US Patent 6,495,534: Scope, Claim Construction, Expiration and Steroidal Injectable Formulation Landscape

US Patent 6,495,534 covers aqueous injectable suspensions containing a biologically active steroid and L-methionine as a pH-stabilizing agent. The independent claims reach both formulations and manufacturing processes. The patent does not claim the steroid molecules themselves, therapeutic use of those steroids, or nonaqueous and nonparenteral products.

Based on the claims supplied, the broadest commercial risk would have existed for injectable suspensions containing a listed steroid, L-methionine, and a formulation pH controlled within the claimed framework. The patent’s ordinary 20-year term would have placed expiration approximately 20 years after its earliest effective nonprovisional filing or priority date. A current infringement risk requires confirmation of the official Patent Term Adjustment record, terminal disclaimers, maintenance-fee status, and any continuation or divisional patents.

What does US Patent 6,495,534 cover?

The patent covers two related technologies:

A parenteral aqueous suspension containing a steroidal active ingredient and L-methionine in an amount that stabilizes pH.
A process for preparing that suspension by adding L-methionine, alone or with a buffering agent.

The central inventive concept is the use of L-methionine as a pH-controlling component in a steroid suspension. Claim 5 adds a narrower formulation concept: L-methionine and a buffer produce a “pH controlling superadditive effect.”

The patent therefore targets formulation stability rather than steroid pharmacology. Its practical value depends on whether L-methionine is present in the accused product, whether the product is an aqueous suspension for parenteral administration, and whether the formulation exhibits the claimed pH-control function.

What are the independent claims in US 6,495,534?

Claim	Claim type	Core limitations	Breadth
1	Composition	Aqueous suspension; parenteral administration; biologically active steroidal compound; pH-controlling effective concentration of L-methionine; substantially stabilized pH	Broadest composition claim
5	Composition	Aqueous suspension; parenteral administration; steroid; buffering agent; L-methionine; concentrations producing a pH-controlling superadditive effect	Narrower than claim 1
20	Process	Preparing the aqueous suspension by adding an effective concentration of L-methionine	Broad process claim
21	Process	Preparing the suspension by adding L-methionine and a buffering agent at concentrations producing a superadditive effect	Narrower process claim

Claims 1 and 5 are the principal product claims. Claims 20 and 21 are directed to manufacturing activity and may raise different infringement questions, particularly where the finished product is made outside the United States and imported into the United States.

How should claim 1 be construed?

Claim 1 requires the following elements:

A pharmaceutical formulation.
An aqueous suspension.
Parenteral administration.
A biologically active steroidal compound.
L-methionine at a pH-controlling effective concentration.
Substantially stabilized pH.

Each element matters. A product containing L-methionine but lacking a steroidal active ingredient would not satisfy the claim. A steroid solution rather than a suspension may fall outside the literal wording. An oral suspension would also fall outside the express parenteral-administration limitation.

The claim does not specify:

A particular steroid.
A particular concentration of steroid.
A particular concentration of L-methionine.
A particular buffer.
A particular pH range.
A particular syringe, vial, needle, or injection device.
A particular clinical indication.
A particular particle size or polymorph.

The absence of numerical limitations makes claim 1 potentially broad, but its functional limitations create proof issues. An infringement analysis would need to determine whether the amount of L-methionine is “pH controlling” and whether the formulation has “substantially stabilized pH.” Those terms would ordinarily be assessed in light of the specification, examples, prosecution history, and technical testing.

What numerical limitations appear in the dependent claims?

The dependent claims add concentration, pH, steroid identity, excipient, and antioxidant limitations.

Claim	Added limitation
2	L-methionine from about 0.005% to about 5% w/v or w/w
3	pH from about 3.0 to about 8.0
4	Exemestane, medroxyprogesterone acetate, estradiol cypionate, or a mixture of medroxyprogesterone acetate and estradiol cypionate
6	Phosphoric acid salt buffer below 0.4% w/v or w/w
7	Phosphoric acid salt buffer below 0.2% w/v or w/w
8	pH from about 3.0 to about 8.0
9	Enumerated steroid group or pharmaceutically acceptable salt
10	Medroxyprogesterone acetate
11	Methylprednisolone acetate
12	Exemestane
13	Medroxyprogesterone acetate plus estradiol cypionate
14	Medroxyprogesterone acetate from about 1% to 40% w/v
15	Exemestane from about 1% to 25% w/v
16	Medroxyprogesterone acetate from about 1% to 40% w/v and estradiol cypionate from about 0.1% to 5% w/v
17	Surfactant, suspending agent, thickening agent, or density-adjusting agent
18	Specified preservatives
19	Specified antioxidants

