{
  "patent_number": "US 6054297",
  "country": "US",
  "title": "How to Redesign Mouse Antibodies for Safe Use in Humans",
  "original_title": "Humanized antibodies and methods for making them",
  "summary": "Genentech's 1995 patent on a systematic method for humanizing rodent antibodies by grafting their disease-targeting loops onto a human consensus framework while carefully swapping key structural support residues to maintain binding strength.",
  "what_it_does": "The patent describes a method to engineer therapeutic antibodies that the human immune system won't reject. It starts with a non-human 'import' antibody (typically from a mouse) that already binds to a disease target, and a human 'consensus' antibody framework (specifically VH subgroup III). The method grafts the mouse's target-binding loops, called Complementarity Determining Regions (CDRs), onto the human framework. To prevent the loops from collapsing, the method aligns the framework sequences and identifies differences. If a mouse framework residue is different from the human consensus, and it is predicted to either bind the antigen directly, interact with a CDR loop, or help the heavy and light antibody chains fit together, that specific mouse residue is substituted back into the human framework. A concrete example is the design of trastuzumab (Herceptin), where specific framework positions like 66L or 93H are retained from the mouse sequence to preserve target affinity.",
  "what_it_does_not_cover": [
    "Does not cover humanizing antibodies using human framework regions other than the VH subgroup III consensus sequence.",
    "Does not cover fully human antibodies generated from transgenic mice or synthetic phage display libraries that do not require grafting.",
    "Does not cover humanization methods that do not substitute framework residues based on the three specific criteria of direct antigen binding, CDR interaction, or VL-VH interface participation.",
    "Does not cover simple CDR grafting where no framework region residues are substituted back to the import sequence."
  ],
  "filed": "1995-05-09",
  "granted": "2000-04-25",
  "expires": null,
  "status": "active",
  "holder": "Genentech Inc",
  "holder_url": "https://patentbrief.org/company/genentech-inc",
  "inventors": [
    {
      "name": "Leonard G. Presta",
      "url": "https://patentbrief.org/inventor/leonard-g-presta"
    },
    {
      "name": "Paul J. Carter",
      "url": "https://patentbrief.org/inventor/paul-j-carter"
    }
  ],
  "times_cited": 1161,
  "tags": [
    "biotech",
    "pharmaceutical"
  ],
  "abstract": "Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.",
  "url": "https://patentbrief.org/patent/us/6054297/rituxan-chop-chemotherapy",
  "markdown_url": "https://patentbrief.org/patent/us/6054297/rituxan-chop-chemotherapy/md",
  "google_patents_url": "https://patents.google.com/patent/US6054297",
  "relatedPatents": []
}