# US 8,465,931 B2 · Therapeutic and diagnostic methods and compositions targeting 4Ig-B7-H3 and its counterpart NK cell receptor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,465,931 B2 - Document ID: US8465931B2 - Status: Granted - Kind: B2 - Application number: 12/775,531 - Filed: 2010-05-07 - Published: 2010-11-11 - Granted: 2013-06-18 - Earliest claimed: 2004-08-03 - Assignees: Innate Pharma; University of Genova - Applicants: Alessandro Moretta; Roberta Castriconi; Christina Bottino; Lorenzo Moretta - Inventors: Alessandro Moretta; Roberta Castriconi; Christina Bottino; Lorenzo Moretta - Web page: https://patentgrep.com/patent/US8465931B2 ## CPC - A61K 39/39558: {against tumor tissues, cells, antigens} - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 37/02: Immunomodulators - A61P 37/04: Immunostimulants - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - C07K 16/30: from tumour cells - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - 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 relates to the identification of 4Ig-B7-H3 protein as a tumor associated molecule that imparts protection from NK cell-mediated lysis via a 4Ig-B7-H3 receptor on NK cells. The invention provides compounds that interfere with interactions between the 4Ig-B7-H3 protein and its receptor that can be used to potentiate NK cell cytotoxicity. Also provided are compounds that bind 4Ig-B7-H3-expressing cells so as to inhibit or eliminate them. The compounds are particularly useful in the treatment of tumors, inflammatory conditions, infections and transplantation. Also provided are methods for diagnosing disease by detecting a 4Ig-B7-H3 protein. ## Claims ### Claim 1 A method of producing an antibody suitable for use in the treatment of a tumor, said method comprising: i) providing one or a plurality of antibodies that specifically bind to a 4Ig-B7-H3 polypeptide; ii) testing the ability of each of the antibodies to block an interaction between a 4Ig-B7-H3 polypeptide and an NK cell; iii) selecting an antibody from the plurality that blocks said interaction; and iv) making the antibody suitable for human administration. ### Claim 2 (depends on 1) The method of claim 1, wherein the antibody is made suitable for human administration by humanizing or chimerizing it. ### Claim 3 (depends on 1) The method of claim 1, further comprising derivatizing the antibody into a cytotoxic antibody. ### Claim 4 (depends on 1) The method of claim 1, further comprising modifying the Fc region of the antibody to enhance the antibody's ADCC activity. ### Claim 5 (depends on 4) The method of claim 4, wherein said antibody is produced by: (a) use of an engineered host cell that is deficient in fucose metabolism such that it has a reduced ability to fucosylate proteins expressed therein; (b) culturing cells under conditions which prevent or reduce fusocylation; (c) post-translational removal of fucose; or (d) purification of the antibody so as to select for a product which is not substantially fucosylated. ### Claim 6 (depends on 1) The method of claim 1, wherein said antibody is capable of inducing the elimination of a cell to which it binds. ### Claim 7 (depends on 6) The method of claim 6, wherein said antibody has a human IgG1 or an IgG3 Fc portion. ### Claim 8 (depends on 6) The method of claim 6, wherein said antibody is linked to a cytotoxic moiety. ### Claim 9 (depends on 1) The method of claim 1, wherein said antibody has a IgG2 or an IgG4 Fc portion. ### Claim 10 (depends on 1) The method of claim 1, wherein the tumor is a neuroblastoma. ### Claim 11 (depends on 1) The method of claim 1, wherein the tumor is a melanoma. ### Claim 12 (depends on 1) The method of claim 1, wherein the tumor is a carcinoma. ### Claim 13 (depends on 4) The method of claim 4, wherein said antibody comprises one or more modifications in the Fc region at an amino acid position selected from the group consisting of 241, 243, 244, 245, 249, 256, 258, 260, 262, 264, 265, 296, 299, 301, 322, 329 and 331. ### Claim 14 (depends on 1) The method of claim 1, wherein the step of testing comprises assessing the capacity of said antibody to reconstitute lysis by 4Ig-B7-H3R-positive NK cells of 4Ig-B7-H3 positive target cells. ### Claim 15 (depends on 1) The method of claim 1, wherein the step of testing comprises assessing the ability of the antibody to inhibit the binding of 4Ig-B7-H3 molecules to 4Ig-B7-H3R expressed on NK cells.