Details for Patent: 6,123,962

Summary for Patent: 6,123,962

Title:	Process for producing stabilized pharmaceutical composition
Abstract:	The pharmaceutical composition of the invention, which comprises a benzimidazole compound of the formula ##STR1## wherein R1 is hydrogen, alkyl, halogen, cyano, carboxy, carboalkoxy, carboalkoxyalkyl, carbamoyl, carbamoylalkyl, hydroxy, alkoxy, hydroxyalkyl, trifluoromethyl, acyl, carbamoyloxy, nitro, acyloxy, aryl, aryloxy, alkylthio or alkylsulfinyl, R2 is hydrogen, alkyl, acyl, carboalkoxy, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarbonylmethyl, alkoxycarbonylmethyl or alkylsulfonyl, R3 and R5 are the same or different and each is hydrogen, alkyl, alkoxy or alkoxyalkoxy, R4 is hydrogen, alkyl, alkoxy which may optionally be fluorinated, or alkoxyalkoxy, and m is an integer of 0 through 4, and a basic inorganic salt stabilizing agent, is physically stable. Magnesium and calcium basic inorganic salt stabilizing agents are particularly useful.
Inventor(s):	Tadashi Makino, Tetsuro Tabata, Shin-Ichiro Hirai
Assignee:	Takeda Pharmaceutical Co Ltd
Application Number:	US09/429,957
Patent Claim Types: see list of patent claims	Formulation; Compound;

United States Patent 6,123,962: Claim Scope, Lansoprazole Formulation Protection, and Patent Landscape

U.S. Patent No. 6,123,962 covers pharmaceutical granules in which nonpareil cores are coated with a mixture containing a benzimidazole compound, a basic inorganic salt stabilizer, and an additive. Claim 7 narrows the invention to lansoprazole. The patent is a formulation patent, not a basic-composition patent covering lansoprazole itself. Its U.S. patent term has expired, so it does not create a current U.S. barrier to generic lansoprazole products.

What does U.S. Patent 6,123,962 protect?

The patent protects a specific multiparticulate dosage-form architecture:

1. Nonpareils act as the core.
2. The core is coated with a mixture.
3. The mixture contains a benzimidazole compound.
4. The mixture contains a basic inorganic salt stabilizing agent.
5. The mixture contains an additive.

The core inventive concept is the stabilization of an acid-labile benzimidazole proton-pump inhibitor in a coated granule system. The basic inorganic salt is intended to reduce degradation of the active ingredient during processing and storage.

The claims do not cover every tablet, capsule, powder, suspension, or granule containing lansoprazole. A potentially infringing product would need to satisfy the limitations of at least one claim, including the nonpareil-core and coating requirements.

What is the claimed dosage form?

The independent claim is claim 1:

“A granule which comprises nonpareils coated with a mixture of a benzimidazole compound, a basic inorganic salt stabilizing agent and an additive.”

The claim is directed to a granule rather than a finished capsule or tablet. A capsule containing the claimed granules could implicate the patent, but the capsule itself is not the central claimed article.

The phrase “nonpareils” generally refers to substantially spherical inert seed particles used as pharmaceutical cores. The claims therefore distinguish the invention from:

• Direct-compression tablets
• Conventional powder blends
• Granules formed solely by wet granulation
• Drug particles without inert spherical cores
• Formulations in which the active ingredient is separated from the stabilizer rather than present in the same coating mixture

How broad is claim 1 of U.S. Patent 6,123,962?

Claim 1 is broad as to the identity of the benzimidazole compound, the basic inorganic salt, and the additive. It is narrow as to the physical structure and the presence of the three coating components.

Claim 1 limitation analysis

Limitation	Scope
“A granule”	Covers a particulate dosage-form unit, not necessarily a complete dosage form
“Comprises”	Open-ended transitional language; additional ingredients or layers may be present
“Nonpareils”	Requires inert or pharmaceutical seed cores with the claimed coating
“Coated with a mixture”	Requires a coating containing the specified components in a mixture
“Benzimidazole compound”	Broad genus covering multiple substituted benzimidazoles
“Basic inorganic salt stabilizing agent”	Requires an inorganic salt with a stabilizing function and basic character
“An additive”	Broad, but at least one additive must be present

The use of “comprises” permits additional excipients, coatings, overcoats, binders, lubricants, enteric polymers, and capsule materials. It does not eliminate the requirement that the accused granule contain the claimed components.

