United States Patent 6,342,530: Scope, Claims, Expiration, and Ibuprofen Injection Patent Landscape

U.S. Patent No. 6,342,530 covers sterile, aqueous injectable formulations of ibuprofen lysine that contain no inert atmosphere, buffer, excipient, organic solvent, or other salt. Its method claims extend to parenteral treatment of pain, inflammation, fever, patent ductus arteriosus, and intraventricular hemorrhage, particularly in premature neonates. The patent was granted on January 29, 2002, and its enforceable term has expired. The patent therefore presents historical and freedom-to-operate relevance, but it should not currently block a generic or competing ibuprofen injectable product.

What does U.S. Patent 6,342,530 protect?

The patent protects three related subject-matter groups:

A sterile aqueous ibuprofen lysine composition in a vial or ampoule.
Therapeutic methods using that composition by parenteral administration.
Manufacturing methods that dissolve ibuprofen lysine, or ibuprofen and lysine in situ, in sterile water before filling and closing the container.

The patent is directed to a narrow formulation concept rather than to ibuprofen generally. The central technical limitation is a stable aqueous solution of an ibuprofen lysine salt that remains suitable for injection for at least two years without an inert atmosphere and without conventional formulation excipients.

Claim group	Claims	Principal subject matter
Composition	1 and 11	Sterile aqueous ibuprofen lysine solution in vial or ampoule
General treatment	2-7 and 12-17	Parenteral treatment of pain, inflammation, or fever
Premature neonates	4, 8, 14, and 18	Treatment of premature neonates, patent ductus arteriosus, or intraventricular hemorrhage
Preparation using ibuprofen lysine	9 and 19	Dissolving the preformed salt in sterile water and filling the container
In situ salt formation	10 and 20	Dissolving lysine and ibuprofen together in sterile water

What active ingredients fall within the patent claims?

The claims cover the following combinations:

R,S-ibuprofen, meaning racemic ibuprofen, combined with DL-lysine.
R,S-ibuprofen combined with L-lysine.
S-ibuprofen combined with DL-lysine.
S-ibuprofen combined with L-lysine.

The wording does not expressly cover:

R-ibuprofen alone;
ibuprofen sodium, ibuprofen arginine, or other ibuprofen salts;
ibuprofen lysine formulations containing a buffer or excipient if the formulation falls outside the “substantially free” limitation;
nonaqueous injectable formulations;
oral tablets, capsules, suspensions, or transdermal products;
formulations stored under nitrogen or another inert gas.

The phrase “d,l or l-lysine salt of R,S or S-ibuprofen” is central. A product containing only S-ibuprofen lysine can fall within the claims even if it does not contain racemic ibuprofen. Conversely, an injectable product containing ibuprofen sodium would generally require a separate infringement theory.

How broad are the composition claims?

Claims 1 and 11 are composition claims, but their breadth is materially restricted by the formulation limitations.

Claim 1

Claim 1 requires a pharmaceutical composition that:

is in unit dosage form;
is contained in a vial or ampoule;
is suitable for parenteral administration;
contains a therapeutically effective amount of ibuprofen lysine;
is dissolved in sterile water;
is prepared and stored without an inert atmosphere;
is substantially free of excipients, organic solvents, buffers, acids, bases, and other salts; and
has excellent storage stability over two years.

The “consists of” transition is significant. It generally excludes additional ingredients that materially alter the claimed composition. An accused product containing a stabilizer, antioxidant, pH adjuster, chelating agent, buffer, or co-salt would have a strong non-infringement position if the added material is outside the permissible meaning of “substantially free.”

Claim 11

Claim 11 repeats the formulation concept but changes “substantially free” to “absolutely free.” It also contains apparent drafting errors, including “shaving excellent storage stability.” Those errors would be interpreted in light of the specification and prosecution history, but they create potential claim-construction and indefiniteness issues.

“Absolutely free” is narrower than “substantially free” on its face. A formulation with trace amounts of an excipient or contaminant may avoid claim 11 while still raising an issue under claim 1. The practical scope depends on whether the limitation is construed as requiring analytical zero or as excluding intentionally added formulation components.

What do the method-of-treatment claims cover?

Claims 2-8 and 12-18 are dependent method claims built on the composition claims. They do not independently cover every parenteral ibuprofen treatment.

