C10RF32 antibodies, and uses thereof for treatment of cancer
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-016/00
A61K-039/00
C07K-016/28
C07K-016/30
A61K-031/675
A61K-039/395
A61K-045/06
A61K-049/00
A61N-005/06
A61N-005/10
G01N-033/574
출원번호
US-0360694
(2013-01-31)
등록번호
US-9617336
(2017-04-11)
국제출원번호
PCT/IL2013/050087
(2013-01-31)
국제공개번호
WO2013/114367
(2013-08-08)
발명자
/ 주소
Cojocaru, Gady S.
Rotman, Galit
Levine, Zurit
Dassa, Liat
Levi, Ofer
Briante, Raffaella
Singh, Shweta
Watson, Susan R.
Pergam, Tania
출원인 / 주소
COMPUGEN LTD
대리인 / 주소
Graeser Associates International Inc
인용정보
피인용 횟수 :
0인용 특허 :
150
초록
This invention relates to C1ORF32-specific antibodies, antibody fragments, alternative scaffolds, conjugates and compositions comprising same, for treatment of cancer.
대표청구항▼
1. A method of a treating a subject for cancer, comprising determining if the cancer expresses one or more C1ORF32 polypeptides on the cancer cells or in immune cells infiltrating the cancer cells congregated as a tumor, wherein the C1ORF32 polypeptides have a sequence selected from the group consis
1. A method of a treating a subject for cancer, comprising determining if the cancer expresses one or more C1ORF32 polypeptides on the cancer cells or in immune cells infiltrating the cancer cells congregated as a tumor, wherein the C1ORF32 polypeptides have a sequence selected from the group consisting of SEQ ID Nos: 1, 7, 9, 13, and 17; administering to the subject, having an increase in C1ORF32 polypeptide level on the cancer cell or in immune cells infiltrating the cancer cells congregated as a tumor, a monoclonal or polyclonal antibody or an antigen binding fragment thereof comprising an antigen binding site that binds specifically to any one of the C1ORF32 polypeptides having the sequence of any one of SEQ ID Nos: 1, 7, 9, 13, and 17, wherein the cancer is selected from the group consisting of Thyroid Carcinoma, carcinoma of the esophagus, Invasive Ductal breast Carcinoma, breast comedocarcinoma, breast Medullary Carcinoma Grade 2, ovarian cancer selected from the group consisting of Serous and Mucinous, Granular cell tumor, Surface epithelial-stromal tumor (Adenocarcinoma), cystadenocarcinoma and Endometrioid tumor; kidney cancer selected from the group consisting of Clear cell carcinoma, Chromophobe adenoma, and sarcomatoides carcinoma; prostate adenocarcinoma having a Gleason score of 5 or higher, stage I to III prostate adenocarcinoma, Benign prostatic hyperplasia, stage II and III hepatocellular carcinoma, malignant hepatoma, fibrolamellar hepatocellular carcinoma, pseudoglandular (adenoid) hepatocellular carcinoma, pleomorphic (giant cell) hepatocellular carcinoma, clear cell HCC, Cholangiocarcinoma, pancreas cancer selected from Ductal and Mucinous Adenocarcinoma, Islet cell carcinoma, familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC), Exocrine pancreas cancers, ductal adenocarcinoma, denosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells, Low- to intermediate-grade neuroendocrine carcinomas and pancreatic carcinoid tumors, stage IV malignant melanoma, Lentigo maligna melanoma, Superficial spreading melanoma, Acral lentiginous melanoma, Mucosal melanoma, Nodular melanoma, Polypoid melanoma, Desmoplastic melanoma, Amelanotic melanoma, Soft-tissue melanoma, Osteogenic sarcoma, Chondrosarcoma, Leiomyosarcoma, Angiosarcoma, Askin's Tumor, Ewing's sarcoma, Kaposi's sarcoma, Liposarcoma, Malignant fibrous histiocytoma, Rhabdomyosarcoma, Neurofibrosarcoma, Hodgkin's lymphoma, B-cell Lymphoma, Mantle cell lymphoma (MCL), T-cell Lymphoma, Endometroid Adenocarcinoma, Bladder Transitional Cell carcinoma, Small Cell Lung Cancer, Non Small Cell Lung Cancer, Large-cell lung carcinoma, testicular seminoma, moderate to poorly differentiated Colo-rectal adenocarcinoma, and spinal cord tumor; and measuring an increase in interferon-gamma production of T-cells in the subject after administration of the monoclonal or polyclonal antibody or fragment. 2. The method of claim 1, wherein said administering said monoclonal or polyclonal antibody or an antigen binding fragment thereof comprises administering said monoclonal or polyclonal antibody or an antigen binding fragment thereof in a pharmaceutical composition. 3. The method of claim 1, further comprising administering an additional therapy to the subject, wherein the additional therapy is radiation therapy, additional antibody therapy, chemotherapy, photodynamic therapy, surgery or combination therapy with conventional drugs. 4. The method of claim 3, wherein said additional therapy is selected from the group consisting of immunosuppressants, cytotoxic drugs, peptides, pepti-bodies, small molecules, chemotherapeutic agents, cytotoxic and cytostatic agents, immunological modifiers, interferons, interleukins, immunostimulatory growth hormones, cytokines, vitamins, minerals, aromatase inhibitors, RNAi, Histone Deacetylase Inhibitors, and proteasome inhibitors. 