Claims for Patent: 8,821,868

Summary for Patent: 8,821,868

Title:	Anti-pancreatic cancer antibodies
Abstract:	Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The subject antibodies show a number of novel and useful therapeutic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. In preferred embodiments, the antibodies bind to pancreatic cancer mucins. The antibodies and fragments are of use for the detection, diagnosis and/or treatment of cancer, such as pancreatic cancer. The antibodies, such as PAM4 antibodies, bind to a PAM4 antigen that shows unique cell and tissue distributions compared with other known antibodies such as CA19.9, DUPAN2, SPAN1, Nd2, B72.3, and Le.sup.a and Le(y) antibodies that bind to the Lewis antigens.
Inventor(s):	Goldenberg; David M. (Mendham, NJ), Hansen; Hans J. (Picayune, MS), Chang; Chien-Hsing (Downingtown, PA), Gold; David V. (Metuchen, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	13/911,667
Patent Claims:	1. A method of treating pancreatic cancer, comprising administering to a subject with pancreatic cancer an antibody construct comprising at least one humanized or human anti-pancreatic cancer antibody or antigen-binding fragment thereof that can bind to a linear peptide comprising the amino acid sequence WTWNITKAYPLP (SEQ ID NO:29) or to a cyclic peptide comprising the amino acid sequence ACPEWWGTTC (SEQ ID NO:30). 2. The method of claim 1, wherein the anti-pancreatic cancer antibody or fragment thereof binds to pancreatic cancer cells and does not bind to normal pancreatic tissue or pancreatitis or benign pancreatic tissue. 3. The method of claim 2, wherein the anti-pancreatic cancer antibody binds to PanIN-1A, PanIN-1B, PanIN-2, invasive pancreatic adenocarcinoma, pancreatic carcinoma, mucinous cyst neoplasms (MCN), intrapancreatic mucinous neoplasms (IPMN) and intraductal papillary mucinous neoplasia. 4. The method of claim 3, wherein the anti-pancreatic cancer antibody or antigen-binding fragment thereof binds to 80% or more of human invasive pancreatic adenocarcinoma, intraductal papillary mucinous neoplasia, PanIN-1A, PanIN-1B and PanIN-2. 5. The method of claim 1, wherein the antibody construct is a DNL (dock and lock) construct comprising: a) at least one humanized or human anti-pancreatic cancer antibody or antigen-binding fragment thereof that can bind to a linear peptide comprising the amino acid sequence WTWNITKAYPLP (SEQ ID NO:29) or to a cyclic peptide comprising the amino acid sequence ACPEWWGTTC (SEQ ID NO:30); and b) a second antibody or antigen-binding fragment thereof attached to the at least one chimeric, humanized or human anti-pancreatic cancer antibody or antigen-binding fragment thereof. 6. The method of claim 5, wherein each humanized or human anti-pancreatic cancer antibody fragment is a Fab fragment attached to a DDD2 (SEQ ID NO:34) sequence and the second antibody fragment is a Fab fragment attached to an AD2 (SEQ ID NO:36) sequence and wherein a dimer of the DDD2 sequence binds to the AD2 sequence to form the DNL construct. 7. The method of claim 5, wherein the second antibody or antigen-binding fragment thereof binds to a tumor associated antigen (TAA) or a hapten. 8. The method of claim 7, wherein the TAA is selected from the group consisting of a Lewis antigen, Le(y), carcinoembryonic antigen (CEACAM5), CEACAM6, colon-specific antigen-p (CSAp), MUC-1, MUC-2, MUC-3, MUC-4, MUC-5ac, MUC-16, MUC-17, HLA-DR, CD40, CD74, CD80, CD138, HER2/neu, EGFR, EGP-1, EGP-2, an angiogenesis factor, VEGF, PlGF, insulin-like growth factor, carbonic anhydrase IX, tenascin, platelet-derived growth factor, IL-6, an oncogene product, bcl-2, Kras, p53, cMET and a tumor necrosis factor. 9. The method of claim 5, wherein the second antibody is selected from the group consisting of CA19.9, DUPAN2, SPAN1, Nd2, B72.3, CC49, hA20, hA19, hIMMU31, hLL1, hLL2, hMu-9, hL243, hMN-3, hMN-14, hMN-15, hRS7 and hR1. 