Claims for Patent: 8,945,554

Summary for Patent: 8,945,554

Title:	Class I anti-CEA antibodies and uses thereof
Abstract:	The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.
Inventor(s):	Hansen; Hans J. (Picayune, MS), Chang; Chien-Hsing (Downingtown, PA), Goldenberg; David M. (Mendham, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	14/289,066
Patent Claims:	1. A method of delivering a diagnostic or therapeutic agent comprising administering to a subject a chimeric, humanized or human Class I anti-CEA antibody or antigen-binding fragment thereof, comprising the light chain variable region CDR (complementarity determining region) sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6), wherein the Class I anti-CEA antibody or antigen-binding fragment thereof is conjugated to at least one diagnostic or therapeutic agent selected from the group consisting of an antibody, an antigen-binding antibody fragment, a cytotoxic agent, a chemotherapeutic agent, a radionuclide, boron atoms, an immunomodulator, a photoactive therapeutic agent, an immunoconjugate, an oligonucleotide, a hormone, a radiological contrast agent, a paramagnetic ion, a metal, a fluorescent label, a chemiluminescent label, and an ultrasound contrast agent. 2. The method of claim 1, wherein the therapeutic agent is a cytotoxic agent selected from the group consisting of a drug and toxin. 3. The method of claim 2, wherein the therapeutic agent is a drug that has a pharmaceutical property selected from the group consisting of antimitotic, alkylating, antimetabolite, antiangiogenic, apoptotic, alkaloid, COX-2 inhibitor and antibiotic agents. 4. The method of claim 2, wherein the therapeutic agent is a drug selected from the group consisting of nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas, triazenes, folic acid analogs, anthracyclines, taxanes, COX-2 inhibitors, pyrimidine analogs, purine analogs, antimetabolites, antibiotics, enzymes, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, antagonists, endostatin, taxols, camptothecins, oxaliplatin and doxorubicins. 5. The method of claim 2, wherein the therapeutic agent is a drug selected from the group consisting of 5-fluorouracil, aplidin, azaribine, anastrozole, anthracyclines, bendamustine, bleomycin, bortezomib, 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, cytarabine, dacarbazine, docetaxel, dactinomycin, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicin (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, estramustine, epipodophyllotoxin, estrogen receptor binding agents, etoposide (VP16), etoposide glucuronide, etoposide phosphate, floxuridine (FUdR), 3',5'-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, farnesyl-protein transferase inhibitors, gemcitabine, hydroxyurea, idarubicin, ifosfamide, L-asparaginase, lenolidamide, leucovorin, lomustine, mechlorethamine, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, navelbine, nitrosurea, plicomycin, procarbazine, paclitaxel, pentostatin, PSI-341, raloxifene, semustine, streptozocin, tamoxifen, taxol, temazolomide, transplatinum, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, vinorelbine, vinblastine, vincristine and vinca alkaloids. 6. The method of claim 2, wherein the therapeutic agent is a toxin selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), onconase, DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin and Pseudomonas endotoxin. 7. The method of claim 1, wherein the therapeutic agent is an oligonucleotide selected from the group consisting of an RNAi and a siRNA. 