An infringing treatment generally would require administration of the claimed ibuprofen lysine solution. The method claims identify:

pain treatment;
inflammation treatment;
fever reduction;
human treatment;
premature-neonate treatment;
treatment of patients with kidney disease;
injection by intravenous, intramuscular, or subcutaneous routes;
treatment of patent ductus arteriosus; and
treatment of intraventricular hemorrhage in premature neonates.

The method claims are therefore narrower than a claim to administering any injectable ibuprofen product. A product using a different ibuprofen salt, a buffered formulation, or an inert-gas-filled container may avoid the composition incorporated through claim 1 or claim 11.

Premature-neonate claims

Claims 4, 8, 14, and 18 are commercially important because they target neonatal use. Their scope is limited in two ways:

The patient must be a premature neonate for claims 4, 8, 14, and 18.
The administered product must satisfy the underlying composition limitations.

Claim 8 is directed to treating patent ductus arteriosus or intraventricular hemorrhage. The phrase “patent ductus arterious” appears to be a typographical error for “patent ductus arteriosus.” Courts generally interpret obvious typographical errors using the specification and prosecution record when the intended correction is reasonably apparent.

The claims do not necessarily require that the composition be approved for the claimed indication. Patent infringement and FDA approval are separate questions. An approved product could infringe a method claim if it is labeled for the claimed use, while an unapproved use can raise separate inducement and contributory-infringement issues.

What manufacturing processes are protected?

Claims 9, 10, 19, and 20 cover two manufacturing routes.

Preformed-salt process

Claims 9 and 19 require:

Dissolving ibuprofen lysine in sterile water.
Maintaining the solution without an inert atmosphere.
Keeping the formulation substantially or absolutely free of specified additives.
Adding the solution to a vial or ampoule.
Closing the vial or ampoule.

A manufacturer using commercially sourced ibuprofen lysine and following this sequence could fall within the claims if all other limitations are met.

In situ salt-formation process

Claims 10 and 20 require dissolving lysine and ibuprofen in sterile water so that the lysine salt forms in situ. This creates a process distinction from a manufacturer that first produces and isolates the salt before formulation.

The in situ claims may be avoided by:

using a preformed alternative salt;
forming the salt in a nonaqueous medium;
adding a buffer or other excipient;
using an inert atmosphere;
using a process that does not involve the claimed lysine and ibuprofen combination.

A process claim can be infringed even if the resulting product is not separately sold as a patented composition, provided the process steps and claim limitations are satisfied.

When did U.S. Patent 6,342,530 lose exclusivity?

U.S. Patent No. 6,342,530 was granted on January 29, 2002. Public patent records identify a late-1997 priority basis, with the ordinary U.S. patent term running approximately 20 years from the applicable nonprovisional or international filing date. The patent’s ordinary term ended in late 2018, subject to any patent-term adjustment or pediatric extension reflected in the official record.[1]

Any pediatric exclusivity associated with an approved ibuprofen lysine product could extend regulatory exclusivity for a limited period, but it would not restore an expired patent. Patent expiration eliminates the ability to obtain an injunction or damages for post-expiration conduct.

Event	Date or status
Earliest reported priority period	December 1997
U.S. patent grant	January 29, 2002
Patent number	U.S. 6,342,530
Ordinary patent term	Expired in late 2018, subject to term adjustment
Current enforceability	No longer an active blocking patent
Product category	Sterile injectable ibuprofen lysine
Regulatory pathway for competing products	NDA, 505(b)(2), or ANDA depending on product and reference listed drug

What is the Orange Book status of U.S. Patent 6,342,530?

The patent was associated with the injectable ibuprofen lysine product category, including NeoProfen. Orange Book relevance depends on the specific approved NDA and the patent-listing history for that NDA. A patent’s presence in the Orange Book does not extend its statutory term.

For an abbreviated application, a Paragraph IV certification would historically have been relevant if the patent was listed and unexpired. After expiration, the patent no longer presents a live Paragraph IV patent challenge. A generic applicant may still need to address any other listed patents, regulatory exclusivity, labeling restrictions, or product-specific requirements.

FDA approval of NeoProfen and later injectable ibuprofen products established separate regulatory positions for neonatal and adult indications. NeoProfen is associated with ibuprofen lysine for premature neonates, while Caldolor is an injectable ibuprofen product used in broader analgesic and antipyretic settings.[2][3]

Which products and companies are relevant to the patent landscape?

NeoProfen

NeoProfen is the product most directly aligned with the patent’s claimed subject matter. It contains ibuprofen lysine and is used in premature neonates, including treatment of patent ductus arteriosus. The product’s formulation and neonatal indication correspond closely to claims 1, 4, 8, 11, 14, and 18.

