# US 10,501,554 B2 · Internalizing moieties for treatment of cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,501,554 B2 - Document ID: US10501554B2 - Status: Granted - Kind: B2 - Application number: 15/507,012 - Filed: 2015-08-27 - Published: 2018-05-10 - Granted: 2019-12-10 - Earliest claimed: 2014-08-27 - Assignees: Valerion Therapeutics, LLC - Applicants: Valerion Therapeutics, LLC - Inventors: Dustin D. Armstrong - Web page: https://patentgrep.com/patent/US10501554B2 ## CPC - C07K 16/30: from tumour cells - A61P 35/00: Antineoplastic agents - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/526: CH3 domain - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/71: Decreased effector function due to an Fc-modification - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract In certain embodiments, the present disclosure provides compositions and methods for treating tumors and cancer. ## Claims ### Claim 1 A method of treating a tumor in a subject in need thereof, comprising administering an antibody or antigen-binding fragment to the subject, wherein the antibody or antigen-binding fragment comprises a light chain variable (VL) domain and a heavy chain variable (VH) domain; wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; a VH CDR2 having the amino acid sequence of SEQ ID NO: 2; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3, which CDRs are according to the IMGT system; or wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 32; a VH CDR2 having the amino acid sequence of SEQ ID NO: 49; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 34, which CDRs are according to the Kabat system; and the VL domain comprises: a VL CDR1 having the amino acid sequence of SEQ ID NO: 35 or 50; a VL CDR2 having the amino acid sequence of SEQ ID NO: 51; and a VL CDR3 having the amino acid sequence of SEQ ID NO: 37, which CDRs are according to the Kabat system, wherein the antibody binds DNA with a KD of less than 100 nM and promotes transit across cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter. ### Claim 2 (depends on 1) The method of treating a tumor of claim 1, wherein the method includes reducing tumor growth, proliferation or survival. ### Claim 3 (depends on 2) The method of claim 2, wherein a reduction in tumor growth, proliferation or survival is determined by assessing mitotic markers in a tumor sample. ### Claim 4 (depends on 2) The method of claim 2, wherein a reduction in tumor growth, proliferation or survival is determined by assessing Ki-67 staining in a tumor sample. ### Claim 5 (depends on 1) The method of treating a tumor of claim 1, wherein the method includes promoting collapse of capillary blood vessels in a tumor. ### Claim 6 (depends on 5) The method of claim 5, wherein a collapse of capillary blood vessels in a tumor is determined by observing CD-31 staining patterns in a tumor sample. ### Claim 7 (depends on 1) The method of claim 1, wherein the tumor is in a subject, and the subject is a human. ### Claim 8 (depends on 1) The method of claim 1, wherein the tumor is a colorectal cancer, an ovarian cancer, a pancreatic cancer, a hereditary non-polyposis colon cancer (HNPCC), or an adenocarcinoma. ### Claim 9 (depends on 1) The method of claim 1, wherein the tumor is platin-resistant, or wherein the tumor is resistant to treatment with DNA repair inhibitors. ### Claim 10 (depends on 1) The method of claim 1, wherein the tumor is associated with microsatellite instability. ### Claim 11 (depends on 1) The method of claim 1, wherein the tumor has deficient DNA mismatch repair, or wherein the tumor has a mutation in any of the hMSH2, hMSH6 or hMLH1 genes, or wherein the tumor is BRCA2 deficient, or wherein the tumor is BRCA2 proficient. ### Claim 12 (depends on 1) The method of claim 1, wherein the method comprises administering the antibody or antigen-binding fragment more than once according to a dose and dosing schedule. ### Claim 13 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered to the subject as a monotherapy. ### Claim 14 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment thereof is administered to the subject in combination with an additional therapeutic treatment. ### Claim 15 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is administered to the subject intravenously, intramuscularly, or subcutaneously. ### Claim 16 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is a full length antibody or comprises a portion of an Fc domain, and which antibody or antigen-binding fragment is effective at a lower dose than a murine 3E10 full length antibody. ### Claim 17 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is a Fab or Fab′, and which antibody or antigen-binding fragment is effective at a lower dose than a murine 3E10 Fv or scFv. ### Claim 18 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment is a F(ab′)2 fragment, and which antibody or antigen-binding fragment is effective at a lower dose than a murine a F(ab′)2 fragment. ### Claim 19 (depends on 1) The method of claim 1, wherein the internalizing moiety is a full length antibody comprising a heavy chain constant domain and a light chain constant domain. ### Claim 20 (depends on 1) The method of claim 1, wherein the VH domain comprises: the amino acid sequence of SEQ ID NO: 38, the amino acid sequence of SEQ ID NO: 39, or the amino acid sequence of SEQ ID NO: 10; and wherein the VL domain comprises: the amino acid sequence of SEQ ID NO: 40, or the amino acid sequence of SEQ ID NO: 8. ### Claim 21 A method of inhibiting proliferation of a cancerous cell or tumor cell, comprising contacting the tumor cell with an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment comprises a light chain variable (VL) domain and a heavy chain variable (VH) domain; wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; a VH CDR2 having the amino acid sequence of SEQ ID NO: 2; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3, which CDRs are according to the IMGT system; or wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 32; a VH CDR2 having the amino acid sequence of SEQ ID NO: 49; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 34, which CDRs are according to the Kabat system; and the VL domain comprises: a VL CDR1 having the amino acid sequence of SEQ ID NO: 35 or 50; a VL CDR2 having the amino acid sequence of SEQ ID NO: 51; and a VL CDR3 having the amino acid sequence of SEQ ID NO: 37, which CDRs are according to the Kabat system, wherein the antibody binds DNA with a KD of less than 100 nM and promotes transit across cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter. ### Claim 22 A method of decreasing Ki-67 or CD31 expression in a tumor, comprising contacting the tumor cell with an antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment comprises a light chain variable (VL) domain and a heavy chain variable (VH) domain; wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; a VH CDR2 having the amino acid sequence of SEQ ID NO: 2; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3, which CDRs are according to the IMGT system; or wherein the VH domain comprises: a VH CDR1 having the amino acid sequence of SEQ ID NO: 32; a VH CDR2 having the amino acid sequence of SEQ ID NO: 49; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 34, which CDRs are according to the Kabat system; and the VL domain comprises: a VL CDR1 having the amino acid sequence of SEQ ID NO 35 or 50; a VL CDR2 having the amino acid sequence of SEQ ID NO 51; and a VL CDR3 having the amino acid sequence of SEQ ID NO: 37, which CDRs are according to the Kabat system, wherein the antibody binds DNA with a KD of less than 100 nM and promotes transit across cellular membranes via an equilibrative nucleoside transporter 2 (ENT2) transporter.