United States Patent 5,852,002: Claim Scope, Exclusivity, Patent Landscape, and Generic Risk

U.S. Patent 5,852,002 protects pharmaceutical compositions and treatment methods that combine hyaluronic acid or a nontoxic salt with a therapeutic agent to improve transport through underperfused or pathological tissue and into individual cells. The claims focus on three technical elements: the therapeutic agent, hyaluronic acid with a molecular weight of 150,000 to 750,000 daltons, and a hyaluronic-acid dosage exceeding 10 mg, with several claims also requiring less than 3,000 mg.

The patent’s claim architecture covers broad therapeutic use, anti-infective treatment, implant-associated infections, and topical infection prevention using antimetabolites. The patent is directed to a drug-delivery combination, not to hyaluronic acid alone or to a specific antibiotic.

What does U.S. Patent 5,852,002 protect?

The patent protects the use of intermediate-molecular-weight hyaluronic acid as a transport-enhancing component for therapeutic agents administered to diseased or poorly perfused tissue.

Claim group	Covered subject matter	Principal limitations
Claim 1	Broad treatment method	Human treatment; underperfused or pathological tissue; medicinal or therapeutic agent; hyaluronic acid or salt; 150,000-750,000 daltons; more than 10 mg and less than 3,000 mg
Claims 2-3	Anti-infective pharmaceutical dosage	Antibiotic, antibacterial, antimicrobial, optionally ascorbic acid; hyaluronic acid dosage above 10 mg; claim 3 requires sodium hyaluronate
Claims 4, 6-7	Implant-associated infection	Antibiotic treatment of infected tissue surrounding an implant; hyaluronic acid within the stated molecular-weight and dosage ranges; claim 7 requires sodium hyaluronate
Claims 5 and 6	Anti-infective treatment methods	Administration of antibiotic, antibacterial, or antimicrobial agent with hyaluronic acid
Claims 8-9	Topical infection-prevention composition	Antimetabolite agent; hyaluronic acid above 10 mg and below 3,000 mg; claim 9 requires sodium hyaluronate
Claims 10-11	Topical infection-prevention method	Administration of an antimetabolite with hyaluronic acid; claim 11 requires sodium hyaluronate

The central inventive concept is the combination of a therapeutic agent and hyaluronic acid intended to improve delivery through tissue and cell membranes. A product that contains hyaluronic acid but does not use it for the claimed transport function would not automatically fall within the claims.

What are the key claim limitations?

Hyaluronic acid identity

The claims cover:

Hyaluronic acid;
Nontoxic salts of hyaluronic acid;
Combinations of hyaluronic acid and its nontoxic salts.

Sodium hyaluronate is expressly covered by dependent claims 3, 7, 9, and 11. Because sodium hyaluronate is a salt of hyaluronic acid, it is also within the broader independent claims when the other limitations are met.

The claims do not expressly require a particular source, purity grade, crosslinking status, concentration, route of administration, dosage form, or commercial supplier.

Molecular-weight range

The molecular-weight limitation is 150,000 to 750,000 daltons. Unless the specification or prosecution history imposes a narrower interpretation, the range presumptively includes both endpoints.

This limitation is material. A formulation using hyaluronic acid below 150,000 daltons or above 750,000 daltons would have a potential literal-infringement defense, although equivalence arguments could remain relevant depending on the product and prosecution history.

The molecular weight must be assessed for the hyaluronic-acid form used in the accused formulation. A product containing a distribution of polymer sizes may raise questions about whether the claimed range applies to average molecular weight, a predominant fraction, or individual polymer molecules. The answer depends on the patent specification, analytical method, and prosecution record.

Dosage limitation

The claims divide into two dosage structures:

Claim 1 and claims 4-11 generally require more than 10 mg and, where stated, less than 3,000 mg.
Claims 2 and 3 require a hyaluronic-acid dosage greater than 10 mg but do not include the express upper limit of less than 3,000 mg.

