US Patent 5,336,691: Tramadol-Acetaminophen Claims, Expiration, Litigation, and Generic Risk

US Patent No. 5,336,691 covered pharmaceutical compositions combining tramadol and acetaminophen, including tramadol hydrochloride and racemic tramadol, across broad weight-ratio ranges. The patent issued on August 9, 1994, and its pre-URAA 17-year term generally expired on August 9, 2011. It no longer creates a patent barrier to generic tramadol-acetaminophen products in the United States. Its commercial significance was primarily connected to Ultracet, the tramadol hydrochloride/acetaminophen product marketed by Ortho-McNeil Pharmaceutical, later Janssen-related entities.

The patent’s strongest historical feature was the breadth of claim 1: it did not limit the product to a tablet, immediate-release formulation, dosage strength, indication, or particular manufacturing process. The patent’s current legal blocking value is zero because the patent term has ended.

What does US Patent 5,336,691 cover?

The patent covers pharmaceutical compositions containing both a tramadol material and acetaminophen in a weight ratio ranging from approximately 1:1 to approximately 1:1600.

Patent element	Scope
Tramadol component	“Tramadol material,” with dependent claims specifying tramadol hydrochloride
Acetaminophen component	Required in every composition claim
Broad ratio	About 1:1 to about 1:1600 tramadol material:acetaminophen
Narrow ratio	About 1:5 to about 1:1600
Preferred subrange	About 1:19 to about 1:50
Dosage form	Not specified
Route of administration	Not specified in composition claims
Carrier	Covered by dependent claim 9
Additional active ingredients	Covered by claims 10-14
Therapeutic method	Treatment of pain in a mammal under claim 15

The patent is directed to a combination of two known analgesic agents: tramadol, an opioid analgesic, and acetaminophen, a non-opioid analgesic. The claim set does not require a particular synergistic effect, pharmacokinetic profile, release profile, tablet architecture, or manufacturing step.

How broad is independent claim 1?

Claim 1 is the principal composition claim. It requires only:

A pharmaceutical composition;
A tramadol material;
Acetaminophen; and
A weight ratio of tramadol material to acetaminophen from about 1:1 to about 1:1600.

The claim is broad because it contains no express limitation on:

Tablet, capsule, solution, suspension, or other dosage form;
Immediate-release or extended-release delivery;
Oral, parenteral, or other administration route;
Specific dosage strength;
Specific excipients;
Specific particle size;
Specific dissolution profile;
Treatment of a particular pain condition.

A product containing tramadol and acetaminophen would therefore fall within the literal framework of claim 1 if the relevant weight ratio were within the claimed range and the composition qualified as pharmaceutical.

The term “about” expands the practical boundary beyond the precise numerical endpoints. The scope would depend on the intrinsic evidence, prosecution history, technical context, and how a court construed the ratio. The patent text alone does not establish a fixed percentage tolerance for “about.”

How do claims 2 through 8 narrow the patent scope?

Claims 2 through 8 create nested limitations around the active ingredient and ratio.

Claim	Limitation
1	Tramadol material and acetaminophen, about 1:1 to about 1:1600
2	Tramadol material is tramadol hydrochloride
3	Tramadol hydrochloride is racemic
4	Ratio is about 1:1
5	Ratio is about 1:5 to about 1:1600
6	Ratio is about 1:5
7	Ratio is about 1:19 to about 1:800
8	Ratio is about 1:19 to about 1:50

Claims 4 and 6 are narrow ratio claims. Claims 7 and 8 are more commercially relevant because conventional tramadol-acetaminophen products often use ratios near the lower end of the claimed range.

Claim 8 is particularly important historically. A 37.5 mg tramadol hydrochloride/325 mg acetaminophen tablet has a nominal ratio of approximately 1:8.67 by weight when calculated using the labeled quantities. If the patent’s ratio is calculated using a different definition of “tramadol material,” such as tramadol free base equivalent rather than tramadol hydrochloride salt weight, the ratio analysis changes. The relevant calculation would depend on the patent’s specification and claim-construction record.

What formulations are protected by US 5,336,691?

The composition claims potentially cover a wide range of dosage forms, provided the formulation contains both active ingredients in the claimed ratio.

Potentially covered dosage forms

Immediate-release tablets;
Capsules;
Powder-filled dosage forms;
Oral solutions;
Oral suspensions;
Sachets;
Multiparticulate formulations;
Combination products containing additional active ingredients.

Claim 9 expressly adds a pharmaceutically acceptable carrier. Most commercial drug products contain excipients, so this dependent claim would have been commercially relevant but narrower than claim 1.

Claims 10 through 14 cover compositions that also contain:

A decongestant or bronchodilator;
An antitussive;
An antihistamine or nonsedating antihistamine;
A muscle relaxant;
A sleep aid.

Those claims extend the combination concept into multi-ingredient products. They do not require a particular identity, dose, or formulation of the additional ingredient.

The patent does not expressly claim an extended-release formulation, a specific dissolution specification, a bilayer tablet, a coated tablet, or a particular excipient system. Separate formulation patents would have been required to protect those technical features.

What does method-of-use claim 15 protect?

