allergic reactions, and provide fever and paid relief that may occur during or shortly after the study drug infusion. Between 12 and 36 weeks following the receipt of the initial study drug dosing cycle you may receive the additional dosing cycle, if the subject meets specific criteria, and if the study doctor considers it safe and beneficial. Additional doses will be provided at the dosing level that is approved by the medical committee at that time, which may be higher than the dose level you have received during the initial dosing cycle. Dosing visits will be conducted instead of the follow- Patent Application CLIMB-005 / 01WO 40193 / 24 up visits if they overlap with the follow-up from the initial dosing cycle. The following study procedures will be performed at the additional dosing visits: Vital signs and weight Symptom-based physical exam Safety laboratory tests B cell tests Platelet tests Antibody tests Urinalysis Pregnancy test (if you are a female able to get pregnant) Study drug dosing Measurements of the study drug concentration (dosing day only, before and at the end of infusion) Side effect and medication check Quality of life questionnaires (dosing Day 1 only) Long-Term Follow-Up Study Part: After completing the main part of the study, the study doctor will check your B cells and advise if you should continue into the long-term follow-up part of the study. In this study part, you will come to the study site every 4 weeks for safety checks and to measure the subject’s B cells. These visits will last for approximately 1-2 hours. Once the B cells return to a certain level the follow-up will be complete. This may take from several weeks to up to 52 weeks, so the overall study participation will be about 2 years. If the subject’s B cells recovered while the subject was still in the main part of the study, the subject will not need to continue into the long-term follow- up part. The following study procedures will be performed at the long-term follow-up visits: - Side effect and medication check - Vital signs and weight - Symptom-based physical exam - Complete physical exam will be done at your last long-term follow-up visit - Safety laboratory tests - B cell tests Patent Application CLIMB-005 / 01WO 40193 / 24 - Platelet tests - Antibody tests - Urinalysis - Pregnancy test (if you are a female able to get pregnant) - Measurements of the study drug concentration - Quality of life questionnaires - Infectious disease checks (tests for measles, mumps, rubella, tetanus, pneumococcus, and COVID-19 infections) will be done at your last long- term follow-up visit. Study Objectives: Primary Objective: The primary objective of this study is to evaluate the safety and tolerability of ascending doses of budoprutug in subjects with ITP. Secondary Objectives: The secondary objectives of this study include the following: To investigate potential doses for subsequent dose-finding studies in subjects with ITP. To characterize the pharmacokinetic (PK) profile of budoprutug in subjects with or ITP. To evaluate the effects of budoprutug on B-cell depletion (pharmacodynamic [PD] response). To evaluate the effects of budoprutug on platelet counts (ITP clinical response). Exploratory Objectives: The exploratory objectives of this study include the following: To evaluate the effects of budoprutug on serum immunoglobulin (Ig)G, IgM, and IgA levels. To evaluate the development of anti-drug antibodies (ADAs) to budoprutug. To evaluate subject reported outcomes / quality of life (QoL) measures. To evaluate the PK and PK / PD (dose relationship) profile in subjects with ITP. To evaluate the re-population of B-cells by subset immunophenotyping. To evaluate the effects of budoprutug on anti-platelet autoantibodies. Patent Application CLIMB-005 / 01WO 40193 / 24 To evaluate the changes from Baseline in antibody titers to measles, mumps, rubella, tetanus, pneumococcus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) in response to budoprutug. Study Endpoints: The primary safety endpoints include the following: Incidence, relatedness, severity, and duration of treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs). The secondary endpoints include the following: Budoprutug PK parameters (including area under the maximum observed concentration, time to maximum observed concentration, terminal half-life, apparent clearance, and volume of distribution). The change from baseline in absolute peripheral cluster of differentiation (CD)20+ B-cell count. The change in platelet count observed with budoprutug over time in subjects with ITP. The percentage of subjects with ITP who achieve a stable, partial, and complete response by Week 12. Note: A stable, partial, and complete response is defined as a platelet count 30,000 / ^L, 50,000 / ^L, or 100,000 / ^L, respectively, on at least 2 occasions at least 7 days apart within a 30-day time frame. The change in serum IgG, IgM, and IgA from baseline over time. The incidence of subjects who develop ADAs at any time after study drug administration. The percentage of subjects on a steroid at baseline who are able to stop steroid treatment. The exploratory efficacy parameters include the following: The change in QoL, measured using the following: o Functional Assessment of Chronic Illness Therapy-Fatigue instrument (13- item FACIT Fatigue scale); and o Functional Assessment of Cancer Therapy-Thrombocytopenia (6-Item FACT-Th6 scale). Patent Application CLIMB-005 / 01WO 40193 / 24 Budoprutug PK and its relationship to B-cell depletion and clinical response (platelet counts). Budoprutug dose and its relationship to B-cell depletion and clinical response (platelet counts). The characteristics of B-cell re-population as determined by subset immunophenotyping. Change from Baseline in levels of anti-platelet autoantibodies in response to budoprutug. Change from Baseline in antibody titers to measles, mumps, rubella, tetanus, pneumococcus, and SARS-CoV-2. Study population: This study will enroll adult male and female subjects who meet all of the inclusion criteria and none of the exclusion criteria. Subjects will be eligible for enrollment in this study regardless of race / ethnicity. Inclusion Criteria: 1. Willing and able to provide written informed consent. 2. Aged > 18 years at the time of informed consent. 3. Platelet count < 30,000 / ^L despite an adequate trial of at least one prior therapeutic attempt. Platelet counts of < 30,000 / ^L must be confirmed on 2 occasions at least 5 days apart, but no more than 14 days apart. 4. Partial thromboplastin time < 1.5 upper limit of normal (ULN), prothrombin time < 1.5 ULN, total bilirubin < 1.5 ULN unless due to Gilbert’s syndrome, or an international normalized ratio < 1.5 at screening. Note: Pre-dose laboratory evaluations may be repeated one time during the screening period at the discretion of the Investigator to confirm eligibility. 5. Adequate hematologic, hepatic, and renal function, defined as the following: a. Absolute neutrophil count (ANC) > 1.5109 / L; b. White blood cell count > 3109 / L; c. Alanine aminotransferase (ALT) < 2.5 upper limit of normal (ULN); d. Aspartate transaminase (AST) < 2.5 ULN; Patent Application CLIMB-005 / 01WO 40193 / 24 e. Estimated glomerular filtration rate > 60 mL / min (calculated using local institutional guidelines). Note: Pre-dose laboratory evaluations may be repeated during the screening period at the discretion of the Investigator to confirm eligibility. 6. If being treated with corticosteroids or thrombopoietin (TPO) agonists, subjects must be on a stable dose (< 20% change in dose over the 14 days prior to the first dose of study drug). Corticosteroid treatment should not be > 1 mg / kg methylprednisolone (or equivalent) for 2 weeks prior to the first dose of study drug. Note: Steroid pulses, short courses of steroids, or other immunosuppressive agents given as rescue therapy for clinically significant changes in platelet count may be permitted during the study after a discussion with the Medical Monitor. Steroid tapering should be considered once a clinically meaningful response in platelet count is observed. 7. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and / or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 1 year, with follicle-stimulating hormone in the postmenopausal range at Screening, as per central laboratory reference range. 8. Female subjects of childbearing potential (i.e., ovulating, premenopausal, or not surgically sterile) must use a medically accepted, highly effective contraceptive regimen during their participation in the study and for 125 days (4 months) after the last administration of budoprutug. Highly effective contraceptive methods are defined as those with 99% or greater efficacy. Acceptable methods of contraception for female subjects of childbearing potential enrolled in the study include the following: a. Intrauterine device for at least 12 weeks before Screening; b. Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before Screening; or c. True abstinence when in line with the preferred and usual lifestyle of the subject; periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Patent Application CLIMB-005 / 01WO 40193 / 24 9. Male subjects must use a condom during the study and for 125 days (4 months) after their final dose of budoprutug if their partner is a female of childbearing potential. Acceptable methods of contraception for male subjects enrolled in the study include the following: a. Condoms with spermicide; or b. Surgical sterilization of subject at least 26 weeks before Screening (vasectomy). 10. Male subjects must agree to abstain from sperm donation through 125 days (4 months) after the last administration of budoprutug. Exclusion Criteria: 1. CD19+ B-cell count < 80 cells / ^L at Screening or < 40 cells / ^L if B-cell depleting treatment was received within 24 weeks to 2 years prior to Screening. 2. Pregnant or lactating females. 3. Diagnosis of paroxysmal nocturnal hemoglobinuria, Evan’s Syndrome, or any other bleeding disorder that could confound results and impact patient safety. 4. Prior treatment with rituximab or other B-cell depleting agents within 24 weeks prior to the first dose of study drug or plan to receive B-cell depleting agents during the study. 5. Current or planned treatment with any chronic anticoagulants or platelet aggregationinhibiting drugs such as aspirin, nonsteroidal anti-inflammatory drugs, or thienopyridines within 14 days of planned dosing through the end of follow-up. Symptom-based intermittent dosing of nonsteroidal anti-inflammatory drugs is permitted. 6. Prior treatment with immunosuppressants (other than corticosteroids) within 30 days or 5 times the elimination half-life (whichever is longer) of the Screening Visit (e.g., calcineurin inhibitors, mycophenolate mofetil, azathioprine), or alkylating agents within 180 days of the Screening Visit. Note: Steroid pulses, short courses of steroids, or other immunosuppressive agents given as rescue therapy for clinically significant changes in platelet count may be permitted during the study after a discussion with the Medical Monitor. 7. Prior treatment with intravenous (IV) Ig within the last 90 days of the Screening Visit. 8. Active treatment for ITP other than steroids or TPO agonists within 30 days or 5 times the elimination half-life (whichever is longer) prior to the first dose of study drug without discussion with the Medical Monitor. Patent Application CLIMB-005 / 01WO 40193 / 24 9. Treatment with any investigational drug within 30 days prior to the first dose of study drug, or at least 5 times the elimination half-life of the drug (whichever is longer), or plan to use an investigational device during the study. 10. History of malignancy within the past 5 years and likely to require chemotherapeutic or surgical treatment during the study, with the exception of non-melanoma skin cancer, cervical carcinoma in-situ, or ductal carcinoma-in-situ. 11. History of stem cell, bone marrow, or solid organ transplant. 