The ranges are limitations on the amount of hyaluronic acid, not necessarily on the total product weight or the amount of therapeutic agent. A product with 10 mg exactly would not satisfy a limitation requiring an amount “greater than 10 mg.” A product with exactly 3,000 mg would not satisfy a limitation requiring an amount “less than 3000 mg.”

Transport and penetration function

Each independent claim requires hyaluronic acid to facilitate transport or penetration of the therapeutic agent through tissue and cell membranes into individual cells.

This functional language creates two issues:

The formulation must be used for the claimed transport purpose.
The scope may depend on whether the limitation is interpreted as a required result, an intended use, or a structural-functional limitation.

For method claims, actual administration for the claimed purpose is central. For composition claims, the analysis may turn on whether the formulation is reasonably capable of performing the claimed function and whether its labeling, instructions, formulation design, or marketing establish the intended use.

How broad is claim 1?

Claim 1 is the broadest claim in the set. It covers treatment of a disease or condition involving:

Underperfused tissue;
Pathological tissue; or
Both categories.

The therapeutic agent can be a medicinal agent, a therapeutic agent, or a combination. The claim does not restrict the agent to antibiotics or antimetabolites. Potentially relevant categories could include anti-infectives, anti-inflammatory agents, cytotoxic agents, wound-healing agents, analgesics, vascular agents, and other drugs, provided the claimed transport and tissue conditions are present.

The breadth is narrowed by five cumulative requirements:

Human treatment.
Underperfused or pathological tissue.
A therapeutically effective amount of the agent.
Hyaluronic acid or a nontoxic salt with a molecular weight of 150,000-750,000 daltons.
More than 10 mg and less than 3,000 mg of the hyaluronic-acid form.

Claim 1 does not expressly require infection, an implant, topical administration, sodium hyaluronate, or a particular route of administration.

What formulations are protected?

The claims cover formulations containing a therapeutic agent and hyaluronic acid or a hyaluronate salt in a pharmaceutically acceptable excipient.

Covered formulation characteristics

A potentially covered product could include:

An antibiotic plus sodium hyaluronate;
An antimicrobial plus hyaluronic acid;
An antibacterial plus hyaluronate;
An antimetabolite plus sodium hyaluronate;
A broader therapeutic agent plus hyaluronic acid for delivery into pathological tissue;
Ascorbic acid in combination with an antibiotic or antimicrobial, under claims 2 and 5.

The claims do not expressly require:

A gel;
An injectable formulation;
A cream, ointment, implant coating, spray, tablet, capsule, or wound dressing;
A specific excipient;
A particular antibiotic;
A particular antimetabolite;
A fixed ratio between hyaluronic acid and the therapeutic agent.

That breadth gives the patent potentially wide formulation coverage, but only where the dosage, molecular-weight, tissue, and functional limitations are satisfied.

What formulations may fall outside the claims?

Potential design-around positions include:

Hyaluronic acid below 150,000 daltons;
Hyaluronic acid above 750,000 daltons;
A hyaluronic-acid amount of 10 mg or less;
A hyaluronic-acid amount of 3,000 mg or more for claims containing the upper limit;
No hyaluronic acid or hyaluronate;
A different polymer used for drug transport;
A formulation not intended to facilitate penetration into individual cells;
Use in normal, adequately perfused tissue where the underperfused or pathological-tissue limitation is absent;
A nonhuman use, for claims expressly limited to humans.

These positions require product-specific analysis. A label change alone may not eliminate risk if the actual use and clinical instructions still satisfy the method claims.

How do the claims differ by therapeutic field?

Anti-infective claims

Claims 2, 3, 5, 6, and 7 cover antibiotics, antibacterials, and antimicrobials. Claims 2 and 5 also refer to optional ascorbic acid.

The anti-infective claims are narrower than claim 1 because they require infection treatment or an anti-infective agent. They may nevertheless be commercially important because implant-associated infections and poorly perfused infected tissue are specialized indications in which enhanced tissue penetration can be a central product rationale.

Implant-associated infection claims

Claims 4 and 6 require infection surrounding an implant. These claims are directed to treatment of infected tissue around an implanted medical device, prosthesis, graft, or similar implant.

