Details for Patent: 12,599,565

Which drugs does patent 12,599,565 protect, and when does it expire?

Patent 12,599,565 protects OMEPRAZOLE and is included in one NDA.

This patent has five patent family members in five countries.

Summary for Patent: 12,599,565

Title:	Stable benzimidazole formulation
Abstract:	An omeprazole delayed release tablet comprises a core and an enteric coating over the core. The core consists essentially of omeprazole, lactose, sodium starch glycolate, sodium stearate, and sodium stearyl fumarate. The enteric coating over the core consists essentially of hydroxypropyl methyl cellulose (HPMC) acetate succinate, triethyl citrate, sodium lauryl sulfate, talc, monoethanol amine, and less than 500 ppm of residual ammonium hydroxide.
Inventor(s):	Adel Penhasi, Avi Avramoff, Maxim Gomberg, Valerie Azoulay
Assignee:	Dexcel Pharma Technologies Ltd
Application Number:	US17/501,237
Patent Claim Types: see list of patent claims	Formulation; Compound; Dosage form;

United States Patent 12,599,565 (Omeprazole Delayed-Release Tablet): Claim Scope, Validity Hot Spots, and US Patent Estate Landscape

Executive summary: US Patent 12,599,565 is an “active + excipient + coating + critical impurity control” formulation patent focused on omeprazole delayed-release tablets with (i) a specific core composition and (ii) an enteric coating built around HPMC acetate succinate plasticized with triethyl citrate, lubricated with sodium lauryl sulfate and talc, colorant, and monoethanolamine (MEA) prepared from aqueous solution in tightly enumerated weight-percent ranges specifically to drive residual ammonium hydroxide below a safety/toxicity threshold. The claim set is narrow in structure but broad in two business-critical ways: (1) it allows multiple enumerated MEA coating levels; (2) it covers any tablet meeting the composition-plus-coating-plus-residual-ammonium limit, rather than a single manufacturing campaign. The main infringement risk is for generics or authorized generics that reuse the same enteric coating system and MEA process/impurity profile; the main design-around vectors are to change the enteric polymer system, alter plasticizer/lubricant package, eliminate aqueous-prepared MEA, or achieve the ammonium hydroxide target via a different impurity-control strategy that avoids the claimed “MEA prepared from aqueous solution + MEA level ranges” structure.

---

What is US Patent 12,599,565 about and what do its claims cover?

Answer (scope in one line): The patent claims an omeprazole delayed-release tablet defined by a specific core excipient blend, a defined HPMC acetate succinate-based enteric coating, and an MEA-in-coating parameter tied to residual ammonium hydroxide reduction (with MEA prepared from aqueous solution and present at specific coating weight percentages).

Claim architecture

The asserted independent claims (1–3) all share the same core concept:

• Dosage form: omeprazole delayed-release tablets (enteric-coated).
• Core: omeprazole plus a defined set of excipients.
• Coating: HPMC acetate succinate + triethyl citrate + sodium lauryl sulfate + talc + MEA (aqueous-prepared) + colorant + residual ammonium hydroxide impurity limit (<500 ppm).
• MEA parameter: MEA prepared from an aqueous solution and present in coating at one of several enumerated weight-percent values designed to reduce residual ammonium hydroxide.

Claims 4–13 are dependent fallbacks that pin:

• omeprazole strength (20 mg or ~8 wt%),
• and/or specific quantitative coating component amounts,
• and/or specific single-point MEA coating levels (e.g., 1.195 wt% or 1.75 wt%).

Core composition boundaries

Independent claim set provides two main core definitions:

• Claim 1 core: includes omeprazole + lactose + sodium starch glycolate + sodium stearate + sodium stearyl fumarate.
• Claim 2 core (example strength): about 20 mg omeprazole with 203 mg lactose monohydrate and fixed excipient amounts.
• Claim 3 core (example ratio): core composition by weight percent:
  • 8 wt% omeprazole
  • 81.2 wt% lactose monohydrate
  • 4 wt% sodium starch glycolate
  • 4 wt% sodium stearate
  • 2.8 wt% sodium stearyl fumarate

Business implication: even though Claim 1 is less numerically explicit than Claims 2–3, it still requires the same excipient identity set in the core (lactose, sodium starch glycolate, sodium stearate, sodium stearyl fumarate). A design-around that swaps any of those core excipients with functionally similar alternatives (e.g., microcrystalline cellulose or different disintegrant/lubricant chemistry) is a direct way to remove a structural element.

