United States Drug Patent 4,233,285: Scope, Claims, Expiration, and Patent Landscape

U.S. Patent No. 4,233,285 covered technetium-99m radiopharmaceuticals made with mercaptocarboxylic acid chelators, particularly technetium-99m-2,3-dimercaptosuccinic acid, commonly known as 99mTc-DMSA or succimer. Its claims covered the radiopharmaceutical, a reagent solution for preparing it, and intravenous imaging methods. The patent issued on November 11, 1980, and its ordinary 17-year patent term expired in 1997. It therefore presents no current U.S. patent barrier to generic or competing 99mTc-DMSA products.[1]

What drug and technology did U.S. Patent 4,233,285 protect?

The patent protected a radiopharmaceutical platform based on three technical elements:

A mercaptocarboxylic acid chelating agent.
A radioactive heavy-metal ion, principally technetium-99m.
Reduction of the metal ion with stannous chloride under acidic conditions, with an approximately 3:1 chelator-to-stannous chloride molar ratio.

The commercially important embodiment is 99mTc-DMSA, in which 2,3-dimercaptosuccinic acid binds reduced technetium-99m and produces a renal cortical imaging agent.

The patent was directed to diagnostic nuclear medicine rather than to a conventional small-molecule therapeutic. Its disclosed uses included imaging of:

Renal cortex;
Brain abnormalities;
Tumors; and
Myocardial infarcts.

The strongest commercial relevance has been renal cortical imaging. Modern FDA labeling for technetium Tc 99m succimer identifies renal cortical imaging as the principal clinical use.[2]

What are the independent claims of U.S. Patent 4,233,285?

The patent contains three principal independent claim groups.

Claim	Claim category	Core subject matter
1	Product	Radiopharmaceutical complex containing a mercaptocarboxylic acid chelator and radioactive heavy-metal ion
4	Reagent composition	Aqueous solution containing mercaptocarboxylic acid, 99mTc pertechnetate and stannous chloride
7	Method of use	Intravenous administration and scanning for specified diagnostic indications

Claim 1: Radiopharmaceutical complex

Claim 1 requires all of the following:

A mercaptocarboxylic acid chelating agent;
At least one carboxylic acid group;
At least one mercapto, or thiol, group;
A radioactive heavy-metal ion;
Reduction with stannous chloride in the presence of the chelator;
Complex formation at approximately pH 2 to 4; and
A chelator-to-stannous chloride molar ratio of approximately 3:1.

The claim is technically broad in its choice of radioactive heavy metal. It is narrower in its required preparation conditions. A product using a different reducing agent, a materially different pH, or a materially different chelator-to-reducer ratio would require separate analysis of literal infringement and equivalents.

The phrase "produced by reduction with stannous chloride" creates a process limitation in a product claim. Its legal effect would depend on how a court construed the claim in the context of the product's measurable characteristics and the prosecution history. Because the patent expired decades ago, this issue has no practical current enforcement consequence in the United States.

Claim 4: Reagent composition

Claim 4 requires an aqueous reagent containing:

A mercaptocarboxylic acid chelator;
Technetium-99m pertechnetate;
Stannous chloride;
An approximately 3:1 chelator-to-stannous chloride mole ratio; and
A pH of approximately 2 to 4.

This claim is directed to a ready-to-use or preparatory radiopharmaceutical solution rather than only the final metal-chelate complex. It would historically have been relevant to kit or solution formats in which pertechnetate, chelator and reducing agent were combined before administration.

The claim is materially narrower than a generic claim to any DMSA radiopharmaceutical. A formulation lacking 99mTc pertechnetate, lacking stannous chloride, or falling outside the specified pH or ratio limitations would not literally satisfy every element of claim 4.

Claim 7: Imaging method

Claim 7 requires:

Intravenous injection into a patient;
A radiopharmaceutical complex formed using a mercaptocarboxylic acid chelator;
Reduction with stannous chloride;
Complex formation at pH 2 to 4;
Approximately a 3:1 chelator-to-stannous chloride ratio; and
Scanning with a suitable apparatus.

The listed disease or imaging targets are renal cortex, brain abnormalities, tumors and myocardial infarcts. The claim is not limited to a particular scanner, imaging protocol, injected dose or scan timing.