8. The method of claim 1, wherein the therapeutic agent is a radionuclide selected from the group consisting of .sup.111In, .sup.111At, .sup.177Lu, .sup.211Bi, .sup.212Bi, .sup.213Bi, .sup.211At, .sup.62Cu, .sup.67Cu, .sup.90Y, .sup.125I, .sup.131I, .sup.133I, .sup.32P, .sup.33P, .sup.47Sc, .sup.111Ag, .sup.67Ga, .sup.153Sm, .sup.161Tb, .sup.152Dy, .sup.166Dy, .sup.161Ho, .sup.166Ho, .sup.186Re, .sup.188Re, .sup.189Re, .sup.211Pb, .sup.212Pb, .sup.223Ra, .sup.225Ac, .sup.77As, .sup.89Sr, .sup.99Mo, .sup.105Rh, .sup.149Pm, .sup.169Er, .sup.194Ir, .sup.58Co, .sup.80mBr, .sup.99mTc, .sup.103mRh, .sup.109Pt, .sup.119Sb, .sup.189mOs, .sup.192Ir, .sup.219Rn, .sup.215Po, .sup.221Fr, .sup.255Fm, .sup.11C, .sup.13N, .sup.15O, .sup.75Br, .sup.198Au, .sup.199Au, .sup.224Ac, .sup.77Br, .sup.113mIn, .sup.95Ru, .sup.97Ru, .sup.103Ru, .sup.105Ru, .sup.107Hg, .sup.203Hg, .sup.121mTe, .sup.122mTe, .sup.125mTe, .sup.165Tm, .sup.167Tm, .sup.168Tm, .sup.197Pt, .sup.109Pd, .sup.142Pr, .sup.143Pr, .sup.161Tb, .sup.57Co, .sup.58Co, .sup.51Cr, .sup.59Fe, .sup.75Se, .sup.201Tl, .sup.76Br and .sup.169Yb. 9. The method of claim 1, wherein the therapeutic agent is an immunomodulator selected from the group consisting of a cytokine, a chemokine, a stem cell growth factor, a lymphotoxin, an hematopoietic factor, a colony stimulating factor (CSF), an interferon, erythropoietin, thrombopoietin, a tumor necrosis factor (TNF), an interleukin (IL), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF) and a stem cell growth factor designated "S1 factor". 10. The method of claim 9, wherein the therapeutic agent is a cytokine 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-1.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 LT. 11. The method of claim 9, wherein the therapeutic agent is a chemokine selected from the group consisting of RANTES, MCAF, MIP1-alpha, MIP1-Beta and IP-10. 12. The method of claim 1, wherein the diagnostic agent is a radionuclide selected from the group consisting of .sup.110In, .sup.111In, .sup.177Lu, .sup.18F, .sup.52Fe, .sup.62Cu, .sup.64Cu, .sup.67Cu, .sup.67Ga, .sup.68Ga, .sup.86Y, .sup.90Y, .sup.89Zr, .sup.94mTc, .sup.94Tc, .sup.99mTc, .sup.120I, .sup.123I, .sup.124I, .sup.125I, .sup.131I, .sup.154-158Gd, .sup.32P, .sup.11C, .sup.13N, .sup.15O, .sup.186Re, .sup.188Re, .sup.51Mn, .sup.52Mn, .sup.55Co, .sup.72As, .sup.75Br, .sup.76Br, .sup.82mRb and .sup.83Sr. 13. The method of claim 1, wherein the diagnostic agent is a paramagnetic ion selected from the group consisting of chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III), gadolinium (III), vanadium (II), terbium (III), dysprosium (III), holmium (III) and erbium (III). 14. The method of claim 1, wherein the diagnostic agent is a fluorescent label selected from the group consisting of Alexa 350, Alexa 430, AMCA, aminoacridine, BODIPY 630/650, BODIPY 650/665, BODIPY-FL, BODIPY--R6G, BODIPY-TMR, BODIPY-TRX, 5-carboxy-4',5'-dichloro-2',7'-dimethoxy fluorescein, 5-carboxy-2',4',5',7'-tetrachlorofluorescein, 5-carboxyfluorescein, 5-carboxyrhodamine, 6-carboxyrhodamine, 6-carboxytetramethyl rhodamine, Cascade Blue, Cy2, Cy3, Cy5,6-FAM, dansyl chloride, Fluorescein, HEX, 6-JOE, NBD (7-nitrobenz-2-oxa-1,3-diazole), Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, phthalic acid, terephthalic acid, isophthalic acid, cresyl fast violet, cresyl blue violet, brilliant cresyl blue, para-aminobenzoic acid, erythrosine, phthalocyanines, azomethines, cyanines, xanthines, succinylfluoresceins, rare earth metal cryptates, europium trisbipyridine diamine, a europium cryptate or chelate, diamine, dicyanins, La Jolla blue dye, allopycocyanin, allococyanin B, phycocyanin C, phycocyanin R, thiamine, phycoerythrocyanin, phycoerythrin R, REG, Rhodamine Green, rhodamine isothiocyanate, Rhodamine Red, ROX, TAMRA, TET, TRIT (tetramethyl rhodamine isothiol), Tetramethylrhodamine, and Texas Red. 15. The method of claim 1, wherein the chimeric, humanized or human Class I anti-CEA antibody or fragment thereof binds to CEACAM5, CEACAM6 and granulocytes. 