Making High-Concentration Antibody Medicines Stable for Injection
Genentech's 2001 patent on a method to create stable, concentrated antibody medicines that can be easily reconstituted for injection, preventing degradation during freezing and storage.
Original patent title: “Protein formulation”
Genentech's 2001 patent on a method to create stable, concentrated antibody medicines that can be easily reconstituted for injection, preventing degradation during freezing and storage. Granted to Genentech Inc in 2001 with 56 claims and 878 forward citations.
Key facts
Coverage
What does this patent actually cover?
This patent describes how to prepare a stable, concentrated liquid medicine from a frozen-dried (lyophilized) powder containing an antibody. The key is using a special ingredient called a 'lyoprotectant' in a specific ratio (about 100 to 510 moles of lyoprotectant for every 1 mole of antibody). This lyoprotectant protects the antibody from breaking down during the freezing and drying process and while it's stored. When you add liquid back to the powder, you get a medicine with a high concentration of antibody, between 50 to 400 mg/mL, which is stable and ready for injection, often for subcutaneous administration. For example, it covers making a stable, concentrated anti-HER2 antibody formulation ready for use.
The gap
What does this patent NOT cover?
- Formulations where the antibody concentration after reconstitution is less than 50 mg/mL.
- Formulations that do not use a lyoprotectant during the lyophilization process.
- Formulations where the molar ratio of lyoprotectant to antibody is outside the range of 100-510:1.
- Reconstituted formulations that are not isotonic (having the same salt concentration as body fluids).
- Medicines that are not antibodies, such as small molecule drugs.
These exclusions are unique to PatentBrief — derived from the actual claim language, not patent-office boilerplate.
What made this novel
The innovation lies in precisely controlling the ratio of lyoprotectant to antibody during lyophilization. This specific ratio ensures the antibody remains stable through the harsh freeze-drying process and storage, allowing for a much higher concentration upon reconstitution than previously thought possible without damaging the antibody.
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
Genentech's Herceptin (trastuzumab) formulations
Other lyophilized monoclonal antibody therapies
Biologic drug products requiring high concentration and stability
Why it matters
The bigger picture
This patent is significant because it enabled the development of highly concentrated antibody-based therapies. Many complex biologic drugs, like monoclonal antibodies, are fragile. This invention provided a way to stabilize them in a dried form and then reconstitute them at high concentrations suitable for convenient patient self-administration, like subcutaneous injections, rather than requiring intravenous infusions.
Filed
March 14, 1996
Granted
July 31, 2001
Market context
Who's building on this
Companies in this space
Genentech, now part of Roche, has been a primary beneficiary and developer of technologies related to this patent. Many other pharmaceutical and biotechnology companies developing biologic drugs, particularly monoclonal antibodies, utilize similar lyophilization and formulation strategies.
Market impact
This patent helped establish the feasibility and commercial viability of stable, high-concentration lyophilized antibody formulations. It paved the way for self-administered subcutaneous antibody therapies, significantly impacting patient convenience and treatment paradigms in areas like oncology and immunology.
Claim 1 — Plain English
What this patent covers
This patent describes how to prepare a stable, concentrated liquid medicine from a frozen-dried (lyophilized) powder containing an antibody. The key is using a special ingredient called a 'lyoprotectant' in a specific ratio (about 100 to 510 moles of lyoprotectant for every 1 mole of antibody). This lyoprotectant protects the antibody from breaking down during the freezing and drying process and while it's stored. When you add liquid back to the powder, you get a medicine with a high concentration of antibody, between 50 to 400 mg/mL, which is stable and ready for injection, often for subcutaneous administration. For example, it covers making a stable, concentrated anti-HER2 antibody formulation ready for use.
The clever bit
The innovation lies in precisely controlling the ratio of lyoprotectant to antibody during lyophilization. This specific ratio ensures the antibody remains stable through the harsh freeze-drying process and storage, allowing for a much higher concentration upon reconstitution than previously thought possible without damaging the antibody.
What it does not cover
- Formulations where the antibody concentration after reconstitution is less than 50 mg/mL.
- Formulations that do not use a lyoprotectant during the lyophilization process.
- Formulations where the molar ratio of lyoprotectant to antibody is outside the range of 100-510:1.
- Reconstituted formulations that are not isotonic (having the same salt concentration as body fluids).
- Medicines that are not antibodies, such as small molecule drugs.
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
56 claims as filed with the patent office.
Concepts involved
Citations
Patent lineage
Cite this patent
Andya, J., Lam, X. M., Yang, J. Y., Cleland, J. L., Overcashier, D. E., Hsu, C. C., Shire, S. J., & Wu, S. S. (2001). Making High-Concentration Antibody Medicines Stable for Injection (U.S. Patent No. 6,267,958). U.S. Patent and Trademark Office. https://patentbrief.org/patent/us/6267958/rituxan-chop
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 Making High-Concentration Antibody Medicines Stable for Injection cover?
Genentech's 2001 patent on a method to create stable, concentrated antibody medicines that can be easily reconstituted for injection, preventing degradation during freezing and storage.
Who owns patent US 6267958?
Genentech Inc owns this patent, granted in 2001.
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 6267958 cited by?
This patent has been cited by 878 later patents that build on its ideas.
What problem does this patent solve?
This patent is significant because it enabled the development of highly concentrated antibody-based therapies. Many complex biologic drugs, like monoclonal antibodies, are fragile. This invention provided a way to stabilize them in a dried form and then reconstitute them at high concentrations suitable for convenient patient self-administration, like subcutaneous injections, rather than requiring intravenous infusions.
What does this patent NOT cover?
Formulations where the antibody concentration after reconstitution is less than 50 mg/mL.
Same assignee
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