Details for Patent: 5,817,338

Summary for Patent: 5,817,338

Title:	Multiple unit tableted dosage form of omeprazole
Abstract:	PCT No. PCT/SE95/00677 Sec. 371 Date Jun. 20, 1995 Sec. 102(e) Date Jun. 20, 1995 PCT Filed Jun. 7, 1995 PCT Pub. No. WO96/01623 PCT Pub. Date Jan. 25, 1996A new pharmaceutical multiple unit tableted dosage form containing omeprazole or one of its single enantiomers or an alkaline salt of omeprazole or one of its single enantiomers, a method for the manufacture of such a formulation, and the use of such a formulation in medicine.
Inventor(s):	Pontus John Arvid Bergstrand, Kurt Ingmar Lovgren
Assignee:	AstraZeneca AB
Application Number:	US08/454,395
Patent Claim Types: see list of patent claims	Use; Composition; Process; Dosage form;

United States Patent 5,817,338 Scope, Claims, and U.S. Patent Landscape for Omeprazole Enteric “Multiple Unit Tablet” Pellets/Granules

United States Patent 5,817,338 covers a specific omeprazole-based, enteric-coated multiple unit tablet architecture: 0.1–2 mm omeprazole (or omeprazole enantiomer or alkaline salt forms) pellets or granules, each covered by an enteric coating layer containing a plasticizer/polymer ratio designed to preserve acid resistance after compression into tablets. Claim scope is tightly anchored to (i) pellet/granule size, (ii) the active ingredient forms (omeprazole and specified variants), (iii) enteric coating plasticization range, and (iv) measurable acid-resistance retention after tableting. The dependent claims expand coverage to crystallinity-defined omeprazole magnesium salt, optional over-coats and separating layers, enteric hardness/thickness, and multiple packaging.

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What is the claim scope of US Patent 5,817,338 for omeprazole enteric-coated multiple unit tablets?

Core independent claim 1: structural and functional coating constraints

Claim 1 requires all of the following elements in combination:

1. Dosage form: a “pharmaceutical multiple unit tablet composition for oral treatment of gastrointestinal disorder.”
2. Multiple unit content: a multiple of pellets or granules sized 0.1 mm to 2 mm.
3. Active ingredient limited to specific omeprazole forms:
   • omeprazole, or
   • a single enantiomer of omeprazole, or
   • an alkaline salt of omeprazole, or
   • an alkaline salt of a single enantiomer of omeprazole.
4. Enteric coating layer: at least one enteric coating layer that includes a plasticizing compound in an amount > about 20% to < about 50% by weight of the enteric coating layer polymer.
5. Functional constraint tied to tableting: plasticization chosen so that compression into tablet form minimizes reduction of acid resistance of the enteric-coated units.

This is a “micro-architecture + coating formulation range” claim. The plasticizer level relative to polymer (20%–50% by weight of polymer) is the main numeric lever, and the “minimize reduction of acid resistance upon compression” is a functional performance limitation.

Dependent claims that lock in testable performance

• Claim 2 (pharmacopeial coherence): acid resistance in line with USP requirements for enteric-coated articles.
• Claim 3 (quantified loss threshold): acid resistance does not decrease more than 10% during compression into the tablet.
• Claim 4 (enteric thickness): enteric coating layer thickness ≥ 10 μm.

These dependent claims add objective laboratory anchors that can be used in freedom-to-operate (FTO) testing and validity/obviousness arguments.

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Which active ingredient forms are covered by US Patent 5,817,338 (omeprazole, enantiomers, magnesium salts)?

Claim 1 limits actives to omeprazole and closely defined variants. The dependent claims narrow further into specific embodiments.

Active forms expressly covered

• omeprazole (racemate or non-specified form as written)
• single enantiomer of omeprazole
• alkaline salt of omeprazole
• alkaline salt of a single enantiomer

Specific dependent limitations

• Claim 7: “active ingredient is a magnesium salt of omeprazole” with degree of crystallinity > 70% by X-ray powder diffraction.
• Claim 8: alkaline salt of (+)-omeprazole or (-)-omeprazole.
• Claim 18: alkaline salt is a magnesium salt.
• Claim 6 and Claim 20: pellets/granules (and process) may include at least one alkaline compound in addition to salt identity.

Practical reading for scope: the baseline protection covers multiple omeprazole forms; magnesium salts plus crystallinity thresholds carve out narrower product/process variants. Any product design choosing different API salt form (eg, sodium, potassium) may avoid the magnesium-specific dependent claims but still could fall within claim 1 if it fits “alkaline salt of omeprazole” language.

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What are the key pellet and granule size and architecture limits in US 5,817,338?

Pellet/granule size is a hard limit

• Claim 1: pellets/granules 0.1 mm to 2 mm.
• Claim 12–13: seed layered with active ingredient, seeds sized 0.1–2 mm.

