# US 10,308,720 B2 · Multivalent and multispecific DR5-binding fusion proteins > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,308,720 B2 - Document ID: US10308720B2 - Status: Granted - Kind: B2 - Application number: 15/213,296 - Filed: 2016-07-18 - Published: 2017-01-19 - Granted: 2019-06-04 - Earliest claimed: 2015-07-16 - Assignees: Inhibrx, Inc. - Applicants: Inhibrx, Inc. - Inventors: John C. Timmer; Kyle S. Jones; Amir S. Razai; Abrahim Hussain; Katelyn M. Willis; Quinn Deveraux; Brendan P. Eckelman - Web page: https://patentgrep.com/patent/US10308720B2 ## CPC - C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95} - A61K 39/39558: {against tumor tissues, cells, antigens} - A61P 35/00: Antineoplastic agents - A61P 37/02: Immunomodulators - A61K 2039/505: {comprising antibodies} - C07K 2317/22: from camelids, e.g. camel, llama or dromedary - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/35: Valency - C07K 2317/567: Framework region [FR] - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/75: Agonist effect on antigen - 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) - 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 ## Abstract The disclosure relates generally to molecules that specifically engage death receptor 5 (DR5), a member of the TNF receptor superfamily (TNFRSF). More specifically the disclosure relates to multivalent and multispecific molecules that bind at least DR5. ## Claims ### Claim 1 An isolated polypeptide that binds death receptor 5 (DR5) and comprises a plurality of DR5 binding domains (DR5BDs), wherein each DR5BD is a VHH comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 128, a CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 130, and wherein adjacent DR5BDs are operably linked by an amino acid linker. ### Claim 2 (depends on 1) The isolated polypeptide of claim 1, wherein the plurality of DR5BDs is two DR5BDs. ### Claim 3 (depends on 1) The isolated polypeptide of claim 1, wherein the plurality of DR5BDs is four DR5BDs. ### Claim 4 (depends on 1) The isolated polypeptide of claim 1, wherein the plurality of DR5BDs is six DR5BDs. ### Claim 5 (depends on 1) The isolated polypeptide of claim 1, wherein each DR5BD comprises the amino acid sequence of SEQ ID NO: 87. ### Claim 6 (depends on 2) The isolated polypeptide of claim 2, wherein each DR5BD comprises the amino acid sequence of SEQ ID NO: 87. ### Claim 7 (depends on 3) The isolated polypeptide of claim 3, wherein each DR5BD comprises the amino acid sequence of SEQ ID NO: 87. ### Claim 8 (depends on 4) The isolated polypeptide of claim 4, wherein each DR5BD comprises the amino acid sequence of SEQ ID NO: 87. ### Claim 9 (depends on 3) The isolated polypeptide of claim 3, wherein the polypeptide is a homodimer of the structure: DR5BD-Linker-DR5BD-Linker-Hinge-Fc, where each DR5BD is a humanized VHH sequence. ### Claim 10 (depends on 9) The isolated polypeptide of claim 9, wherein each DR5BD comprises the amino acid sequence of SEQ ID NO: 87. ### Claim 11 (depends on 1) The isolated polypeptide of claim 1, wherein the isolated polypeptide comprises an immunoglobulin hinge region and an immunoglobulin Fc region. ### Claim 12 (depends on 11) The isolated polypeptide of claim 11, wherein the immunoglobulin hinge region comprises an amino acid sequence selected from EPKSSDKTHTCPPC (SEQ ID NO: 6), DKTHTCPPC (SEQ ID NO: 7), ESKYGPPCPPC (SEQ ID NO: 8). ### Claim 13 (depends on 11) The isolated polypeptide of claim 11, wherein the immunoglobulin Fc region is an IgG1 Fc region, an IgG2 Fc region, an IgG3 Fc region, or an IgG1 Fc region. ### Claim 14 (depends on 11) The isolated polypeptide of claim 11, wherein the immunoglobulin Fc region comprises an amino acid sequence selected from SEQ ID NOs: 1-5 or 127. ### Claim 15 (depends on 1) The isolated polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 113. ### Claim 16 (depends on 15) The isolated polypeptide of claim 15, wherein the polypeptide is a homodimer of the amino acid sequence of SEQ ID NO: 113 fused to an Fc region polypeptide. ### Claim 17 (depends on 1) The isolated polypeptide of claim 1, wherein each amino acid linker consists of 5-20 amino acids. ### Claim 18 (depends on 17) The isolated polypeptide of claim 17, wherein each amino acid linker is composed predominantly of glycine and serine. ### Claim 19 (depends on 18) The isolated polypeptide of claim 18, wherein each amino acid linker comprises an amino acid sequence selected from GGSGGS (SEQ ID NO: 11); GGSGGSGGS (SEQ ID NO: 12); GGSGGSGGSGGS (SEQ ID NO: 13); and GGSGGSGGSGGSGGS (SEQ ID NO: 14). ### Claim 20 (depends on 10) The isolated polypeptide of claim 10, wherein each amino acid linker consists of 5-20 amino acids. ### Claim 21 (depends on 20) The isolated polypeptide of claim 20, wherein each amino acid linker is composed predominantly of glycine and serine. ### Claim 22 (depends on 21) The isolated polypeptide of claim 21, wherein each amino acid linker comprises an amino acid sequence selected from GGSGGS (SEQ ID NO: 11); GGSGGSGGS (SEQ ID NO: 12); GGSGGSGGSGGS (SEQ ID NO: 13); and GGSGGSGGSGGSGGS (SEQ ID NO: 14). ### Claim 23 (depends on 1) The isolated polypeptide of claim 1, wherein each VHH is a humanized VHH. ### Claim 24 An isolated polypeptide that binds death receptor 5 (DR5), wherein the polypeptide is a homodimer of the amino acid sequence of SEQ ID NO: 113 fused to an Fc region polypeptide of SEQ ID NO: 2.