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Summary for Patent: 9,963,507
|Title:||Therapeutic use of anti-CD22 antibodies for inducing trogocytosis|
|Abstract:||Disclosed are methods and compositions of anti-B cell antibodies, preferably anti-CD22 antibodies, for diagnosis, prognosis and therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. In certain embodiments, trogocytosis induced by anti-B cell antibodies may determine antibody efficacy, disease responsiveness and prognosis of therapeutic intervention. In other embodiments, optimal dosages of therapeutic antibody may be selected by monitoring the degree of trogocytosis induced by anti-B cell antibodies. Other characteristics of anti-B-cell antibodies that may be monitored include inducing phosphorylation of CD22, CD79a and CD79b; inducing translocation of CD22, CD79a and CD79b to lipid rafts; inducing caspase-dependent apoptosis; increasing pLyn, pERKs and pJNKs; decreasing constitutively-active p38; or inducing mitochondrial membrane depolarization, generation of reactive oxygen species, upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-xl, Mcl-1 and Bcl-2.|
|Inventor(s):||Chang; Chien-Hsing (Downingtown, PA), Goldenberg; David M. (Mendham, NJ), Hansen; Hans J. (Diamondhead, MS), Rossi; Edmund A. (Woodland Park, NJ)|
|Assignee:||Immunomedics, Inc. (Morris Plains, NJ)|
|Patent Claims:||1. A method of depleting malignant B cells in a human patient comprising: a) exposing B cells from the human patient to epratuzumab, RGB4 or a chimeric or humanized version
thereof in vitro in the presence of PBMCs (peripheral blood mononuclear cells) or Fc.gamma.R-positive cells; b) measuring the depletion of one or more antigens selected from the group consisting of CD19, CD20, CD21, CD22 and CD79b on the surface of the
B cells, wherein the antigens are depleted by trogocytosis, to determine the sensitivity of the B cells to the anti-CD22 antibody; and c) administering epratuzumab, RGB4 or a chimeric or humanized version thereof to the human patient, wherein the
antibody is capable of inducing trogocytosis of the one or more antigens from the patient's B cells, and further wherein the antibody depletes malignant B cells from said patient.
2. The method of claim 1, wherein the patient has not previously been treated with an anti-CD22 antibody.
3. The method of claim 1, wherein the anti-CD22 antibody is epratuzumab or RFB4.
4. The method of claim 3, wherein the anti-CD22 antibody is epratuzumab.
5. The method of claim 3, wherein the anti-CD22 antibody is RFB4.
6. The method of claim 1, wherein the anti-CD22 antibody is a naked antibody.
7. The method of claim 1, wherein the anti-CD22 antibody is conjugated to at least one therapeutic agent.
8. The method of claim 1, wherein the antigen is CD19.
9. The method of claim 1, wherein the antigen is CD20.
10. The method of claim 1, wherein the antigen is CD21.
11. The method of claim 1, wherein the antigen is CD22.
12. The method of claim 1, wherein the antigen is CD79b.
13. The method of claim 1, further comprising administering at least one other therapeutic agent to the patient, said therapeutic agent being attached to the anti-CD22 antibody or administered as a free therapeutic agent.
14. The method of claim 13, wherein the therapeutic agent is selected from the group consisting of a radionuclide, an anti-angiogenic agent, a pro-apoptotic agent, a toxin, an immunoconjugate, a second antibody and an antigen-binding fragment of a second antibody.