5. The method of claim 4, wherein said additional therapy is selected from the group consisting of bevacizumab, erbitux, paclitaxel, cisplatin, vinorelbine, docetaxel, gemcitabine, temozolomide, irinotecan, 5FU, carboplatin, folic acid, Gemcitabine, Oxaliplatin, cisplatin, carboplatin, cyclophosphamide, anthracyclines, doxorubicin, daunorubicin, taxanes, paclitaxel, docetaxel, microtubule inhibitors, vincristine, Folate antagonists, methotrexate, mTOR pathway inhibitors, temsirolimus, rapamycin, oxaliplatin, cyclophosphamide, doxorubicin, and mitoxantrone. 6. The method of claim 4, wherein said additional therapy is selected from the group consisting of histone deacetylase (HDAC) inhibitors, vorinostat, sodium butyrate and MS-275, Bortezomib, Vemurafenib, JAK2 inhibitors, tyrosine kinase inhibitors (TKIs), erlotinib, imatinib, sunitinib, sorafenib, anti-EGFR mAbs cetuximab, anatimumab and trastuzumab. 7. The method of claim 4, wherein said administering said additional therapy comprises administering said additional therapy together with said monoclonal or polyclonal antibody or an antigen binding fragment thereof in a pharmaceutical composition. 8. The method of claim 1, wherein the antibody is coupled to a moiety selected from a drug, a radionuclide, a fluorophore, an enzyme, a toxin, a therapeutic agent, or a chemotherapeutic agent; and wherein the detectable marker is a radioisotope, a metal chelator, an enzyme, a fluorescent compound, a bioluminescent compound or a chemiluminescent compound. 9. The method of claim 1, wherein said antibody or fragment modulates B7 related costimulation, increases T cell activation, alleviates T-cell suppression, increases cytokine secretion, increases IL-2 secretion; increases Th1 response, decreases Th2 response, promotes cancer epitope spreading, reduces inhibition of T cell activation, increases T cell response in a mammal, stimulates antigen-specific memory responses, elicits apoptosis or lysis of cancer cells, stimulates cytotoxic or cytostatic effect on cancer cells, induces direct killing of cancer cells, induces complement dependent cytotoxicity and/or antibody dependent cell-mediated cytotoxicity, and/or has CDC activity. 10. The method of claim 9, wherein said antibody or fragment increases immune response against the cancer. 11. The method of claim 10, wherein said antibody or fragment reduces activity of regulatory T lymphocytes (T-regs). 12. The method of claim 10, wherein said antibody or fragment inhibits iTreg differentiation. 13. The method of claim 10, further comprising administering one or more of therapeutic agents targeting Treg, MDSCs or both, an immunostimulatory antibody, a therapeutic cancer vaccine or adoptive cell transfer. 14. The method of claim 13, wherein the therapeutic agent targeting immunosuppressive cells Tregs, MDSCs or both is selected from antimitotic drugs, cyclophosphamide, gemcitabine, mitoxantrone, fludarabine, thalidomide, thalidomide derivatives, COX-2 inhibitors, depleting or killing antibodies that directly target Tregs through recognition of Treg cell surface receptors, anti-CD25 daclizumab, basiliximab, ligand-directed toxins, denileukin diftitox (Ontak)—a fusion protein of human IL-2 and diphtheria toxin, or LMB-2—a fusion between an scFv against CD25 and the pseudomonas exotoxin, antibodies targeting Treg cell surface receptors, TLR modulators, agents that interfere with the adenosinergic pathway, ectonucleotidase inhibitors, or inhibitors of the A2A adenosine receptor, TGF-.beta. inhibitors, chemokine receptor inhibitors, retinoic acid, all-trans retinoic acid (ATRA), Vitamin D3, phosphodiesterase 5 inhibitors, sildenafil, ROS inhibitors and nitroaspirin. 15. The method of claim 13, wherein the immunostimulatory antibody is selected from antagonistic antibodies targeting one or more of CTLA4, ipilimumab, PD-1, BMS-936558, MDX-1106, PDL-1, BMS-936559/MDX-1105, LAG-3, IMP-321, TIM-3 or BTLA, or agonistic antibodies targeting one or more of CD40, CP-870,893, CD137, BMS-663513, OX40, Anti-OX40, GITR or TRX518, or both. 16. The method of claim 13, wherein the therapeutic cancer vaccine is selected from exogenous cancer vaccines including proteins or peptides used to mount an immunogenic response to a tumor antigen, recombinant virus and bacteria vectors encoding tumor antigens, DNA-based vaccines encoding tumor antigens, proteins targeted to dendritic cells, dendritic cells and gene modified tumor cells expressing at least one of GM-CSF or Flt3-ligand. 17. The method of claim 16, wherein the therapeutic cancer vaccine comprises a dendritic-cell-based vaccine. 