Claims for Patent: 10,137,196

Summary for Patent: 10,137,196

Title:	Dosages of immunoconjugates of antibodies and SN-38 for improved efficacy and decreased toxicity
Abstract:	The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. In preferred embodiments, the antibody may be an hRS7 antibody. The methods and compostions are of use to treat Trop-2 expressing cancers in human patients, preferably in patients who are resistant to or relapsed from at least one prior anti-cancer therapy, more preferably in patients who are resistant to or relapsed from treatment with irinotecan. The immunoconjugate may be administered at a dosage of 3 mg/kg to 18 mg/kg, preferably 8 to 12 mg/kg, more preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size and reduce or eliminate metastases. Preferred tumors to treat with the subject immunoconjugates include triple-negative breast cancer, HER+, ER+, progesterone+ breast cancer, metastatic non-small-cell lung cancer, a metastatic small-cell lung cancer and metastatic pancreatic cancer.
Inventor(s):	Govindan; Serengulam V. (Summit, NJ), Goldenberg; David M. (Mendham, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	15/069,208
Patent Claims:	1. A method of treating colorectal, lung, stomach, urinary bladder, renal, pancreatic, breast, ovarian, uterine, esophageal, urothelial or prostatic cancer comprising administering to a human patient with colorectal, lung, stomach, urinary bladder, renal, pancreatic, breast, ovarian, uterine, esophageal, urothelial or prostatic cancer an immunoconjugate comprising sacituzumab govitecan; wherein the immunoconjugate is administered at a dosage of between 6 mg/kg and 16 mg/kg, wherein the patient has failed to respond to at least one other therapy, prior to treatment with the immunoconjugate. 2. The method of claim 1, wherein the dosage is selected from the group consisting of 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 11 mg/kg, 12 mg/kg, and 16 mg/kg. 3. The method of claim 1, wherein the treatment results in a reduction in tumor size of at least 15%, at least 20%, at least 30%, or at least 40%. 4. The method of claim 1, wherein the cancer is selected from the group consisting of triple-negative breast cancer, HER+, ER+, progesterone+breast cancer, metastatic non-small-cell lung cancer, a metastatic small-cell lung cancer, metastatic urothelial cancer and metastatic pancreatic cancer. 5. The method of claim 1, wherein the patient has relapsed from or failed to respond to treatment with irinotecan, prior to administration of the immunoconjugate. 6. The method of claim 1, wherein the cancer is refractory to other therapies but responds to the immunoconjugate. 7. The method of claim 1, wherein the cancer is metastatic. 8. The method of claim 7, further comprising reducing in size or eliminating the metastases. 9. The method of claim 1, wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 12 mg/kg. 10. The method of claim 1, wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 10 mg/kg. 11. The method of claim 1, further comprising administering to the patient at least one other anti-cancer therapy selected from the group consisting of surgery, external radiation, radioimmunotherapy, immunotherapy, chemotherapy, antisense therapy, interference RNA therapy, treatment with a therapeutic agent and gene therapy. 12. The method of claim 11, wherein the therapeutic agent is a drug, toxin, immunomodulator, second antibody, antigen-binding fragment of a second antibody, pro-apoptotic agent, toxin, RNase, hormone, radionuclide, anti-angiogenic agent, siRNA, RNAi, chemotherapeutic agent, cytokine, chemokine, prodrug or enzyme. 