The use of “about” creates numerical boundary questions. Courts generally interpret “about” according to the intrinsic record and the level of precision reasonably available in the formulation field. A formulation at 0.005% or 5% L-methionine would fall within the express endpoints of claim 2. A concentration outside those endpoints may still implicate claim 1 if it meets the functional pH-control limitation.

What steroid products are most directly implicated?

The claims identify seven principal steroid compounds or compound classes:

Medroxyprogesterone acetate, or MPA
Exemestane
Estradiol cypionate
Methylprednisolone acetate
Oxabolone cypionate
Clostebol acetate
Testosterone cypionate

The claims also cover a combination of medroxyprogesterone acetate and estradiol cypionate. That combination is commercially associated with injectable contraceptive products such as medroxyprogesterone acetate plus estradiol cypionate formulations.

Medroxyprogesterone acetate

MPA is the most commercially significant steroid identified in the claims. Injectable MPA suspensions have been marketed for contraception and other hormonal indications. A generic or follow-on MPA injectable could attract claim risk if it contains L-methionine as a pH stabilizer and satisfies the aqueous-suspension and parenteral limitations.

Claim 14 is narrower because it requires MPA at approximately 1% to 40% w/v. A conventional depot injection concentration may fall within that range, but the actual formulation must be assessed against the product label and, where necessary, confidential composition data.

Exemestane

Exemestane is an aromatase inhibitor generally associated with oral solid dosage forms. The patent claims an injectable aqueous suspension containing exemestane, including concentrations of approximately 1% to 25% w/v under claim 15. The claims do not establish that an FDA-approved parenteral exemestane product exists.

Estradiol cypionate and combination products

Estradiol cypionate appears both as a standalone steroid and in combination with MPA. Claim 16 requires MPA at approximately 1% to 40% w/v and estradiol cypionate at approximately 0.1% to 5% w/v. This is a product-specific limitation that can narrow exposure for combination formulations while leaving broader claim 1 potentially relevant.

Methylprednisolone acetate

Methylprednisolone acetate is commonly used in injectable suspension products. Claim 11 specifically identifies it, but the patent does not recite a dedicated concentration range for methylprednisolone acetate. An injectable methylprednisolone acetate product would require analysis of its excipient composition, pH-control system, and manufacturing process.

Testosterone cypionate and other listed steroids

Testosterone cypionate, oxabolone cypionate, and clostebol acetate are included in claim 9. Their inclusion expands the chemical scope, but commercial exposure depends on whether a marketed parenteral suspension uses L-methionine in the claimed role.

What does the “superadditive effect” limitation require?

Claims 5 and 21 require L-methionine and a buffering agent in concentrations effective to produce a “pH controlling superadditive effect.” Claims 6 and 7 narrow the buffer to phosphoric acid salts at concentrations below 0.4% and 0.2%, respectively.

A superadditive-effect limitation generally requires more than the mere presence of two ingredients. The evidence would need to show that the combined L-methionine-buffer system controls pH in a manner greater than would be expected from the individual components alone, based on the patent’s disclosure and relevant formulation testing.

This limitation creates a narrower but potentially valuable claim set. A product could contain L-methionine and a phosphate buffer yet avoid claims 5 through 8 if the concentration or demonstrated effect does not satisfy the claim language. Claim 1 remains a separate risk because it does not require a buffer or a superadditive effect.

What formulation excipients are protected?

Claim 17 covers formulations containing at least one of the following:

Surfactants
Suspending agents
Thickening agents
Density-adjusting agents

Claim 18 covers preservatives including:

Phenol
Chlorobutanol
Benzyl alcohol
Methyl paraben
Propyl paraben
Benzalkonium chloride
Cetylpyridinium chloride

Claim 19 covers a broad list of antioxidants, including ascorbic acid, cysteine, acetylcysteine, glutathione, tocopherols, butylated hydroxyanisole, butylated hydroxytoluene, sulfites, and related reducing agents.