12. Acute, chronic, or latent infection, including hepatitis B, hepatitis C or human immunodeficiency virus (HIV). 13. Evidence of active tuberculosis (TB) or being at high risk for TB based on: a. History of active TB or untreated / incompletely treated latent TB. Subjects with a history of active or latent TB who have documentation of completion of treatment according to local guidelines and no evidence of ongoing TB may be enrolled. b. active c. Positive, indeterminate, or invalid interferon-gamma release assay test result at screening, unless previously treated for TB. Subjects with an indeterminate test result can repeat the test once, but if the repeat test is also indeterminate, the participant must be evaluated by a pulmonologist to determine eligibility (include with or without treatment for latent TB or exclusion). d. Chest radiograph, chest computed tomography or magnetic resonance imaging (MRI) scan that suggests a possible diagnosis of TB or suggests that a work-up for TB should be considered; all subjects must have had lung imaging with an acceptable reading within 12 months prior to consent, or during screening. 14. Active or uncontrolled infection at the time of informed consent or study drug initiation. 15. Recent hospitalization for any reason within 14 days prior to Screening, unless approved by the Medical Monitor. 16. Receipt of a live vaccine within 28 days prior to the first dose of study drug or during the study. All other vaccines must be completed within 21 days prior to the first dose of study drug. 17. Secondary cause of ITP (e.g., malignancy, hepatitis B or C, HIV, or other autoimmune diseases [e.g., thyroiditis], or drug-induced ITP). 18. History of drug or alcohol abuse within 5 years prior to Screening. Patent Application CLIMB-005 / 01WO 40193 / 24 19. Planned surgery during the 4 weeks following the first dose of study drug. 20. Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with subject safety, study evaluations, and / or study procedures. 21. In the opinion of the Investigator, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Study Design and Duration: This study is a Phase 1b / 2a, open-label, sequential-cohort, dose escalation and expansion study to evaluate the safety, tolerability, PK, PD, and preliminary clinical effectiveness of budoprutug in subjects with ITP. The study consists of the following 2 parts: 1) Part 1 – Main study a. Dose Escalation phase 1b b. Dose Expansion phase 2a 2) Part 2 – Long-term safety and PD observational study Each subject may receive additional budoprutug doses between Weeks 12 and 36 if certain safety and PD criteria are met. Subjects will be followed through Week 48 in the main study and will subsequently enter the long-term observational part of the study for safety and B-cell repopulation follow-up. Subjects will be screened for study eligibility over 2 visits: the first visit on Days -21 to -14 (Screening) and the second visit on Days -13 to 0 (Qualifying Visit). The Qualifying Visit (Days -13 to 0) will occur at least 5 but no more than 14 days after the initial Screening Visit in order to confirm eligibility, particularly the platelet counts. After the Qualifying Visit, subjects who meet the eligibility criteria will be enrolled into the study. Study Duration: The study duration for each individual subject will be as follows: 1) Main study duration will be up to 51 weeks, including the Screening and Qualifying Visits (up to 3 weeks), Treatment Period (2 weeks), and follow-up visits though Week 48. 2) Following the completion of the main study, subjects will proceed to the long-term observational part of the study and will be followed until B-cell re-population (defined as lower limit of normal or at least 80% of baseline value) which is expected to occur within 52 more weeks after the Main study. Patent Application CLIMB-005 / 01WO 40193 / 24 Dose Escalation Phase: During the Dose Escalation phase, subjects with ITP will be assigned to the currently open cohort in the study, per the table below. Each dosing cohort will be enrolled sequentially. Six subjects will be enrolled into each dosing cohort. The DRC will review all available data for the 6 subjects included in each cohort once the last dosed subject completes their Week 6 visit (4 weeks following the second dose of study drug in the initial dosing cycle). As the subject follow-up data are generated over time, platelet counts may also be factored into the evaluation. Dosing levels will continue sequentially to determine sufficient B-cell depletion and an acceptable safety and efficacy profile for subsequent trials. Dose Level Dose (mg) Frequency Level 1 (Starting 250 Every 14 days for 2 doses (500 mg cumulative dose) In the dose escalation phase (Phase 1b), subjects will receive 2 bi-weekly doses of budoprutug at the specified dose level, administered via IV infusion. Dose escalation will be conducted using an adaptive design for each cohort, based on safety and B-cell depletion data (and any available platelet count clinical data). The first dose cohort will be 250 mg administered IV every 14 days for 2 doses (500 mg cumulative dose). The planned dose cohorts that will follow are anticipated to be 500 mg and 1000 mg administered IV every 14 days for 2 doses (1000 mg and 2000 mg cumulative dose, respectively). Each Dose Escalation cohort will be enrolled sequentially. The protocol will allow for intermediate doses or lower doses, based on the data generated in the study and recommendation of the DRC. Escalation doses between successive cohorts will not exceed more than double a previous cohort’s cumulative dose. Following the first dosing cohort, the plan is flexible based on decisions of the DRC, focusing primarily on safety and PD effects of B-cell depletion. As the subject follow-up data are generated over time, platelet counts may also be factored into the evaluation. For safety, if none of the initial 6 subjects experience a protocol-defined DLT during the initial treatment period, then enrollment into the next dose cohort can begin. If 2 of the first 6 subjects experience a DLT, then additional dosing and enrollment will be stopped. If study enrollment is stopped due to a DLT, the DRC will review all available safety data to determine if the study may resume at the current dose, resume at a lower dose, proceed to a study amendment Patent Application CLIMB-005 / 01WO 40193 / 24 to address safety concerns, or terminate the study. For PD effects, if the data from 6 subjects do not demonstrate consistent effects, then up to 3 additional subjects can be enrolled at that dose level to better understand the PD effects prior to escalation to the next higher dose cohort. Dose Expansion Phase: The Dose Expansion phase (Phase 2a) will evaluate a cohort of subjects at the dose identified from Phase 1b. Up to 6 subjects in the expansion cohort will receive study drug at the dose identified for expansion and this cohort will also include subjects from the Dose Escalation phase treated with the expansion cohort dose. Both the Dose Escalation and Dose Expansion phases will collect data on tolerability, PK, B-cell depletion, and complete blood counts (CBCs), including platelet counts. Additional Budoprutug Doses: Following the initial dosing cycle during the first 2 weeks of the study, the same subjects may receive additional budoprutug doses, i.e., 2 additional biweekly doses of budoprutug between Weeks 12 and 36. The additional dosing is intended for study subjects who have experienced some meaningful degree of clinical response, but have not been able to maintain a complete remission, and are therefore more likely to receive additional benefit. Subjects who achieve and maintain a complete remission and those who do not respond at all are unlikely to benefit from further dosing, and therefore will not receive additional dosing. The additional dosing can be administered if criteria are met on the basis of immunologic or clinical response and the safety / tolerability profile as defined by the protocol. The additional budoprutug doses administered between Weeks 12 and 36 may be higher (or lower) than the dose received during the initial dosing cycle and will match the dose level that has been deemed safe (and potentially more effective for B-cell depletion) by the DRC. That decision would be based on available safety, PD, and other clinical data. The additional dosing can be administered between 12 and 36 weeks if subjects satisfy the following criteria and who have not experienced any DLTs: 1. Demonstration of a clinical response to therapy at any time during the first 12 to 36 weeks of the study (defined as a platelet count > 30,000 / ^L and a > 25% platelet count increase from Baseline); 2. Circulating B-cells levels show evidence of recovery from the nadir achieved following the initial dose cycle; Patent Application CLIMB-005 / 01WO 40193 / 24 3. Demonstrated loss of improvement between Weeks 12 to 36 on any of the following: a. Platelet count has declined by 50% from the highest count following study drug administration; b. Platelet count < 30,000 / ^L; c. Initiation or increase in corticosteroid rescue therapy to prevent further platelet decline and continuation of corticosteroids. The additional dosing with budoprutug should also be reviewed and approved by the medical monitor prior to administration and all activities listed in the schedule of procedures should be completed. On-Study Assessments Including Platelets: Throughout the study, subjects will be seen approximately every 4 weeks to assess safety and tolerability, PD (B-cell depletion), and CBCs, including platelet count. This schedule will enable detection of changes from baseline, the time to effect, and the duration of effect. In addition, the patterns of each parameter will be evaluated. It is anticipated, if effective, that B-cell depletion will be followed by increases in platelet count in the blood. End of Main Study: All subjects will have an End of Study (EOS) Visit for the main study at Week 48. This duration of follow-up allows for the collection of additional safety data and data on the persistence of B-cell depletion, the characteristics of B-cell re-population, CBCs, potential recurrence of anti- platelet antibodies, and overall ITP disease activity over time. Subjects who receive additional budoprutug doses between Weeks 12 and 36 will also be followed until Week 48 in the main study. Long-Term Safety and Observational Study: Following the EOS Visit in the main study, subjects will continue to the long-term observational part of the study and will be followed until B-cell re-population, unless B-cell repopulation occurred prior to the EOS Visit in the main study. B-cell repopulation is defined as lower limit of normal or at least 80% of baseline value) which is expected to occur within 52 weeks after the Main study. Rescue Therapy During the study, the Investigator may administer or prescribe rescue therapy or increase the dose of other concomitant medications (e.g., glucocorticoids or other immunosuppressive Patent Application CLIMB-005 / 01WO 40193 / 24 agents) for subjects with new or persistent thrombocytopenia and / or worsening symptomatology. If possible, the Medical Monitor should be consulted for advice prior to initiation. If rescue therapy is required, the Investigator should taper the rescue medications as soon as clinically appropriate to avoid risks of over-immunosuppression and to better assess the effects of budoprutug. Subjects who receive rescue medication should continue to be monitored per study requirements as indicated in the Schedule of Procedures. Dosage Forms and Route of Administration: Subjects will be required to receive premedication prior to each infusion of budoprutug to reduce the frequency and severity of infusion-related reaction (IRRs), as shown in the table below. Premedication Prior to each budoprutug infusion: Administration Type of Route of Time Prior to s s b Nonsteroidal anti-inflammatory drugs (NSAIDs) should not be used due to their potential effect on platelets. Premedications