10. The method of claim 7, wherein the hapten is HSG (histamine-succinyl-glycine) or In-DTPA (diethylenetriaminepentaacetic acid). 11. The method of claim 10, further comprises administering to the subject a targetable construct comprising at least one HSG or In-DTPA moiety, wherein the targetable construct is attached to at least one therapeutic agent. 12. The method of claim 1, wherein the anti-pancreatic cancer antibody or antigen-binding fragment thereof is a naked antibody or fragment thereof. 13. The method of claim 12, further comprising administering at least one therapeutic agent to the individual. 14. The method of claim 1, wherein the anti-pancreatic cancer antibody or antigen-binding fragment thereof is conjugated to at least one therapeutic agent. 15. The method of claim 14, wherein the therapeutic agent is selected from the group consisting of a radionuclide, an immunomodulator, a hormone, a hormone antagonist, an enzyme, an anti-sense oligonucleotide, an siRNA, an enzyme inhibitor, a photoactive therapeutic agent, a cytotoxic agent, a drug, a pro-drug, a toxin, an angiogenesis inhibitor and a pro-apoptotic agent. 16. The method of claim 15, wherein the drug is selected from the group consisting of nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas, gemcitabine, triazenes, folic acid analogs, anthracyclines, taxanes, COX-2 inhibitors, pyrimidine analogs, purine analogs, antibiotics, enzyme inhibitors, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, hormone antagonists, endostatin, taxols, camptothecins, SN-38, doxorubicin, antimetabolites, alkylating agents, antimitotics, anti-angiogenic agents, tyrosine kinase inhibitors, mTOR inhibitors, heat shock protein (HSP90) inhibitors, proteosome inhibitors, HDAC inhibitors, pro-apoptotic agents, methotrexate and CPT-11. 17. The method of claim 15, 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. 18. The method of claim 15, 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 interleukin (IL), an interferon (IFN), a stem cell growth factor, erythropoietin, thrombopoietin, tumor necrosis factor (TNF), granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-.alpha., interferon-.beta., interferon-.gamma. and the stem cell growth factor designated "S1 factor". 19. The method of claim 18, 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, glycoprotein follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), placenta growth factor (PlGF), 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, TNF-.alpha. and LT (lymphotoxin). 20. The method of claim 15, wherein the radionuclide is selected from the group consisting of .sup.111In, .sup.177Lu, .sup.212Bi, .sup.213Bi, .sup.211At, .sup.62Cu, .sup.67Cu, .sup.90Y, .sup.125I, .sup.131I, .sup.32P, .sup.33P, .sup.47Sc, .sup.111Ag, .sup.67Ga, .sup.143Pr, .sup.153Sm, .sup.161Tb, .sup.166Dy, .sup.166Ho, .sup.186Re, .sup.188Re, .sup.189Re, .sup.212Pb, .sup.223Ra, .sup.225Ac, .sup.59Fe, .sup.75Se, .sup.77As, .sup.89Sr, .sup.99Mo, .sup.105Rh, .sup.109Pd, .sup.143Pr, .sup.149Pm, .sup.169Er, .sup.194Ir, .sup.198Au, .sup.199Au, .sup.211Pb, .sup.58Co, .sup.80mBr, .sup.99mTc, .sup.103mRh, .sup.109Pt, .sup.119Sb, .sup.189mOs, .sup.192Ir, .sup.219Rn, .sup.215Po, .sup.221Fr, .sup.217At, .sup.255Fm, .sup.11C, .sup.13N, .sup.15O, .sup.75Br, .sup.224Ac, .sup.126I, .sup.133I, .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.143Pr, .sup.57Co, .sup.51Cr, .sup.75Se, .sup.20Tl, .sup.76Br and .sup.169Yb. 21. The method of claim 15, wherein the radionuclide is .sup.90Y. 22. The method of claim 15, wherein the anti-pancreatic cancer antibody or antigen-binding fragment thereof is conjugated to a radionuclide and method further comprises administering a radiosensitizing agent to the subject before the anti-pancreatic cancer antibody or fragment is administered.

Details for Patent 8,821,868

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2022-06-14
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2022-06-14