Claim 15 covers a method of treating pain in a mammal by administering an effective amount of the composition of claim 1.

Its required elements are:

A mammal;
Pain;
Administration of the claimed tramadol-acetaminophen composition;
An effective amount.

The claim is broader than a disease-specific method claim because it does not limit treatment to postoperative pain, osteoarthritis, neuropathic pain, dental pain, back pain, or another defined indication.

The method claim is narrower than claim 1 in one respect: it requires use for treating pain. A composition manufacturer could infringe claim 1 without practicing claim 15, while a treatment using a composition outside the claimed ratio would not satisfy claim 15.

When did US Patent 5,336,691 lose exclusivity?

The patent issued August 9, 1994. Because it was filed and issued before the Uruguay Round Agreement Act transition, its ordinary term was generally 17 years from grant rather than 20 years from its earliest effective nonprovisional filing date. The resulting expiration date was August 9, 2011, subject to any applicable patent-term adjustment, extension, disclaimer, or pediatric exclusivity.

Event	Date
Priority date listed in patent records	December 10, 1991
Patent issued	August 9, 1994
Ordinary 17-year expiration	August 9, 2011
Current status	Expired
Current blocking effect	None

The FDA Orange Book historically listed US 5,336,691 for Ultracet-related regulatory protection. An expired patent cannot support a current 30-month stay under the Hatch-Waxman framework. Generic applicants therefore no longer need to establish a commercial launch strategy around Paragraph IV litigation against this patent. The FDA’s Orange Book remains the relevant source for historical and current listed-patent status.[1,2]

What was the relationship between the patent and Ultracet?

Ultracet is the commercial tramadol hydrochloride/acetaminophen combination associated with this patent. The FDA approved Ultracet under NDA 21-123 in 2001 for the short-term management of acute pain when treatment with tramadol and acetaminophen is appropriate.[3]

A conventional Ultracet tablet contained:

Tramadol hydrochloride: 37.5 mg;
Acetaminophen: 325 mg.

The patent’s claimed combination ratio and its treatment claim aligned closely with that commercial product. The patent therefore had direct product-level relevance rather than merely covering a peripheral manufacturing technology.

The patent did not control tramadol alone or acetaminophen alone. It controlled the claimed combination. Separate patents, regulatory exclusivities, controlled-substance requirements, labeling obligations, and manufacturing approvals remained legally distinct issues.

What was the Orange Book status of US 5,336,691?

US 5,336,691 was historically listed in the Orange Book in connection with the Ultracet reference product. Its listing provided the basis for patent certifications by abbreviated new drug application applicants during the patent term.

After expiration, the patent ceased to provide a current Orange Book patent barrier. The practical consequences were:

No continuing patent-based 30-month stay;
No live Paragraph IV exposure based solely on this patent;
No need for a generic applicant to design around the claim for US launch purposes;
Continued need to satisfy FDA requirements for bioequivalence, labeling, chemistry, manufacturing, and controls.

FDA’s generic approval pathway remained available because tramadol-acetaminophen is a small-molecule combination product, not a biologic requiring a biosimilar application under section 351(k) of the Public Health Service Act.[2,4]

Which companies challenged the patent, and what is the litigation status?

The patent’s principal competitive pressure came from ANDA applicants seeking approval of generic tramadol hydrochloride/acetaminophen tablets. The relevant regulatory mechanism was an ANDA with a Paragraph IV certification during the patent term, or a certification reflecting expiration after August 2011.

The patent is now expired. No ongoing infringement case based solely on US 5,336,691 can prevent a generic launch. Historical litigation records should be reviewed separately for:

District court validity challenges;
Infringement actions against ANDA applicants;
Claim-construction rulings;
Settlements containing launch dates;
Covenants not to sue;
Separate patents covering formulation or manufacturing features.

The expiration of the patent eliminates present infringement exposure under its claims, but it does not eliminate potential disputes involving later patents, trade secrets, product labeling, regulatory exclusivity, or non-patent manufacturing rights.

How strong was the patent estate?

Historical strength

The patent had meaningful historical breadth because claim 1 covered the active-ingredient combination across a very wide ratio range. Its composition claims were not confined to a particular product architecture. That structure reduced the number of obvious formulation design-arounds.

The method claim also had commercial relevance because it covered administration of the combination for pain generally rather than a narrow disease indication.

Vulnerabilities

The principal validity pressure points would have included:

Anticipation by prior-art disclosures of tramadol and acetaminophen combinations;
Obviousness based on combining two known analgesics;
Written-description support for the full 1:1 to 1:1600 ratio range;
Enablement across all claimed dosage forms and ratios;
Interpretation of “tramadol material”;
Interpretation of “about”;
Whether the specification supported the claimed therapeutic result across the entire range.

A court would also examine the patent’s prosecution history and prior-art record. The issued claims alone do not establish whether the claims survived a particular validity challenge.

Current strength

The estate has no remaining exclusionary strength in the United States because the patent expired in 2011. Its current value is historical, documentary, and potentially relevant to freedom-to-operate analyses involving foreign counterparts with different expiration dates.

Are biosimilar risks relevant?

