Claims for Patent: 7,238,786

Summary for Patent: 7,238,786

Title:	Monoclonal antibody cPAM4
Abstract:	This invention relates to monovalent and multivalent, monospecific antibodies and to monovalent and multivalent, multispecific antibodies. One embodiment of these antibodies has one or more identical binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these antibodies has two or more binding sites where these binding sites have affinity towards different epitopes on a target antigen or different target antigens, or have affinity towards a target antigen and a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional antibodies in a host. More specifically, the present invention relates to the tumor-associated antibody designated PAM4. The invention further relates to chimeric PAM4 antibodies, and the use of such antibodies in diagnosis and therapy.
Inventor(s):	Gold; David V. (Metuchen, NJ), Goldenberg; David M. (Mendham, NJ), Hansen; Hans J. (Picayune, MS)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	10/461,878
Patent Claims:	1. A chimeric antibody or fragment thereof that binds to a domain located between the amino terminus and the start of a repeat domain of MUC1, wherein said antibody or fragment thereof comprises the PAM4 V.sub.k polypeptide sequence encoded by SEQ ID NO:8 and the PAM4 V.sub.h polypeptide sequence encoded by SEQ ID NO:10. 2. A chimeric antibody or fragment thereof, comprising the complementarity-determining regions (CDRs) and framework regions (FR) of a murine PAM4 monoclonal antibody (MAb) and the light and heavy chain constant regions of a human antibody, wherein the CDRs of the light chain variable region of the chimeric PAM4 MAb comprise CDR1 (SASSSVSSSYLY, (SEQ ID NO: 1); CDR2 (STSNLAS, SEQ ID NO:2); and CDR3 (HQWNRYPYT, SEQ ID NO:3); and the CDRs of the heavy chain variable region of the chimeric PAM4 MAb comprise CDR1 (SYVLH, SEQ ID NO:4); CDR2 (YINPYNDGTQYNEKFKG, SEQ ID NO:5)and CDR3 (GFGGSYGFAY, SEQ ID NO:6). 3. A cancer cell targeting diagnostic or therapeutic conjugate comprising an antibody component that comprises an antibody or fragment thereof of claim 2 that binds to said cell, wherein said antibody component is bound to at least one diagnostic/detection and/or at least one therapeutic agent. 4. The diagnostic conjugate of claim 3, wherein said diagnostic/detection agent is selected from the group comprising a radionuclide, a contrast agent, and a photoactive diagnostic/detection agent. 5. The diagnostic conjugate of claim 4, wherein said diagnostic agent is a radionuclide. 6. The diagnostic conjugate of claim 5, wherein said radionuclide has an energy between 20 and 4,000 keV. 7. The diagnostic conjugate of claim 6, wherein said radionuclide is a gamma-, beta- or a positron-emitting isotope. 8. The diagnostic conjugate of claim 7, wherein said radionuclide is selected from the group consisting of .sup.110In, .sup.111In, .sup.77Lu, .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.52mMn, .sup.55Co, .sup.72As, .sup.75Br, .sup.76Br, .sup.82mRb, .sup.83Sr, or other gamma-, beta-, or positron-emitters. 9. The diagnostic conjugate of claim 4, wherein said diagnostic/detection agent is a contrast agent. 10. The diagnostic conjugate of claim 9 wherein said contrast agent is a paramagnetic ion. 11. The diagnostic conjugate of claim 10, wherein said paramagnetic ion is a metal comprising 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) or erbium (III). 12. The diagnostic conjugate of claim 9, wherein said contrast agent is a metal comprising lanthanum (III), gold (III), lead (II) or bismuth (III). 13. The diagnostic conjugate of claim 9, wherein said contrast agent is an ultrasound enhancing agent. 14. The diagnostic conjugate of claim 13, wherein said ultrasound enhancing agent is a liposome. 15. The diagnostic conjugate of claim 14, wherein said liposome is gas filled. 16. The diagnostic conjugate of claim 9, wherein said contrast agent is a radiopaque material selected from the group comprising iodine compounds, barium compounds, gallium compounds, and thallium compounds. 17. The diagnostic conjugate of claim 16, wherein said radiopaque material is selected from the group comprising barium, diatrizoate, ethiodized oil, gallium citrate, iocarmic acid, iocetamic acid, iodamide, iodipamide, iodoxamic acid, iogulamide, iohexol, iopamidol, iopanoic acid, ioprocemic acid, iosefamic acid, ioseric acid, iosulamide meglumine, iosemetic acid, iotasul, iotetric acid, iothalamic acid, iotroxic acid, ioxaglic acid, ioxotrizoic acid, ipodate, meglumine, metrizamide, metrizoate, propyliodone, and thallous chloride. 18. The diagnotic conjugate of claim 4, wherein said diagnostic/detection agent is a photactive diagnostic/detection agent. 19. The diagnostic conjugate of claim 18, wherein said photoactive diagnostic/detection agent is a fluorescent labeling compound selected from the group comprising fluorescein isothiocyanate, rhodamine, phycoerytherin, phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine. 20. The diagnostic conjugate of claim 18, wherein said photoactive diagnostic/detection agent is a chemiluminescent labeling compound selected from the group comprising luminol, isoluminol, an aromatic acridinium ester, an imidazole, an acridinium salt and an oxalate ester. 