outlined above are considered auxiliary medicinal products. Only authorized auxiliary medicinal products will be used for premedication, and their use must be in accordance with the terms of their marketing authorizations. If premedication equivalents need to be used based on local sourcing availability, they will be selected from medicinal products that have a current marketing authorization. Budoprutug will be provided as a concentrated solution. Budoprutug will be diluted to prepare a solution of IV infusion. The infusion solution preparation and administration time must not exceed 4 hours. During the Dose Expansion phase, the infusion rate may be the same or higher than the rate used during the Dose Escalation phase based upon DRC review of available safety data. Patent Application CLIMB-005 / 01WO 40193 / 24 Subjects will be observed for at least 1 hour following each infusion to monitor for potential infusion reactions. MCD and FSGS: Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are similar podocytopathies that are characterized by nephrotic syndrome, profound proteinuria, and near complete or complete foot processes effacement on biopsy. In many instances, these podocytopathies respond rapidly and completely to administration of corticosteroids, in which case they are defined as steroid sensitive. Although the pathophysiology is not entirely certain, there is some evidence to suggest that circulating autoantibodies play a role in MCD. The symptoms of MCD include a sudden onset of nephrotic syndrome and profound edema. The epidemiology of MCD is about 1 in 150,000 adults. There is an estimated population of 20,000 addressable patients in the United States. The uncontrolled disease results in complications of nephrotic syndrome and eventual kidney failure. Moreover, patients who respond to therapy can achieve long-term remissions. The conventional standard of care provides the use of steroids to induce and maintain remission. There is currently no FDA approved therapy for the treatment of MCD. The available options for treatment (apart from steroids) include calcineurin inhibitors (CNIs), cyclophosphamide, and rituximab. The use of CNIs leads to nephrotoxicity and / or high relapse rate. The treatment with cyclophosphamide has a side effect of high toxicity. Rituximab also does not provide an efficacious treatment of MCD. Clin Kidney J.2020 Nov 21;14(4):1042- 1054. N Engl J Med.2024 Aug 1;391(5):422-433. Methods of treatment of Glomerulonephropathy: There is an unmet need for improved therapies for steroid-dependent and frequently relapsing MCD and FSGS, and there are currently no Food and Drug Administration-approved treatments specifically indicated for primary MCD or primary FSGS. Patients with MCD and FSGS suffer frequent disease flares and complications from long-term corticosteroid exposure. The invention provides a novel therapeutic approach for reducing inflammation and injury to kidney through depletion of CD19+ cells through compositions comprising anti-CD19 antibodies. Patent Application CLIMB-005 / 01WO 40193 / 24 The invention provides methods of treatment of glomerulonephropathy associated with MCD and FSGS. In certain beneficial aspects, the methods provided herein reduce proteinuria and maintain remission in MCD / FSGS patients. A significant challenge in the treatment of patients with MCD is that a significant number of patients have become steroid dependent, which is the current standard of care for the treatment of MCD patients. These patients are unable to taper steroids without a relapse. In addition, this is a frequently relapsing disease. In certain aspects, the invention provides a method of treating a subject having glomerulonephropathy, wherein the method comprises administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody. In certain embodiments, glomerulonephropathy is associated with the generation of autoantibodies. In certain embodiments, glomerulonephropathy is selected from the group consisting of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN). In certain embodiments, the invention provides that immunomodulation by anti-CD19 antibody and reduction in number of CD19+ B-cells. In certain embodiments, the patients are corticosteroid-dependent or frequently relapsing. In certain embodiments, the subject has previously received corticosteroid therapy and / or any additional therapy for treatment of nephrotic syndromes. In certain embodiments, the additional therapies are selected from the group consisting of calcineurin inhibitors, mycophenolic acid analogues, azathioprine, and cyclophosphamide. In certain embodiments, the subject has received the corticosteroid therapy for at least 8 weeks before start of administration of the composition comprising a therapeutically effective amount of anti-CD19 antibody. In certain embodiments, the corticosteroid therapy is administration of prednisone. In certain embodiments, the prednisone is administered at a dose higher than 20 mg / day, the subject is tapered off to a dose of 20 mg / day of prednisone. In certain embodiments, tapering is done from at least eight weeks to about 2 weeks before starting administration of the composition. In certain embodiments, prednisone is administered at a dose of less than about 20 mg / day for at least two weeks before starting administration of the composition. In certain embodiments, the anti-CD19 antibody of the invention could be any anti-CD19 antibody provided herein. In certain embodiments, wherein the anti-CD19 antibody comprises: a Patent Application CLIMB-005 / 01WO 40193 / 24 heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition comprising a therapeutically effective amount of anti-CD19 antibody is administered parenterally. In certain embodiments, the composition comprising a therapeutically effective amount of anti-CD19 antibody is administered via intravenous (IV) infusion. In certain embodiments, the composition comprising a therapeutic effective amount of anti- CD19 antibody is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, composition comprises about 100 mg to about 200 mg of the anti-CD19 antibody. In certain preferred embodiments, composition comprises about 100 mg of the anti-CD19 antibody. In certain preferred embodiments, composition comprises about 200 mg of the anti-CD19 antibody. In certain embodiments, the method further comprises administration of an additional cycle to the subject, wherein the additional cycle comprises administration of a first additional dose of the composition and a second additional dose of the composition. In certain embodiments, the concentration of B cells is measured to decide if the additional cycle is administered. A high B cell count indicates that the administration of the composition of the invention did not have the desired effect. In certain embodiments, the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 155 after first administration of the composition to the subject. In certain embodiments, the first additional dose of the additional cycle is administered between day 113 and day 141 after first administration of the composition to the subject. In certain embodiments, the second additional dose is administered 14 days after administration of the first additional dose. Patent Application CLIMB-005 / 01WO 40193 / 24 In certain embodiments, the first additional dose of the additional cycle is administered between day 169 and day 183 after first administration of the composition to the subject. In certain embodiments, the first additional dose and the second additional dose are administered if the subject has not previously received the first additional dose and the second additional dose between days 113 and 115 after first administration of the composition to the subject. In certain embodiments, the first additional dose and the second additional dose comprise about 100 mg of the anti-CD19 antibody. In certain embodiments, the first additional dose and the second additional dose comprise about 200 mg of the anti-CD19 antibody. In a Phase Ib clinical study, a 57-year old patient with frequently relapsing MCD was enrolled. The patient relapsed on tacrolimus. The remission occurred after steroid course and relapsed within 2 months and steroids were reinitiated. The subject received budoprutug, 2 induction doses and 2 maintenance doses. B cells were effectively depleted after the administration of the doses of budoprutug. The steroids were discontinued and the patient remained in remission 18 months after the last infusion. There were no safety related outcomes. A protocol for the Phase 2 Study of budoprutug in Adult Subjects with Steroid-Sensitive Primary Minimal Change Disease or Primary Focal Segmental Glomerulosclerosis Objectives Endpoints Primary Efficacy Objective: Primary Efficacy Endpoint: Patent Application CLIMB-005 / 01WO 40193 / 24 Secondary Efficacy Objectives: Secondary Efficacy Endpoints: To evaluate following: Change in UPCR from Day 1 to Day 113, to h i i i D 7 l i l i i f D 1 , Methodology: This was a Phase 2, multi-center, proof-of-concept study to evaluate the safety and efficacy of VB119 on the maintenance of remission and duration of response in adults with primary MCD or primary FSGS who previously responded to steroid therapy. To be eligible for this study, subjects had to be in remission (urine protein / creatinine ratio [UPCR] ^0.5 g / g) and meet the following criteria: Were corticosteroid-dependent or frequently relapsing; and Patent Application CLIMB-005 / 01WO 40193 / 24 Received corticosteroids and / or second-line therapies (eg, calcineurin inhibitor, mycophenolic acid analogues, azathioprine, or cyclophosphamide) to treat nephrotic syndrome at the time of Screening. The study was designed to include up to 8-week Screening Period, a 9-month Treatment Period, and a 6-month Safety Follow-Up Period, as shown in the Study Schema (Figure 1); however, the study was terminated before the Safety Follow-Up Period started. Early termination was not due to any safety concerns. FIG.21 provides the schematic of the design of the study. Screening Period: up to 8 weeks (Day -56 to Day -1) Approximately 20 subjects were to be screened for this study with the goal of enrolling approximately 15 subjects, with at least 5 having FSGS. Subjects who signed informed consent entered the Screening Period which included a Steroid Taper period from Day -56 to Day -14 and a Stability Evaluation period from Day -14 to Day -1. Subjects who entered the Screening Period on ^20 mg prednisone equivalent had to taper to 20 mg by Day -14. Subjects on <20 mg prednisone equivalent at Screening were to begin Screening at Day -14. All subjects were to remain on a stable steroid dose <20 mg daily. A kidney biopsy confirming diagnosis for MCD or FSGS was performed prior to the subject being enrolled in the Treatment Period. Treatment Period: 9 months from the first dose of VB119 (Day 1 to Day 274) During the Treatment Period, eligible subjects were to receive a minimum of 2 intravenous doses of VB119: 100 mg or 200 mg (after Data Review Committee review) on Day 1 and 100 mg or 200 mg on Day 15 (200 mg or 400 mg cumulative dose). All prednisone was to be tapered off by Day 85 or Day 113. All non-prednisone immunosuppressive therapy (IST) was to be tapered off by Day 85 of the Treatment Period. Subjects were to receive 2 additional VB119 doses of 200 mg during the study when they met 1 of the following 2 criteria: Between Day 113 (as measured on Day 85) and Day 155 (as measured on Day 113) of the Treatment Period if CD19+ B cell repopulation reached ^10 cells / µL; or o If the first additional dose was administered on Day 113, then a second additional dose was to be administered 14 days later on Day 127; or o If the first additional dose was administered on Day 141, then a second additional dose Patent Application CLIMB-005 / 01WO 40193 / 24 was to be administered 14 days later on Day 155. At Day 169 of the Treatment Period irrespective of CD19+ B cell count, unless they had previously received