Caldolor

Caldolor is an injectable ibuprofen product used for pain and fever. Its formulation, labeling, sponsor, and patent estate must be analyzed separately from NeoProfen. A product containing a different ibuprofen salt or different excipients would not automatically fall within the claims of U.S. 6,342,530.

Generic and alternative injectable ibuprofen products

Potential competitors include:

ANDA products referencing an approved injectable ibuprofen product;
505(b)(2) products with modified concentration, container, route, or excipient profile;
hospital-compounded ibuprofen lysine preparations;
products using ibuprofen sodium or another water-soluble ibuprofen salt;
products using buffered or antioxidant-stabilized aqueous solutions.

The critical distinction is whether the competing product reproduces the claimed “excipient-free” and “absence of inert atmosphere” formulation architecture.

Product strategy	Likely relevance to Patent 6,342,530
Ibuprofen lysine in sterile water, no buffer or excipient	High historical relevance
Ibuprofen lysine with pH adjuster or buffer	Potential claim 1 and 11 avoidance
Ibuprofen sodium injection	Outside the expressly recited salt
Ibuprofen with nitrogen headspace	Potentially outside the claims
Oral ibuprofen lysine	Outside the parenteral composition claims
S-ibuprofen lysine injection	Within the active-ingredient language if other limitations are met
Racemic ibuprofen lysine injection	Within the active-ingredient language if other limitations are met

What Paragraph IV challenge risks existed?

Before expiration, a generic applicant could have filed a Paragraph IV certification asserting that the patent was invalid, unenforceable, or not infringed. The principal technical and legal attack points would have included:

Anticipation

An earlier injectable ibuprofen lysine formulation containing sterile water and no inert atmosphere could anticipate the composition claims. The reference would need to disclose the combination of the active salt, container, aqueous vehicle, absence of listed additives, parenteral suitability, and relevant stability characteristics.

Obviousness

The claims combine known elements:

water-soluble ibuprofen lysine;
sterile water;
injectable packaging;
oxygen exposure;
storage stability.

An obviousness challenge would focus on whether a skilled formulator would have expected ibuprofen lysine to remain stable for two years without a buffer, antioxidant, or inert gas.

Indefiniteness

The terms “excellent storage stability,” “substantially free,” and “absolutely free” could be challenged as insufficiently precise. The specification’s test methods and stability data would determine whether those terms have objective boundaries.

Enablement and written description

The claims cover both racemic and S-ibuprofen, two lysine forms, multiple treatment routes, and multiple indications. A challenger could argue that the disclosure does not enable the full genus without undue experimentation or does not adequately support every claimed species.

Claim construction

The use of “consists of” and “absolutely free” creates a narrow claim scope. The absence of an inert atmosphere is also unusual. A product manufactured under nitrogen, even if later exposed to air, could generate a dispute over whether the claim requires the entire preparation and storage process to occur without inert gas.

How strong was the patent estate?

The patent had strong product relevance for a very specific formulation but limited breadth outside that formulation.

Strength factor	Assessment
Product-formulation fit	Strong for excipient-free ibuprofen lysine injection
Active-ingredient breadth	Moderate; covers racemic and S-ibuprofen with specified lysine salts
Dosage-form breadth	Narrow; vial or ampoule, unit-dose sterile solution
Route breadth	Moderate; parenteral, with injection subclaims
Indication breadth	Moderate; general pain, inflammation, fever, and neonatal uses
Manufacturing coverage	Meaningful; includes preformed and in situ salt routes
Design-around potential	High; buffers, alternative salts, inert gas, or different formulations
Current enforcement value	None after expiration
Biosimilar protection	Not applicable

The patent was more vulnerable to formulation design-arounds than a broad compound patent. Its commercial value depended on whether competitors needed the particular unbuffered ibuprofen lysine solution and whether the product had to match the neonatal formulation.

What patent litigation and settlements affected the patent?

No currently enforceable litigation right arises from U.S. Patent 6,342,530 because the patent term has expired. Historical litigation, Paragraph IV notices, or settlement agreements would need to be assessed from the relevant NDA holder’s court docket and FDA patent-listing history. The patent number alone does not establish that a specific generic applicant litigated or settled with the patentee.