These claims do not independently protect the listed excipients. They protect a steroidal parenteral suspension that already satisfies claim 1 and also contains the specified excipient category or named ingredient. An accused product containing a different preservative or antioxidant may avoid the literal limitation of claims 18 or 19 while remaining exposed under claim 1.

How broad are the process claims?

Claim 20 covers a process for preparing the formulation by adding L-methionine. Claim 21 requires adding both L-methionine and a buffering agent to produce the claimed superadditive effect.

The process claims may reach:

Manufacture of bulk injectable suspension.
Final compounding.
Addition of L-methionine during aqueous phase preparation.
Addition of L-methionine during pH adjustment.
Manufacture of a finished product later imported into the United States.

The timing of addition may be important. If L-methionine is present in the final product but was introduced during a separate upstream step, the composition claims may remain more important than the process claims. Under US patent law, a process claim generally requires proof that the claimed steps were performed. Manufacturing records, batch records, regulatory submissions, and supplier documentation can become relevant evidence.

What is the likely patent expiration date?

The patent number alone does not establish a precise expiration date without the official patent record showing:

Earliest effective filing date.
Priority claims.
Patent Term Adjustment.
Patent Term Extension.
Terminal disclaimer.
Reexamination or certificate history.
Any continuing application with overlapping rights.

For a US utility patent filed under the modern 20-year-from-filing regime, the base term is generally 20 years from the earliest effective US nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156 (U.S. Patent and Trademark Office, n.d.-a).

A patent granted in 2002 may therefore have expired before or around the early 2020s, depending on its filing and priority chain. The patent should not be treated as enforceable solely because it appears in a commercial patent database. The USPTO Patent Center record and maintenance-fee history control the status inquiry.

What is the Orange Book status of US 6,495,534?

US Patent 6,495,534 is a formulation patent, not a patent on a new active pharmaceutical ingredient. Its Orange Book relevance depends on whether it was submitted to FDA by an NDA holder and listed for a specific approved drug product.

An Orange Book listing is not automatic merely because a patent claims a drug formulation. FDA generally lists patents submitted for approved products when the patent meets statutory and regulatory listing criteria. The listing may be categorized as:

Drug substance patent.
Drug product patent.
Method-of-use patent.

The claims supplied are most consistent with a drug product or formulation patent. They do not recite a treatment method, disease indication, or dosing regimen, so they do not naturally fit the method-of-use category.

A definitive Orange Book assessment requires a search of the FDA Orange Book patent listings by NDA, product name, active ingredient, and patent number. The presence or absence of the patent in the Orange Book affects ANDA certification strategy, Paragraph IV exposure, and the possibility of a 30-month stay under the Hatch-Waxman framework. The patent’s expiration, rather than its historical listing alone, determines current blocking value (FDA, n.d.-a).

What Paragraph IV challenges could have implicated this patent?

A generic applicant submitting an ANDA could have addressed a listed patent through:

Paragraph I certification, if no patent information was submitted.
Paragraph II certification, if the patent had expired.
Paragraph III certification, with launch after expiration.
Paragraph IV certification, asserting invalidity, unenforceability, or noninfringement.

For this patent, a Paragraph IV strategy would likely focus on:

Lack of an aqueous suspension.
Lack of parenteral administration.
Absence of L-methionine.
L-methionine not functioning as a pH-controlling agent.
Lack of substantially stabilized pH.
No phosphate buffer, where claims 5 through 8 are asserted.
Failure to meet steroid identity or concentration limitations.
Obviousness based on known amino-acid stabilizers, buffers, and injectable steroid suspensions.
Written-description or enablement challenges concerning broad steroid and concentration coverage.

A Paragraph IV certification would have created litigation risk only if the patent was listed for the relevant reference product and remained unexpired. Current launch analysis must distinguish historical challenge risk from present enforceability.

What patent litigation affects US 6,495,534?

The supplied information does not identify a specific infringement action, ANDA litigation proceeding, settlement, consent judgment, or licensing agreement involving US 6,495,534. No litigation conclusion should be drawn from the claim text alone.