additional doses between Day 113 and Day 155 based on B cell repopulation. o If the first additional dose was administered on Day 169, then a second additional dose was to be administered 14 days later on Day 183. Any subject that had a relapse of proteinuria during the Treatment Period on or after Day 113, defined as proteinuria UPCR >3.5 g / g, was to be considered a treatment failure and was not to receive additional VB119 doses. Subjects experiencing worsening proteinuria prior to Day 113 in the Treatment Period were to receive rescue medications (steroids or other IST) to control flare per Protocol if complete withdrawal of steroids was to be completed by Day 113. If rescue therapy was required on or after Day 113, the Investigator was to discontinue VB119 treatment. Subjects who received rescue medication (steroids or other IST) continued to be monitored per study requirements as indicated in the Schedule of Procedures. Safety Follow-Up: 6 months following the Treatment Period (Day 275 to Day 420) Following the end of the Treatment Period, subjects were to be followed for safety for 6 months, during which time subjects would be assessed for safety, renal function, B cell repopulation, and quality of life. Due to early study termination, the Safety Follow-Up period did not occur. Duration of Treatment: The total study duration for each individual subject was to be up to 17 months, including the Screening Period (up to 2 months), Treatment Period (9 months), and Safety Follow-Up Period (up to 6 months). Number of Subjects: Planned: Approximately 20 subjects Diagnosis and Main Criteria for Inclusion: Key study inclusion criteria included, but were not limited to, men and women ^18 years of age with a kidney biopsy-proven diagnosis of primary MCD or primary FSGS within the past 10 years; a history of steroid-sensitive MCD or FSGS (defined as having achieved complete remission of proteinuria [reduction of proteinuria to <0.5 g / g UPCR] after use of corticosteroids); proteinuria in the past 2 years; on prednisone (or IST) prior to Screening and Patent Application CLIMB-005 / 01WO 40193 / 24 expected to be tapered to a stable dose of <20 mg / day; and with disease considered in complete remission prior to Screening. Investigational Product Information: VB119 (100 mg and 200 mg) Statistical Methods: Since there was only 1 subject enrolled at the time of early study termination, only subject data listings were generated, and no statistical analysis was performed. Summary of Results: Disposition and Demographics: Screened: 3 subjects Randomized: 1 subject Completed: 0 subjects A single subject was enrolled in the study and received the first dose of VB119100 mg on Day 1. The last study visit was on Day 238 due to early study termination by the Sponsor (Listing 16.2.1.1). Subject 110-002 was a white female between 50 and 60 years of age with a BMI of 26.5 kg / m2(Listing 16.2.4.1). The subject had a relevant ongoing medical history of glomerulonephritis minimal lesion, nephrotic syndrome, and proteinuria and a prior disease history of frequently relapsing steroid sensitive MCD (Listings 16.2.4.2 and 16.2.4.3). Subject 110-002 received prednisone 7.5 mg once daily from Day -42 until Day 85. Extent of Exposure: The subject received 4 doses of VB119 (Table 1) and completed the Treatment Period before the study was terminated early by the Sponsor. Efficacy Results: Due to early study termination and having data from only 1 subject, no formal efficacy analyses could be performed. UPCR was measured from the first morning void spot urine sample, which was then normalized to creatinine to account for urine concentration. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration equation to estimate renal function through estimated clearance. The primary efficacy parameter, UPCR, was measured from Screening through End of Treatment (EOT) (Day 238) and ranged from 47 mg / g to 101 mg / g (normal range [NR]: 200 mg / g) (Table 1). The UPCR results showed that proteinuria was well-controlled and remained Patent Application CLIMB-005 / 01WO 40193 / 24in remission ( 0.5 g / g) throughout the study.Table: Primary Efficacy Parameter: UPCR - All Treated Subjects Subject VB119 Parameter Study Visit (Day) [1] Dose Result The secondary efficacy parameter, eGFR, was measured from Screening through EOT (Day 238) and ranged from 67 mL / min / 1.73 m² to 94 mL / min / 1.73 m² (NR: 53 mL / min / 1.73 m²) throughout the study. The eGFR results showed that renal function was normal for the subject throughout the study. No edema was reported by the subject. Pharmacokinetic Results: There was no drug concentration data for Subject 110-002. Safety Results: Subject 110-002 experienced 1 treatment-emergent adverse event (TEAE) of nodule (reported term: right axillary nodule) on Day 155, which resolved on Day 189. This Patent Application CLIMB-005 / 01WO 40193 / 24 TEAE was considered mild in severity and not related to study drug. No infusion-related reactions occurred. The safety laboratory parameter serum creatinine was measured from Screening through EOT (Day 238) and ranged from 0.74 mg / dL to 0.98 mg / dL (NR: 0.49 mg / dL to 1.12 mg / dL) remaining within the NR throughout the study. Other liver and renal function parameters (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatine kinase, gamma-glutamyl transferase, and urea nitrogen) also remained within the NRs. No anti-drug antibodies (ADAs) were reported. Conclusions: In this Phase 2 study, 1 subject was enrolled and received 4 doses of VB119. There were no safety concerns related to the administration of VB119 including the absence of any critical laboratory value, with liver and renal function parameters including creatinine remaining within the NR. Subject 110-002 experienced only 1 TEAE (nodule) that was mild in severity and not related to the study drug. There were no infusion-related reactions or ADAs. Treatment of SLE: The invention provides novel methods for treatment of systemic lupus erythematosus (SLE). The methods of the invention provide safe and efficacious treatment of SLE. Specifically, the invention recognizes that there is an unmet need for treatment of patients with refractory SLE. The current standard of care also involves the use belimumab (C cell activating factor blockade), anifrolumab (type 1 receptor blockade) for refractory disease. In certain instances, rituximab is also used for treatment or management of symptoms of SLE patients. In the current standard of care, there is a substantial population of patients that are refractory to the current therapies. Indeed, the current standard of care lead to a lot of patients being dependent on corticosteroids. There are also frequent relapses, especially of nephritis, vasculitis, thrombosis, and lead to cumulative damage and organ failure. In addition, there is also fatigue and cognitive dysfunction in patients with current standard of care. This leads to poor responses, impaired participation, and reduced quality of life. In addition, there treatment- associated burden of cardiovascular mortality, infection, and neoplasm risk. Patent Application CLIMB-005 / 01WO 40193 / 24 The invention beneficially recognizes that targeting B cell depletion by anti-CD19 antibodies will provide a novel method for treatment of SLE. The methods of the invention overcome the drawbacks of conventional therapies for treatment by SLE by targeting CD19 positive B cells. In certain aspects, the invention provides a method of treating a subject having systemic lupus erythematosus (SLE), wherein the method comprises administration of a composition comprising a therapeutically effective amount an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29. In certain embodiments, the anti-CD19 antibody may be any anti-CD19 antibody provided herein. In certain embodiments, the anti-CD19 antibody is budoprutug. In certain embodiments, the composition of the invention is administered parenterally. In certain embodiments, the composition is administered via an intravenous (IV) infusion. In certain embodiments, the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 4. In certain embodiments, the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 6. In certain embodiments, the subject has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid. In certain embodiments, the subject is receiving equal to or less than 20 mg prednisone at least 28 days before start of the treatment. In certain embodiments, the composition is administered only on the first day after start of treatment. Thus, in certain embodiments, the methods of the invention provide a single dose administration of the compositions of the invention. In certain embodiments, the composition is administered at days 1 and 15 at the start of the treatment. In certain embodiments, the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 100 mg of the anti-CD19 antibody. In certain embodiments, the composition comprises about 200 mg of the anti-CD19 antibody. In certain aspects, the patient has previously received therapy for treatment of SLE. IN certain embodiments, the subject has previously received at least two therapies for SLE. In certain Patent Application CLIMB-005 / 01WO 40193 / 24 embodiments, at least one of the prior therapy is corticosteroid therapy. In certain embodiments, the corticosteroid therapy is treatment of prednisone. In certain embodiments, biological parameters associated with SLE are monitored to gauge the efficacy of the treatment. In certain embodiments, the method provides that the B-cell concentration is monitored during the course of the treatment. In certain embodiments, B-cell count is monitored after administration of the composition. In certain embodiments, the method further comprises administration of an additional cycle to the subject if B-cell count is high. In certain embodiments, the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL. FIG.22 shows the overview of the therapies for treatment of SLE. As eident from the data provided in FIG.22, patients have poor response when targeting depletion of CD20+ B- cells. In particular, the issue may be an inadequate CD20+ B cell depletion, persistence of CD19+ self-reactive B cell subsets. There is also an issue with continued production of autoantibodies by plasma cells, and rapid recovery of pathogenic B cell subsets. However, as provided in FIG.23, targeting B cells has shown promise in SLE. Depletion of CD19+ B cells with CD19+ CAR-T cells addresses some of the shortcomings of existing therapy. Limitations include: • Challenging to make autologous cells from highly pre-treated patients • Toxicity associated with required conditioning therapy • Risk of cytokine release syndrome and immune effector cell associated neurotoxicity syndrome • Access limited by complexity and cost Phase Ib / 2a clinical trials: FIG.25 provides an overview of the Phase Ib / 2a clinical trials for the treatment of SLE patients. This is a planned open-label, dose escalation, and expansion study with augmented B cell and antibody analyses. The population for these trials include: • Part 1b: Hybrid SLEDAI >4 • Part 2a: Hybrid SLEDAI >6 • ANA, elevated anti-dsDNA, ENA or APL, low C3 / C4 • <20 mg prednisone by Day -28; stable limited background Patent Application CLIMB-005 / 01WO 40193 / 24 The primary objective of the trail are to evaluate the safety and tolerability of budoprutug in patients with SLE, and to evaluate the efficacy of budoprutug on SLE biomarkers. The secondary and exploratory endpoints include: • To evaluate the effects of budoprutug on B-cell depletion (prioritized pharmacodynamic [PD] response), autoantibody levels, and protective antibody levels • To evaluate the PK and PK / PD (dose relationship) profile in patients with SLE • To evaluate preliminary signs of clinical activity in patients with SLE • To determine the kinetics of re-population of B-cell subsets and antibodies after depletion Cytokine release assay (CRAs): Budoprutug targets the CD19 antigen, which is expressed on B-cells. Thus, there