The most significant construction issue is whether the benzimidazole, basic inorganic salt, and additive must be present in the same coating layer or merely in a coating mixture used during manufacture. The claim language favors a requirement that the three components be part of the coating mixture, although a multilayer product could raise factual questions concerning layer arrangement and claim construction.

What do dependent claims 2 through 7 add?

Claims 2 through 7 progressively narrow claim 1. They do not stand independently from claim 1.

Claim 2: basicity measured in aqueous solution or suspension

Claim 2 requires the stabilizing salt to have a pH of at least 7 in a 1% aqueous solution or suspension.

This limitation excludes acidic or effectively neutral inorganic salts. The test is formulation-specific because some salts have limited water solubility and may be assessed as suspensions rather than true solutions.

Claim 3: stabilizer-to-drug ratio

Claim 3 requires approximately 0.3 to 20 parts by weight of basic inorganic salt for each part by weight of benzimidazole compound.

The ratio is commercially important because it creates a quantitative infringement issue. Analytical testing of the finished granules may be required to determine:

• Active pharmaceutical ingredient content
• Stabilizer content
• Whether the ratio is calculated against the benzimidazole compound alone
• Whether “about” permits variation around the stated boundaries

A product using a stabilizer ratio below the lower range or materially above the upper range could avoid literal infringement of claim 3 while remaining potentially relevant to claim 1.

Claims 4 and 5: magnesium and calcium salts

Claim 4 limits the stabilizer to a basic inorganic salt of magnesium. Claim 5 limits it to a basic inorganic salt of calcium.

The claims do not identify a single magnesium or calcium salt. They can encompass multiple salts if the salt otherwise satisfies the basicity and stabilizing-agent requirements. Magnesium carbonate and calcium carbonate are commercially relevant examples for acid-labile proton-pump-inhibitor formulations, but the claim language is not restricted to those compounds.

Claim 6: Markush benzimidazole genus

Claim 6 defines a broad substituted benzimidazole structure using variable groups R1 through R5 and the integer m.

The genus includes a wide range of substituents, including alkyl, halogen, alkoxy, acyl, carbamoyl, trifluoromethyl, nitro, aryl, alkylthio, and alkylsulfinyl groups. The claim is limited by:

• The claimed benzimidazole structural formula
• The substituent definitions
• The requirement that the compound be present in the claim 1 granule
• The requirement for the nonpareil, stabilizer, and additive combination

Claim 6 is not a standalone patent on all compounds within the Markush formula. The compound must be used in the claimed granule.

Claim 7: lansoprazole

Claim 7 identifies:

2-[3-methyl-4-(2,2,2-trifluoroethoxy-2-pyridyl)methylsulfinyl]benzimidazole

This is lansoprazole, the active ingredient in Prevacid.

Claim 7 is the most commercially specific claim. It covers lansoprazole granules only when the product also satisfies the limitations inherited from claim 1. It does not cover:

• Lansoprazole as a bulk active ingredient
• Lansoprazole tablets lacking the claimed granule structure
• Lansoprazole capsules containing a different multiparticulate design
• All enteric-coated lansoprazole products regardless of core construction

What patent protects the active ingredient lansoprazole?

U.S. Patent 6,123,962 does not appear to be the principal compound patent for lansoprazole. It protects a formulation and stabilization arrangement.

Lansoprazole’s earlier patent estate included compound, therapeutic-use, salt, formulation, and manufacturing patents. The earliest compound protection and later formulation protection were separate rights with different expiration dates. A formulation patent could remain relevant after the compound patent expired, but only for products that practiced the formulation limitations.

The commercial product Prevacid used enteric-protected lansoprazole dosage forms. The relevant patent estate historically included patents directed to the active compound, delayed-release dosage forms, stabilizers, coating systems, and manufacturing processes. The U.S. patent term for those earlier patents has also expired or lapsed in the ordinary course.

When did U.S. Patent 6,123,962 lose exclusivity?

The patent no longer provides enforceable U.S. patent exclusivity. U.S. Patent 6,123,962 issued on September 26, 2000. Under the modern U.S. patent-term framework, utility patents generally expire 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and transitional rules (35 U.S.C. § 154).

Because the patent issued in 2000 and concerns a pre-existing lansoprazole formulation technology, its enforceable term ended years before 2026. Any patent-term adjustment would not preserve the patent into the current market period.

Exclusivity status

Exclusivity category	Status for Patent 6,123,962
U.S. composition-of-matter exclusivity	Not provided by this patent
U.S. formulation patent exclusivity	Expired
FDA new chemical entity exclusivity	Not provided by this patent
Orphan-drug exclusivity	Not relevant
Pediatric exclusivity	Not created by the patent
Current Paragraph IV leverage	None based solely on this patent
Current injunction risk	None based solely on this expired patent

Patent expiration does not erase historical infringement exposure for conduct occurring during the enforceable term. It does eliminate prospective infringement liability after expiration.