No. Tramadol-acetaminophen is a conventional small-molecule combination, not a biologic. The competitive threat is from generic ANDA products, not biosimilars.

Generic applicants must address:

Active-ingredient identity;
Strength;
Dosage form;
Route of administration;
Bioequivalence;
Labeling;
Manufacturing controls;
Combination-product quality requirements.

The patent did not create a biologics-style interchangeability issue.

What generic entry risks remain?

For the specific claims of US 5,336,691, no meaningful patent-entry risk remains in the United States. Generic manufacturers can produce tramadol-acetaminophen products without infringing an unexpired claim of this patent.

Remaining launch risks may involve:

Risk category	Current relevance
US 5,336,691	No current patent barrier
Later formulation patents	Requires separate review
Manufacturing patents	Requires separate review
FDA approval	Material
Bioequivalence	Material
Controlled-substance compliance	Material
Product liability	Material
Supply of tramadol hydrochloride	Commercial and regulatory issue
Foreign patents	Jurisdiction-specific

Tramadol is subject to controlled-substance regulation in the United States. That requirement affects manufacturing, distribution, recordkeeping, and supply-chain operations but does not revive the expired patent.[5]

How does US 5,336,691 compare with later formulation patents?

US 5,336,691 is an active-ingredient combination patent. It protects the presence of tramadol and acetaminophen in specified ratios.

A later formulation patent would normally protect a narrower technical feature, such as:

Extended release;
Abuse deterrence;
Specific dissolution performance;
Multiparticulate delivery;
Reduced adverse effects;
Improved stability;
A particular manufacturing process.

The older patent was broader at the ingredient-combination level. A later formulation patent could remain enforceable after 2011, but it would not restore exclusivity over every immediate-release tramadol-acetaminophen product.

What geographic coverage did the patent provide?

US 5,336,691 provided protection only in the United States. Patent protection in Europe, Canada, Australia, Japan, or other jurisdictions depended on separately filed national or regional counterparts.

Expiration was jurisdiction-specific. A foreign family member could have a different term because of:

Different filing dates;
National-phase timing;
Patent-term adjustment or extension;
Supplementary protection certificates;
Local prosecution history;
Local terminal disclaimers.

A US freedom-to-operate conclusion cannot be applied to foreign markets without reviewing the relevant national patent families.

Key Takeaways

US 5,336,691 covered tramadol-acetaminophen compositions in ratios from about 1:1 to about 1:1600.
Dependent claims covered tramadol hydrochloride, racemic tramadol, preferred ratios, carriers, and additional active ingredients.
Claim 15 covered treating pain in a mammal with the claimed composition.
The patent issued August 9, 1994, and generally expired August 9, 2011.
The patent was historically associated with Ultracet.
It is no longer a US patent barrier to generic tramadol-acetaminophen products.
No biosimilar pathway is relevant because this is a small-molecule combination.
Current launch analysis should focus on later patents, FDA requirements, controlled-substance compliance, manufacturing capacity, and foreign patent rights.

FAQs

Does US 5,336,691 cover tramadol without acetaminophen?

No. Every composition claim requires acetaminophen, and claim 15 requires administration of the claimed combination.

Does the patent cover a 37.5 mg/325 mg tramadol-acetaminophen tablet?

Historically, that product configuration was closely aligned with the claimed combination and Ultracet product. The exact ratio analysis depends on whether “tramadol material” is measured as tramadol hydrochloride salt or tramadol active-moiety equivalent.

Can a generic company launch after expiration without a Paragraph IV challenge?

Yes. Once the patent expired, an applicant no longer needed to challenge the patent as an unexpired barrier. The applicant still needed FDA approval and compliance with all applicable regulatory requirements.

Does adding an antihistamine avoid the patent claims?

Not necessarily. Claim 1 does not exclude additional active ingredients, and claim 12 expressly covers compositions containing an antihistamine or nonsedating antihistamine. The patent is expired in the United States in any event.

Could a foreign patent still block tramadol-acetaminophen sales?

Yes. The US expiration date does not establish the status of foreign counterparts. Each jurisdiction requires a separate patent-family and expiration analysis.

References

United States Patent and Trademark Office. (1994). Pharmaceutical compositions containing tramadol and acetaminophen (U.S. Patent No. 5,336,691).
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations (Orange Book).
U.S. Food and Drug Administration. (2001). Ultracet prescribing information.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA): Generics.
U.S. Drug Enforcement Administration. (2014). Schedules of controlled substances: Placement of tramadol into schedule IV. Federal Register.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0566709	⤷ Start Trial	91079	Luxembourg	⤷ Start Trial
European Patent Office	0566709	⤷ Start Trial	SPC/GB04/012	United Kingdom	⤷ Start Trial
European Patent Office	0566709	⤷ Start Trial	300152	Netherlands	⤷ Start Trial
European Patent Office	0566709	⤷ Start Trial	SPC023/2008	Ireland	⤷ Start Trial
European Patent Office	0566709	⤷ Start Trial	C300152	Netherlands	⤷ Start Trial
Austria	169498	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,336,691

Summary for Patent: 5,336,691