Claims for Patent: 9,492,566

Summary for Patent: 9,492,566

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:	14/844,772
Patent Claims:	1. A method of treating cancer comprising administering to a human patient with a Trop-2 positive cancer an immunoconjugate comprising SN-38 conjugated to an anti-Trop-2 antibody or antigen-binding fragment thereof; wherein the cancer is resistant to or relapsed from treatment with irinotecan, wherein the immunoconjugate is administered at a dosage of between 4 mg/kg and 16 mg/kg. 2. The method of claim 1, wherein the dosage is selected from the group consisting of 4 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 12 mg/kg, and 16 mg/kg. 3. The method of claim 1, wherein the dosage is between 8 mg/kg to 10 mg/kg. 4. The method of claim 1, wherein the antibody is hRS7 (anti-Trop-2). 5. The method of claim 1, wherein the cancer is a gastrointestinal cancer. 6. The method of claim 5, wherein the cancer is colorectal cancer, esophageal cancer or gastric cancer. 7. The method of claim 1, wherein the cancer is colorectal, lung, stomach, urinary bladder, renal, breast, ovarian, uterine or prostatic cancer. 8. The method of claim 1, wherein the cancer is metastatic. 9. 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%. 10. The method of claim 8, further comprising reducing in size or eliminating the metastases. 11. The method of claim 1, wherein the cancer is refractory to other therapies but responds to the immunoconjugate. 12. The method of claim 1, wherein there is a CL2A linker between the SN-38 and the antibody and the structure of the immunoconjugate is MAb-CL2A-SN-38. ##STR00001## 13. The method of claim 1, wherein there are 6 or more SN-38 molecules attached to each antibody molecule. 14. The method of claim 1, wherein there are 6-8 SN-38 molecules attached to each antibody molecule. 15. The method of claim 1, wherein there are 7-8 SN-38 molecules attached to each antibody molecule. 16. The method of claim 1, wherein the antibody is an IgG1 or IgG4 antibody. 17. The method of claim 1, wherein the antibody has an allotype selected from the group consisting of G1m3, G1m3,1, G1m3,2, G1m3,1,2, nG1m1, nG1m1,2 and Km3 allotypes. 18. 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. 19. The method of claim 18, wherein the cycle is repeated 4, 6, 8, 10, 12, 16 or 20 times. 20. 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. 21. The method of claim 20, wherein the drug, toxin or chemotherapeutic agent is 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, celebrex, chlorambucil, cisplatin (CDDP), Cox-2 inhibitors, irinotecan (CPT-11), SN-38, carboplatin, cladribine, camptothecans, cyclophosphamide, crizotinib, cytarabine, dacarbazine, dasatinib, dinaciclib, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicine (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, erlotinib, estramustine, epidophyllotoxin, 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 (an aqueous form of DTIC), transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vatalanib, vinorelbine, vinblastine, vincristine, vinca alkaloids and ZD1839. 22. The method of claim 1, wherein the cancer is a metastatic colon cancer and the patient has failed FOLFIRI or FOLFOX chemotherapy prior to administration of the immunoconjugate.

Details for Patent 9,492,566

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