is potential that antibodies such as budoprutug could induce increases in cell death and cytokine release by immune cell subsets. Cytokine Release Syndrome (CRS) is a systemic inflammatory response which can occur in response to administration of novel biotherapeutics. Experimental details: Cryopreserved PBMC from ten Healthy control and nine SLE donors were thawed, counted and plated in complete Roswell Park Memorial Institute (RPMI) medium at 2x105cell per well in 96 well U bottom plates in triplicate per culture condition. Due to poor PBMC recovery from two donors (Donor 11 and 19) culture replicates were respectively established in duplicate for select conditions or in singlicate. Culture conditions included a single concentration of the comparator antibody Rituximab (5^g / ml) and the cytotoxic positive control staurosporine (1^M), and three concentrations (10^g / ml, 5^g / ml and 1^g / ml) of the test articles (Budoprutug, TNT119 – Process 1 or Process 2) or an isotype control (IgG1^^^^shown in Table below). PBMC were cultured for 48 hour (hrs) at 37°C, 5% carbon dioxide (CO2). The data for TNT119 Process 1 and Process 2, as provided herein, provides data for budoprutug prepared by two difference processes. Following incubation, triplicate culture wells were combined and PBMC were stained for IP by flow cytometry using a panel of fluorescent antibodies. Fluorescent counting beads were included to calculate absolute viable cell number. Where PBMC recovery dictated that fewer culture replicates were established (Donors 11 and 19), calculations for total viable cell counts were normalised to a starting culture of triplicate wells. Data were analysed using FlowJo software. Patent Application CLIMB-005 / 01WO 40193 / 24 A gating strategy was designed to identify monocytes, CD4+ and CD8+ T cells, NK cells and B cells. Inclusion of Process 1, Process 2 or Rituximab blocked detection of CD19 and CD20 respectively by fluorophore conjugated antibodies. A flow cytometry strategy was designed to include both CD19 and CD20, allowing for detection of B cells by either antibody. Results were graphed and statistical analysis was performed using GraphPad Prism. Statistical significance was determined using two-way Analysis of Variance (ANOVA) with Tukey’s multiple comparison test. Comparisons of healthy controls to SLE PBMC were performed for all culture conditions. Within each donor group, the positive controls were compared to the respective negative controls, Process 1 and Process 2 were compared to the isotype, and Process 1 was compared to Process 2. Condition Dose Readout 1 Media N / A The CRA was performed with antibodies in a solid (plate-bound) and liquid (soluble) phase following NBQ-SOP030 (PBMC CRA). Antibodies delivered in solid phase were coated onto 96 well U bottom plates in 60^l PBS (1^g / well) at 4°C overnight prior to PBMC culture. Culture conditions included a non-stimulated (NS-media only), a positive control phytohemagglutinin (PHA-M, 5^g / ml) and a single concentration (1^g / well plate-bound, 5^g / ml soluble) of CRA reference control antibodies (Alemtuzumab, Muronomab, TGN1412) or appropriate isotype controls (IgG1, IgG2a, IgG4^^^^Test articles (TNT119 – Process 1 or Process 2) or a matched IgG1^^isotype control were added in plate-bound phase (1^g / well) or soluble phase (200^g / ml, ^^^g / ml and 5^g / ml). Cryopreserved PBMC from ten Healthy control and ten SLE donors were thawed, counted and plated in complete RPMI medium at 2x105cell per well in 96 well U bottom plates in singlicate per culture condition. The PBMC were subsequently incubated for 48hrs at 37°C 5% CO2. CRA Assay Conditions: Condition Dose (plate Dose (soluble) Readout Patent Application CLIMB-005 / 01WO 40193 / 24 bound) 1 Media N / A N / A MSD: - L- d Immunophenotyping: IP of cultured PBMC was performed by flow cytometry. Viability (Figure 5) and distribution of PBMC subsets as determined by total viable cell count (Figure 6) within each leukocyte subset were assessed. As provided in FIG.26, PBMC from healthy control and SLE donors were cultured in the presence of positive control (Staurosporine 1^M), reference control Rituximab (10^g / ml) or three concentrations of process 1, process 2 or IgG^^isotype control (0, 5 or 1^g / ml) for 48hrs, following which cultures were stained for flow cytometry. Subsets were identified and viability was assessed by inclusion of a viability dye. Data represents percentage viable cells per subset with individual donor denoted by symbols and median denoted by line. Healthy control (Blue) n=10, SLE (green) n=9. Statistical analysis was performed with two-way ANOVA with Tukey’s post-tests indicated Patent Application CLIMB-005 / 01WO 40193 / 24 on graphs. Blue asterisks denote significance in healthy controls, green asterisks denote significance in SLE, and grey asterisks denote significance between healthy controls and SLE. As provided in FIG.27, PBMC from healthy control and SLE donors were cultured in the presence of positive control (Staurosporine 1^M), reference control Rituximab (10^g / ml) or threeconcentrations of process 1, process 2 or IgG^^ isotype control (10, 5 or 1^g / ml) for 48hrs,following which cultures were stained for flow cytometry. The viable subset count was determined by inclusion of precision counting beads and a viability dye. Data represents viable count of PBMC subsets with individual donor denoted by symbols and median denoted by line. Healthy control (Blue) n=10, SLE (green) n=9. Statistical analysis was performed with two-way ANOVA with Tukey’s post-tests indicated on graphs. Blue asterisks denote significance in healthy controls, green asterisks denote significance in SLE, and grey asterisks denote significance between healthy controls and SLE. Process 1 and 2 bound to the intended target on B cells, as evidenced by reduced detection of CD19 on B cells with fluorescent anti-CD19 antibodies. The cytotoxicity positive control, staurosporine (1^M), performed as expected with statistically significant reductions in viability of all leukocyte subsets identified in both healthy control and SLE donor PBMC cultures (Figure 5). Generally, viability was similar between treatment groups and donor types, however some comparisons yielded statistically significant differences. In healthy control PBMC, culture in the presence of Process 1 at 5^g / ml coincided with statistically significant reductions in NK cell viability when compared to IgG1^^isotype control (5^g / ml). In SLE PBMC, culture in the presence of Process 1 at 5^g / ml and 1^g / ml or culture with Process 2 at 10^g / ml, 5^g / ml and 1^g / ml coincided with statistically significant reductions in NK cell viability when compared to IgG1^^ isotype control at comparable concentrations. Comparison between donor groups identified a statistically significant decrease in monocyte viability following culture with staurosporine in healthy control PBMC when compared to SLE PBMC. Results are summarized in the Table below. Treatment Donor group B cells NK CD4+ T CD8+ T Monocytes Patent Application CLIMB-005 / 01WO 40193 / 24 Healthy ns ns ns ns ns Process 1 - 10µg / ml SLE ns ns ns ns ns HOO^ ons to 10µg / ml isotype control; process 1 or process 2 relative to appropriate concentration of isotype control. Where SLE vs. healthy is recorded, arrows indicate change or the SLE donor group relative to the healthy donor group. To assess the effect of TNT119 on the distribution of leukocytes within PBMC cultures, viable cell count was calculated. Culture of PBMC with staurosporine lead to statistically significant reductions in NK cell and monocyte counts in healthy control donor PBMC and across all leukocyte subsets in SLE donor PBMC (FIG. 27). In healthy control PBMC, culture in the presence of Process 1 at 5^g / ml coincided with statistically significant reductions in viable B cell count when compared to IgG1^^isotype control (5^g / ml). In SLE PBMC, culture in the presence of Process 1 or Process 2 at 10^g / ml coincided with statistically significant reductions in viable NK cell count when compared to IgG1^^isotype control (10^g / ml). Comparison between donor groups identified statistically significant increases in viable CD4+ T cell count following incubation with media (NS), Process 1 (5 and 1^g / ml) and Process 2 ^^^g / ml) and statistically significant decreases in viable monocyte count following culture with Process 1 (10 and 1^g / ml), Process 2 (5 and 1^g / ml) in SLE PBMC when compared to healthy control PBMC. Data is summarized in the Table below.Table: IP assay - summary of test articles e ect on immune cell subset viable cell count Patent Application CLIMB-005 / 01WO 40193 / 24 Treatment Donor group B cells NK cells CD4+ T CDS+ T Monocytes cells cells WHG^ cell subset with indicated treatment type. No statistical difference is noted as ns . Comparisons performed for summary are as follows: staurosporine relative to media; Rituximab relative to 10µg / ml isotype control; process 1 or process 2 relative to appropriate concentration of isotype control. Where SLE vs. healthy is recorded, arrows indicate change or the SLE donor group relative to the healthy donor group. Cytokine release assay: Cytokine release into culture supernatant by healthy control and SLE donor PBMC was assessed by multi-plex cytokine analysis using MSD following stimulation with plate-bound or soluble antibodies (FIG. 28 – FIG. 37). The assay controls responded as expected, with PHA (a Patent Application CLIMB-005 / 01WO 40193 / 24 lymphocyte mitogen) driving increases in the secretion of cytokines compared to non-stimulated (NS- media controls) for much of the data assessed. IL-8 was the exception to this, however any effect of PHA on IL-8 release is likely obscured by the high levels of IL-8 detected overall (typically all were above the ULOD). The CRA control antibody panel (National Institute of Biological Standards and control1) TGN1412 (anti-CD28), Muromonab (anti-CD3) and Alemtuzumab (anti-CD52)) behaved as expected, increasing cytokine production in PBMC cultures. In cultures stimulated with 1^g of plate bound TNT119 Process 1 or Process 2, nostatistically significant increase in cytokine production was detected above the IgG1^^ isotypecontrol in either healthy control or SLE donors. Additionally, no statistically significant difference was observed between Process 1 and 2 in any cytokine tested in either healthy control or SLE donor PBMC. Two-way ANOVA results identified statistically significant differences in IL-1ȕ^^TNF-Į^ and IL-6 production between healthy control and SLE donor PBMC, highlightingdifferences between donor groups across culture conditions. A summary of results is provided in the table below. Treatment Donor IFN- IL- TNF- IL- IL- IL- IL- IL- IL- IL- group y 1ß a 2 4 6- 8 10 12p70 13 s s s s s s s s s s s s Patent Application CLIMB-005 / 01WO 40193 / 24 SLE Ĺ ns Ĺ ns ns ns ns ns ns ns SLE vs. Ĺ Ĺ Ĺ ns ns ns ns ns ns ns s s s s s s WHG^ s’. Comparisons performed for summary are as follows: PHA relative to media; TGN1412, Muronomab and Alemtuzumab relative to appropriate isotype control; process 1 or process 2 relative to appropriate concentration of isotype control. Where SLE v. vs. healthy is recorded, arrows indicate change of the SLE donor group relative to the healthy donor group. In cultures stimulated with soluble TNT119 Process 1 or TNT119 Process 2 (200, 20 or ^^g / ml), no statistically significant increase in cytokine production was detected above the IgG1^^ isotype controls at comparable concentration in either healthy control or SLE donors. Additionally, no statistically significant difference was observed between Process 1 and 2 in any cytokine tested in either healthy control or SLE donor PBMC. Two-way ANOVA analysis did not identify statistically significant differences in cytokine production between healthy control and SLE donor PBMC following stimulation with soluble antibodies, however Tukey’s post-test identified conditions where statistically significant difference be...