16. The method of claim 1, wherein administering the Class I anti-CEA antibody or fragment thereof to a subject with cancer sensitizes the cancer to a therapeutic agent. 17. The method of claim 1, wherein the Class I anti-CEA antibody or fragment thereof comprises human antibody IgG1 constant region sequences. 18. The method of claim 1, wherein the Class I anti-CEA antibody or fragment thereof is a chimeric antibody or fragment thereof. 19. The method of claim 18, wherein the chimeric Class I anti-CEA antibody or fragment thereof comprises the variable region amino acid sequences of SEQ ID NO:9 and SEQ ID NO:10. 20. The method of claim 1, wherein Class I anti-CEA antibody or fragment thereof is a humanized antibody or fragment thereof. 21. The method of claim 20, wherein the humanized Class I anti-CEA antibody or fragment thereof comprises the amino acid sequences of SEQ ID NO:7 and SEQ ID NO:8. 22. The method of claim 20, wherein the humanized Class I anti-CEA antibody or fragment thereof comprises the light chain FR sequences of a human REI antibody and the heavy chain FR sequences of a human KOL antibody. 23. The method of claim 20, wherein the framework regions of the light and heavy chain variable regions of the humanized antibody or fragment thereof comprise at least one amino acid substitution selected from the heavy chain amino acid residues 28, 29, 30, 48 and 49 of SEQ ID NO:10 and the light chain amino acid residues 21, 47 and 60 of SEQ ID NO:9. 24. The method of claim 1, wherein the antibody fragment is selected from the group consisting of F(ab').sub.2, Fab', Fab, Fv, scFv and single domain antibody. 25. The method of claim 1, wherein the chimeric, humanized or human Class I anti-CEA antibody or antigen-binding fragment thereof is part of a bispecific or multispecific antibody. 26. The method of claim 25, wherein the bispecific antibody comprises a first chimeric, humanized or human Class I anti-CEA antibody or antigen-binding fragment thereof and a second antibody or antigen-binding fragment thereof. 27. The method of claim 25, wherein the bispecific or multispecific antibody is a fusion protein. 28. The method of claim 26, wherein the second antibody or fragment thereof binds to a tumor-associated antigen (TAA) or a hapten on a targetable construct. 29. The method of claim 28, wherein the TAA is selected from the group consisting of carbonic anhydrase IX, CCCL19, CCCL21, CSAp, CD1, CD1a, CD2, CD3, CD4, CD5, CD8, CD11A, CD14, CD15, CD16, CD18, CD19, IGF-1R, CD20, CD21, CD22, CD23, CD25, CD29, CD30, CD32b, CD33, CD37, CD38, CD40, CD40L, CD45, CD46, CD52, CD54, CD55, CD59, CD64, CD66a-e, CD67, CD70, CD74, CD79a, CD80, CD83, CD95, CD126, CD133, CD138, CD147, CD154, AFP, PSMA, CEACAM5, CEACAM6, B7, ED-B of fibronectin, Factor H, FHL-1, Flt-3, folate receptor, GROB, HMGB-1, hypoxia inducible factor (HIF), HM1.24, insulin-like growth factor-1 (ILGF-1), IFN-13, IL-2, IL-4R, IL-6R, IL-13R, IL-15R, IL-17R, IL-18R, IL-6, IL-8, IL-12, IL-15, IL-17, IL-18, IL-25, IP-10, MAGE, mCRP, MCP-1, MIP-1A, MIP-1B, MIF, MUC1, MUC2, MUC3, MUC4, MUC5, PAM4 antigen, NCA-95, NCA-90, Ia, HM1.24, EGP-1, EGP-2, HLA-DR, tenascin, Le(y), RANTES, T101, TAC, Tn antigen, Thomson-Friedenreich antigens, tumor necrosis antigens, TNF-.alpha., TRAIL receptor (R1 and R2), VEGFR, EGFR, P1GF, complement factors C3, C3a, C3b, C5a, C5 and an oncogene product. 30. The method of claim 26, wherein the second antibody is selected from the group consisting of hPAM4, hA20, hA19, hIMMU31, hLL1, hLL2, hMu-9, hL243, hMN-14, hMN-3, hRl, h679 and 734.

Details for Patent 8,945,554

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2029-09-16
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2029-09-16