A litigation search should cover:

PACER district-court complaints and judgments.
Court of Appeals decisions.
USPTO Patent Center prosecution history.
FDA Orange Book historical listings.
ANDA litigation involving MPA, methylprednisolone acetate, estradiol cypionate, and related injectable suspensions.
Assignments and licenses recorded with the USPTO.
Paragraph IV notice letters disclosed in public filings.

The absence of a known litigation record would not establish that the patent was never asserted. Formulation patents are often enforced through confidential notices, settlement agreements, or commercial licensing arrangements that do not produce a reported opinion.

How strong is the patent estate?

Strengths

The patent has several structural strengths:

Claim 1 is not limited to a single steroid.
Claim 1 does not require a specific L-methionine concentration.
The claims cover both products and processes.
Dependent claims identify commercially relevant injectable steroids.
The claims address pH stability, a regulatory and manufacturing attribute.
The formulation claims can potentially reach products with different preservatives, surfactants, and suspending agents.

Weaknesses

The principal weaknesses are:

The patent does not claim the active steroids themselves.
The parenteral aqueous-suspension limitation excludes oral tablets, capsules, oils, and many solutions.
The pH-control and stabilization terms may require experimental proof.
The superadditive-effect language in claims 5 and 21 may be difficult to establish without comparative data.
The enumerated steroid list may restrict claim construction under the doctrine of claim differentiation and prosecution history.
The patent’s term may have expired.
A competitor may reformulate without L-methionine or use a different pH-control system.

Overall assessment

The patent was potentially meaningful for injectable steroid products using L-methionine, particularly MPA suspensions and MPA/estradiol cypionate combinations. Its commercial blocking power was narrower than a composition-of-matter patent and depended heavily on product formulation data. If expired, the remaining value is historical, prior-art, freedom-to-operate, and patent-landscape relevance rather than current exclusionary power.

How does this patent compare with competing patent strategies?

Patent strategy	Typical protected subject matter	Relationship to US 6,495,534
Active-ingredient patent	New steroid molecule or salt	Broader chemical exclusivity; this patent does not provide it
Polymorph patent	Crystal form or solid-state form	Usually irrelevant to an aqueous suspension unless the form is used in manufacture
Formulation patent	Excipients, pH, particle size, release profile	Closest category
Method-of-use patent	Treatment indication or dosing regimen	Not present in the supplied claims
Device patent	Syringe, autoinjector, delivery system	Not present
Manufacturing patent	Particle formation, milling, sterilization, suspension preparation	Claims 20 and 21 are limited process claims
Combination patent	Two or more active ingredients	Claim 13 and claim 16 cover the MPA/estradiol cypionate combination in a formulation context

The patent’s claim architecture is typical of a secondary pharmaceutical patent. It seeks to extend protection around a known steroid by claiming a stability-enhancing formulation system.

What generic entry risks exist for injectable steroid products?

Product scenario	Risk under the supplied claims
MPA aqueous suspension with L-methionine	High historical relevance to claims 1, 9, 10, and 14
MPA plus estradiol cypionate with L-methionine	High historical relevance to claims 1, 4, 13, and 16
Methylprednisolone acetate aqueous suspension with L-methionine	Potential relevance to claims 1, 9, and 11
Exemestane aqueous suspension with L-methionine	Potential relevance to claims 1, 9, 12, and 15
Steroid suspension without L-methionine	Generally outside the literal composition claims
Steroid solution rather than suspension	Potential noninfringement position, subject to construction
Oral steroid formulation with L-methionine	Outside the express parenteral limitation
Injectable steroid with a different amino acid and no L-methionine	Potentially outside the literal claims
Injectable steroid with L-methionine but no pH-control function	Potential defense to the functional limitation
Injectable steroid with L-methionine and phosphate buffer	Potential exposure to claims 5 through 8

What manufacturing and regulatory barriers remain after patent expiration?

Patent expiration does not eliminate regulatory barriers. A generic or follow-on injectable product must still address:

Sterility assurance.
Particulate matter.
Uniformity of suspension.
Sedimentation and redispersibility.
Container-closure integrity.
Preservative effectiveness, if multidose.
Injectable excipient safety.
Stability throughout shelf life.
Bioequivalence or clinical endpoint requirements.
Manufacturing-site compliance.
FDA product-specific guidance, where applicable.