The claims do not specify:

The type of implant;
The anatomical location;
The antibiotic;
Whether the implant is removed;
Whether the treatment is local or systemic;
Whether hyaluronic acid is applied to the implant, surrounding tissue, or delivered separately.

A product marketed for infection around orthopedic, dental, cardiovascular, ophthalmic, or other implants could raise claim questions if its use and formulation satisfy the remaining limitations.

Topical antimetabolite claims

Claims 8-11 cover prevention or treatment of topical infection using an antimetabolite with hyaluronic acid. These claims are structurally narrower because they require an antimetabolite rather than any therapeutic agent.

The term “topical” limits the claims to a local application or use. The claims do not identify a particular antimetabolite, skin condition, wound type, or topical dosage form.

How strong is the patent estate based on the asserted claims?

The claim set has broad conceptual coverage but several technical and legal pressure points.

Strength	Risk or limitation
Claim 1 covers a broad range of therapeutic agents	Requires underperfused or pathological tissue and a specific transport function
Covers hyaluronic acid and nontoxic salts	Molecular-weight range may exclude many commercial grades
Covers composition and method claims	Composition claims depend on dosage and formulation facts; method claims depend on actual use
Covers implant-associated infections	Narrow indication and potentially limited commercial products
Covers sodium hyaluronate expressly	Dependent claims add no protection against products using other qualifying salts unless the independent claim is satisfied
Claims multiple therapeutic categories	Written-description, enablement, definiteness, and construction issues may arise across the full breadth
Claims dosage amounts	Dosage records and batch specifications become important infringement evidence

The strongest practical coverage is likely against a product that expressly combines an antibiotic or other therapeutic agent with sodium hyaluronate in the claimed molecular-weight range and dosage, and that is labeled for infected, poorly perfused, or pathological tissue.

The weakest scenarios involve products with unclear tissue targeting, no stated transport function, molecular-weight specifications outside the range, or hyaluronic-acid quantities near the claim thresholds.

When did U.S. Patent 5,852,002 lose exclusivity?

Patent term must be determined from the patent’s effective filing date, applicable pre- or post-URAA term rules, patent-term adjustment, patent-term extension, terminal disclaimers, and maintenance-fee status.

For a patent issued in 1998, the ordinary statutory term would generally have ended by the mid-to-late 2010s, depending on the effective filing date and the governing term regime. The patent therefore should not be treated as a currently enforceable U.S. exclusion right without confirming the USPTO Patent Center record and any term adjustment or extension.

A patent expiration date is not the same as regulatory exclusivity. Even if the patent had remained in force, it would not itself establish FDA approval, New Drug Application exclusivity, or a right to market a product.

What is the Orange Book status of U.S. Patent 5,852,002?

The patent is not shown in the supplied material as an Orange Book-listed patent. The claims describe a drug-delivery platform and broad treatment methods rather than a clearly identified FDA-approved drug product.

Orange Book listing generally depends on an approved New Drug Application and patent information submitted for the approved product. A patent can be technically relevant to a drug product without being listed in the Orange Book. Conversely, the absence of an Orange Book listing does not resolve validity, infringement, or regulatory approval questions (U.S. Food and Drug Administration, 2024).

For generic applicants, a Paragraph IV certification would be relevant only if the patent were listed for the reference product and had not expired. If the patent term had ended, a Paragraph IV challenge would ordinarily have no practical role for that patent.

What Paragraph IV challenges and generic-entry risks exist?

The supplied claims do not identify a reference listed drug, NDA, ANDA, generic challenger, or Paragraph IV notice letter. The patent’s claim structure suggests the following risk analysis:

Small-molecule generic

A conventional generic antibiotic would not necessarily infringe. Risk increases only if the generic:

Contains hyaluronic acid or a qualifying hyaluronate salt;
Uses the claimed molecular-weight range;
Contains more than 10 mg of the polymer;
Is labeled for the claimed tissue or infection indications;
Is intended to facilitate intracellular transport.

A generic containing the antibiotic alone would generally present a different infringement profile.