What is the Orange Book status of U.S. Patent 6,123,962?

The Orange Book lists patents submitted by an NDA holder for an approved drug product when the patents claim the drug substance, drug product, or an approved method of use. Historical listing does not preserve enforceability after patent expiration.

For lansoprazole, Orange Book relevance centered on Prevacid and related dosage forms. U.S. Patent 6,123,962 should be analyzed as a formulation patent, not as a current Orange Book barrier. Any listing associated with an expired patent has no continuing ability to block an ANDA approval through the statutory 30-month stay mechanism.

An ANDA applicant challenging a currently listed patent could use a Paragraph IV certification. That mechanism is no longer commercially material for an expired patent because the patent cannot support a current injunction or delay approval.

Which companies challenged the lansoprazole patent estate?

Generic companies challenged the Prevacid patent estate during the period when compound and formulation patents remained enforceable. The relevant commercial challengers included manufacturers seeking approval for generic lansoprazole delayed-release capsules and orally disintegrating products.

The public record for each Abbreviated New Drug Application must be evaluated patent by patent. A Paragraph IV challenge to an earlier lansoprazole patent does not necessarily constitute a challenge to U.S. Patent 6,123,962. Patent-specific analysis requires separating:

• Compound patent challenges
• Formulation patent challenges
• Method-of-use challenges
• Certifications based on expiration
• Declaratory-judgment actions
• Settlements involving delayed generic entry

There is no current Paragraph IV risk arising from Patent 6,123,962 because the patent has expired.

What patent litigation affected lansoprazole?

Lansoprazole litigation historically involved disputes over generic entry, delayed-release formulations, and the scope of Prevacid-related patents. The key legal issues in this class of litigation generally included:

• Whether the generic granules used nonpareil cores
• Whether the active ingredient and basic salt were present in the same coating mixture
• Whether the generic used the claimed magnesium or calcium stabilizer
• Whether the generic formulation met the claimed stabilizer-to-drug ratio
• Whether the generic product practiced an asserted method of treatment
• Whether the asserted patent was valid and enforceable

Patent 6,123,962 should not be treated as a current litigation obstacle. Any historical lawsuit involving related Prevacid patents must be distinguished from litigation specifically asserting this patent.

How strong was the patent estate?

Strengths

The patent had several features that could support enforcement during its term:

• Claim 1 was structurally focused on a recognizable multiparticulate design.
• Claim 3 added a measurable quantitative ratio.
• Claims 4 and 5 identified commercially plausible stabilizer families.
• Claim 7 focused on the commercial active ingredient, lansoprazole.
• The claimed architecture could be investigated through formulation analysis and manufacturing records.

Weaknesses

The estate also had material limitations:

• The patent did not cover lansoprazole broadly.
• Claim 1 required a specific nonpareil-based granule.
• “Additive” is broad but may create construction and definiteness questions depending on the specification.
• “Stabilizing agent” may require proof of functional stabilization.
• The “about” range in claim 3 creates boundary issues.
• A competitor could design around the claim using a different core, a separated stabilizer layer, a different stabilization system, or a non-granular dosage form.
• The patent’s term has expired.

The current strength of the estate is therefore zero as an enforceable exclusionary right, although the claims remain relevant for historical freedom-to-operate analysis and prosecution strategy.

What formulation alternatives could avoid the claims?

A generic manufacturer could potentially reduce literal infringement risk by using a formulation that does not include one or more required elements. Possible design-around categories include:

Design-around approach	Claim limitation potentially avoided
Drug-loaded pellets formed without nonpareils	“Nonpareils”
Separate stabilizer layer rather than a mixture with the drug	“Coated with a mixture”
Organic stabilizer or buffering system	“Basic inorganic salt”
Dosage form without coated granules	“A granule”
Lansoprazole in a different multiparticulate architecture	Nonpareil coating structure
Stabilizer amount outside the claim 3 range	0.3 to 20 parts by weight
Alternative benzimidazole compound	Claim 7’s lansoprazole limitation

These approaches would have mattered during the patent term. They have limited present commercial importance because the patent is expired.

How does this patent compare with competing proton-pump-inhibitor patent estates?

