Claims for Patent: 10,206,918

Summary for Patent: 10,206,918

Title:	Efficacy of anti-HLA-DR antiboddy drug conjugate IMMU-140 (hL243-CL2A-SN-38) in HLA-DR positive cancers
Abstract:	The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-HLA-DR antibody or antigen-binding antibody fragment. The immunoconjugate may be administered at a dosage of between 3 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, more preferably 8, 10 or 12 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. The methods and compositions are particularly useful for treating AML, ALL or multiple myeloma.
Inventor(s):	Govindan; Serengulam V. (Summit, NJ), Cardillo; Thomas M. (Cedar Knolls, NJ), Goldenberg; David M. (Mendham, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	15/669,264
Patent Claims:	1. A method of treating an HLA-DR.sup.+ cancer comprising administering to a human patient with an HLA-DR.sup.+ acute myeloid leukemia, an immunoconjugate IMMU-140. 2. The method of claim 1, wherein the HLA-DR.sup.+ cancer does not respond to treatment with unconjugated anti-HLA-DR antibody. 3. The method of claim 1, wherein the immunoconjugate is administered as a front-line therapy to patients who have not previously been treated for the cancer. 4. The method of claim 1, wherein the immunoconjugate is administered to a patient who has previously relapsed from or been resistant to at least one anti-cancer therapy. 5. The method of claim 1, wherein the immunoconjugate is administered to a patient who is not eligible for stem-cell or bone-marrow transplantation. 6. The method of claim 1, wherein the immunoconjugate is administered at a dosage of between 3 mg/kg and 18 mg/kg. 7. The method of claim 6, wherein the dosage is selected from the group consisting of 4 mg/kg, 6 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 12 mg/kg, 16 mg/kg and 18 mg/kg. 8. The method of claim 1, wherein the immunoconjugate is administered at a dosage of between 6 mg/kg and 12 mg/kg. 9. The method of claim 1, wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 10 mg/kg. 10. The method of claim 1, wherein the cancer is metastatic. 11. The method of claim 10, further comprising reducing in size or eliminating the metastases. 12. The method of claim 4, wherein the patient has failed to respond to therapy with irinotecan, prior to treatment with the immunoconjugate. 13. The method of claim 6, wherein the immunoconjugate dosage is administered to the human patient once or twice a week on a schedule with a cycle selected from the group consisting of: (i) weekly; (ii) every other week; (iii) one week of therapy followed by two, three or four weeks off; (iv) two weeks of therapy followed by one, two, three or four weeks off; (v) three weeks of therapy followed by one, two, three, four or five weeks off; (vi) four weeks of therapy followed by one, two, three, four or five weeks off; (vii) five weeks of therapy followed by one, two, three, four or five weeks off; and (viii) monthly. 14. The method of claim 13, wherein the cycle is repeated 4, 6, 8, 10, 12, 16 or 20 times. 15. The method of claim 1, wherein the immunoconjugate is administered in combination with one or more therapeutic modalities selected from the group consisting of unconjugated antibodies, radiolabeled antibodies, drug-conjugated antibodies, toxin-conjugated antibodies, gene therapy, chemotherapy, therapeutic peptides, cytokine therapy, oligonucleotides, localized radiation therapy, surgery and interference RNA therapy. 