15. The method of claim 14, wherein the drug is selected from the group consisting of 5-fluorouracil, aplidin, azaribine, anastrozole, anthracyclines, bendamustine, bleomycin, bortezomib, bryostatin-1, busulfan, calicheamycin, camptothecin, carboplatin, 10-hydroxycamptothecin, carmustine, celecoxib, chlorambucil, cisplatinum, Cox-2 inhibitors, irinotecan (CPT-11), SN-38, carboplatin, cladribine, camptothecans, cyclophosphamide, cytarabine, dacarbazine, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicine (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, estramustine, epipodophyllotoxin, estrogen receptor binding agents, etoposide (VP16), etoposide glucuronide, etoposide phosphate, floxuridine (FUdR), 3',5'-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, farnesyl-protein transferase inhibitors, gemcitabine, hydroxyurea, idarubicin, ifosfamide, L-asparaginase, lenolidamide, leucovorin, lomustine, mechlorethamine, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, navelbine, nitrosourea, plicomycin, procarbazine, paclitaxel, pentostatin, PSI-341, raloxifene, semustine, streptozocin, tamoxifen, taxol, temazolomide, transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vinorelbine, vinblastine, vincristine, a vinca alkaloid, a tyrophostin, canertinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, leflunomide, nilotinib, pazopanib, semaxinib, sorafenib, sunitinib, sutent, vatalanib, PCI-32765 (ibrutinib), PCI-45292, GDC-0834, LFM-A13 and RN486.
16. The method of claim 14, wherein the toxin is selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), onconase, DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin.
17. The method of claim 14, wherein the radionuclide is selected from the group consisting of .sup.111In, .sup.111At, .sup.177Lu, .sup.211Bi, .sup.212Bi, .sup.213Bi, .sup.211At, .sup.62Cu, .sup.67Cu, .sup.90Y, .sup.125I, .sup.131I, .sup.133I, .sup.32P, .sup.33P, .sup.47Sc, .sup.111Ag, .sup.67Ga, .sup.153Sm, .sup.161Tb, .sup.152Dy, .sup.166Dy, .sup.161Ho, .sup.166Ho, .sup.186Re, .sup.188Re, .sup.189Re, .sup.211Pb, .sup.212Pb, .sup.223Ra, .sup.225Ac, .sup.77As, .sup.89Sr, .sup.99Mo, .sup.105Rh, .sup.149Pm, .sup.169Er, .sup.194Ir, .sup.58Co, .sup.80mBr, .sup.99mTc, .sup.103mRh, .sup.109Pt, .sup.119Sb, .sup.125I, .sup.189mOs, .sup.192Ir, .sup.219Rn, .sup.215Po, .sup.221Fr, .sup.255Fm, .sup.11C, .sup.13N, .sup.15O, .sup.75Br, .sup.198Au, .sup.199Au, .sup.224Ac, .sup.77Br, .sup.113mIn, .sup.95Ru, .sup.97Ru, .sup.103Ru, .sup.105Ru, .sup.107Hg, .sup.203Hg, .sup.121mTe, .sup.122mTe, .sup.125mTe, .sup.165Tm, .sup.167Tm, .sup.168Tm, .sup.197Pt, .sup.109Pd, .sup.142Pr, .sup.143Pr, .sup.161Tb, .sup.57Co, .sup.58Co, .sup.51Cr, .sup.59Fe, .sup.75Se, .sup.201Tl, .sup.76Br and .sup.169Yb.
|Applicant||Tradename||Biologic Ingredient||Dosage Form||BLA||Number||Approval Date||Patent No.||Assignee||Estimated Patent Expiration||Status||Orphan||Source|
|Merck||ELSPAR||asparaginase||VIAL||101063||001||1978-01-10||Start Trial||Immunomedics, Inc. (Morris Plains, NJ)||2031-12-05||RX||search|
|>Applicant||>Tradename||>Biologic Ingredient||>Dosage Form||>BLA||>Number||>Approval Date||>Patent No.||>Assignee||>Estimated Patent Expiration||>Status||>Orphan||>Source|
|Country||Patent Number||Estimated Expiration|
|World Intellectual Property Organization (WIPO)||2013085893||Start Trial|
|World Intellectual Property Organization (WIPO)||2013181087||Start Trial|
|United States of America||2013142787||Start Trial|
|United States of America||2013323204||Start Trial|
|United States of America||2014212425||Start Trial|
|United States of America||2016000915||Start Trial|
|>Country||>Patent Number||>Estimated Expiration|
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