# US 2013/0156781 A1 · Anti-dr4 agonist antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0156781 A1 - Document ID: US20130156781A1 - Status: Published application - Kind: A1 - Application number: 13/704,577 - Filed: 2011-06-16 - Published: 2013-06-20 - Earliest claimed: 2010-06-16 - Assignees: The Govt. of the United States of America H.H.N.I. H., Office of Technology Transfer - Inventors: Dimiter Dimitrov; Yang Feng - Web page: https://patentgrep.com/patent/US20130156781A1 ## CPC - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/55: Fab or Fab' - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract The present invention provides antibodies and antibody fragments that specifically recognize and agonize the death receptor 4 (DR4). Also provided in the invention are polynucleotides and vectors that encode such molecules and host cells that harbor the polynucleotides or vectors. ## Claims ### Claim 1 An antibody that binds to and is an agonist of DR4, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region each comprise the following three complementary determining regions (CDRs): CDR1, CDR2 and CDR3; wherein: i) the CDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8; ii) the CDR2 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9; iii) the CDR3 of the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO:10 or SEQ ID NO:13; iv) the CDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:5; v) the CDR2 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:31; vi) the CDR3 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:30. ### Claim 2 (depends on 1) The antibody of claim 1, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region each comprise the following three complementary determining regions (CDRs): CDR1, CDR2 and CDR3; wherein: i) the CDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8; ii) the CDR2 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9; iii) the CDR3 of the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO:10; iv) the CDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:5; v) the CDR2 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:6; vi) the CDR3 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:7. ### Claim 3 (depends on 1) The antibody of claim 1, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region each comprise the following three complementary determining regions (CDRs): CDR1, CDR2 and CDR3; wherein: i) the CDR1 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:8; ii) the CDR2 of the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:9; iii) the CDR3 of the heavy chain variable region comprises an amino acid sequence selected from SEQ ID NO:13; iv) the CDR1 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:5; v) the CDR2 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:11; vi) the CDR3 of the light chain variable region comprises the amino acid sequence of SEQ ID NO:12. ### Claim 4 (depends on 1) The antibody of claim 1, wherein the antibody comprises a light chain variable segment of SEQ ID NO:33 and a heavy chain variable segment of SEQ ID NO:34. ### Claim 5 (depends on 1) The antibody of claim 1, wherein the antibody comprises a light chain variable region having at least 50% sequence identity to SEQ ID NO:1 and a heavy chain variable region having at least 50% sequence identity to SEQ ID NO:2. ### Claim 6 (depends on 1) The antibody of claim 1, wherein the antibody comprises a light chain variable region having at least 50% sequence identity to SEQ ID NO:3 and a heavy chain variable region having at least 50% sequence identity to SEQ ID NO:4. ### Claim 7 (depends on 1) The antibody of claim 1, wherein the antibody is a human antibody. ### Claim 8 (depends on 1) The antibody of claim 1, wherein the antibody is a multivalent antibody. ### Claim 9 (depends on 8) The antibody of claim 8, wherein the antibody is a multispecific antibody. ### Claim 10 (depends on 9) The antibody of claim 9, wherein the antibody is a bispecific antibody. ### Claim 11 (depends on 1) The antibody of claim 1, wherein the antibody is cross-linked. ### Claim 12 (depends on 1) A composition comprising an antibody of claim 1, and a pharmaceutically acceptable carrier. ### Claim 13 (depends on 1) A polynucleotide encoding an antibody of claim 1. ### Claim 14 (depends on 13) An expression cassette comprising the polynucleotide of claim 13. ### Claim 15 (depends on 14) A host cell comprising the expression cassette of claim 14. ### Claim 16 (depends on 1) A method of inducing apoptosis in a target cell expressing DR4 comprising contacting the cancer cell with an antibody of claim 1. ### Claim 17 (depends on 16) The method of claim 16, wherein the cell is in vivo. ### Claim 18 (depends on 16) The method of claim 16, wherein the cell is in vitro. ### Claim 19 (depends on 16) The method of claim 16, wherein the cell is a cancer cell. ### Claim 20 (depends on 1) A method of reducing, inhibiting or preventing the growth of a cancer expressing DR4 in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antibody of claim 1. ### Claim 21 (depends on 20) The method of claim 20, further comprising administering to the subject an anticancer chemotherapeutic drug and/or irradiation. ### Claim 22 (depends on 1) A kit comprising an antibody of claim 1. ### Claim 23 (depends on 22) The kit of claim 22, further comprising a second agent for co administration with the antibody.