There is no biosimilar pathway for ibuprofen. Ibuprofen is a small-molecule active pharmaceutical ingredient, so competitive entry is governed by the ANDA, 505(b)(2), or full NDA pathways rather than the biosimilar provisions of the Public Health Service Act.

What generic entry risks remain?

Patent risk from U.S. Patent 6,342,530 is no longer material. Remaining entry risks are regulatory and commercial:

unexpired patents listed against the relevant reference product;
six-month pediatric exclusivity, if applicable to a specific regulatory product;
product-specific clinical requirements;
sterile injectable manufacturing capability;
container-closure integrity;
particulate and endotoxin controls;
concentration and dosing differences;
neonatal labeling requirements;
hospital contracting and formulary access;
limited market size for premature-neonate indications.

A generic manufacturer can generally design around the historical patent by using a different ibuprofen salt, adding a permitted formulation component, using a different container or headspace, or pursuing a different regulatory reference.

What manufacturing and geographic barriers remain?

The patent’s geographic effect was limited to the United States. Foreign counterparts, if any, required separate validity and expiration analysis in each jurisdiction. Expiration of the U.S. patent does not establish expiration of related European, Canadian, Japanese, or other national patents.

The principal current barriers are manufacturing rather than patent-based:

aseptic filling;
validated sterilization and filtration;
low-particulate injectable production;
stability testing;
container-closure validation;
neonatal dosing and labeling;
reliable supply of pharmaceutical-grade lysine and ibuprofen;
regulatory approval for the selected injectable presentation.

The historical patent does not block a manufacturer that uses an alternative formulation architecture, but manufacturing under sterile injectable standards remains capital-intensive.

Key Takeaways

U.S. Patent 6,342,530 covers sterile aqueous ibuprofen lysine injection in a vial or ampoule.
The claims require the absence of an inert atmosphere and substantially exclude buffers, excipients, organic solvents, acids, bases, and other salts.
The patent covers both racemic and S-ibuprofen when combined with DL-lysine or L-lysine.
Claims 8 and 18 target patent ductus arteriosus and intraventricular hemorrhage in premature neonates.
Claims 9, 10, 19, and 20 cover both preformed-salt and in situ manufacturing routes.
The patent’s ordinary term expired in late 2018, subject to any applicable term adjustment or pediatric extension.
Paragraph IV risk under this patent is historical rather than current.
The patent does not cover all injectable ibuprofen products, ibuprofen sodium, oral ibuprofen, or formulations containing materially different excipients.
Biosimilar analysis is not applicable because ibuprofen is a small-molecule drug.
Current competition is governed primarily by regulatory requirements, sterile manufacturing capability, remaining product-specific patents, and commercial access.

FAQs

Does U.S. Patent 6,342,530 cover Caldolor?

Not automatically. Coverage depends on Caldolor’s active salt, excipients, headspace, container, and manufacturing process. A formulation containing a different salt or material excipients may fall outside the claims.

Can a company market ibuprofen lysine injection after expiration of Patent 6,342,530?

Yes, patent expiration removes this patent as a blocking right. The product still requires an appropriate FDA approval pathway and compliance with sterile injectable manufacturing requirements.

Does the patent cover S-ibuprofen lysine?

Yes. The claim language expressly includes S-ibuprofen combined with DL-lysine or L-lysine, provided the remaining composition limitations are satisfied.

Is an ibuprofen lysine formulation with a buffer outside the patent?

It may be. The claims require the formulation to be substantially or absolutely free of buffers and other listed components. The result depends on the amount, purpose, and legal construction of the added buffer.

Are hospital-compounded ibuprofen injections protected by the patent?

The patent historically could have applied to a compounded product or process if all claim limitations were met. Since the patent has expired, the principal issues are now compounding law, FDA requirements, sterility, quality control, and product liability.

References

United States Patent and Trademark Office. (2002). U.S. Patent No. 6,342,530, Stable injectable ibuprofen formulation.
U.S. Food and Drug Administration. (2006). NeoProfen (ibuprofen lysine) injection prescribing information.
U.S. Food and Drug Administration. (2009). Caldolor (ibuprofen) injection prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
United States Code, 35 U.S.C. §§ 154, 271, and 282.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	293444	⤷ Start Trial
Canada	2361160	⤷ Start Trial
Germany	60110185	⤷ Start Trial
European Patent Office	1205181	⤷ Start Trial
Japan	2002193799	⤷ Start Trial
Mexico	PA01011629	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,342,530

Summary for Patent: 6,342,530