Claims for Patent: 10,653,793

Summary for Patent: 10,653,793

Title:	Antibody-drug conjugates and uses thereof
Abstract:	The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to Trop-2 or CEACAM5 and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 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. Surprisingly, the immunoconjugate is effective to treat cancers that are refractory to or relapsed from irinotecan.
Inventor(s):	Goldenberg; David M. (Mendham, NJ), Govindan; Serengulam V. (Summit, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	16/143,680
Patent Claims:	1. A method of treating metastatic breast cancer comprising administering to a human patient with a Trop-2 positive metastatic breast cancer an immunoconjugate sacituzumab govitecan (IMMU-132) wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 10 mg/kg. 2. The method of claim 1, wherein the cancer is a solid tumor and the treatment results in a reduction in tumor size of at least 15%, at least 20%, at least 30%, or at least 40%. 3. The method of claim 1, further comprising reducing in size or eliminating the metastases. 4. The method of claim 1, wherein the immunoconjugate dosage is administered to the human subject 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. 5. The method of claim 4, wherein the cycle is repeated 4, 6, 8, 10, 12, 16 or 20 times. 6. 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. 7. The method of claim 6, wherein the immunoconjugate is administered simultaneously with the one or more therapeutic modalities. 8. The method of claim 6, wherein the immunoconjugate is administered sequentially with the one or more therapeutic modalities. 9. The method of claim 6, wherein the unconjugated antibody is a checkpoint inhibitor antibody. 10. The method of claim 9, wherein the checkpoint inhibitor antibody is selected from the group consisting of pembrolizumab, nivolumab, pidilizumab, durvalumab (MEDI4736), atexolizumab (MPDL3280A), tremelimumab and ipilimumab. 11. The method of claim 6, wherein the chemotherapy is performed 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, cisplatin, Cox-2 inhibitors, irinotecan (CPT-11), SN-38, carboplatin, cladribine, camptothecans, cyclophosphamide, crizotinib, cytarabine, dacarbazine, dasatinib, dinaciclib, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicin (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, erlotinib, estramustine, epipodophyllotoxin, erlotinib, 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, transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vatalanib, vinorelbine, vinblastine, vincristine, vinca alkaloids and ZD1839.

Details for Patent 10,653,793

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2032-12-13
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2032-12-13
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2032-12-13
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2032-12-13
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2032-12-13
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2032-12-13