16. The method of claim 15, wherein the therapeutic modality comprises treatment with a therapeutic agent selected from the group consisting of 5-fluorouracil, afatinib, aplidin, azaribine, anastrozole, anthracyclines, axitinib, AVL-101, AVL-291, bendamustine, bleomycin, bortezomib, bosutinib, bryostatin-1, busulfan, calicheamycin, camptothecin, carboplatin, 10-hydroxycamptothecin, carmustine, celecoxib, chlorambucil, cisplatinum, Cox-2 inhibitors, irinotecan (CPT-11), SN-38, carboplatin, cladribine, camptothecans, cyclophosphamide, crizotinib, dacarbazine, dasatinib, dinaciclib, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicine (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, erlotinib, estramustine, epidophyllotoxin, entinostat, estrogen receptor binding agents, etoposide (VP16), etoposide glucuronide, etoposide phosphate, exemestane, fingolimod, flavopiridol, floxuridine (FUdR), 3',5'-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, farnesyl-protein transferase inhibitors, fostamatinib, ganetespib, GDC-0834, GS-1101, gefitinib, gemcitabine, hydroxyurea, ibrutinib, idarubicin, idelalisib, ifosfamide, imatinib, L-asparaginase, lapatinib, lenolidamide, leucovorin, LFM-A13, lomustine, mechlorethamine, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, navelbine, neratinib, nilotinib, nitrosurea, olaparib, plicomycin, procarbazine, paclitaxel, PCI-32765, pentostatin, PSI-341, raloxifene, semustine, sorafenib, streptozocin, SU11248, sunitinib, tamoxifen, temazolomide (an aqueous form of DTIC), transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vatalanib, vinorelbine, vinblastine, vincristine, vinca alkaloids and ZD1839. 17. The method of claim 15, wherein the immunoconjugate is administered in combination with a second antibody or antigen-binding fragment thereof that binds to a tumor-associated antigen (TAA) selected from the group consisting of carbonic anhydrase IX, alpha-fetoprotein (AFP), .alpha.-actinin-4, ART-4, Ba 733, BAGE, BrE3-antigen, CA125, CAMEL, CAP-1, CASP-8/m, CCL19, CCL21, CD1, CD1a, CD2, CD3, CD4, CD5, CD8, CD11A, CD14, CD15, CD16, CD18, CD19, CD20, CD21, CD22, CD23, CD25, CD29, CD30, CD32b, CD33, CD37, CD38, CD40, CD40L, CD44, CD45, CD46, CD52, CD54, CD55, CD59, CD64, CD66a-e, CD67, CD70, CD7OL, CD74, CD79a, CD80, CD83, CD95, CD126, CD132, CD133, CD138, CD147, CD154, CDC27, CDK-4/m, CDKN2A, CTLA-4, CXCR4, CXCR7, CXCL12, HIF-1.alpha., colon-specific antigen-p (CSAp), CEA (CEACAM5), CEACAM6, c-Met, DAM, EGFR, EGFRvIII, EGP-1 (TROP-2), EGP-2, ELF2-M, Ep-CAM, fibroblast growth factor (FGF), Flt-1, Flt-3, folate receptor, G250 antigen, GAGE, gp100, GRO-.beta., HLA-DR, HM1.24, human chorionic gonadotropin (HCG), HER2/neu, HMGB-1, hypoxia inducible factor (HIF-1), HSP70-2M, HST-2, Ia, IGF-1R, IFN-.gamma., IFN-.alpha., IFN-.beta., IFN-.lamda., IL-4R, IL-6R, IL-13R, IL-15R, IL-17R, IL-18R, IL-2, IL-6, IL-8, IL-12, IL-15, IL-17, IL-18, IL-23, IL-25, insulin-like growth factor-1 (IGF-1), KS1-4, Le-Y, LDR/FUT, macrophage migration inhibitory factor (MIF), MAGE, MAGE-3, MART-1, MART-2, NY-ESO-1, TRAG-3, CRP, MCP-1, MIP-1A, MIP-1B, MUC1, MUC2, MUC3, MUC4, MUC5ac, MUC13, MUC16, MUM-1/2, MUM-3, NCA66, NCA95, NCA90, pancreatic cancer mucin, PD-1 receptor, placental growth factor, p53, PLAGL2, prostatic acid phosphatase, PSA, PRAME, PSMA, P1GF, ILGF, ILGF-1R, IL-6, IL-25, RS5, RANTES, T101, SAGE, 5100, survivin, survivin-2B, TAC, TAG-72, tenascin, TRAIL receptors, TNF-.alpha., Tn antigen, Thomson-Friedenreich antigens, tumor necrosis antigens, VEGFR, ED-B fibronectin, WT-1, 17-1A-antigen, complement factor C3, C3a, C3b, C5a, C5, an angiogenesis marker, bc1-2, bc1-6, Kras, and an oncogene product. 18. The method of claim 17, wherein the TAA is selected from the group consisting of CD19, CD20, CD22 and CD74. 19. The method of claim 17, wherein the second antibody is selected from the group consisting of hA19, hA20, hLL1 and hLL2. 20. The method of claim 1, wherein the immunoconjugate is administered subcutaneously. 21. The method of claim 20, wherein the immunoconjugate is administered at a dosage of 2 to 4 mg/kg. 22. The method of claim 20, wherein the immunoconjugate is administered in a volume of 1, 2 or 3 ml or less. 23. The method of claim 20, wherein a maintenance dose of the immunoconjugate is administered subcutaneously after the immunoconjugate is administered intravenously to the same subject.

Details for Patent 10,206,918

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	01/15/1974		2032-12-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	12/27/1984		2032-12-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/15/1985		2032-12-13
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	02/16/1990		2032-12-13