Claims for Patent: 9,879,227

Summary for Patent: 9,879,227

Title:	Diffusible factors and cancer cells
Abstract:	The present invention relates to modified cancer cells that are defective in the production of diffusible factors (e.g., growth factors), and to the use of such cells for impairing the growth of a population of human cells, in particular wherein the cells are human cancer cells and the population of cells is a neoplasm, tumor or cancer. The invention preferably comprises the step of modifying tumor cells by deleting or modifying endogenous genes that code for (or affect the production of), diffusible growth factors that promote cell survival and proliferation.
Inventor(s):	Archetti; Marco (Perugia, IT)
Assignee:
Application Number:	14/441,075
Patent Claims:	1. A method of impairing the rate of growth of a population of cancer cells in a cancer tumor in a patient, wherein said population of cancer cells in the cancer tumor produce one or more diffusible growth factors which promote said population of cancer cells' maintenance or growth, the method comprising the step(s) of administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising a population of genetically modified cancer cells, wherein the modified cancer cells are cancer cells which are autologous or allogenic to the patient and are from the same type of cancer as the cancer tumor and which have been modified to eliminate production of said one or more diffusible growth factors which promote the maintenance or growth of the population of cancer cells in the cancer tumor, wherein the elimination of the production of one or more diffusible growth factors has been achieved by a modification of the gene encoding a diffusible growth factor or the promoter for a diffusible growth factor or by knocking out the gene encoding a diffusible growth factor, wherein the population of modified cancer cells are inserted by direct injection into the cancer tumor, wherein the population of cancer cells in the cancer tumor consists essentially of cancer cells producing the one or more diffusible growth factors, and wherein the rate of growth of the population of cancer cells in the cancer tumor in the patient is impaired compared to the rate of growth of the population of cancer cells in the cancer tumor before the population of modified cancer cells were inserted by direct injection into the cancer tumor. 2. The method as claimed in claim 1, wherein the genetically modified cancer cells are from a cancer tumor selected from the group consisting of a carcinoma, sarcoma, lymphoma, germ cell tumour and blastoma. 3. The method as claimed in claim 1, wherein the genetically modified cancer cells are from a cancer tumor selected from the group consisting of: Adrenocortical carcinoma, Aids-related cancers, Aids-related lymphoma, Anal cancer, Appendix cancer, Astrocytoma, Basal cell carcinoma, Bile duct cancer, Bladder cancer, Bone cancer, Brain cancer, Brainstem glioma, Breast cancer, Bronchial adenoma, Bronchial carcinoid, Burkitt lymphoma, Cancer of the bone-marrow, Cancer of unknown primary site, Carcinoid tumor, Carcinoma of unknown primary, Carcinoma of unknown primary site, Central nervous system lymphoma, Cerebellar astrocytoma, Cervical cancer, Colon cancer, Desmoplastic small round cell tumor, Endometrial cancer, Endometrial uterine cancer, Ependymoma, Esophageal cancer, Ewing family of tumor (sarcoma), Ewing's sarcoma, Extracranial germ cell tumor, Extragonadal germ cell tumor, Extrahepatic bile duct cancer, Eye cancer, Gallbladder cancer, Gastric (stomach) cancer, Gastric carcinoid, Gastrointestinal carcinoid tumor, Gastrointestinal stromal tumor, Germ cell tumor, Gestational trophoblastic tumor, Glioma of the brain stem, Head and neck cancer, Heart cancer, Hepatocellular (liver) cancer, Hodgkin lymphoma, Hypopharyngeal