Claims for Patent: 8,188,239

Summary for Patent: 8,188,239

Title:	Multivalent carriers of bi-specific antibodies
Abstract:	Provided herein are targetable constructs that are multivalent carriers of bi-specific antibodies, i.e., each molecule of a targetable construct can serve as a carrier of two or more bi-specific antibodies. Also provided are targetable complexes formed by the association of a targetable construct with two or more bi-specific antibodies. The targetable constructs and targetable complexes of the invention are incorporated into biosensors, kits and pharmaceutical compositions, and are used in a variety of therapeutic and other methods.
Inventor(s):	Hansen; Hans J. (Picayune, MS), McBride; William J. (Boonton, NJ), Qu; Zhengxing (Warren, NJ)
Assignee:	Immunomedics, Inc. (Morris Plains, NJ)
Application Number:	13/089,645
Patent Claims:	1. A composition comprising a tetravalent targetable complex comprising the structure (IgG1).sub.2-(scFv).sub.4, wherein said tetravalent targetable complex is formed by linking two IgG1-(scFv).sub.2 molecules with a targetable construct comprising four DTPA (diethylenetriamine-pentaacetic acid) residues, wherein each IgG1-(scFv).sub.2 molecule comprises a pair of heavy chains and a pair of light chains, wherein each heavy chain comprises a humanized, chimeric or human IgG1 heavy chain and an scFv, wherein said scFv is fused to the C-terminus of said IgG1 heavy chain, wherein each scFv binds to a DTPA residue and wherein greater than 75% of the complexes in the composition have a stoichiometry of two molecules of IgG1-(scFv).sub.2 and one molecule of the targetable construct. 2. The composition according to claim 1, wherein each of said scFv molecules is murine or humanized. 3. The composition according to claim 1, wherein each IgG1 is an I253A human IgG1. 4. The composition according to claim 1, wherein said targetable complex further comprises a moiety selected from the group consisting of a drug, a prodrug, an enzyme, a hormone, an immunomodulator, an oligonucleotide, a radionuclide, an image enhancing agent and a toxin. 5. The composition according to claim 4, wherein said moiety is attached to the targetable construct. 6. The composition according to claim 4, wherein said enzyme is selected from the group consisting of 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. 7. The composition according to claim 4, wherein said immunomodulator is selected from the group consisting of a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic growth factor, a colony stimulating factor (CSF), an interferon (IFN), erythropoietin and thrombopoietin. 8. The composition according to claim 4, wherein said immunomodulator is selected from the group consisting of IL-1, IL-2, IL-3, IL-6, IL-10, IL-12, IL-18, IL-21, G-CSF, GM-CSF, interferon-.gamma., interferon-.alpha., interferon-.beta., TNF-.alpha. and S1 factor. 9. The composition according to claim 4, wherein said drug is selected from the group consisting of doxorubicin, daunomycin, calicheamicin, maytansinoid, methotrexate, etoposide, CPT-11 and SN38. 10. The composition according to claim 4, wherein said radionuclide is selected from the group consisting of Ac-225, Ag-111, As-77, At-211, At-217, Au-198, Au-199, Bi-211, Bi-212, Bi-213, Br-80m, Co-58, Cu-64, Cu-67, Dy-152, Er-169, Fe-59, Fm-255, Fr-221, Ga-67, Ho-161, Ho-166, I-125, I-131, In-111, Ir-192, Ir-194, Lu-177, Mo-99, Os-189m, P-32, P-33, Pb-211, Pb-212, Pd-109, Pm-149, Po-215, Pr-142, Pr-143, Pt-109, Ra-223, Re-186, Re-188, Re-189, Rh-103m, Rh-105, Rn-219, Sb-119, Sc-47, Se-75, Sm-153, Sr-89, Tb-161, Tc-99m and Y-90. 11. The composition according to claim 1, wherein each IgG binds to a tumor-associated antigen selected from the group consisting of A3, CD1, CD1a, CD3, CD5, CD15, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD33, CD45, CD74, CD79a, CD80, NCA90, NCA95, HLA-DR, CEA, CSAp, EGFR, EGP-1, EGP-2, Ep-CAM, Ba 733, HER2/neu, KC4, KS-1, KS1-4, Le-Y, S100, MAGE, MUC1, MUC2, MUC3, MUC4, PSA, PSMA, AFP, HCG, RS5, TAG-72, tenascin, IL-6, IL-2 receptor, insulin-like growth factor-1 (IGF-1), Tn antigen, Thomson-Friedenreich antigens, tumor necrosis antigens, VEGF, 17-1A, an angiogenesis marker, a cytokine, an immunomodulator and an oncogene product. 12. The composition of claim 1, wherein the targetable complex is constructed with two IgG1 antibodies having the same specificity. 13. The composition of claim 1, wherein the targetable complex is constructed with two IgG1 antibodies having different specificities. 14. The composition according to claim 1, wherein said composition is a pharmaceutical composition.

Details for Patent 8,188,239

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2023-07-01