13. The method of claim 12, wherein the drug 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, celecoxib, chlorambucil, cisplatinum, Cox-2 inhibitors, irinotecan (CPT-11), SN-38, carboplatin, cladribine, camptothecans, crizotinib, cyclophosphamide, cytarabine, dacarbazine, dasatinib, dinaciclib, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicine (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, floxuridine (FUdR), 3',5'-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, farnesyl-protein transferase inhibitors, flavopiridol, 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. 14. The method of claim 12, wherein the wherein the immunomodulator is selected from the group consisting of cytokines, lymphokines, monokines, stem cell growth factors, lymphotoxins, hematopoietic factors, colony stimulating factors (CSF), interferons (IFN), parathyroid hormone, thyroxine, insulin, proinsulin, relaxin, prorelaxin, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), hepatic growth factor, prostaglandin, fibroblast growth factor, prolactin, placental lactogen, OB protein, transforming growth factor (TGF), TGF-.alpha., TGF-.beta., insulin-like growth factor (IGF), erythropoietin, thrombopoietin, tumor necrosis factor (TNF), TNF-.alpha., TNF-.beta., mullerian-inhibiting substance, mouse gonadotropin-associated peptide, inhibin, activin, vascular endothelial growth factor, integrin, interleukin (IL), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-.alpha., interferon-.beta., interferon-.gamma., S1factor, IL-1, IL-1 cc, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18 IL-21, IL-23, IL-25, LIF, kit-ligand, FLT-3, angiostatin, thrombospondin and endostatin. 15. The method of claim 12, wherein the radionuclide is selected from the group consisting of .sup.11C, .sup.13N, .sup.15O, .sup.32P, .sup.33P, .sup.47Sc, .sup.51Cr, .sup.57Co, .sup.58Co, .sup.59Fe, .sup.62Cu, .sup.67Cu, .sup.67Ga, .sup.68Ga, .sup.75Br, .sup.75Se, .sup.76Br, .sup.77As, .sup.77Br, .sup.80mBr, .sup.89Sr, .sup.90Y, .sup.95Ru, .sup.97Ru, .sup.99Mo, .sup.99mTc, .sup.103mRh, .sup.103Ru, .sup.105Rh, .sup.107Hg, .sup.109Pd, .sup.109Pt, .sup.111Ag, .sup.111In, .sup.113mIn, .sup.119Sb, .sup.121mTe, .sup.122mTe, .sup.125I, .sup.125mTe, .sup.126I, .sup.131I, .sup.133I, .sup.142Pr, .sup.143Pr, .sup.149Pm, .sup.152Dy, .sup.153Sm, .sup.161Ho, .sup.161Tb, .sup.165Tm, .sup.166Dy, .sup.166Ho, .sup.167Tm, .sup.168Tm, .sup.169Er, .sup.169Yb, .sup.177Lu, .sup.186Re, .sup.188Re, .sup.189mOs, .sup.189Re, .sup.192Ir, .sup.194Ir, .sup.197Pt, .sup.198Au, .sup.199Au, .sup.201Tl, .sup.203Hg, .sup.211At, .sup.211Bi, .sup.211Pb, .sup.212Bi, .sup.212Pb, .sup.213Bi, .sup.215Po, .sup.217At, .sup.219Rn, .sup.221Fr, .sup.223Ra, .sup.225Ac, .sup.227Th and .sup.255Fm. 16. The method of claim 12, wherein the toxin is selected from the group consisting of ricin, abrin, ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin. 17. A method of treating colorectal, lung, stomach, urinary bladder, renal, pancreatic, breast, ovarian, uterine, esophageal, urothelial or prostatic cancer comprising administering to a human patient with colorectal, lung, stomach, urinary bladder, renal, pancreatic, breast, ovarian, uterine, esophageal, urothelial or prostatic cancer an immunoconjugate comprising sacituzumab govitecan; wherein the immunoconjugate is administered at a dosage of between 6mg/kg and 16 mg/kg, wherein the patient is resistant to or has relapsed from therapy with a camptothecin, prior to treatment with the immunoconjugate. 18. The method of claim 17, wherein the camptothecin is selected from the group consisting of irinotecan, topotecan and SN-38. 19. The method of claim 17, wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 12 mg/kg. 20. The method of claim 17, wherein the immunoconjugate is administered at a dosage of between 8 mg/kg and 10 mg/kg.

Details for Patent 10,137,196

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
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2032-12-13
Gilead Sciences, Inc.	TRODELVY	sacituzumab govitecan-hziy	For Injection	761115	04/22/2020		2032-12-13