Product	Active ingredient	Primary patent issue	Current U.S. risk from Patent 6,123,962
Prevacid	Lansoprazole	Historical compound and delayed-release formulation patents	None
Prilosec	Omeprazole	Earlier compound and formulation patents	None
Nexium	Esomeprazole	Enantiomer, formulation, and method patents	None from this patent
Protonix	Pantoprazole	Separate compound and formulation estate	None
AcipHex	Rabeprazole	Separate compound and formulation estate	None
Dexilant	Dexlansoprazole	Dual delayed-release formulation patents	None

The patent does not cover omeprazole, esomeprazole, pantoprazole, rabeprazole, or dexlansoprazole merely because those products belong to the proton-pump-inhibitor class. Its compound coverage is limited by the benzimidazole definitions, and its product coverage is further limited by the nonpareil coating structure.

Does biosimilar risk apply to lansoprazole?

No. Lansoprazole is a chemically synthesized small-molecule drug. The relevant competitors use the ANDA pathway for generic approval, not the 351(k) biosimilar pathway under the Public Health Service Act.

The principal regulatory risks were therefore generic drug-product equivalence, delayed-release performance, stability, impurity control, and manufacturing consistency. Biosimilar interchangeability and biologic reference-product exclusivity are not relevant to Patent 6,123,962.

What manufacturing and intellectual-property barriers remain?

No patent barrier from U.S. Patent 6,123,962 remains. Commercial barriers may still include:

• Reproducible coating of spherical nonpareils
• Protection of lansoprazole from gastric acid
• Uniform enteric coating
• Stability control for acid-labile drug substance
• Control of degradation products
• Dissolution performance across pH conditions
• Scale-up of multiparticulate coating processes
• FDA requirements for bioequivalence and product-quality equivalence

Those barriers are technical and regulatory rather than exclusivity rights created by the expired patent.

Key Takeaways

• U.S. Patent 6,123,962 is a formulation patent covering benzimidazole-coated nonpareil granules.
• Claim 7 specifically covers lansoprazole granules that satisfy all claim 1 limitations.
• The patent does not broadly cover lansoprazole, proton-pump inhibitors, or all delayed-release formulations.
• Claims 2 and 3 add pH and stabilizer-ratio limitations.
• Claims 4 and 5 focus on magnesium and calcium basic inorganic salts.
• The patent’s U.S. term has expired.
• It cannot currently support a Paragraph IV stay, injunction, or generic-entry block.
• Biosimilar analysis is irrelevant because lansoprazole is a small-molecule drug.
• Current commercial risk lies in FDA manufacturing, stability, dissolution, and bioequivalence requirements rather than this patent.

FAQs

Does U.S. Patent 6,123,962 cover Prevacid?

It covers a formulation arrangement associated with lansoprazole-type products, but it does not cover every Prevacid dosage form or all lansoprazole products. The product must contain the claimed nonpareil granules and coating mixture.

Can a generic manufacturer launch lansoprazole despite this patent?

Yes. The patent has expired and cannot block a current U.S. generic launch. The manufacturer must still satisfy FDA approval and product-quality requirements.

Is magnesium carbonate required by claim 1?

No. Claim 1 broadly recites a basic inorganic salt stabilizing agent. Magnesium salts are specifically addressed in claim 4, while calcium salts are addressed in claim 5.

Does an enteric coating alone infringe this patent?

No. An enteric coating alone does not satisfy the claim. The claimed product requires nonpareils coated with a mixture containing a benzimidazole compound, a basic inorganic salt stabilizer, and an additive.

Is U.S. Patent 6,123,962 a compound patent for lansoprazole?

No. Claim 7 identifies lansoprazole, but only in the claimed granule formulation. The patent does not provide broad composition-of-matter protection for lansoprazole.

References

1. U.S. Patent No. 6,123,962. (2000). Granule comprising a benzimidazole compound, a basic inorganic salt stabilizing agent and an additive. United States Patent and Trademark Office.

2. United States Code, Title 35, § 154. (2024). Contents and term of patent; provisional rights.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

4. U.S. Food and Drug Administration. (2023). Orange Book: Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

5. United States Code, Title 21, § 355. (2024). New drugs.

6. United States Patent and Trademark Office. (2024). Patent Center. U.S. Department of Commerce.

Drugs Protected by US Patent 6,123,962

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 6,123,962

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	61-29567	Feb 13, 1986
Japan	61-38059	Feb 21, 1986

International Family Members for US Patent 6,123,962

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Bulgaria	61202
Canada	1327010
Canada	1338377
Canada	1338399
Germany	3750431
Germany	3751845
Germany	3780045