18. The method of claim 1, wherein said Thyroid Carcinoma is selected from one or more of Thyroid Papillary Carcinoma, Thyroid Follicular Carcinoma (preferably stage II and III), incidental papillary carcinoma (IPC), Medullary thyroid cancer, Anaplastic thyroid cancer; or wherein said carcinoma of the esophagus is a squamous cell carcinoma of the esophagus; or wherein said Invasive Ductal Carcinoma is selected from stage II to IV and/or poorly differentiated Invasive Ductal Carcinoma, and/or wherein said Medullary Carcinoma is Grade 2 Medullary Carcinoma; or wherein said Serous and Mucinous ovarian carcinoma is selected from stages Ic to IIIb Serous and Mucinous ovarian carcinoma; or wherein said kidney Clear cell carcinoma is selected from stage I to II renal Clear cell carcinoma; or wherein said hepatocellular carcinoma is selected from stage II and III hepatocellular carcinoma; or wherein said Hodgkin's lymphoma is selected from Nodular sclerosing, Mixed-cellularity subtype, Lymphocyte-rich or Lymphocytic predominance, Lymphocyte depleted and Unspecified; or wherein said B-cell Lymphoma is selected from the group consisting of Diffuse large B cell lymphoma, Follicular lymphoma, Mucosa-Associated Lymphatic Tissue lymphoma (MALT), Small cell lymphocytic lymphoma, Burkitt lymphoma, Mediastinal large B cell lymphoma, Waldenstrom macroglobulinemia, Nodal marginal zone B cell lymphoma (NMZL), Splenic marginal zone lymphoma (SMZL), Intravascular large B-cell lymphoma, Primary effusion lymphoma, Lymphomatoid granulomatosis; or wherein said T-cell Lymphoma is selected from the group consisting of Extranodal T cell lymphoma, Cutaneous T cell lymphomas: Sezary syndrome and Mycosis fungoides, Anaplastic large cell lymphoma, and Angioimmunoblastic T cell lymphoma; or wherein said Endometroid Adenocarcinoma is selected from stage I to Inc Endometroid Adenocarcinoma; or wherein said bladder Transitional Cell carcinoma is selected from stage II to IV Transitional Cell carcinoma; or wherein said Small Cell Lung Cancer is selected from stage I to IIIb Small Cell Lung Cancer, and/or wherein said Non Small Cell Lung Cancer is selected from poorly to moderately differentiated squamous and adeno carcinoma. 19. The method of claim 1, wherein said monoclonal or polyclonal antibody or antigen binding fragment thereof comprises an antigen binding site that binds specifically to any of SEQ ID NOS: 2, 3, 5, 6. 20. The method of claim 1, wherein the antibody is a chimeric antibody, humanized or primatized antibody. 21. The method of claim 1, wherein the antibody is selected from the group consisting of Fab, Fab′, F(ab′)2, F(ab′), F(ab), Fv or scFv fragment and minimal recognition unit. 22. The method of claim 1, wherein the C1ORF32 polypeptide has the sequence of SEQ ID No: 1. 23. The method of claim 1, wherein the cancer is selected from the group consisting of: wherein the cancer is selected from the group consisting of Thyroid Carcinoma, carcinoma of the esophagus, Invasive Ductal breast Carcinoma, breast comedocarcinoma, breast Medullary Carcinoma Grade 2, ovarian cancer selected from the group consisting of Serous and Mucinous, Granular cell tumor, Surface epithelial-stromal tumor (Adenocarcinoma), cystadenocarcinoma and Endometrioid tumor; kidney cancer selected from the group consisting of Clear cell carcinoma, Chromophobe adenoma, and sarcomatoides carcinoma; prostate adenocarcinoma having a Gleason score of 5 or higher, stage I to III prostate adenocarcinoma, stage II and III hepatocellular carcinoma, malignant hepatoma, fibrolamellar hepatocellular carcinoma, pseudoglandular (adenoid) hepatocellular carcinoma, pleomorphic (giant cell) hepatocellular carcinoma, clear cell HCC, Cholangiocarcinoma, pancreas cancer selected from Ductal and Mucinous Adenocarcinoma, Islet cell carcinoma, familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC), Exocrine pancreas cancers, ductal adenocarcinoma, denosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells, Low- to intermediate-grade neuroendocrine carcinomas and pancreatic carcinoid tumors, Lentigo maligna melanoma, Superficial spreading melanoma, Acral lentiginous melanoma, Mucosal melanoma, Nodular melanoma, Polypoid melanoma, Desmoplastic melanoma, Amelanotic melanoma, Soft-tissue melanoma, Chondrosarcoma, Leiomyosarcoma, Angiosarcoma, Askin's Tumor, Ewing's sarcoma, Kaposi's sarcoma, Liposarcoma, Malignant fibrous histiocytoma, Rhabdomyosarcoma, Neurofibrosarcoma, Mantle cell lymphoma (MCL), T-cell Lymphoma, Endometroid Adenocarcinoma, Bladder Transitional Cell carcinoma, testicular seminoma, moderate to poorly differentiated Colo-rectal adenocarcinoma, and spinal cord tumor.
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이 특허에 인용된 특허 (150)
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