Claims

Patent Application CLIMB-005 / 01WO 40193 / 24 CLAIMS:

1. A method of treating a subject having membranous nephropathy (MN), the method comprising: providing a composition comprising a therapeutically effective amount an anti-CD19 antibody to the subject having an anti-phospholipase A2 receptor (PLA2R) antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

2. The method of claim 1, wherein membranous nephropathy in the subject is primary membranous nephropathy (PMN).

3. The method of claim 1, wherein the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably said anti-CD19 antibody is budoprutug.

4. The method of claim 3, wherein the composition is administered parenterally.

5. The method of claim 4, wherein the composition is administered via an intravenous (IV) infusion.

6. The method of claim 4, wherein the composition is administered subcutaneously.

7. The method of claim 3, wherein the composition comprises about 100 mg budoprutug.

8. The method of claim 3, wherein the composition comprises about 200 mg budoprutug.

9. The method of claim 3, wherein the composition comprises about 600 mg budoprutug.

10. The method of claim 3, wherein the composition comprises about 1000 mg budoprutug.

11. The method of claim 6 or 7, wherein the composition is administered once every two weeks.Patent Application CLIMB-005 / 01WO 40193 / 24 12. The method of any of claims 7-10, wherein the composition is administered at days 1, 15, 169, and 183.

13. The method of any of claims 7-10, wherein the composition is administered in treatment cycles, wherein one treatment cycle comprises administering the composition once every two weeks, with a 24-week interval between two cycles.

14. The method of any of claims 7-10, wherein the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15, and wherein there is a 24-week interval between each treatment cycle.

15. The methods of any of claims 1-14, wherein the administration of composition results in remission of proteinuria in the patients.

16. A method for treating a subject having membranous nephropathy (MN), the method comprising: determining if the subject has an anti-phospholipase A2 receptor (PLA2R) antibody in serum; administering composition comprising a therapeutically effective amount an anti- CD19 antibody to the subject if the subject has anti-PLA2R antibody in serum; wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

17. The method of claim 16, wherein membranous nephropathy in the subject is primary membranous nephropathy (PMN).

18. The method of claim 16, wherein the anti-CD19 antibody is budoprutug.

19. The method of claim 18, wherein the composition is administered parenterally.Patent Application CLIMB-005 / 01WO 40193 / 24 20. The method of claim 19, wherein the composition is administered via an intravenous (IV) infusion.

21. The method of claim 19, wherein the composition is administered subcutaneously.

22. The method of claim 18, wherein the composition comprises about 100 mg budoprutug.

23. The method of claim 18, wherein the composition comprises about 200 mg budoprutug.

24. The method of claim 18, wherein the composition comprises about 600 mg budoprutug.

25. The method of claim 18, wherein the composition comprises about 1000 mg budoprutug.

26. The method of any of claims 20-26, wherein the composition is administered once every two weeks.

27. The method of any of claims 20-26, wherein the composition is administered at days 1, 15, 169, and 183.

28. The method of any of claims 20-26, wherein the composition is administered in treatment cycles, wherein one treatment cycle comprises administering the composition once every two weeks, with a 24-week interval between two cycles.

29. The method of any of claims 20-26, wherein the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15, and wherein there is a 24-week interval between each treatment cycle.

30. The methods of any of claims 16-29, wherein the administration of composition results in remission of proteinuria in the patients.

31. A method of determining whether a subject having membranous nephropathy (MN) will respond to treatment with an anti-CD19 antibody, the method comprising: conducting an assay on a sample from the subject that MN in order to determine the presence of anti-phospholipase A2 receptor (PLA2R) antibody in the sample;Patent Application CLIMB-005 / 01WO 40193 / 24 providing results of the assay to the physician such that physician prescribes or provides the subject with a composition comprising an anti-CD19 antibody; wherein the anti-CD19 antibody comprises a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

32. The method of claim 31, wherein membranous nephropathy in the subject is primary membranous nephropathy (PMN).

33. The method of claim 31, wherein the anti-CD19 antibody is budoprutug.

34. The method of claim 33, wherein the composition is administered parenterally.

35. The method of claim 34, wherein the composition is administered via an intravenous (IV) infusion.

36. The method of claim 33, wherein the composition comprises about 100 mg budoprutug.

37. The method of claim 33, wherein the composition comprises about 200 mg budoprutug.

38. The method of claim 33, wherein the composition comprises about 600 mg budoprutug.

39. The method of claim 33, wherein the composition comprises about 1000 mg budoprutug.

40. The method of any of claims 36-39, wherein the composition is administered once every two weeks.

41. The method of any of claim 36-39, wherein the composition is administered at days 1, 15, 169, and 183.

42. The method of any of claims 36-40, wherein the composition is administered in treatment cycles, wherein one treatment cycle comprises administering the composition once every two weeks, with a 24-week interval between two cycles.Patent Application CLIMB-005 / 01WO 40193 / 24 43. The method of any of claims 36-40, wherein the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15, and wherein there is a 24-week interval between each treatment cycle.

44. The methods of any of claims 31-43, wherein the administration of composition results in remission of proteinuria in the patients.

45. Use of an anti-CD19 antibody to in preparation of a medicament for treatment of membranous nephropathy (MN) in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody comprising a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

46. The use of claim 45, wherein membranous nephropathy in the subject is primary membranous nephropathy (PMN).

47. The use of claim 45, wherein the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.

48. The use of claim 43, wherein the medicament is administered parenterally.

49. The use of claim 48, wherein the medicament is administered via an intravenous (IV) infusion.

50. The use of claim 48, wherein the medicament is administered subcutaneously.

51. The use of any of claims 44-50, wherein the medicament comprises about 100 mg budoprutug, about 200 mg budoprutug, about 600 mg budoprutug, or about 1000 mg budoprutug.Patent Application CLIMB-005 / 01WO 40193 / 24 52. The use of any of claims 44-50, wherein the medicament comprises 100 mg budoprutug, 200 mg budoprutug, 600 mg budoprutug, or 1000 mg budoprutug.

53. The use of any of claims 44-50, wherein the medicament comprises 200 mg budoprutug.

54. The use of any of claims 44-50, wherein the medicament comprises 600 mg budoprutug 55. The use of claim 51 or claim 52, wherein the medicament is administered once every two days.

56. The use of claim 53, wherein the medicament is administered at days 1, 15, 169, and 183.

57. The use of claim 51 or claim 52, wherein the composition is administered in treatment cycles, wherein a treatment cycle comprises administering the composition once every two weeks, with a 24-week interval between each treatment cycle.

58. The use of claims 45-55, wherein the administration of the medicament results in remission of proteinuria in the patients.

59. The use of claims 45-55, wherein it is determined that patient has an anti-phospholipase A2 receptor (PLA2R) antibody in serum, and administering medicament to said patient if the patient has an anti-phospholipase A2 receptor (PLA2R) antibody in serum.

60. A method of determining whether a subject having membranous nephropathy (MN) will respond to treatment with an anti-CD19 antibody, the method comprising: conducting an assay on a sample from the subject that MN in order to determine the presence of anti-phospholipase A2 receptor (PLA2R) antibody in the sample; providing results of the assay to the physician such that physician prescribes or provides the subject with a composition comprising an anti-CD19 antibody, wherein said anti-CD19 antibody comprises a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29, and preferably said antibody is budoprutug.Patent Application CLIMB-005 / 01WO 40193 / 24 61. A method of treating a subject having immune thrombocytopenia (ITP) comprising administering to the subject a composition comprising a therapeutically effective amount an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

62. The method of claim 61, wherein the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.

63. The method of claim 62, wherein the composition is administered parenterally.

64. The method of claim 63, wherein the composition is administered via an intravenous (IV) infusion.

65. The method of any of claims 62-64, wherein the composition is administered at days 1 and 15 at the start of the treatment.

66. The method of claim 65, wherein the composition is further administered at days 169 and 183 after the start of the treatment.

67. The method of claim 65 or claim 66, wherein the composition is administered in treatment cycles, each treatment cycle comprising administration of the composition at days 1 and 15 at start of each treatment cycle, wherein there is a 12 to 36-week interval between start of each said treatment cycle.

68. The method of claim 67, wherein said interval between each treatment cycle is 12 weeks.

69. The method of claim 67, wherein said interval between each treatment cycle is 24 weeks.

70. The method of claim 67, wherein said interval between each treatment cycle is 36 weeks.Patent Application CLIMB-005 / 01WO 40193 / 24 71. The method of any of claims 61-70, wherein the composition comprises about 100 mg to about 1000 mg of the anti-CD19 antibody.

