Claims for Patent: 7,901,680

Summary for Patent: 7,901,680

Title:	Dock-and-lock (DNL) vaccines for cancer therapy
Abstract:	The present invention concerns methods and compositions for forming anti-cancer vaccine DNL complexes using dock-and-lock technology. In preferred embodiments, the anti-cancer vaccine DNL complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the DNL complex. The anti-cancer vaccine DNL complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138.sup.negCD20.sup.+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.
Inventor(s):	Chang; Chien-Hsing (Downingtown, PA), Goldenberg; David M. (Mendham, NJ)
Assignee:	IBC Pharmaceuticals, Inc. (Morris Plains, NJ)
Application Number:	12/544,476
Patent Claims:	1. A DNL (dock and lock) complex comprising: a) an antibody moiety that binds to a dendritic cell antigen selected from the group consisting of CD209 (DC-SIGN), CD34, CD74, CD205, TLR 2 (toll-like receptor 2), TLR 4, TLR 7, TLR 9, BDCA-2, BDCA-3, BDCA-4, and HLA-DR, wherein the antibody moiety is attached to a DDD (dimerization and docking domain) moiety, wherein said DDD moiety has a peptide sequence from a dimerization and docking domain of protein kinase A selected from the group consisting of the amino acid sequence of SEQ ID NO: 10 and SEQ ID NO: 11; and b) a xenoantigen moiety attached to an AD (anchor domain) moiety, wherein the AD moiety has a peptide sequence from an anchoring domain of an AKAP (A-kinase anchoring protein) selected from the group consisting of the amino acid sequence of SEQ ID NO: 13; SEQ ID NO: 12; SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 21; SEQ ID NO: 22; SEQ ID NO: 23; SEQ ID NO: 24; SEQ ID NO: 25; SEQ ID NO: 26; SEQ ID NO: 27 and SEQ ID NO: 28; wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex and wherein the DNL complex induces an immune response in vivo. 2. The DNL complex of claim 1, wherein the antibody moiety is an anti-CD74 antibody or antigen-binding fragment thereof. 3. The DNL complex of claim 1, wherein the xenoantigen is selected from the group consisting of carbonic anhydrase IX, alpha-fetoprotein, .alpha.-actinin-4, ART-4, B7, BAGE, CA125, CAMEL, CAP-1, CASP-8/m, CCCL19, CCCL21, CD1, CD1a, CD2, CD3, CD4, CD5, CD8, CD11A, CD14, CD15, CD16, CD18, CD19, 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, CDC27, CDK-4/m, CDKN2A, colon-specific antigen-p (CSAp), CEA (CEACAM5), CEACAM6, DAM, EGFR, EGFRvIII, EGP-1, EGP-2, ELF2-M, Ep-CAM, Flt-1, Flt-3, folate receptor, G250 antigen, GAGE, gp100, GROB, HLA-DR, HM1.24, human chorionic gonadotropin (HCG) and its subunits thereof, HER2/neu, HMGB-1, hypoxia inducible factor (HIF-1), HSP70-2M, HST-2, Ia, IGF-1R, IFN-.gamma., IFN-.alpha., IFN-.beta., 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, insulin growth factor-1 (IGF-1), KC4-antigen, KS-1-antigen, KS1-4, Le-Y, LDR/FUT, macrophage migration inhibitory factor (MIF), MAGE, MAGE-3, MART-1, MART-2, NY-ESO-1, TRAG-3, mCRP, MCP-1, MIP-1A, MIP-1B, MIF, MUC1, MUC2, MUC3, MUC4, MUM-1/2, MUM-3, NCA66, NCA95, NCA90, placental growth factor, p53, prostatic acid phosphatase, PSA, PRAME, PSMA, PlGF, ILGF, ILGF-1R, IL-6, IL-25, RS5, RANTES, T101, SAGE, S100, survivin, survivin-2B, TAC, TAG-72, tenascin, TRAIL receptor, TNF-.alpha., Tn antigen, Thomson-Friedenreich antigens, tumor necrosis antigen, VEGFR, ED-B fibronectin, WT-1, 17-1A-antigen, complement factors C3, C3a, C3b, C5a, C5, an angiogenesis marker, bcl-2, bcl-6, Kras, and cMET. 4. The DNL complex of claim 2, wherein the xenoantigen is CD20. 5. The DNL complex of claim 1, further comprising disulfide bonds between the DDD and AD moieties. 6. The DNL complex of claim 1, wherein the DDD moiety consists of the amino acid sequence of SEQ ID NO:10. 7. The DNL complex of claim 6, wherein the DDD moiety consists of the amino acid sequence of SEQ ID NO:11. 8. The DNL complex of claim 1, wherein the AD moiety consists of the amino acid sequence of SEQ ID NO:13. 9. The DNL complex of claim 1, wherein the antibody moiety is selected from the group consisting of an IgG antibody and an antigen binding fragment thereof. 10. The DNL complex of claim 9, wherein the antibody moiety is a humanized or chimeric LL1 anti-CD74 antibody or antigen-binding fragment thereof comprising the light chain variable complementarity-determining region (CDR) sequences CDR1 (RSSQSLVHRNGNTYLH; SEQ ID NO:1), CDR2 (TVSNRFS; SEQ ID NO:2), and CDR3 (SQSSHVPPT; SEQ ID NO:3) and the heavy chain variable region CDR sequences CDR1 (NYGVN; SEQ ID NO:4), CDR2 (WINPNTGEPTFDDDFKG; SEQ ID NO:5), and CDR3 (SRGKNEAWFAY; SEQ ID NO:6). 