Details for Patent: RE45198

Summary for Patent: RE45198

Title:	Omeprazole solution and method for using same
Abstract:	A pharmaceutical composition includes an aqueous solution/suspension of omeprazole or other substituted benzimidazoles and derivatives thereof in a pharmaceutically acceptable carrier comprising a bicarbonate salt of a Group IA metal. A method for treating and/or preventing gastrointestinal conditions by administering to a patient a pharmaceutical composition including an aqueous solution/suspension of omeprazole or other substituted benzimidazoles and derivatives thereof in a pharmaceutically acceptable carrier including a bicarbonate salt of a Group IA metal wherein the administering step consists of a single dosage form without requiring further administering of the bicarbonate salt of the Group IA metal. A pharmaceutical composition for making a solution/suspension of omeprazole or other substituted benzimidazoles and derivatives thereof includes omeprazole or other substituted benzimidazoles and derivatives thereof and a bicarbonate salt of a Group IA metal in a form for convenient storage whereby when the composition is dissolved in aqueous solution, the resulting solution is suitable for enteral administration.
Inventor(s):	Jeffrey O. Phillips
Assignee:	University of Missouri System , University of Missouri St Louis
Application Number:	US11/960,934
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Drug Patent RE45198: Claim Scope, Expiration, Litigation, and Omeprazole Patent Landscape

US Patent RE45,198 covers oral, single-dose formulations of omeprazole or lansoprazole buffered with a Group IA metal bicarbonate, principally sodium bicarbonate. Its core commercial concept is an immediate-release proton-pump inhibitor suspension or solution that uses bicarbonate both as the carrier and as an acid-neutralizing buffer. The patent does not cover omeprazole generally, enteric-coated products, or every omeprazole/sodium bicarbonate formulation.

RE45,198 is a reissue patent associated with the Zegerid formulation platform. Its claims are method-of-treatment claims. The relevant U.S. patent term has ended, and the patent does not create a current U.S. barrier to generic launch. Historically, however, its claims supported Hatch-Waxman litigation over generic omeprazole/sodium bicarbonate products.

What patent is US RE45198 and what does it protect?

RE45,198 is titled “Pharmaceutical Compositions of Benzimidazole Compounds.” It reissued from US Patent No. 6,489,346 and is assigned in the public patent record to Santarus, Inc., the developer associated with Zegerid. The patent concerns benzimidazole proton-pump inhibitors, particularly omeprazole and lansoprazole, administered with an alkaline bicarbonate carrier.

Item	Details
U.S. patent	RE45,198
Original patent	US 6,489,346
Technology	Immediate-release buffered PPI composition
Principal active ingredients	Omeprazole; lansoprazole
Buffer	Group IA metal bicarbonate, principally sodium bicarbonate
Dosage form	Oral aqueous solution or suspension
Claim type	Method of treating gastric-acid disorders
Commercial product association	Zegerid and related omeprazole/sodium bicarbonate products
Reissue grant	September 30, 2014
Publicly reported adjusted expiration	March 19, 2020
Current status	Expired

The patent’s central distinction is the use of bicarbonate to protect the acid-sensitive PPI in the stomach without requiring a separate administration of bicarbonate. Conventional delayed-release omeprazole products generally rely on enteric protection. RE45,198 instead claims an immediate-release buffered administration.

What are the independent claims of RE45198?

Claims 1, 13, 14, 15, and 16 are the principal independent claims.

Claim 1 is the broadest independent claim. It requires:

1. Treatment of one of six specified gastric-acid disorders.
2. Omeprazole or lansoprazole powder.
3. A pharmaceutically acceptable carrier consisting essentially of a Group IA metal bicarbonate.
4. Oral administration in a single dose.
5. Administration as an aqueous solution or suspension.
6. No separate subsequent administration of bicarbonate.
7. Absorption of at least some active ingredient within approximately 10 to 12 minutes.

Claims 13 through 16 narrow or rearrange these limitations:

Claim	Main limitation
1	Omeprazole or lansoprazole; Group IA bicarbonate; single oral dose; solution or suspension; absorption in about 10-12 minutes
13	Omeprazole; concentration of approximately 1.0-4.0 mg/mL
14	Omeprazole at approximately 2.0 mg/mL
15	Omeprazole; less than approximately 12 mEq bicarbonate per 20 mg dose
16	Omeprazole or lansoprazole; administration volume of approximately 10-20 mL

The independent claims are cumulative. A product or method must satisfy every limitation of the asserted claim. A formulation containing omeprazole and sodium bicarbonate is not automatically within the claims unless the administration method, concentration, volume, disorder, and rapid-absorption limitations are also met.

How do the dependent claims narrow the patent scope?

The dependent claims create narrower commercial embodiments centered on a 20 mg omeprazole dose in 10 mL of solution or suspension.