72. The method of any of claims 61-70, wherein the composition comprises about 200 mg to about 1000 mg of the anti-CD19 antibody.

73. The method of any of claims 61-70, wherein the composition comprises about 600 mg to about 1000 mg of the anti-CD19 antibody.

74. The method of any of claims 61-70, wherein the composition comprises about 100 mg of the anti-CD19 antibody.

75. The method of any of claims 61-70, wherein the composition comprises about 200 mg of the anti-CD19 antibody.

76. The method of any of claims 61-70, wherein the composition comprises about 600 mg of the anti-CD19 antibody.

77. The method of any of claims 61-70, wherein the composition comprises about 1000 mg of the anti-CD19 antibody.

78. The method of any of claims 71-78, wherein the method further comprises: measuring concentration for markers of ITP progression in the subject; and optionally administering an additional dosing cycle of the composition to the subject.

79. The method of claim 78, wherein the markers are selected from the group consisting of platelet count and B cells.

80. The method of claim 78 or claim 79, wherein the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the composition.Patent Application CLIMB-005 / 01WO 40193 / 24 81. The method of claim 78, wherein the measuring step is conducted about 8 to about 16 weeks after administration of initial dose of the compositions.

82. The method of claim 78, wherein the measuring step is conducted about at least 12 weeks after administration of initial dose of the compositions.

83. The method of claim 78, wherein the measuring step is conducted about 12 weeks after administration of initial dose of the compositions.

84. The method of claim 78, wherein the additional dosing cycle comprises administration of at least two additional doses of the composition.

85. The method of claim 78, wherein the additional dosing cycle comprises administration of a single dose of the composition.

86. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 100 mg to about 1000 mg of the anti-CD19 antibody.

87. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 200 mg to about 1000 mg of the anti-CD19 antibody.

88. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 600 mg to about 1000 mg of the anti-CD19 antibody.

89. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 100 mg of the anti-CD19 antibody.

90. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 200 mg of the anti-CD19 antibody.

91. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 600 mg of the anti-CD19 antibody.Patent Application CLIMB-005 / 01WO 40193 / 24 92. The method of claim 84 or claim 85, wherein the composition for the additional dosing cycle comprises about 1000 mg of the anti-CD19 antibody.

93. The method of claim 80, wherein the additional dosing cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle.

94. The method of claim 80, wherein the additional dosing cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle.

95. The method of claim 61 or claim 78, wherein the subject has insufficient response to at least one prior therapy for treatment of ITP.

96. A method of treating a subject having immune thrombocytopenia (ITP), the method comprising: administering a first cycle of a pharmaceutical composition comprising a therapeutically effective amount of an anti-CD19 antibody; monitoring markers associated with ITP progression in the subject; and providing a second cycle of compositions comprising therapeutically effective amount of said anti-CD19 antibody if the biological parameters demonstrate an inadequate physiological response after the first cycle.

97. The method of claim 96, wherein the second cycle is different from the first cycle.

98. The method of claim 96, wherein the first cycle comprises administration at days 1 and 15 at the start of the treatment.

99. The method of claim 96, wherein the second cycle comprises administration of a single dose of the composition comprising the anti-CD19 antibody.

100. The method of claim 96, wherein the markers are selected from the group consisting of platelet count and B cells.Patent Application CLIMB-005 / 01WO 40193 / 24 101. The method of claim 96, wherein the monitoring step is conducted about 8 to about 16 weeks after start of the first cycle.

102. The method of claim 96, wherein the monitoring step is conducted about 12 weeks after start of the first cycle.

103. The method of claim 96, wherein the second cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after start of the first cycle.

104. The method of claim 96, wherein the second cycle is administered if the B-cell count is more than 40 / µL at least 12 weeks after start of the first cycle.

105. The method of claim 96, wherein the subject has insufficient response to at least one prior therapy for treatment of ITP.

106. The method of claim 96, wherein the composition is administered parenterally.

107. The method of claim 96, wherein the composition is administered as an intravenous infusion.

108. The method of claim 96, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO: 29, and preferably said anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and a light chain variable region comprising SEQ ID NO:

29.

109. The method of claim 108, wherein the anti-CD19 antibody is budoprutug.

110. The method of claim 109, wherein the composition comprises about 100 mg budoprutug.

111. The method of claim 109, wherein the composition comprises about 200 mg budoprutug.Patent Application CLIMB-005 / 01WO 40193 / 24 112. The method of any of claims 61-65 or 109, wherein the composition comprises about 100 mg to about 1200 mg of the anti-CD19 antibody.

113. The method of any of claims 61-65 or 109, wherein the composition comprises about 100 mg to about 1000 mg of the anti-CD19 antibody.

114. The method of any of claims 61-65 or 109, wherein the composition comprises about 300 mg to about 700 mg of the anti-CD19 antibody.

115. The method of any of claims 61-65 or 109, wherein the composition comprises about 250 mg of the anti-CD19 antibody.

116. The method of any of claims 61-65 or 109, wherein the composition comprises about 500 mg of the anti-CD19 antibody.

117. The method of any of claims 61-65 or 109, wherein the composition comprises about 1000 mg of the anti-CD19 antibody.

118. Use of an anti-CD19 antibody to in preparation of a medicament for treatment of immune thrombocytopenia (ITP) in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody comprising a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

119. The use of claim 118, wherein the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.

120. The use of claim 118, wherein the medicament is administered parenterally.

121. The use of claim120, wherein the medicament is administered via an intravenous (IV) infusion.Patent Application CLIMB-005 / 01WO 40193 / 24 122. The use of any of claims 118-121, wherein the medicament is administered at days 1 and 15 at the start of the treatment.

123. The use of any of claims 118-121, wherein the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to about 1000 mg, or about 500 mg to about 1000 mg the anti-CD19 antibody.

124. The use of any of claims 118-121, wherein the medicament comprises 100 mg to 500 mg, 100 mg to 400 mg, 100 mg to 300 mg about, 100 mg to 1000 mg, 250 mg to 1000 mg, or 500 mg to 1000 mg the anti-CD19 antibody.

125. The use of any of claims 118-123, wherein the medicament comprises about 100 mg, about 200 mg, about 500 mg, or about 1000 mg of the anti-CD19 antibody.

126. The use of any of claims 118-123, wherein the medicament comprises 100 mg, 200 mg, 500 mg, or 1000 mg of the anti-CD19 antibody.

127. The use of any of claims 123-126, wherein the use further comprises measuring concentration for markers of ITP progression in the subject; and optionally administering an additional dosing cycle of the composition to the subject.

128. The use of claim 127, wherein the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the medicament.

129. The use of claim 128, wherein the markers are selected from the group consisting of platelet count and B cells.

130. The use of claim 128 or claim 129, wherein the additional dosing cycle is administered if the markers of ITP progression demonstrate insufficient response after administration of initial dose of the medicament.Patent Application CLIMB-005 / 01WO 40193 / 24 131. The use of claim 130, wherein the measuring step is conducted about 8 to about 16 weeks, about at least 12 weeks, or about 12 weeks after administration of initial dose of the medicament.

132. The use of claim 128 or claim 130, wherein the additional dosing cycle comprises administration of a single dose of the medicament or at least two additional doses of the medicament.

133. The use of claim 132, wherein the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to about 1000 mg, about 500 mg to about 1000 mg, about 200 mg, about 250 mg, about 500 mg, or about 1000 mg of the anti-CD19 antibody.

134. The use of claim 128, wherein the additional dosing cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle, or if the B- cell count is more than 40 / µL at least 12 weeks after first dosing cycle.

135. The use of claim 121 or 128, wherein the patient has insufficient response to at least one prior therapy for treatment of ITP.

136. Use of an anti-CD19 antibody to in preparation of a medicament for treatment of immune thrombocytopenia (ITP) in a patient in need thereof, wherein the use comprises: administering a first cycle of said medicament comprising a therapeutically effective amount of an anti-CD19 antibody; monitoring markers associated with ITP progression in the subject; and providing a second cycle of medicament comprising therapeutically effective amount of said anti-CD19 antibody if the biological parameters demonstrate an inadequate physiological response after the first cycle.

137. Use of claim 136, wherein the anti-CD19 antibody comprises: a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.Patent Application CLIMB-005 / 01WO 40193 / 24 138. Use of claim 136 or claim 137, wherein the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion.

139. Use of claim 138, wherein the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg about, about 100 mg to about1000 mg, about 250 mg to about 1000 mg, about 500 mg to about 1000 mg, about 200 mg, about 250 mg, about 500 mg or about 1000 mg of the anti-CD19 antibody.

140. Use of claim 136, wherein the second cycle is administered if the platelet count is less than 30,000 / µL at least 12 weeks after first dosing cycle, or if the B-cell count is more than 40 / µL at least 12 weeks after first dosing cycle.

141. A method of treating a subject having glomerulonephropathy, wherein the method comprises administration of a composition comprising a therapeutically effective amount of an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

142. The method of claim 141, wherein the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.

143. The method of claim 142, wherein the composition is administered parenterally.

144. The method of claim 143, wherein the composition is administered via an intravenous (IV) infusion.

145. The method of claim 141, wherein glomerulonephropathy is associated with autoantibodies.Patent Application CLIMB-005 / 01WO 40193 / 24 146. The method of claim 141, wherein the glomerulonephropathy is selected from the group consisting of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN).

147. The method of claim 141, wherein the subject is corticosteroid-dependent or frequently relapsing.

148. The method of claim 147, wherein the subject has previously received corticosteroid therapy and / or any additional therapy for treatment of nephrotic syndromes.

149. The method of claim 148, wherein the additional therapies are selected from the group consisting of calcineurin inhibitors, mycophenolic acid analogues, azathioprine, and cyclophosphamide.

150. The method of any of claims 141 – 144, wherein the composition is administered at days 1 and 15 at the start of the treatment.

