{
  "patent_number": "US 6682736",
  "country": "US",
  "title": "How Human Antibodies Block the Immune System's Off-Switch",
  "original_title": "Human monoclonal antibodies to CTLA-4",
  "summary": "Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells.",
  "what_it_does": "This patent claims a fully human monoclonal antibody that targets CTLA-4, a receptor on T-cells that acts as an off-switch for the immune system. According to Claim 1, the antibody uses a specific human gene sequence (VH 3-33 family) with key amino acid mutations to bind tightly to CTLA-4. Claim 4 specifies that the antibody must bind with high affinity (at least 10^-9 M) and be highly selective—at least 100 times more attracted to CTLA-4 than to similar proteins like CD28 or B7-2. By binding to CTLA-4, the antibody blocks it from interacting with its natural partners (B7-1 and B7-2), which prevents the immune system from shutting down. An example of its action is boosting the production of Interleukin-2 (IL-2), a signaling molecule that tells T-cells to multiply and fight.",
  "what_it_does_not_cover": [
    "Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.",
    "Does not cover antibodies that bind to CTLA-4 but also cross-react with lower mammals like mice, rats, or rabbits.",
    "Does not cover antibodies with low binding affinity weaker than 10^-9 M or poor selectivity less than 100:1 over CD28.",
    "Does not cover therapies that target the CTLA-4 pathway using non-antibody molecules, such as small-molecule drugs or soluble receptor proteins."
  ],
  "filed": "1999-12-23",
  "granted": "2004-01-27",
  "expires": null,
  "status": "active",
  "holder": "Abgenix Inc",
  "holder_url": "https://patentbrief.org/company/abgenix-inc",
  "inventors": [
    {
      "name": "Jose Ramon Corvalan",
      "url": "https://patentbrief.org/inventor/jose-ramon-corvalan"
    },
    {
      "name": "Steven Christopher Gilman",
      "url": "https://patentbrief.org/inventor/steven-christopher-gilman"
    },
    {
      "name": "C. Geoffrey Davis",
      "url": "https://patentbrief.org/inventor/c-geoffrey-davis"
    },
    {
      "name": "Mark Joseph Neveu",
      "url": "https://patentbrief.org/inventor/mark-joseph-neveu"
    },
    {
      "name": "Douglas Charles Hanson",
      "url": "https://patentbrief.org/inventor/douglas-charles-hanson"
    },
    {
      "name": "Eileen Elliott Mueller",
      "url": "https://patentbrief.org/inventor/eileen-elliott-mueller"
    },
    {
      "name": "Jeffrey Herbert Hanke",
      "url": "https://patentbrief.org/inventor/jeffrey-herbert-hanke"
    }
  ],
  "times_cited": 500,
  "tags": [
    "biotech",
    "pharmaceutical"
  ],
  "abstract": "In accordance with the present invention, there are provided fully human monoclonal antibodies against human cytotoxic T-lymphocyte antigen 4 (CTLA-4). Nucelotide sequences encoding and amino acid sequences comprising heavy and light chain immunoglobulin molecules, particularly contiguous heavy and light chain sequences spanning the complementarity determining regions (CDRs), specifically from within FR1 and/or CDR1 through CDR3 and/or within FR4, are provided. Further provided are antibodies having similar binding properties and antibodies (or other antagonists) having similar functionality as antibodies disclosed herein.",
  "url": "https://patentbrief.org/patent/us/6682736/enbrel-etanercept",
  "markdown_url": "https://patentbrief.org/patent/us/6682736/enbrel-etanercept/md",
  "google_patents_url": "https://patents.google.com/patent/US6682736",
  "relatedPatents": []
}