cancer, Hypothalamic and visual pathway glioma, Hypothalamic glioma, Intraocular (eye) melanoma, Intraocular melanoma, Islet cell carcinoma, Islet cell pancreatic cancer, Kaposi sarcoma, Kidney cancer (renal cell cancer), Laryngeal cancer, Lip and oral cavity cancer, Liposarcoma, Liver cancer, Lymphoma, Malignant fibrous histiocytoma, Malignant fibrous histiocytoma of bone, Malignant glioma, Medulloblastoma, Melanoma, Merkel cell carcinoma, Merkel cell skin carcinoma, Mesothelioma, Metastatic squamous neck cancer with occult primary, Mouth cancer, Multiple endocrine neoplasia syndrome, Multiple myeloma, Mycosis fungoides, Myelodysplastic syndrome, Myeloproliferative disease, Nasal cavity and paranasal sinus cancer, Nasopharyngeal carcinoma, Neuroblastoma, Non-hodgkin lymphoma, Non-small cell lung cancer, Oral cancer, Oropharyngeal cancer, Osteosarcoma, Ovarian cancer, Ovarian epithelial cancer (surface epithelial-stromal tumor), Ovarian germ cell tumor, Ovarian low malignant potential tumor, Pancreatic cancer, Paranasal sinus and nasal cavity cancer, Parathyroid cancer, Penile cancer, Pharyngeal cancer, Pheochromocytoma, Pineal astrocytoma, Pineal germinoma, Pineoblastoma and supratentorial primitive neuroectodermal tumor, Pituitary adenoma, Plasma cell neoplasia, Plasma cell neoplasm, Pleuropulmonary blastoma, Primary central nervous system lymphoma, Prostate cancer, Rectal cancer, Renal cell carcinoma (kidney cancer), Retinoblastoma, Rhabdomyosarcoma, Salivary gland cancer, Sarcoma of unknown primary site, Sezary syndrome, Skin cancer (melanoma), Skin cancer (nonmelanoma), Small cell lung cancer, Small intestine cancer, Soft tissue sarcoma, Squamous cell carcinoma, Squamous neck cancer with occult primary, Stomach cancer, Supratentorial primitive neuroectodermal tumor, T-cell lymphoma, cutaneous, Testicular cancer, Throat cancer, Thymoma, Thyroid cancer, Transitional cell cancer of the renal pelvis and ureter, Urethral cancer, Uterine sarcoma, Vaginal cancer, Visual pathway and hypothalamic glioma, Vulvar cancer, Waldenstrom macroglobulinemia, and Wilms tumor (kidney cancer). 4. The method as claimed in claim 1, wherein the genetically modified cancer cells are human cancer cells which have been modified to eliminate production of said one or more diffusible growth factors which promote the maintenance or growth of the population of cancer cells. 5. The method as claimed in claim 1, wherein the diffusible growth factor is one which promotes cell division, cell growth or resistance against apoptosis. 6. The method as claimed in claim 1, wherein the diffusible growth factor is selected from the group consisting of: Chemokines CCL1, CCL2/MCP-1, CCL3/MIP-1.alpha., CCL4/MIP-1.beta., CCL5/RANTES, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CXCL1/KC, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8/IL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CXCL15, CXCL16, CXCL17, CX3CL1, XCL1, XCL2; TNF (Tumor Necrosis Factor): TNFA, Lymphotoxin (TNFB/LTA, TNFC/LTB), TNFSF4, TNFSF5/CD40LG, TNFSF6, TNFSF7, TNFSF8, TNFSF9, TNFSF10, TNFSF11, TNFSF13B, EDA; Interleukin: IL1, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IL9, IL10, IL11, IL12, IL13, IL14, IL15, IL16, IL17, IL18, IL19, IL20, IL21, IL22, IL23, IL24, IL25, IL26, IL27, IL28, IL29, IL30, IL31, IL32, IL33, IL34, IL35, IL36, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21, IFNB1, IFNK, IFNW1, IFNG, IL1A/IL1F1, IL1B/IL1F2, 1Ra/IL1F3, IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, IL1F10, 33/IL1F11, 18/IL1G, IL17/IL25 (IL17A), CSF1 (macrophage colony-stimulating factor), CSF2 (Granulocyte macrophage colony-stimulating factors, GM-CSF, sargramostim), CSF3 (Granulocyte colony-stimulating factors, G-CSF, filgrastim); Endothelial growth factor, VEGF-A, VEGF-B, VEGF-C, VEGF-D, PGF; Epidermal growth