# US 12,622,935 B2 · Modified oncolytic adenoviruses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,622,935 B2 - Document ID: US12622935B2 - Status: Granted - Kind: B2 - Application number: 17/040,017 - Filed: 2019-03-19 - Published: 2021-01-21 - Granted: 2026-05-12 - Earliest claimed: 2018-03-21 - Assignees: Valo Therapeutics Oy - Applicants: Valo Therapeutics Oy - Inventors: Tuuli Ranki; Sari Pesonen; Petri Priha; Erkko Ylösmäki; Vincenzo Cerullo; Beatriz Martins - Web page: https://patentgrep.com/patent/US12622935B2 ## CPC - A61K 35/761: Adenovirus - A61K 39/0011: {Cancer antigens} - C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)} - C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)} - C12N 15/86: Viral vectors - A61K 39/001186: {MAGE} - A61K 39/001188: {NY-ESO} - A61K 2039/6031: {Proteins} - A61K 2039/876: {Skin, melanoma} - A61P 35/00: Antineoplastic agents - C12N 2710/10321: Viruses as such, e.g. new isolates, mutants or their genomic sequences - C12N 2710/10332: Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent - C12N 2710/10343: viral genome or elements thereof as genetic vector - C12N 2710/10371: Demonstrated in vivo effect - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The invention concerns a modified replication competent, oncolytic adenovirus; a pharmaceutical composition comprising same; and a method of treating cancer using same. ## Claims ### Claim 1 A modified replicating adenovirus (Ad) of serotype 5 (Ad5) having lytic activity in target cancer cells comprising: a) a E1A gene deletion wherein the deletion is of nucleotides encoding amino acids 923-946 with respect to the wild-type Ad5 sequence; b) a 5/3 chimeric substitution of a knob of an adenoviral fiber protein wherein the knob of Ad5 is replaced by the knob of a serotype 3 Ad (Ad3); c) a 14.7k gene deletion wherein the deletion is of base pairs 30448-30834 with respect to the wild type Ad5 sequence and wherein the sequence GGA GGA GAT GAC TGA (SEQ ID NO: 1) is substituted for GGA GGA GAC GAC TGA (SEQ ID NO: 2); d) a gp19k gene deletion and a 7.1k gene deletion wherein the deletions are of base pairs 28541-29211 with respect to the wild type Ad5 sequence; and e) an insertion of a molecule encoding OX40L and a molecule encoding CD40L in the E3B region, replacing the 14.7K gene deletion, wherein the molecule encoding CD40L is inserted immediately downstream from the molecule encoding OX40L using a 2A processing site, and the 2A processing site is preceded by a cleavage site and a SGSG-linker (SEQ ID NO: 28) to ensure effective cleavage of OX40L and CD40L. ### Claim 2 (depends on 1) The modified adenovirus according to claim 1 wherein said OX40L is human OX40L. ### Claim 3 (depends on 1) The modified adenovirus according to claim 1 wherein said CD40L is human CD40L. ### Claim 4 (depends on 1) The modified adenovirus according to claim 1 wherein said 2A processing site is a foot-and-mouth disease virus 2A processing site (F2A) or a porcine teschovirus-1 2A processing site. ### Claim 5 (depends on 1) The modified adenovirus according to claim 1 wherein a molecule encoding the whole cDNA of each of OX40L and CD40L is inserted into said adenovirus. ### Claim 6 (depends on 1) A pharmaceutical composition comprising at least one modified replication-competent and target cell lytic adenovirus according to claim 1 and a suitable carrier. ### Claim 7 (depends on 6) The pharmaceutical composition according to claim 6 wherein said composition is formulated for intratumoral, intramuscular, intra-arterial, intravenous, intrapleural, intravesicular, intradermal, intracavitary or peritoneal injection, or an oral administration. ### Claim 8 (depends on 1) A method of treating cancer in a patient comprising administering to a patient an effective amount of a composition comprising at least one modified replication-competent and target cell lytic adenovirus according to claim 1. ### Claim 9 (depends on 8) The method of treating cancer according to claim 8 wherein the at least one modified replication-competent and target cell lytic adenovirus is administered with a cell checkpoint modulator. ### Claim 10 (depends on 9) The method of treating cancer according to claim 9 wherein the checkpoint modulator is an anti-PD1 molecule, an anti-PD-L1 molecule or an anti-CTLA-4 molecule. ### Claim 11 (depends on 8) The method according to claim 8 wherein said cancer is selected form the list comprising or 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, oligodendroglioma, neuroblastoma, meningioma, spinal cord tumor, osteochondroma, chondrosarcoma, Ewing's sarcoma, cancer of unknown primary site, carcinoid, carcinoid of gastrointestinal tract, fibrosarcoma, breast cancer, Paget's disease, cervical cancer, esophagus cancer, gall bladder cancer, head cancer, eye cancer, neck cancer, kidney cancer, Wilms' tumor, liver cancer, Kaposi's sarcoma, prostate cancer, testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, skin cancer, mesothelioma, multiple myeloma, ovarian cancer, endocrine pancreatic cancer, glucagonoma, 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.