What compounds are covered by the patent?

Claim 2 and its dependent claims identify five chelator classes or specific compounds:

Chelator named in claim 2	Technical relevance
Mercaptoacetic acid	Monothiol carboxylic acid chelator
2-Mercaptopropionic acid	Monothiol, substituted carboxylic acid
3-Mercaptopropionic acid	Monothiol carboxylic acid
Mercaptosuccinic acid	Dicarboxylic acid, monothiol chelator
2,3-Dimercaptosuccinic acid	Dicarboxylic acid, dithiol chelator; commercially important DMSA embodiment

Claim 3 specifically covers 2,3-dimercaptosuccinic acid with technetium-99m. Claim 6 covers the same chelator in the reagent composition of claim 4. Claim 9 covers the corresponding imaging method.

The patent's commercial center of gravity is therefore claim 3 and the related claims 6 and 9, not the broader list of alternative chelators.

How broad is the scope of claim 1?

Claim 1 has a broad chemical genus but a narrow manufacturing profile.

Breadth of the chelator definition

The independent claim requires only one carboxylic acid group and one mercapto group. On its face, that language could encompass compounds beyond the five listed in claim 2, provided they satisfy the structural definition.

Claim 2 narrows the scope to the five named chelators. Claim 3 then narrows the invention to DMSA and technetium-99m.

Breadth of the radioactive-metal definition

"Radioactive heavy metal ion" is broader than technetium-99m. The claim could potentially encompass other radioactive heavy metals if they form the claimed complex under the specified reduction conditions. The dependent claims substantially focus the invention on 99mTc.

Process restrictions

The pH and ratio limitations are central claim constraints:

pH: about 2 to 4;
Chelator-to-stannous chloride ratio: about 3:1.

The term "about" introduces tolerance, but it does not eliminate the numerical limitations. The scope would turn on the ordinary meaning of "about," analytical measurement methods, experimental variability and the patent's disclosure.

Product versus process distinction

Claims 1 through 3 characterize a radiopharmaceutical product by reference to how the complex is produced. Claims 4 through 6 expressly claim the reagent composition itself. A competing product would require separate analysis under the product claims and the composition claims. Avoiding the claimed preparation process would not necessarily avoid a product claim if the resulting product were otherwise within the claim's scope.

What formulations are protected by U.S. Patent 4,233,285?

The patent does not claim every formulation containing DMSA or technetium-99m. Its formulation coverage is tied to the specific reagent architecture.

A covered reagent formulation historically required:

Water or an aqueous medium;
The mercaptocarboxylic acid chelator;
99mTc pertechnetate;
Stannous chloride;
Approximately a 3:1 chelator-to-stannous chloride ratio; and
pH 2 to 4.

The claims do not expressly require a particular vial, excipient, preservative, stabilizer, concentration, fill volume or lyophilization process. Those features could have been relevant to later formulation patents or regulatory specifications, but they are not express limitations in the claims provided.

A lyophilized kit would require careful claim construction. Claim 4 is written as an "aqueous solution," which creates a potential distinction between a fully aqueous product and a dry or lyophilized kit before reconstitution. After reconstitution, the resulting solution could raise a separate question, but the patent's expired status eliminates present U.S. enforcement risk.

When did U.S. Patent 4,233,285 lose exclusivity?

The patent issued on November 11, 1980. For a U.S. utility patent issued before the 1995 patent-term change, the standard term was 17 years from grant. On that basis, U.S. Patent 4,233,285 expired on November 11, 1997.[1,3]

Milestone	Date or status
Patent issued	November 11, 1980
Applicable term	17 years from grant
Ordinary expiration	November 11, 1997
Current status	Expired
Patent-term adjustment	Not relevant under the pre-1995 term framework
Current blocking effect	None in the United States

A patent-term-extension analysis is not material to the original patent's current status. Even if regulatory review had affected the term under a modern framework, the original patent is far beyond any plausible remaining term.

What is the Orange Book status of U.S. Patent 4,233,285?

U.S. Patent 4,233,285 has no current Orange Book protection.