11. The DNL complex of claim 4, wherein the CD20 xenoantigen moiety comprises the amino acid sequence of SEQ ID NO:7. 12. The DNL complex of claim 4, wherein the anti-CD74 antibody moiety attached to a DDD moiety forms a first fusion protein and the CD20 xenoantigen moiety attached to an AD moiety forms a second fusion protein. 13. The DNL complex of claim 12, wherein the DNL complex is capable of inducing an immune response against CD138.sup.negCD20.sup.+ MM stem cells. 14. A DNL complex comprising: c) an antibody moiety that binds to a dendritic cell antigen selected from the group consisting of CD209 (DC-SIGN), CD34, CD74, CD205, TLR 2 (toll-like receptor 2), TLR 4, TLR 7, TLR 9, BDCA-2, BDCA-3, BDCA-4, and HLA-DR, wherein the antibody moiety is attached to an AD moiety, wherein the AD moiety has a peptide sequence from an anchoring domain of an AKAP (A-kinase anchoring protein) selected from the group consisting of the amino acid sequence of SEQ ID NO: 13; SEQ ID NO: 12; SEQ ID NO:19; SEQ ID NO:20; SEQ ID NO:21; SEQ ID NO:22; SEQ ID NO:23; SEQ ID NO:24; SEQ ID NO:25; SEQ ID NO:26; SEQ ID NO:27 and SEQ ID NO:28; and d) a xenoantigen moiety attached to a DDD moiety, wherein said DDD moiety has a peptide sequence from a dimerization and docking domain of protein kinase A selected from the group consisting of the amino acid sequence of SEQ ID NO: 10 and SEQ ID NO: 11; wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex and wherein the DNL complex induces an immune response in vivo. 15. The DNL complex of claim 14, wherein each heavy chain of the antibody moiety is attached at its C-terminal end to an AD moiety and the complex comprises one antibody moiety and four xenoantigen moieties. 16. The DNL complex of claim 14, wherein the antibody moiety binds to CD74. 17. The DNL complex of claim 16, wherein the antibody moiety is a humanized or chimeric LL1 anti-CD74 antibody or antigen-binding fragment thereof comprising the light chain variable complementarity-determining region (CDR) sequences CDR1 (RSSQSLVHRNGNTYLH; SEQ ID NO:1), CDR2 (TVSNRFS; SEQ ID NO:2), and CDR3 (SQSSHVPPT; SEQ ID NO:3) and the heavy chain variable region CDR sequences CDR1 (NYGVN; SEQ ID NO:4), CDR2 (WINPNTGEPTFDDDFKG; SEQ ID NO:5), and CDR3 (SRGKNEAWFAY; SEQ ID NO:6). 18. The DNL complex of claim 14, wherein the xenoantigen is selected from the group consisting of carbonic anhydrase IX, alpha-fetoprotein, .alpha.-actinin-4, ART-4, B7, BAGE, CA125, CAMEL, CAP-1, CASP-8/m, CCCL19, CCCL21, CD1, CD1a, CD2, CD3, CD4, CD5, CD8, CD11A, CD14, CD15, CD16, CD18, CD19, 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, CDC27, CDK-4/m, CDKN2A, colon-specific antigen-p (CSAp), CEA (CEACAM5), CEACAM6, DAM, EGFR, EGFRvIII, EGP-1, EGP-2, ELF2-M, Ep-CAM, Flt-1, Flt-3, folate receptor, G250 antigen, GAGE, gp100, GROB, HLA-DR, HM1.24, human chorionic gonadotropin (HCG) and its subunits thereof, HER2/neu, HMGB-1, hypoxia inducible factor (HIF-1), HSP70-2M, HST-2, Ia, IGF-1R, IFN-.gamma., IFN-.alpha., IFN-.beta., 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, insulin growth factor-1 (IGF-1), KC4-antigen, KS-1-antigen, KS 1-4, Le-Y, LDR/FUT, macrophage migration inhibitory factor (MIF), MAGE, MAGE-3, MART-1, MART-2, NY-ESO-1, TRAG-3, mCRP, MCP-1, MIP-1A, MIP-1B, MIF, MUC1, MUC2, MUC3, MUC4, MUM-1/2, MUM-3, NCA66, NCA95, NCA90, placental growth factor, p53, prostatic acid phosphatase, PSA, PRAME, PSMA, PlGF, ILGF, ILGF-1R, IL-6, IL-25, RS5, RANTES, T101, SAGE, S100, survivin, survivin-2B, TAC, TAG-72, tenascin, TRAIL receptor, TNF-.alpha., Tn antigen, Thomson-Friedenreich antigen, tumor necrosis antigen, VEGFR, ED-B fibronectin, WT-1, 17-1A-antigen, complement factors C3, C3a, C3b, C5a, C5, bcl-2, bcl-6, Kras, and cMET. 19. The DNL complex of claim 14, wherein the xenoantigen is CD20.

Details for Patent 7,901,680

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	January 15, 1974		2029-08-20
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	December 27, 1984		2029-08-20
Ferring Pharmaceuticals Inc.	NOVAREL	chorionic gonadotropin	For Injection	017016	February 15, 1985		2029-08-20