How to Redesign Mouse Antibodies for Safe Use in Humans
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.
Original patent title: “Humanized antibodies and methods for making them”
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. Granted to Genentech Inc in 2000 with 40 claims and 1,161 forward citations.
Key facts
Coverage
What does this patent actually cover?
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.
The gap
What does this patent 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.
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
What made this novel
Instead of just copying the binding loops, the inventors realized that the surrounding framework acts like a physical scaffold. If you change the scaffold entirely to human, the loops warp; by identifying a precise set of support residues in the framework to keep as mouse-derived, they preserved the loop shape.
Schematic visualization of the patent's claim structure. Hand-drawn diagrams in progress for each landmark patent.
Where you've seen this
Real-world examples
Herceptin (trastuzumab) breast cancer therapy
Avastin (bevacizumab) cancer therapy
Xolair (omalizumab) asthma treatment
Genentech's humanized monoclonal antibody pipeline
Why it matters
The bigger picture
This patent laid the technical foundation for some of the most successful cancer and autoimmune drugs in history, including Herceptin (trastuzumab) and Avastin (bevacizumab). Before this systematic approach, simply grafting mouse binding loops onto human antibodies often caused them to lose their ability to bind targets tightly, making them useless as drugs.
Filed
May 9, 1995
Granted
April 25, 2000
Market context
Who's building on this
Companies in this space
Genentech (now a member of the Roche Group) used this method to build its multi-billion dollar oncology portfolio. Other major biopharma companies like Amgen, AbbVie, and Regeneron have built on these humanization principles, though many now also use fully human transgenic mice.
Market impact
This patent was a cornerstone of the modern biologics industry. It enabled the transition from highly toxic, immunogenic mouse antibodies to highly tolerated humanized blockbusters, triggering massive patent litigationlitigationA lawsuit over patent infringement. Litigated patents often signal commercial importance.Read more → and licensing deals across the biopharmaceutical sector.
Claim 1 — Plain English
What this patent covers
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.
The clever bit
Instead of just copying the binding loops, the inventors realized that the surrounding framework acts like a physical scaffold. If you change the scaffold entirely to human, the loops warp; by identifying a precise set of support residues in the framework to keep as mouse-derived, they preserved the loop shape.
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.
Patent timeline
Application submitted to the patent office
Application published, typically 18 months after filing
Patent officially issued
PatentBrief Score
Impact Score
High impact
Citation count
40/40
Highly cited
Claim breadth
20/20
Very broad protection
Recency
0/20
Older than 20 years
Assignee scale
20/20
Major company or institution
PatentBrief Impact Score — based on citation count, claim breadth, recency, and assignee scale. Not a legal assessment.
Heuristic Value Estimate
What this patent might be worth
$270K – $864K
Midpoint $540K · expired or expiring · industry ×3.0
Heuristic only — blends forward/backward citation counts, claim scope, time remaining, litigation history, and CPC-derived industry baseline. Real valuations need a professional appraisal.
The original legal language
Original claims
40 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Presta, L. G., & Carter, P. J. (2000). How to Redesign Mouse Antibodies for Safe Use in Humans (U.S. Patent No. 6,054,297). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/6054297/rituxan-chop-chemotherapy
Auto-generated from the patent record. Double-check author order and the issue date against the official USPTO document before submitting.
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Common Questions
Frequently Asked Questions
What does How to Redesign Mouse Antibodies for Safe Use in Humans cover?
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.
Who owns patent US 6054297?
Genentech Inc owns this patent, granted in 2000.
When does this patent expire?
This patent has expired and is now in the public domain — anyone can use the invention freely.
What is patent US 6054297 cited by?
This patent has been cited by 1161 later patents that build on its ideas.
What problem does this patent solve?
This patent laid the technical foundation for some of the most successful cancer and autoimmune drugs in history, including Herceptin (trastuzumab) and Avastin (bevacizumab). Before this systematic approach, simply grafting mouse binding loops onto human antibodies often caused them to lose their ability to bind targets tightly, making them useless as drugs.
What does this patent NOT cover?
Does not cover humanizing antibodies using human framework regions other than the VH subgroup III consensus sequence.
Same assignee
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