The Orange Book lists patents and exclusivity information associated with approved drug products, subject to FDA listing rules. An expired 1980 patent does not provide current listed-patent protection against an abbreviated new drug application. The patent also predates the modern Hatch-Waxman listing and Paragraph IV framework.[4]

For technetium Tc 99m succimer products, regulatory exclusivity must be distinguished from patent exclusivity. The FDA-approved product and its labeling may remain commercially relevant even though the patent has expired. Regulatory approval does not revive the patent or create a continuing monopoly over the claimed chelate chemistry.

Which companies are challenging the patent?

No current Paragraph IV challenge can be directed against U.S. Patent 4,233,285 because the patent expired in 1997. A Paragraph IV certification is used in relation to patents listed for an approved reference drug and not to an expired patent that no longer creates an enforceable exclusion right.[4]

The practical competitive issue is therefore not patent litigation against this patent. It is the ability of manufacturers and radiopharmacies to obtain regulatory approval, secure technetium supply, satisfy current good manufacturing practice requirements and produce a clinically acceptable product.

What patent litigation affects 99mTc-DMSA?

The provided patent record does not establish an active U.S. litigation dispute involving U.S. Patent 4,233,285. Because the patent expired more than 25 years ago, it cannot support a current infringement action.

Historical litigation, if any, would be relevant only to claim construction, validity or ownership history. It would not restore enforceability. A current freedom-to-operate review should focus on later patents covering:

Kit architecture;
Lyophilized or stabilized formulations;
Automated radiopharmacy preparation;
Chelator analogues;
Alternative technetium-binding agents;
Imaging protocols; and
Manufacturing and quality-control methods.

Those rights would have to be assessed patent by patent. They cannot be inferred from the expired claims of U.S. Patent 4,233,285.

How strong was the patent estate for 99mTc-DMSA?

The historical patent position was strongest for the specific DMSA-technetium combination prepared with stannous chloride at acidic pH and the specified approximate ratio.

Dimension	Historical assessment	Current assessment
Core molecule	Strong for claimed DMSA-technetium embodiment	No enforceable value
Preparation conditions	Important and relatively specific	No enforceable value
Alternative chelators	Broader but less commercially central	No enforceable value
Reagent solution	Potentially important for kit products	No enforceable value
Imaging method	Covered specified intravenous diagnostic uses	No enforceable value
Formulation details	Limited express coverage	Later patents require separate review
Regulatory moat	Separate from patent rights	Depends on current FDA approvals
Litigation leverage	Historical only	None from this patent

The patent had a focused platform claim rather than a broad franchise covering all nuclear renal imaging. It did not expressly claim every technetium-labeled renal agent, every DMSA formulation or every method of imaging kidney function.

How does the patent compare with later DMSA and technetium patents?

The patent occupies the early composition-and-preparation layer of the technology. Later patent activity, where present, would generally fall into one of four categories:

Chelator and ligand patents

These cover new ligands, ligand combinations or metal-binding structures. A later ligand patent may avoid the '285 patent by using a compound outside the mercaptocarboxylic acid genus or by using a different coordination chemistry.

Kit and formulation patents

These may claim:

Lyophilized vials;
Specific excipient systems;
Stabilizers;
Defined concentrations;
Shelf-life improvements;
Reconstitution procedures; or
Multi-vial preparation systems.

Such claims are technically distinct from claim 4 unless they reproduce the claimed aqueous composition.

Imaging-use patents

A later method patent may claim a specific patient population, imaging sequence, dose, timing, renal function assessment or combination with another diagnostic modality. Such a patent would be separate from the general intravenous scanning method in claim 7.

Manufacturing patents

Manufacturing rights may cover sterile compounding, generator eluate handling, automated dispensing, radiochemical purity testing or process controls. Those rights can create operational constraints even when the original active-ingredient patent has expired.

What generic launch risks exist for 99mTc-DMSA?

The original patent creates no generic launch risk. Current risk is concentrated in regulatory and operational factors.