Tablet architecture: “multiple unit tablet” mechanics

The claims emphasize preservation of enteric unit integrity through compression. That means:

• The enteric-coated pellets/granules must be compressed into a tablet without destroying acid resistance beyond stated limits (claim 3).
• The coating mechanical properties are addressed indirectly via plasticizer selection and via process steps.

This structure aims to protect against formulations that use enteric-coated microunits but lose enteric robustness when pressed into tablets.

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How does US 5,817,338 define the enteric coating plasticizer/polymer range and hardness/thickness?

Numeric plasticizer constraint (claim 1)

• Plasticizing compound is present at >20% to <50% by weight of enteric coating layer polymer.

This is the most direct quantitative constraint on enteric polymer plasticization. It will matter for:

• enteric dissolution behavior,
• mechanical flexibility under compression,
• and resistance to cracking/defects.

Acid-resistance performance limits (claims 2–3)

• USP enteric performance compliance (claim 2)
• ≤10% decrease in acid resistance after compression (claim 3)

Mechanical coating properties (hardness and thickness)

• Claim 4: enteric coating thickness ≥10 μm.
• Claim 23: enteric coating layer applied has Vickers hardness < 8.

These are strong parameters because they can be used to distinguish “harder, more brittle” enteric systems that fracture during tableting.

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What optional layers are covered (over-coating layers, separating layers under enteric coating)?

Over-coating layer

• Claim 5: each enteric-coated unit can be covered with an over-coating layer using a pharmaceutically acceptable excipient.
• Claim 14 (process): further coating of enteric-coated units with over-coat.

Separating layer under the enteric layer

• Claim 22: enteric-coated units include a separating layer under the enteric coating. The separating layer is a pharmaceutically acceptable excipient that is either:
  • soluble, or
  • insoluble but disintegrating in water.

This likely addresses migration, incompatibility, and moisture/chemical interactions between cores and enteric polymers.

Separating-layer plus alkalinity

• Claim 19: separating layer further comprises at least one alkaline compound.

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What processes are claimed by US 5,817,338 (manufacturing and tableting steps)?

Independent process claim 11

Claim 11 covers manufacture, tied to the same core coating and compression logic:

1. Shape multiple of pellet/granule containing omeprazole variants.
2. Cover pellets/granules with at least one enteric coating layer with advantageous mechanical properties.
3. Mix enteric-coated pellets/granules with tablet excipients.
4. Compress into tablets without significantly affecting acid resistance due to advantageous mechanical properties.

Dependent process claims add:

• Claim 12: seed layered with active ingredient.
• Claim 13: seeds sized 0.1–2 mm.
• Claim 14: optional over-coating step.
• Claim 20: pellet/granule includes at least one alkaline compound.
• Claim 21: optional separating layer covering.
• Claim 24: enteric thickness ≥10 μm (mirrors claim 4).
• Claim 25: shaping by layering active ingredient on seed sized 0.1–2.0 mm.

Process scope implication

If a competitor uses different tableting mechanics (eg, fluid bed coating to avoid compression effects) they may still infringe if they follow the claim 11 steps with the required coating mechanics and acid-resistance preservation.

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What medical method claims are included (GI acid secretion and GI inflammatory diseases)?

Method of use claims

• Claim 15: inhibiting gastric acid secretion in mammals and man.
• Claim 16: treatment of gastrointestinal inflammatory diseases in mammals and man.

These are broad therapeutic method claims tied only to administration of “the composition according to claim 1.” They do not add dosing units or specific regimens beyond “therapeutically effective dose.”

For validity and enforcement, the core limitation driving infringement is still the claim 1 composition, not the specific indication language.

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What packaging claim is covered?

• Claim 17: a press-through blister package comprising at least one press-through blister including the multiple unit tablet of claim 1.

This introduces a downstream product/packaging claim. In practice, packaging design workarounds can matter if the formulation is the same but blister type differs.

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What do the claims imply about enforceable infringement “touchpoints” in U.S. litigation?

The claims are structured so infringement can be proven by:

• measuring pellet/granule size distribution (0.1–2 mm),
• confirming active salt/epimer identity (omeprazole, enantiomer, alkaline salt; magnesium and crystallinity for dependent claims),
• testing enteric coating thickness (≥10 μm),
• determining plasticizer content relative to polymer (20%–50% by weight),
• testing hardness (Vickers <8),
• and measuring acid resistance retention after compression (≤10% decrease).

This gives plaintiffs multiple experimental handles. Defense strategies usually target one or more hard numeric/structural requirements, especially the plasticizer range and acid-resistance retention.

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What is the U.S. patent landscape around US 5,817,338 (related omeprazole enteric multiparticulates)?

Landscape map (how this patent fits)

US 5,817,338 sits at the intersection of:

• omeprazole API salt/enantiomer variants,
• enteric-coated multiparticulates,
• tableting of enteric pellets as “multiple unit tablets,”
• and coating formulation parameters chosen to preserve performance after compression.