Enteric coating composition boundaries

All independent claims require:

• Enteric polymer: HPMC acetate succinate
• Plasticizer: triethyl citrate
• Surfactant/lubricant: sodium lauryl sulfate
• Anti-tack/glidant: talc
• Colorant
• MEA: monoethanol amine prepared from aqueous solution
• Impurity constraint: less than 500 ppm residual ammonium hydroxide

Dependent claims (6 and 7) further specify amounts (absolute mg or wt% of coating) for particular formulations:

• Claim 6 (coating amounts):
  • HPMC acetate succinate 32 mg
  • triethyl citrate 4.5 mg
  • sodium lauryl sulfate 0.5 mg
  • talc 8.14 mg
  • coloring agent 10.8 mg
  • MEA is present per Claim 1’s MEA parameter and ammonium hydroxide constraint.
• Claim 7 (coating wt%):
  • HPMC acetate succinate 56.14 wt% of coating
  • triethyl citrate 7.89 wt%
  • sodium lauryl sulfate 0.88 wt%
  • talc 14.28 wt%
  • coloring agent 18.95 wt%

Business implication: The claims are “composition-specific.” A generic developer cannot simply swap MEA for another neutralizer or change the enteric polymer while keeping all else constant and hope to avoid the claims. To avoid claim 1, the product must fail at least one required element: polymer package, plasticizer, sodium lauryl sulfate, talc, colorant inclusion, or the MEA aqueous-prepared parameter at the enumerated coating levels tied to ammonium hydroxide reduction.

---

How is residual ammonium hydroxide controlled in the claims and where is the infringement risk?

Answer: The claims explicitly tie residual ammonium hydroxide <500 ppm to an enteric coating strategy where MEA is aqueous-prepared and present at enumerated coating wt% levels to reduce the impurity for toxicity/safety reasons.

Key claim phrase mechanics

Independent claims use a structure that is unusually specific for formulation patents:

• They don’t just require MEA and a coating impurity spec.
• They require that MEA is prepared from an aqueous solution and is present at one of the specific coating wt% values:
  • 1.195, 1.251, 1.28, 1.282, 1.325, 1.35, 1.360, 1.368, 1.388, 1.396, 1.44, 1.477, 1.59, or 1.75 wt%
• The claim explains the functional intent: lower residual ammonium hydroxide to a safety level.

Infringement risk profile

There are two ways a product could land inside:

1. Direct formulation match: If a tablet matches the coating system and MEA aqueous-prepared parameter at one of the enumerated wt% values, then it likely meets the structural claim elements. The product then must also meet the impurity limit (<500 ppm).
2. “Impurity-driven” equivalence is not needed: The claims require the impurity limit and MEA-level/aqueous-prep structure, so a developer cannot avoid infringement by arguing that the final residual ammonium hydroxide is acceptable unless they also eliminate one of the structural requirements.

Litigation friction points

If this were litigated, the fact pattern will likely hinge on:

• Analytical chemistry results for residual ammonium hydroxide and how it’s measured and reported.
• Whether MEA used in the accused coating was prepared from an aqueous solution (process-related limitation).
• Whether the accused coating MEA is present at one of the enumerated weight-percent levels, including whether formulation tolerances could land outside the exact claimed discrete options.

---

What are the exact MEA weight-percentage options that matter for claim coverage?

Answer: The patent lists discrete MEA coating wt% values that can independently satisfy the MEA requirement, each combined with aqueous preparation and the ammonium hydroxide residual target.

MEA levels explicitly enumerated in Claims 1–3

MEA is present in the coating at one of:

• 1.195 wt%
• 1.251 wt%
• 1.28 wt%
• 1.282 wt%
• 1.325 wt%
• 1.35 wt%
• 1.360 wt%
• 1.368 wt%
• 1.388 wt%
• 1.396 wt%
• 1.44 wt%
• 1.477 wt%
• 1.59 wt%
• 1.75 wt%

Single-point dependent claims

• Claim 8 pins MEA = 1.195 wt%
• Claim 9 pins MEA = 1.75 wt%
• Claim 10–13 similarly tie MEA at 1.195 or 1.75 wt% for Claims 2 and 3 variants.

Business implication: A “nearby” design-around that changes MEA slightly but lands on a still-enumerated value does not help. The safe zone is either:

• eliminate MEA entirely, or
• use MEA but at a coating wt% not listed, or
• ensure it is not “prepared from an aqueous solution,” or
• remove other required coating components (polymer, triethyl citrate, sodium lauryl sulfate, talc, colorant) or alter core excipient package.

---

Which specific tablet strengths and proportions are claimed?

Answer: The claims cover both a 20 mg example and an ~8 wt% omeprazole composition variant, with corresponding core excipient specifications.

Omeprazole amount anchors

• Claim 4: omeprazole in core = 20 mg.
• Claim 5: omeprazole in core = about 8 wt%.
• Claim 2: includes “about 20 mg omeprazole” and numeric core amounts.
• Claim 3: uses core percentage breakdown.

Core component exactness vs. flexibility

• Claim 1 is identity-based (which excipients are present) rather than percentage-based.
• Claims 2 and 3 provide both identity and quantity anchor points.

Business implication: A generic developer could still infringe Claim 1 even if they don’t copy the 20 mg or 8 wt% ratios, as long as the core includes the same excipient set and the coating matches the enteric requirements and MEA parameter.

---

What patents likely exist around this formulation strategy, and how strong is this patent’s likely position?

Answer: Based solely on the claim text, US 12,599,565 is positioned as a formulation improvement patent focused on enteric coating excipient packaging and an impurity reduction mechanism. The likely estate around it typically includes: (i) earlier baseline omeprazole delayed-release tablet coating patents, (ii) secondary patents for enteric polymer blends and plasticizers, and (iii) later “impurity/processing” continuation patents around controlling residual ammonium species using specific amines.

