Claims for Patent: 9,797,907

Summary for Patent: 9,797,907

Title:	Isolation, detection, diagnosis and/or characterization of circulating Trop-2-positive cancer cells
Abstract:	Described herein are compositions and methods of use of anti-Trop-2 antibodies or antigen-binding fragment thereof to isolate, enrich, detect, diagnose and/or characterize circulating tumor cells (CTCs) from patients with a Trop-2 positive cancer. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. The compositions and methods are of use to detect, diagnose and/or treat metastatic Trop-2.sup.+ cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, rectum, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer.
Inventor(s):	Goldenberg; David M. (Mendham, NJ), Hansen; Hans J. (Picayune, MS), Chang; Chien-Hsing (Downingtown, PA)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	15/135,758
Patent Claims:	1. A method of treating Trop-2.sup.+ tumors consisting of: a) exposing an anti-Trop-2 antibody or antigen-binding fragment thereof to blood from a subject suspected of having a Trop-2.sup.+ cancer; b) allowing the anti-Trop-2 antibody or fragment thereof to bind to Trop-2.sup.+ circulating tumor cells (CTCs); c) detecting CTCs bound to the anti-Trop-2 antibody or fragment thereof; and d) treating the subject with an anti-Trop-2 antibody conjugated to at least one therapeutic agent. 2. A method of treating Trop-2.sup.+ tumors consisting of: a) exposing an anti-Trop-2 antibody or antigen-binding fragment thereof to blood from a human subject suspected of having a Trop-2.sup.+ cancer; b) allowing the anti-Trop-2 antibody or fragment thereof to bind to Trop-2.sup.+ circulating tumor cells (CTCs); c) detecting CTCs bound to the anti-Trop-2 antibody or fragment thereof; d) analyzing the copy number of Trop-2 in the CTCs; and e) treating the human subject with an anti-Trop-2 antibody conjugated to at least one therapeutic agent. 3. The method of claim 2, wherein the presence of Trop-2.sup.+ CTCs with a high copy number of Trop-2, wherein a high copy number is 3 or more per cell, is predictive of response to a therapeutic anti-Trop-2 antibody. 4. A method of treating Trop-2.sup.+ tumors consisting of: a) exposing an anti-Trop-2 antibody or antigen-binding fragment thereof to blood from a human subject suspected of having a Trop-2.sup.+ cancer; b) allowing the anti-Trop-2 antibody or fragment thereof to bind to Trop-2.sup.+ circulating tumor cells (CTCs); c) detecting CTCs bound to the anti-Trop-2 antibody or fragment thereof; d) treating the human subject with an anti-Trop-2 antibody conjugated to at least one therapeutic agent; and e) monitoring the presence of Trop-2.sup.+ CTCs in the circulation to determine the response of the tumor to therapeutic anti-Trop-2 antibody. 5. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of an antibody, an antibody fragment, a drug, a toxin, a hormone, an immunomodulator, a pro-apoptotic agent, an anti-angiogenic agents, a boron compound, a photoactive agent and a radionuclide. 6. The method of claim 5, wherein the drug is selected from the group consisting of an anthracycline, a camptothecin, a tubulin inhibitor, a maytansinoid, a calicheamycin, an auristatin, a nitrogen mustard, an ethylenimine derivative, an alkyl sulfonate, a nitrosourea, a triazene, a folic acid analog, a taxane, a COX-2 inhibitor, a pyrimidine analog, a purine analog, an antibiotic, an enzyme inhibitor, an epipodophyllotoxin, a platinum coordination complex, a vinca alkaloid, a substituted urea, a methyl hydrazine derivative, an adrenocortical suppressant, a hormone antagonist, an antimetabolite, an alkylating agent, an antimitotic, an anti-angiogenic agent, a tyrosine kinase inhibitor, an mTOR inhibitor, a heat shock protein (HSP90) inhibitor, a proteosome inhibitor, an HDAC inhibitor, and a pro-apoptotic agent. 7. The method of claim 5, 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, DM1, DM3, DM4, doxorubicin, 2-pyrrolinodoxorubicine (2-PDox), a pro-drug form of 2-PDox (pro-2-PDox), cyano-morpholino doxorubicin, doxorubicin glucuronide, endostatin, epirubicin glucuronide, erlotinib, estramustine, epidophyllotoxin, erlotinib, entinostat, estrogen receptor binding agents, etoposide (VP 16), 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, lapatinib, lenolidamide, leucovorin, LFM-A13, lomustine, mechlorethamine, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, monomethylauristatin F (MMAF), monomethylauristatin D (MMAD), monomethylauristatin E (MMAE), navelbine, neratinib, nilotinib, nitrosurea, olaparib, plicomycin, procarbazine, paclitaxel, PCI-32765, pentostatin, PSI-341, raloxifene, semustine, SN-38, sorafenib, streptozocin, SU11248, sunitinib, tamoxifen, temazolomide, transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vatalanib, vinorelbine, vinblastine, vincristine, vinca alkaloids and ZD1839. 8. The method of claim 5, wherein the drug is selected from the group consisting of SN-38, pro-2-pyrrolinodoxorubicin (pro-2-PDox), paclitaxel, calichemicin, DM1, DM3, DM4, MMAE, MMAD and MMAF. 9. The method of claim 1, wherein the cancer is resistant to treatment with at least one anti-cancer therapy. 10. The method of claim 1, wherein the cancer is pancreatic cancer. 11. The method of claim 5, 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.67Ga, .sup.75Br, .sup.75Se, .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.105Ru, .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.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.224Ac, .sup.225Ac, .sup.255Fm and .sup.227Th. 12. The method of claim 5, wherein the toxin is selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin. 13. The method of claim 5, wherein the immunomodulator is selected from the group consisting of a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), an interleukin, erythropoietin and thrombopoietin. 14. The method of claim 13, wherein the cytokine is selected from the group consisting of human growth hormone, N-methionyl human growth hormone, bovine growth hormone, 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, tumor necrosis factor-.alpha., tumor necrosis factor-.beta., mullerian-inhibiting substance, mouse gonadotropin-associated peptide, inhibin, activin, vascular endothelial growth factor, integrin, thrombopoietin (TPO), NGF-.beta., platelet-growth factor, TGF-.alpha., TGF-.beta., insulin-like growth factor-I, insulin-like growth factor-II, erythropoietin (EPO), osteoinductive factors, interferon-.alpha., interferon-.beta., interferon-.gamma., macrophage-CSF (M-CSF), IL-1, IL-l.alpha., 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-25, LIF, FLT-3, angiostatin, thrombospondin, endostatin, tumor necrosis factor and lymphotoxin. 15. The method of claim 1, wherein the anti-Trop-2 antibody or fragment thereof binds to the same epitope as an anti-Trop-2 antibody comprising the light chain CDR sequences CDR1 (KASQDVSIAVA, SEQ ID NO:1); CDR2 (SASYRYT, SEQ ID NO:2); and CDR3 (QQHYITPLT, SEQ ID NO:3) and the heavy chain CDR sequences CDR1 (NYGMN, SEQ ID NO:4); CDR2 (WINTYTGEPTYTDDFKG, SEQ ID NO:5) and CDR3 (GGFGSSYWYFDV, SEQ ID NO:6).

Details for Patent 9,797,907

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2035-04-22