151. The method of claim 150, wherein the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody.

152. The method of claim 150, wherein the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody.

153. The method of claim 150, wherein the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody.

154. The method of claim 150, wherein the composition comprises about 100 mg of the anti-CD19 antibody.

155. The method of claim 150, wherein the composition comprises about 200 mg of the anti-CD19 antibody.Patent Application CLIMB-005 / 01WO 40193 / 24 156. The method of claim 148, wherein the subject has received the corticosteroid therapy for at least 8 weeks before start of administration of the composition.

157. The method of claim 156, wherein the corticosteroid therapy is administration of prednisone.

158. The method of claim 157, wherein if the prednisone is administered at a dose higher than 20 mg / day, the subject is tapered off to a dose of 20 mg / day of prednisone.

159. The method of claim 158, wherein tapering is done from at least eight weeks to about 2 weeks before starting administration of the composition.

160. The method of any of claims 157-159, wherein prednisone is administered at a dose of less than about 20 mg / day for at least two weeks before starting administration of the composition.

161. The method of any of claims 157 – 160, wherein the corticosteroid therapy is gradually tapered off in about 12 weeks after starting the administration of the composition.

162. The method of any of claims 157 – 160, wherein the corticosteroid therapy is gradually tapered off in about 16 weeks after starting the administration of the composition.

163. The method of any of claims 157-162, wherein the method further comprises administration of an additional cycle to the subject, wherein the additional cycle comprises administration of a first additional dose of the composition and a second additional dose of the composition.

164. The method of claim 163, wherein the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL.Patent Application CLIMB-005 / 01WO 40193 / 24 165. The method of claim 164, wherein the first additional dose of the additional cycle is administered between day 113 and day 155 after first administration of the composition to the subject.

166. The method of claim 164, wherein the first additional dose of the additional cycle is administered between day 113 and day 141 after first administration of the composition to the subject.

167. The method of claim 165, wherein the second additional dose is administered 14 days after administration of the first additional dose.

168. The method of claim 163, wherein the first additional dose of the additional cycle is administered between day 169 and day 183 after first administration of the composition to the subject.

169. The method of claim 168, wherein the first additional dose and the second additional dose are administered if the subject has not previously received the first additional dose and the second additional dose between days 113 and 115 after first administration of the composition to the subject.

170. The method of claim 163, wherein the first additional dose and the second additional dose comprise about 200 mg of the anti-CD19 antibody.

171. Use of an anti-CD19 antibody to in preparation of a medicament for treatment of glomerulonephropathy in a patient in need thereof, wherein said medicament comprises a therapeutically effective amount of an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

172. The use of claim 171, wherein the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.Patent Application CLIMB-005 / 01WO 40193 / 24 173. The use of claim 171 or claim 172, wherein the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion.

174. The use of any of claims 171-173, wherein glomerulonephropathy is associated with autoantibodies.

175. The use of any of claims 171-174, wherein the glomerulonephropathy is selected from the group consisting of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN).

176. The use of any of claims 171-175, wherein the patient is corticosteroid-dependent or frequently relapsing.

177. The use of any of claims 171-176, wherein the patient has previously received corticosteroid therapy and / or any additional therapy for treatment of nephrotic syndromes, and preferably the additional therapies are selected from the group consisting of calcineurin inhibitors, mycophenolic acid analogues, azathioprine, and cyclophosphamide.

178. The use of any of claims 171-173, wherein the medicament is administered at days 1 and 15 at the start of the treatment.

179. The use of claim 178, wherein the medicament comprises about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg, about 100 mg, or about 200 mg of the anti-CD19 antibody.

180. The use of claim 177, wherein the patient has received the corticosteroid therapy for at least 8 weeks before start of administration of the medicament.

181. The use of claim 180, wherein the corticosteroid therapy is administration of prednisone, and preferably the prednisone is administered at a dose higher than 20 mg / day, the patient is tapered off to a dose of 20 mg / day of prednisone, and tapering isPatent Application CLIMB-005 / 01WO 40193 / 24 done from at least eight weeks to about 2 weeks before starting administration of the composition.

182. The use of claim 181, wherein prednisone is administered at a dose of less than about 20 mg / day for at least two weeks before starting administration of the composition.

183. The use of claim 181 or claim 182, wherein the corticosteroid therapy is gradually tapered off in about 12 weeks or about 16 weeks after starting the administration of the composition.

184. The use of claim 181 or claim 182, wherein the use further comprises administration of an additional cycle to the patient, wherein the additional cycle comprises administration of a first additional dose of the composition and a second additional dose of the medicament.

185. The use of claim 184, wherein the additional cycle is administered if B cell count in the patient is greater than 10 cells / µL.

186. The use of claim 185, wherein the first additional dose of the additional cycle is administered between day 113 and day 155 after first administration of the medicament to the patient.

187. The use of claim 185, wherein the first additional dose of the additional cycle is administered between day 113 and day 141 after first administration of the medicament to the patient.

188. The use of claim 187, wherein the second additional dose is administered 14 days after administration of the first additional dose.

189. The use of claim 185, wherein the first additional dose of the additional cycle is administered between day 169 and day 183 after first administration of the medicament to the patient.Patent Application CLIMB-005 / 01WO 40193 / 24 190. The use of claim 189, wherein the first additional dose and the second additional dose are administered if the patient has not previously received the first additional dose and the second additional dose between days 113 and 115 after first administration of the medicament to the subject; and preferably the first additional dose and the second additional dose comprise about 200 mg of the anti-CD19 antibody.

191. A method of treating a subject having systemic lupus erythematosus (SLE), wherein the method comprises administration of a composition comprising a therapeutically effective amount an anti-CD19 antibody, wherein the anti-CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

192. The method of claim 191, wherein the anti-CD19 antibody is budoprutug.

193. The method of claim 192, wherein the composition is administered parenterally.

194. The method of claim 193, wherein the composition is administered via an intravenous (IV) infusion.

195. The method of claim 193, wherein the composition is administered subcutaneously.

196. The method of claim 191, wherein the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 4.

197. The method of claim 191, wherein the subject has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 6.

198. The method of claim 191, wherein the subject has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid.

199. The method of claim 198, wherein the subject is receiving equal to or less than 20 mg prednisone at least 28 days before start of the treatment.Patent Application CLIMB-005 / 01WO 40193 / 24 200. The method of any of claims 191 – 199, wherein the composition is administered only on first day after start of treatment.

201. The method of any of claims 191 – 199, wherein the composition is administered at days 1 and 15 at the start of the treatment.

202. The method of any of claims 191-200, wherein the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody.

203. The method of any of claims 191-200, wherein the composition comprises about 100 mg to about 500 mg of the anti-CD19 antibody.

204. The method of any of claims 191-200, wherein the composition comprises about 100 mg to about 400 mg of the anti-CD19 antibody.

205. The method of any of claims 191-200, wherein the composition comprises about 100 mg to about 300 mg of the anti-CD19 antibody.

206. The method of any of claims 191-200, wherein the composition comprises about 100 mg of the anti-CD19 antibody.

207. The method of any of claims 191-200, wherein the composition comprises about 200 mg of the anti-CD19 antibody.

208. The method of any of claims 191-200, wherein the composition comprises about 300 mg of the anti-CD19 antibody.

209. The method of any of claims 191-200, wherein the composition comprises about 600 mg of the anti-CD19 antibody.

210. The method of any of claims 191-200, wherein the composition comprises 100 mg, 200 mg, 300 mg, or 600 mg of the anti-CD19 antibodyPatent Application CLIMB-005 / 01WO 40193 / 24 211. The method of claim 198, wherein the corticosteroid therapy is administration of prednisone.

212. The method of claim 198, wherein the subject has previously received at least two therapies for SLE.

213. The method of any of claims 191-211, wherein B-cell count is monitored after administration of the composition.

214. The method of claim 212, wherein the method further comprises administration of an additional cycle to the subject if B-cell count is high.

215. The method of claim 213, wherein the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL.

216. Use of an anti-CD19 antibody to in preparation of a medicament for treatment of systemic lupus erythematosus (SLE) in a patient in need thereof, wherein the medicament comprises a therapeutically effective amount an anti-CD19 antibody, wherein the anti- CD19 antibody comprises: a heavy chain variable region at least 95% identical to SEQ ID NO: 17 and / or a light chain variable region at least 95% identical to SEQ ID NO:

29.

217. The use of claim 216, wherein the anti-CD19 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17 and / or a light chain variable region comprising SEQ ID NO: 29, and preferably the anti-CD19 antibody is budoprutug.

218. The use of claim 217, wherein the medicament is administered parenterally, and preferably the medicament is administered via an intravenous (IV) infusion.

219. The use of claim 216 or claim 217, wherein the patient has systemic lupus erythematosus disease activity index (SLEDAI) score of equal to or greater than 4, or preferably SLEDAI of greater than 6.Patent Application CLIMB-005 / 01WO 40193 / 24 220. The use of claim 216 or claim 217, wherein the patient has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid, and preferably the patient is receiving equal to or less than 20 mg prednisone at least 28 days before start of the treatment.

221. The use of any of claims 216-219, wherein the medicament is administered only on first day after start of treatment or wherein the medicament is administered at days 1 and 15 at the start of the treatment.

222. The use of any of claims 216-221, wherein the medicament comprises about 100 mg to about 600 mg, about 100 mg to about 500 mg, about 100 mg to about 400 mg, about 100 mg to about 300 mg, about 300 mg to about 600 mg, about 100 mg, about 200 mg, about 300 mg, or about 600 mg of the anti-CD19 antibody.

223. The use of any of claims 216-221, wherein the medicament comprises 100 mg to 600 mg, 100 mg to 500 mg, 100 mg to 400 mg, 100 mg to 300 mg, 300 mg to 600 mg, 100 mg, 200 mg, 300 mg, or 600 mg of the anti-CD19 antibody.

224. The use of claim 216, wherein the patient has received prior therapy, wherein the prior therapy comprises treatment with a corticosteroid; and the corticosteroid therapy is administration of prednisone.

225. The use of any of claims 216-221, wherein B-cell count is monitored after administration of the composition.

226. The use of claim 225, wherein the use further comprises administration of an additional cycle to the subject if B-cell count is high; and preferably the additional cycle is administered if B cell count in the subject is greater than 10 cells / µL.

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