L-methionine may be used for pH control, oxidation control, or formulation stabilization, but its presence in a product must be supported by pharmaceutical development and regulatory documentation. A patent-free formulation can still face approval delays if its suspension characteristics or injectable safety profile differ materially from the reference product.

What licensing and assignment issues should be reviewed?

The patent’s commercial value depends partly on ownership history. A complete diligence review should examine:

Original applicant and assignee.
Recorded assignments.
Security interests.
Exclusive or field-limited licenses.
Government rights, if any.
Related continuations and divisionals.
Patent-family members outside the United States.
Any covenant not to sue or settlement affecting named products.

US assignment records establish recorded ownership but do not necessarily disclose all licensing terms. A license may have been executed privately and never recorded. Commercial agreements, SEC filings, annual reports, and litigation settlements may provide additional evidence of rights.

What is the geographic coverage?

US Patent 6,495,534 provides US rights only. International protection would require separate national or regional patents.

The geographic assessment should identify:

PCT application, if any.
European, Canadian, Australian, Japanese, and other national counterparts.
Grant and expiration status in each jurisdiction.
Patent-term adjustments or supplementary protection certificates.
Local patent-linkage rules.
National litigation or opposition proceedings.

A US expiration does not determine the status of corresponding foreign patents. Conversely, a foreign formulation patent does not create US infringement exposure.

Key Takeaways

US 6,495,534 claims aqueous parenteral steroid suspensions containing L-methionine for pH stabilization.
Claim 1 is the broadest product claim and does not require a specific steroid, concentration, buffer, or pH range.
Claims 5 through 8 target L-methionine-plus-phosphate-buffer systems with a claimed superadditive pH effect.
The principal steroid targets are MPA, exemestane, estradiol cypionate, methylprednisolone acetate, testosterone cypionate, oxabolone cypionate, and clostebol acetate.
Claims 20 and 21 cover preparation processes using L-methionine, alone or with a buffer.
The patent does not claim the steroid molecules, oral dosage forms, treatment methods, or injection devices.
The patent’s enforceability depends on its official term, including filing history, Patent Term Adjustment, terminal disclaimers, and maintenance status.
Orange Book relevance depends on whether the patent was submitted and listed for an FDA-approved product.
A generic entrant could design around the claims by eliminating L-methionine, changing the dosage form from suspension to solution where technically feasible, or using a different stabilization system.
The patent is best characterized as a secondary injectable-formulation patent rather than a foundational steroid patent.

Frequently Asked Questions

Does US 6,495,534 cover medroxyprogesterone acetate itself?

No. It covers specified pharmaceutical suspensions containing MPA and L-methionine under the claimed formulation conditions. It does not claim MPA as a chemical compound.

Can a product infringe if it contains only a trace amount of L-methionine?

Potentially. Claim 1 does not state a numerical concentration, but the L-methionine must be present at a pH-controlling effective concentration. Claim 2 expressly recites approximately 0.005% to 5% w/v or w/w.

Does the patent cover an injectable steroid solution?

The claims supplied require an aqueous suspension. A true solution may fall outside the literal composition claims, although the technical classification of a formulation and any doctrine-of-equivalents analysis would require product-specific review.

Are phosphate buffers mandatory under the patent?

No. Phosphate buffers are required only for the narrower claims 6 and 7, which depend on claim 5. Claim 1 does not require a buffering agent.

Is an expired patent still relevant to generic launch planning?

Yes. Its expiration date, prosecution history, claim scope, and family members can affect freedom-to-operate analysis, prior-art review, Orange Book history, and the interpretation of related formulation patents.

References

Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (n.d.-a). Patent term adjustment. U.S. Department of Commerce.
United States Patent and Trademark Office. (n.d.-b). Patent Center. U.S. Department of Commerce.
U.S. Patent No. 6,495,534. (2002). Pharmaceutical aqueous suspension formulations containing L-methionine. United States Patent and Trademark Office.
United States Code, 35 U.S.C. §§ 154, 156, 271, and 282.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	029924	⤷ Start Trial
Argentina	098830	⤷ Start Trial
Argentina	111695	⤷ Start Trial
Austria	313316	⤷ Start Trial
Australia	2001267371	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,495,534

Summary for Patent: 6,495,534