Patent application EP19169818A (EP), filed 2019-04-17
Publication number: EP3725322A1
Title: ONCOLYTIC ADENOVIRAL VECTOR EXPRESSING GRANZYME AND PERFORIN
Abstract: [0001]    The present invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to a use of said vectors in the manufacture of a medicament for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing granzyme and perforin in a cell and increasing anti-tumor effect and induction of specific immune response in a subject, as well as uses of the oncolytic adenoviral vector of the invention for producing transgenes in a cell and increasing anti-tumor effect and generation of specific immune response in a subject.
IPC codes: A61K  35/   761            A I
A61K  48/    00            A I
C07K  14/    47            A I
C12N  15/    86            A I
C12N   9/    64            A I
Claims: number: 1
text: An oncolytic adenoviral vector comprising an adenovirus serotype 5 (Ad5) nucleic acid backbone, a 24 bp deletion (D24) in the Rb binding constant region 2 of E1, a nucleic acid sequence encoding granzyme and a nucleic acid sequence encoding perforin.
number: 2
text: The oncolytic adenoviral vector according to claim 1, wherein the nucleic acid sequence encoding granzyme is located at the E3 region and the nucleic acid sequence encoding perforin is located between the L5 and E4 polyA signals.
number: 3
text: The oncolytic adenoviral vector according to claim 1 or 2, wherein the nucleic acid sequence encoding granzyme is under CMV promoter.
number: 4
text: The oncolytic adenoviral vector according to any one of claims 1-3, wherein the nucleic acid sequence encoding perforin is under RSV promoter.
number: 5
text: The oncolytic adenoviral vector according to any one of claims 1-4, wherein the nucleic acid sequence encoding granzyme and the nucleic acid sequence encoding perforin are connected with IRES.
number: 6
text: The oncolytic adenoviral vector according to any one of claims 1, 2 or 5, wherein the nucleic acid sequence encoding perforin and the nucleic acid sequence encoding granzyme are under E3 promoter.
number: 7
text: The oncolytic adenoviral vector according to any one of claims 1-6, wherein granzyme is Granzyme B is and perforin is Perforin1.
number: 8
text: The oncolytic adenoviral vector according to any one of claims 1-7 comprising a native E1 A promoter.
number: 9
text: The oncolytic adenoviral vector according to any one of claims 1-8 further comprising an Ad5/3 chimerism as a capsid modification.
number: 10
text: The oncolytic adenoviral vector according to any one of claims 1-4 or 6-9 comprising a nucleotide sequence having at least 70% identity to SEQ ID NO: 1 or according to any one of claims 1-9 comprising a nucleotide sequence having at least 70% identity to SEQ ID NO:2.
number: 11
text: A cell comprising the adenoviral vector according to any one of claims 1-10.
number: 12
text: A pharmaceutical composition comprising the adenoviral vector according to any one of claims 1-10.
number: 13
text: The adenoviral vector according to any one of claims 1-10 for use in the treatment of cancer or in the manufacture of a medicament for treating cancer in a subject.
number: 14
text: The adenoviral vector for use according to claim 13, wherein the cancer is selected from a group consisting of nasopharyngeal cancer, synovial cancer, hepatocellular cancer, renal cancer, cancer of connective tissues, melanoma, lung cancer, bowel cancer, colon cancer, rectal cancer, colorectal cancer, brain cancer, throat cancer, oral cancer, liver cancer, bone cancer, pancreatic cancer, choriocarcinoma, gastrinoma, pheochromocytoma, prolactinoma, T-cell leukemia/lymphoma, neuroma, von Hippel-Lindau disease, Zollinger-Ellison syndrome, adrenal cancer, anal cancer, bile duct cancer, bladder cancer, ureter cancer, brain cancer, oligodendroglioma, neuroblastoma, meningioma, spinal cord tumor, bone cancer, osteochondroma, chondrosarcoma, Ewing's sarcoma, cancer of unknown primary site, carcinoid, carcinoid of gastrointestinal tract, fibrosarcoma, breast cancer, Paget's disease, cervical cancer, colorectal cancer, rectal cancer, esophagus cancer, gall bladder cancer, head cancer, eye cancer, neck cancer, kidney cancer, Wilms' tumor, liver cancer, Kaposi's sarcoma, prostate cancer, lung cancer, testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, oral cancer, skin cancer, mesothelioma, multiple myeloma, ovarian cancer, endocrine pancreatic cancer, glucagonoma, pancreatic cancer, parathyroid cancer, penis cancer, pituitary cancer, soft tissue sarcoma, retinoblastoma, small intestine cancer, stomach cancer, thymus cancer, thyroid cancer, trophoblastic cancer, hydatidiform mole, uterine cancer, endometrial cancer, vagina cancer, vulva cancer, acoustic neuroma, mycosis fungoides, insulinoma, carcinoid syndrome, somatostatinoma, gum cancer, heart cancer, lip cancer, meninges cancer, mouth cancer, nerve cancer, palate cancer, parotid gland cancer, peritoneum cancer, pharynx cancer, pleural cancer, salivary gland cancer, tongue cancer and tonsil cancer.
number: 15
text: The adenoviral vector for use according to claim 13 or 14, wherein the treatment of cancer in a subject is conducted through an intratumoral, intramuscular, intra-arterial, intravenous, intrapleural, intravesicular, intracavitary or peritoneal injection, or an oral administration.
number: 16
text: The adenoviral vector for use according to claim 15, wherein the injection or the administration is conducted several times during the treatment period, or wherein an oncolytic adenoviral vector having a different fiber knob of the capsid compared to the vector of the earlier treatment is used.
number: 17
text: The adenoviral vector for use according to any one of claims 13-16, wherein the treatment of cancer in a subject further comprises an administration of a checkpoint inhibitor, verapamil or another calcium channel blocker, autophagy inducing agents, temozolomide, chemotherapy or anti-CD20 therapy or other approaches for blocking of neutralizing antibodies, substances capable to downregulating regulatory T-cells in a subject.
number: 18
text: A method of producing granzyme and perforin in a cell in vitro, wherein the method comprises:
number: 19
text: A use of the oncolytic adenoviral vector according to any one of claims 1-10 for producing granzyme and perforin in a cell in vitro.
Office action: search_report, dated 2020-10-21
Rejection reasons: inventive_step_epc_56
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Final disposition: pending (2020-10-21)