21. The diagnostic conjugate of claim 18, wherein said photoactive diagnostic/detection agent is a bioluminescent compound selected from the group comprising luciferin, luciferase and aequorin. 22. The diagnostic conjugate of claim 4, wherein said conjugate is used in intraoperative, endoscopic, or intravascular tumor diagnosis. 23. The therapeutic conjugate of claim 3, wherein said therapeutic agent is selected from the group consisting of a radionuclide, an immunomodulator, a hormone, a hormone antagonist, an enzyme, an enzyme inhibitor, an oligonucleotide, a photoactive therapeutic agent, a cytotoxic agent, an antibody, an angiogenesis inhibitor, and a combination thereof. 24. The therapeutic conjugate of claim 23, wherein said oligonucleotide is an antisense oligonucleotide. 25. The therapeutic conjugate of claim 24, wherein said oligonucleotide is an antisense oligonucleotide against an oncogene. 26. The therapeutic conjugate of claim 25, wherein said oncogene is bcl-2 or p53. 27. The therapeutic conjugate of claim 23, wherein said therapeutic agent is a cytotoxic agent. 28. The therapeutic conjugate of claim 27, wherein said cytotoxic agent is a drug or a toxin. 29. The therapeutic conjugate of claim 28, wherein said drug possesses the pharmaceutical property selected from the group consisting of antimitotic, alkylating, antimetabolite, antiangiogenic, apoptotic, alkaloid, and antibiotic agents and combinations thereof. 30. The therapeutic conjugate of claim 28, wherein said drug is selected from the group consisting of nitrogen mustards, gemcitabine, ethylenimine derivatives, alkyl sulfonates, nitrosoureas, triazenes, folic acid analogs, anthracyclines, SN-38, taxanes, COX-2 inhibitors, pyrimidine analogs, purine analogs, antibiotics, enzymes, enzyme inhibitors, epipodophyllotoxins, platinum coordination complexes, vinca alkaloids, substituted ureas, methyl hydrazine derivatives, adrenocortical suppressants, hormone antagonists, endostatin, taxols, camptothecins, doxorubicins and their analogs, antimetabolites, alkylating agents, antimitotics, antiangiogenic, apoptotoic agents, methotrexate, CPT-11, and a combination thereof. 31. The therapeutic conjugate of claim 28, wherein said toxin derived from a source selected from the group comprising an animal, a plant, and a microbial source. 32. The therapeutic conjugate of claim 28, wherein said toxin is selected from the group consisting of ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtherin toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin. 33. The therapeutic conjugate of claim 23, wherein said therapeutic agent is an immunomodulator. 34. The therapeutic conjugate of claim 33, wherein said 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), a stem cell growth factor, erythropoietin, thrombopoietin and a combination thereof. 35. The therapeutic conjugate of claim 34, wherein said lymphotoxin is tumor necrosis factor (TNF), said hematopoietic factor is an interleukin (IL), said colony stimulating factor is granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF)), said interferon is interferons-.alpha., -.beta.or -.gamma., and said stem cell growth factor is designated "S1 factor". 36. The therapeutic conjugate of claim 33, wherein said immunomodulator comprises IL-1, IL-2, IL-3, IL-6, IL-10, IL-12, IL-18, IL-21, interferon-.gamma., TNF-.alpha. or a combination thereof. 37. The therapeutic conjugate of claim 23, wherein said therapeutic agent is a radionuclide. 38. The therapeutic conjugate of claim 37 wherein said radionuclide has an energy between 60 and 700 keV. 39. The therapeutic conjugate of claim 38, wherein said radionuclide is selected from the group consisting of .sup.32P, .sup.33P, .sup.47Sc, .sup.64Cu, .sup.67Cu, .sup.67Ga, .sup.86Y, .sup.90Y, .sup.111Ag, .sup.111In, .sup.125I, .sup.131I, .sup.142Pr, .sup.153Sm, .sup.161Tb, .sup.166Dy, .sup.166Ho, .sup.177Lu, .sup.186Re, .sup.188Re, .sup.189Re, .sup.212Pb, .sup.212Bi, .sup.213Bi, .sup.211At, .sup.223Ra and .sup.225Ac, and combinations thereof. 40. The therapeutic conjugate of claim 23, wherein said therapeutic agent is a photoactive therapeutic agent. 41. The therapeutic conjugate of claim 40, wherein said photoactive therapeutic agent is selected from the group comprising chromogens and dyes. 42. The therapeutic conjugate of claim 27, wherein said therapeutic agent is an enzyme. 43. The therapeutic conjugate of claim 42, wherein said enzyme is selected from the group comprising malate dehydrogenase, staphylococcal nuclease, delta-V-steroid isomerase, yeast alcohol dehydrogenase, .alpha.-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, .beta.-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. 44. A multivalent, multispecific antibody or fragment thereof comprising a chimeric antibody or fragment thereof of claim 2 and one or more hapten binding sites having affinity towards hapten molecules. 45. The antibody or fragment thereof of claim 44, further comprising a diagnostic or therapeutic agent. 46. An antibody fusion protein or fragment thereof comprising at least two chimeric PAM4 MAbs or fragments thereof of claim 1.

Details for Patent 7,238,786

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2039-03-29