Combination product

A combination product pairing an antibiotic with sodium hyaluronate presents the highest direct claim risk. The product should be assessed against each limitation, including polymer molecular weight, polymer dosage, tissue indication, and administration instructions.

Implant coating or local delivery product

An implant coating or local depot containing an antibiotic and hyaluronate may implicate claims 4 and 6 if the product is used for infection surrounding an implant. The product’s physical location and label would be important.

Biosimilar risk

There is no meaningful biosimilar pathway issue apparent from these claims. The patent does not claim a biologic active ingredient. Hyaluronic acid is a polysaccharide excipient or delivery component in the claim structure, while the therapeutic agents may be small molecules or other medicines. FDA biosimilar competition under the Biologics Price Competition and Innovation Act is therefore not the primary competitive pathway for this patent (FDA, 2024).

Which companies are challenging U.S. Patent 5,852,002?

No challenger, litigation, settlement, licensing transaction, or Paragraph IV notice is identified in the supplied patent claims. The claims alone do not establish:

Whether the patent was litigated;
Whether it was reexamined;
Whether any claim was canceled or amended;
Whether a terminal disclaimer applies;
Whether a license was granted;
Whether a company commercialized a covered product;
Whether any settlement restricted generic or competing entry.

A reliable litigation and licensing analysis requires the patent’s prosecution and litigation records, including USPTO Patent Center, PACER, district-court dockets, Federal Circuit decisions, and FDA patent-listing records.

What is the competitive landscape?

The relevant competitive landscape is platform-based rather than molecule-specific.

Competitive approach	Relationship to Patent 5,852,002
Antibiotic without hyaluronic acid	Usually outside the central combination concept
Antibiotic with low-molecular-weight hyaluronic acid	Potential molecular-weight design-around
Antibiotic with high-molecular-weight hyaluronic acid	Potential molecular-weight design-around
Sodium hyaluronate plus antibiotic	Closest technical overlap
Polymer-based delivery using chitosan, cyclodextrins, liposomes, or nanoparticles	Potentially outside the claimed hyaluronic-acid limitation
Local implant antibiotic delivery without hyaluronic acid	May avoid the combination claims
Systemic therapy for infection without a claimed tissue-penetration purpose	Potentially outside method claims
Topical antimetabolite without hyaluronic acid	Outside the combination requirement

The patent’s economic value would depend on whether a commercial product needs the claimed molecular-weight and dosage window to achieve a clinically meaningful transport effect. If competing polymers or different hyaluronic-acid molecular weights provide similar performance, the patent’s practical market power would be reduced.

What manufacturing and intellectual-property barriers matter?

The principal technical barriers are:

Controlling hyaluronic-acid molecular-weight distribution;
Demonstrating stability of the polymer and therapeutic agent together;
Maintaining a polymer dosage within the claimed range;
Establishing reproducible penetration into pathological or underperfused tissue;
Controlling microbial contamination and endotoxin levels;
Demonstrating compatibility with the selected excipient and route;
Supporting the transport function with pharmacokinetic, tissue-distribution, or cellular data.

The claims do not appear to require a particular manufacturing process. A manufacturer could therefore face claim risk even when it uses a different synthesis, purification, blending, sterilization, or filling process, provided the finished product and intended use satisfy the claims.

How does this patent compare with formulation and method-of-use patents?

U.S. Patent 5,852,002 combines both categories:

Claims 2, 4, and 8 are dosage or composition claims.
Claims 1, 5, 6, and 10 are treatment or prevention method claims.
Claims 3, 7, 9, and 11 narrow the composition or method to sodium hyaluronate.

Composition claims can create product-level exposure because infringement may be based on the formulation itself. Method claims usually require performance of the claimed treatment, which can make labeling, instructions, clinical use, and promotional materials important.

The patent is broader than a conventional formulation patent limited to a defined ratio or dosage form, but narrower than a pure composition-of-matter patent because it does not claim hyaluronic acid or a therapeutic agent in isolation.

What generic launch scenarios exist?

Immediate launch after patent expiry

If the patent has expired and no later family patent covers the same product, a generic or competing combination product would not face ongoing exclusion from this patent.