factor, Heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor-.alpha. (TGF-.alpha.), Amphiregulin (AR), Epiregulin (EPR), Epigen, Betacellulin (BTC), neuregulin-1 (NRG1), neuregulin-2 (NRG2), neuregulin-3 (NRG3), neuregulin-4 (NRG4); Fibroblast growth factor: FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22, FGF23; Nerve growth factor, Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin-3 (NT-3), Neurotrophin 4/5 (NT-4/5); Platelet-derived growth factor: PDGFA, PDGFB, PDGFC, PDGFD; TGF (transforming growth factor): TGF-.beta.1, TGF-.beta.2, TGF-.beta.3, Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10, BMP15), Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15), EGF, HB-EGF; Adipokines: Chemerin, Monocyte chemotactic protein-1 (MCP-1), Plasminogen activator inhibitor-1 (PAI-1), Retinol binding protein 4 (RBP4), Tumor necrosis factor-alpha (TNF.alpha.), Visfatin, Leptin, Adiponectin, Apelin; Wnt: Wnt1, Wnt2, Wnt2B, Wnt3, Wnt3A, Wnt4, Wnt5A, Wnt5B, Wnt6, Wnt7A, Wnt7B, Wnt8A, Wnt8B, Wnt9A, Wnt9B, Wnt10A, Wnt10B, Wnt11, Wnt16; Hedgehog proteins: DHH, IHH, SHH; Somatomedin: Somatomedin A (insulin-like growth factor 2), Somatomedin B, Somatomedin C (insulin-like growth factor 1); Semaphorins (SEMA3A, SEMA3B, SEMA3C, SEMA3D, SEMA3E, SEMA3F, SEMA3G, SEMA4A, SEMA4B, SEMA4C, SEMA4D, SEMA4F, SEMA4G, SEMA5A, SEMA5B, SEMA6A, SEMA6B, SEMA6C, SEMA6D, SEMA7A); Interferon: IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17; Endothelin (EDN1 EDN2 EDN3); CCN intercellular signaling protein: CCN1 (CYR61), CCN2 (CTGF, connective tissue growth factor), CCN3 (NOV, nephroblastoma overexpressed protein), CCN4 (WISP', WNT1 inducible signaling pathway protein-1), CCN5 (WISP2, WNT1 inducible signaling pathway protein-2), and CCN6 (WISP3, WNT1 inducible signaling pathway protein-3). 7. The method as claimed in claim 1, wherein the modification of the gene encoding the diffusible growth factor or the promoter for the diffusible growth factor comprises an insertion, deletion or substitution of one or more nucleotides in the gene or promoter. 8. The method as claimed in claim 1, wherein prior to administering the population of genetically modified cancer cells, the population of cancer cells in the cancer tumor consists of cancer cells producing the one or more diffusible growth factors. 9. A method of impairing the rate of growth of a population of cancer cells in a cancer tumor in a patient, the method comprising the steps of: genetically modifying cancer cells obtained from a sample of cancer cells from the patient to eliminate production of one or more diffusible growth factors which promote the maintenance or growth of the population of cancer cells; and administering the genetically modified cancer cells to the patient directly to the cancer tumor from which the cancer cells were obtained, wherein the population of cancer cells in the cancer tumor consists essentially of cancer cells producing the one or more diffusible growth factors, and wherein the rate of growth of the population of cancer cells in the cancer tumor in the patient is impaired compared to the rate of growth of the population of cancer cells in the cancer tumor before the modified cancer cells were administered to the patient directly to the cancer tumor. 10. The method as claimed in claim 9, wherein prior to administering the genetically modified cancer cells, the population of cancer cells in the cancer tumor consists of cancer cells producing the one or more diffusible growth factors.

Details for Patent 9,879,227

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	02/20/1991		2032-11-09
Amgen, Inc.	NEUPOGEN	filgrastim	Injection	103353	06/28/2000		2032-11-09
Partner Therapeutics, Inc.	LEUKINE	sargramostim	For Injection	103362	03/05/1991		2032-11-09
Partner Therapeutics, Inc.	LEUKINE	sargramostim	Injection	103362	03/05/1991		2032-11-09