Risk category	Relevance to 99mTc-DMSA
Expired composition patent	No current barrier
Expired preparation patent	No current barrier
Orange Book patent listing	No current protection from the '285 patent
Paragraph IV exposure	Not applicable to the expired patent
Biosimilar pathway	Not applicable; DMSA is a chemical radiopharmaceutical
FDA approval	Required for marketed drug products
Radiochemical purity	Material quality requirement
Sterility and aseptic processing	Material manufacturing requirement
Technetium supply	Operational and supply-chain risk
Hospital or radiopharmacy contracts	Commercial access risk
Later formulation patents	Requires product-specific review
State and federal radioactive-material controls	Operational compliance issue

A competitor would generally pursue an abbreviated or appropriate drug approval pathway depending on the reference product, product classification and FDA requirements. The absence of patent protection does not eliminate the need to demonstrate pharmaceutical quality, sterility, labeling compliance and radiochemical performance.

Is there biosimilar risk for 99mTc-DMSA?

No. Biosimilar law applies to biological products. 99mTc-DMSA is a radiolabeled chemical drug product, not a biologic. Competitive entry would involve generic, follow-on or independently approved radiopharmaceutical products rather than biosimilars.

Are there licensing deals associated with the patent?

The patent record and the claim set do not establish a continuing license that affects present U.S. market entry. Any historical license, assignment or commercial agreement would not extend the expired patent term.

A separate license could still be relevant to later patents, trademarks, manufacturing know-how or regulatory dossiers. Such rights are distinct from U.S. Patent 4,233,285 and cannot be presumed from the patent claims.

What geographic coverage did the patent have?

U.S. Patent 4,233,285 provided rights only in the United States. Foreign counterparts, if filed, would have had separate prosecution histories, claim scope and expiration dates.

The U.S. expiration date does not establish the status of corresponding patents in Canada, Europe, Japan or other jurisdictions. A multinational launch requires country-by-country review of:

Patent family members;
National-phase status;
Local expiration dates;
Supplementary protection rights;
Regulatory exclusivity;
Local product registrations; and
Radioisotope manufacturing controls.

Key Takeaways

U.S. Patent 4,233,285 covered 99mTc-DMSA and related mercaptocarboxylic-acid radiopharmaceuticals.
Its core limitations were stannous chloride reduction, pH 2 to 4 and an approximately 3:1 chelator-to-stannous-chloride ratio.
Claims 1 through 3 covered the radiopharmaceutical complex, with claim 3 focused on DMSA and technetium-99m.
Claims 4 through 6 covered an aqueous reagent containing DMSA or another listed chelator, 99mTc pertechnetate and stannous chloride.
Claims 7 through 9 covered intravenous imaging methods.
The patent expired on November 11, 1997.
It has no current U.S. blocking effect and no current Paragraph IV significance.
It is not a current Orange Book patent barrier.
Biosimilar analysis is not applicable because 99mTc-DMSA is a chemical radiopharmaceutical.
Current market risk lies in FDA approval, radiochemical manufacturing, sterile production, technetium supply and any later formulation or manufacturing patents.

FAQs

Can a company sell 99mTc-DMSA without a license to U.S. Patent 4,233,285?

Yes. The patent expired in 1997, so it cannot require a current license in the United States.

Does the patent cover technetium-99m MAG3 or other renal imaging agents?

No. The claims are directed to mercaptocarboxylic acid chelators and their complexes. Technetium-99m MAG3 uses a different chelator and is outside the express DMSA claims.

Does a DMSA kit infringe claim 4 if it is supplied as a lyophilized vial?

The claim expressly recites an aqueous solution. A dry lyophilized kit would require separate construction, but the issue has no current enforcement consequence because the patent is expired.

Can FDA approval of a new DMSA product be blocked by this patent?

No. The expired patent cannot block FDA approval or commercial launch. FDA requirements and any later enforceable patents remain separate issues.

Does the 3:1 chelator-to-stannous-chloride ratio have commercial relevance today?

It may remain relevant to reproducing the patented historical preparation and to understanding the original technology. It does not impose a current legal restriction because the patent term has ended.

References

United States Patent and Trademark Office. (1980). U.S. Patent No. 4,233,285. Patent Center. https://patentcenter.uspto.gov/
U.S. Food and Drug Administration. (n.d.). Technetium Tc 99m succimer injection prescribing information. https://www.accessdata.fda.gov/
United States Code, 35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights. https://uscode.house.gov/
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Switzerland	585050	⤷ Start Trial
Germany	2423167	⤷ Start Trial
France	2229421	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,233,285

Summary for Patent: 4,233,285