Paragraph VIII or non-infringement route

If the patent were listed for an approved product but did not cover the generic’s formulation or use, an applicant could consider a non-infringement or Paragraph VIII position, subject to the Orange Book listing and applicable FDA procedures.

Paragraph IV challenge

A Paragraph IV certification would be relevant only if the patent remained listed and unexpired. Potential grounds could include:

The generic lacks hyaluronic acid;
The molecular weight falls outside 150,000-750,000 daltons;
The dosage is 10 mg or less;
The dosage is 3,000 mg or more where the upper limit applies;
The label does not include treatment of underperfused or pathological tissue;
The product is not directed to implant-associated infection;
The claimed transport function is absent;
The claims are invalid for anticipation, obviousness, lack of enablement, written-description failure, or indefiniteness.

At-risk launch

An at-risk launch would be commercially relevant only if the patent were enforceable and the product’s label or formulation closely matched the claim limitations. The highest-risk product would be an antibiotic-sodium-hyaluronate combination expressly labeled for infected, poorly perfused tissue or implant-associated infection.

Key Takeaways

U.S. Patent 5,852,002 claims therapeutic-agent delivery using hyaluronic acid or a nontoxic hyaluronate salt.
The principal molecular-weight range is 150,000 to 750,000 daltons.
Most claims require more than 10 mg of hyaluronic acid; several also require less than 3,000 mg.
Claim 1 is broad and covers medicinal or therapeutic agents used in underperfused or pathological tissue.
Claims 2-7 focus on antibiotics, antibacterials, antimicrobials, and implant-associated infections.
Claims 8-11 focus on topical infection prevention or treatment using antimetabolites.
Sodium hyaluronate is expressly covered by dependent claims 3, 7, 9, and 11.
The strongest commercial overlap is an antibiotic-sodium-hyaluronate product within the stated molecular-weight and dosage ranges.
The patent does not establish FDA approval, Orange Book listing, biosimilar protection, or current enforceability.
Based on ordinary U.S. patent-term rules for a patent issued in 1998, the patent’s original term would generally have ended by the mid-to-late 2010s, subject to the official term record.
Later family patents, continuation claims, licensing rights, or product-specific Orange Book patents could create separate exposure.

FAQs

Does U.S. Patent 5,852,002 claim sodium hyaluronate?

Yes. Sodium hyaluronate is expressly recited in dependent claims 3, 7, 9, and 11. It also falls within the broader references to hyaluronic acid and its nontoxic salts in the independent claims.

Does an antibiotic gel automatically infringe the patent?

No. The gel would need to satisfy the relevant limitations, including qualifying hyaluronic-acid molecular weight, dosage, tissue or infection indication, and the claimed transport or penetration function.

Are implant coatings covered by the patent?

Potentially. Claims 4 and 6 address infections surrounding implants, but an implant coating would need to satisfy the remaining limitations, including the hyaluronic-acid molecular-weight and dosage requirements.

Is hyaluronic acid below 150,000 daltons outside the claims?

It is outside the literal molecular-weight range recited in the claims. Equivalence and claim-construction issues would depend on the patent record and the specific formulation.

Does the patent cover a therapeutic agent without hyaluronic acid?

No. Hyaluronic acid or a qualifying hyaluronate salt is a required element of every claim supplied.

References

U.S. Patent No. 5,852,002. (1998). United States Patent and Trademark Office.

United States Code, 35 U.S.C. §§ 154, 271, 282, 283, 284, 285.

United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure. U.S. Department of Commerce.

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Canada	612307	Sep 21, 1989

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	175	⤷ Start Trial
African Regional IP Organization (ARIPO)	448	⤷ Start Trial
African Regional IP Organization (ARIPO)	475	⤷ Start Trial
African Regional IP Organization (ARIPO)	476	⤷ Start Trial
African Regional IP Organization (ARIPO)	618	⤷ Start Trial
African Regional IP Organization (ARIPO)	9000206	⤷ Start Trial
African Regional IP Organization (ARIPO)	9300491	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,852,002