Within the U.S. IP landscape, this generally competes with other patents that cover one or more of:

• different omeprazole salt forms,
• different enteric polymers/plasticizers,
• alternative multiparticulate size ranges,
• different coating thickness/hardness targets,
• and different tablet compression strategies.

Claim-driven “design-around” logic for competitors

Common ways a generic or follow-on innovator can reduce risk of matching claim 1:

• use multiparticulates outside 0.1–2 mm,
• use non-alkaline salt active forms that fall outside the defined “alkaline salt” language,
• select plasticizer/polymer ratios at or below 20% or at or above 50%,
• use enteric coating compositions that produce higher brittleness such that acid resistance loss exceeds the ≤10% limitation,
• use enteric coating thickness below 10 μm (if that is material to the specific coating used),
• use different encapsulation architectures that remove the defined separating layer/over-coating combinations (relevant mainly for dependent claims),
• avoid press-through blister packaging if the packaging claim is asserted.

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How many claims are enforceable “anchors” in US 5,817,338?

Anchor set for claim 1 (composition)

• multiple unit tablet
• 0.1–2 mm pellets/granules
• active ingredient: omeprazole/enant/enantiomer or alkaline salt variant
• enteric coating with plasticizer/polymer ratio >20% and <50%
• compression does not materially reduce acid resistance

Anchor set for independent claim 11 (manufacturing)

• shape pellets/granules
• enteric coat with mechanical-property coating
• mix with tablet excipients
• compress without significant acid resistance loss

Main anchor upgrades via dependent claims

• USP acid resistance coherence (claim 2)
• ≤10% acid resistance decrease (claim 3)
• enteric thickness ≥10 μm (claims 4 and 24)
• optional over-coat and separating layer architecture (claims 5, 14, 22, 21)
• magnesium salt crystallinity >70% (claim 7)
• (+)/(−) enantiomer alkaline salts (claim 8)
• Vickers hardness <8 (claim 23)
• divisible/dispersible unit behavior is claimed (claim 9–10)

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Key takeaways

• US 5,817,338 is a focused composition/process patent covering enteric-coated 0.1–2 mm omeprazole multiparticulates compressed into multiple unit tablets, where enteric coating plasticization is set to preserve acid resistance.
• The claim 1 novelty and enforceability hinge on the combined limits of:
  (i) active ingredient definition, (ii) pellet/granule size, (iii) plasticizer/polymer ratio >20% and <50%, (iv) acid resistance retention upon tableting, supported by dependent test metrics (USP compliance; ≤10% reduction).
• Dependent claims add measurable differentiators including enteric thickness ≥10 μm, Vickers hardness <8, optional over-coat and separating layer, and magnesium salt omeprazole crystallinity >70%.
• Downstream risk includes packaging (press-through blister) and method-of-use claims tied to administration of the protected composition.

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FAQs

1) Does US 5,817,338 require a specific enteric polymer type?
The provided claim text specifies a plasticizer/polymer weight ratio but does not enumerate a particular enteric polymer in your excerpt; polymer identity is therefore not explicit in the claims you provided, while the plasticizer proportion and functional acid-resistance constraints are explicit.

2) What is the most litigable numerical limit in claim 1?
The enteric coating plasticizer content is numerically constrained as >20% to <50% by weight of enteric coating layer polymer.

3) Can a product infringe claim 1 if acid resistance is partially lost after compression?
Claim 1 uses a “minimize reduction” functional standard, while claim 3 narrows with a hard threshold: acid resistance does not decrease more than 10% during compression. A design matching claim 1 but exceeding the claim 3 threshold may still fall under claim 1, depending on how “minimize reduction” is litigated, but claim 3 provides a clearer boundary.

4) Are magnesium salt and crystallinity requirements optional or mandatory?
Magnesium salt and crystallinity thresholds apply to dependent claims (not claim 1). They become mandatory only when the dependent claim is asserted.

5) Does the patent cover enantiomer-specific omeprazole only, or also racemic omeprazole?
Claim 1 expressly includes omeprazole generally and also a single enantiomer, plus alkaline salt variants. The enantiomer-specific dependent claim (claim 8) tightens coverage for (+)- or (-)-omeprazole salt forms.

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References (APA)

No external patent-bibliographic sources were provided in the prompt; citations cannot be generated without authoritative document text/record verification.

Drugs Protected by US Patent 5,817,338

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: 5,817,338

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	9402432	Jul 08, 1994
Sweden	9402433	Jul 08, 1994

PCT Information
PCT Filed	June 07, 1995	PCT Application Number:	PCT/SE95/00677
PCT Publication Date:	January 25, 1996	PCT Publication Number:	WO96/01623

International Family Members for US Patent 5,817,338

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	206044
Austria	414509
Australia	2993795
Australia	695966
Brazil	1100458