However: A complete landscape requires actual record lookups (priority chain, family members, assignees, prosecution history, and citations). With only the claim text provided, the precise US patent family size, expiration dates, and specific competing patent numbers cannot be stated accurately.

---

Where are the design-around opportunities for generics or authorized generics?

Answer: The strongest design-arounds attack claim elements that are (a) identity-specific and (b) process-limited: core excipients, coating polymer/plasticizer/lubricant package, MEA aqueous preparation, and the discrete MEA wt% set.

High-leverage design-around vectors

1. Change the enteric polymer system

   • Replace HPMC acetate succinate with a different enteric polymer (even if functional equivalence exists) to eliminate a required coating component.

2. Remove or replace triethyl citrate, sodium lauryl sulfate, or talc

   • Claim coverage requires these specific excipients in the enteric coating.

3. Eliminate MEA

   • The MEA aqueous-prepared limitation is central to the patent’s novelty as claimed.

4. Use an alternate base/amine or alter MEA process

   • The patent requires MEA prepared from an aqueous solution. Changing synthesis or procurement route can be a path to non-infringement if it removes the “prepared from aqueous solution” limitation.

5. Move MEA outside the enumerated wt% values

   • Even small formulation shifts could be outcome-determinative if they move the coating MEA concentration to a value not in the list.

6. Rebuild impurity control without the claimed MEA parameter

   • If residual ammonium hydroxide is controlled via different process steps or different excipients, then the product may still meet the impurity spec but avoid the specific “MEA aqueous-prepared and at enumerated wt% values” structure.

---

What does this mean for FDA development, Orange Book risk, and Paragraph IV planning?

Answer: This is the type of formulation patent that can be listed in the Orange Book against an NDA/ANDAs for omeprazole delayed-release tablets, creating potential Paragraph IV risk if a generic uses an enteric coating with the same core and coating excipient package and MEA/impurity profile.

Practical regulatory touchpoints

• ANDA formulations that match the coating system and MEA impurity-control strategy could face claim infringement allegations even if pharmacokinetics and label dosing are equivalent.
• If residual ammonium hydroxide is a monitored quality attribute, applicants may be expected to demonstrate impurity controls, which also becomes discoverable evidence in a patent dispute.

Landscape note: A definitive Orange Book status and Paragraph IV history requires Orange Book data tied to a specific NDA/ANDA. The provided information does not include the relevant drug product identity (NDA number, ANDA number, label strength, manufacturer) needed to map US 12,599,565 to listed patents.

---

Key Takeaways

• US 12,599,565 claims an omeprazole delayed-release tablet with a defined core excipient set and an HPMC acetate succinate-based enteric coating.
• The novelty focus is impurity control: residual ammonium hydroxide <500 ppm achieved via monoethanolamine prepared from aqueous solution at one of 14 enumerated coating weight-percentage values.
• Dependent claims further lock in omeprazole strength/proportions (20 mg or ~8 wt%) and specific coating component amounts.
• The infringement risk is highest when a product matches both the structural composition elements and the MEA aqueous preparation and discrete wt% parameter, plus meets the residual ammonium hydroxide constraint.
• The most direct design-arounds target at least one required element: enteric polymer package, triethyl citrate/sodium lauryl sulfate/talc requirements, MEA absence, MEA process not “aqueous-prepared,” or MEA concentration not in the enumerated list.

---

FAQs

1) Can a generic avoid infringement by keeping residual ammonium hydroxide <500 ppm but changing MEA?
Yes if the product fails the claim’s structural requirements, particularly “MEA prepared from an aqueous solution” and/or MEA being present at one of the enumerated coating wt% values.

2) Does Claim 1 require the exact 20 mg or ~8 wt% omeprazole numbers?
No. Those quantities appear in dependent claims (Claims 4–5) and in Claims 2–3 exemplars. Claim 1 is excipient-identity based for the core.

3) Are the MEA wt% values alternative options or cumulative ranges?
They are alternative enumerated options. A product needs to land on a claimed option value for the MEA limitation.

4) What coating excipient substitutions would be most likely to fall outside the claims?
Substitutions that remove or replace required coating components, especially the enteric polymer (HPMC acetate succinate), triethyl citrate, sodium lauryl sulfate, talc, or colorant, or remove MEA.

5) Is this patent a method-of-manufacture patent or a product-by-process/product formulation patent?
It is a product claim with a process-limited component: it recites the tablet composition and includes the process descriptor “monoethanol amine prepared from an aqueous solution.”

---

References

No sources were cited because the analysis is derived solely from the claim text provided.

Drugs Protected by US Patent 12,599,565

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Dexcel Pharma	OMEPRAZOLE	omeprazole	TABLET, DELAYED RELEASE;ORAL	022032-001	Dec 4, 2007		OTC	Yes	Yes	12,599,565		Y

International Family Members for US Patent 12,599,565

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2293782
Spain	2552723
Hong Kong	1156209
Israel	208925