Claim group	Limitation
2	Sodium as the Group IA metal
3	Potassium as the Group IA metal
4	Omeprazole concentration of approximately 0.5-6.0 mg/mL
5	Omeprazole concentration of approximately 1.0-4.0 mg/mL
6	Omeprazole concentration of approximately 2.0 mg/mL
7	Bicarbonate concentration of approximately 5%-60%
8	Bicarbonate concentration of approximately 7.5%-10.0%
9	Bicarbonate concentration of approximately 8.4%
10	Bicarbonate concentration of approximately 0.75-1.5 mEq/mL
11	Less than approximately 12 mEq bicarbonate per 20 mg omeprazole dose
12	Administration volume of approximately 10-20 mL
17	Thickening agent
18	Sodium bicarbonate as the carrier
19-20	0.75-1.5 mEq sodium bicarbonate per 2 mg omeprazole
21-22	Approximately 20 mg omeprazole per 10 mL solution
23-24	Therapeutically effective absorption within approximately 10-12 minutes

The most commercially relevant claim cluster is claims 17-24. It covers a thickened sodium bicarbonate suspension containing approximately 20 mg omeprazole in 10 mL, with rapid absorption.

What formulation does RE45198 describe?

The claimed formulation is an immediate-release alkaline suspension or solution. The principal technical elements are:

• Omeprazole or lansoprazole powder.
• Sodium or potassium bicarbonate.
• Water or another aqueous vehicle.
• Optional thickening agent.
• A relatively low administration volume.
• A bicarbonate amount sufficient to create an alkaline environment.
• Rapid PPI absorption.

The claimed bicarbonate is not merely an incidental excipient. It is the defining carrier and buffer. The specification and claim structure indicate that bicarbonate is intended to address the acid instability of the benzimidazole PPI and facilitate delivery without an enteric-coated dosage form.

What does “consisting essentially of” mean in these claims?

“Consisting essentially of” generally permits additional ingredients that do not materially affect the basic and novel characteristics of the claimed composition. The basic characteristics here are the bicarbonate-buffered, immediate-release delivery of omeprazole or lansoprazole.

A thickener is expressly addressed by claims 17-24. Other excipients could create a claim-construction dispute if they materially change the formulation’s release, buffering, stability, or absorption characteristics. An accused product would be assessed against the exact claim language and the intrinsic record, not against the general concept of a PPI suspension.

What concentrations and dose volumes are protected?

The principal numerical ranges are:

Parameter	Claimed range or target
Omeprazole concentration	Approximately 0.5-6.0 mg/mL
Narrow omeprazole range	Approximately 1.0-4.0 mg/mL
Preferred concentration	Approximately 2.0 mg/mL
Bicarbonate concentration	Approximately 5%-60%
Narrow bicarbonate range	Approximately 7.5%-10.0%
Preferred bicarbonate concentration	Approximately 8.4%
Bicarbonate concentration per volume	Approximately 0.75-1.5 mEq/mL
Bicarbonate per 20 mg omeprazole dose	Less than approximately 12 mEq
Administration volume	Approximately 10-20 mL
Preferred product embodiment	20 mg omeprazole in 10 mL

At 2.0 mg/mL, a 10 mL dose contains approximately 20 mg of omeprazole. That concentration and volume correspond closely to the commercial immediate-release Zegerid powder-for-suspension model.

What diseases and treatment methods are covered?

The claims identify six gastric-acid disorders:

• Active duodenal ulcers.
• Gastric ulcers.
• Gastroesophageal reflux disease.
• Severe erosive esophagitis.
• Poorly responsive systemic GERD, although the claim language appears to contain a drafting error and likely intended “poorly responsive symptomatic GERD.”
• Zollinger-Ellison Syndrome.

Because these are method claims, the relevant infringement analysis concerns the labeled or actual method of administering the product. The patent does not claim a composition in the abstract. A composition could have the same ingredients and still present a different infringement analysis if it is used outside the claimed dosage, volume, route, formulation, or indication.

How important is the 10-to-12-minute absorption limitation?

The rapid-absorption limitation is a material narrowing feature. Claim 1 requires that at least some omeprazole or lansoprazole be absorbed within approximately 10 to 12 minutes. Claims 23 and 24 require therapeutically effective absorption in that period.

This limitation has two effects:

1. It distinguishes immediate-release buffered delivery from conventional delayed-release products.
2. It creates proof issues in litigation because the patentee may need pharmacokinetic, formulation, or clinical evidence showing that the accused method satisfies the absorption limitation.

The limitation does not necessarily require that the entire dose be absorbed within 10 to 12 minutes. Claim 1 requires absorption of “at least some” active ingredient. Claims 23 and 24 use the more demanding phrase “a therapeutically effective amount.”

What is the relationship between RE45198 and Zegerid?

Zegerid is an immediate-release omeprazole and sodium bicarbonate product. Its formulation differs from conventional proton-pump inhibitors such as Prilosec delayed-release capsules because it uses bicarbonate rather than an enteric-coated pellet system as the principal delivery approach.

The product’s commercial formulation historically included:

• Omeprazole.
• Sodium bicarbonate.
• An aqueous reconstituted suspension or solution.
• A 20 mg or 40 mg omeprazole strength, depending on product.
• A relatively small administration volume.

RE45,198 is therefore closely aligned with the commercial formulation and administration method underlying Zegerid. The patent did not, however, provide a perpetual monopoly over all omeprazole/sodium bicarbonate products.

When did RE45198 lose exclusivity?

The public patent record reports an adjusted expiration date of March 19, 2020. A reissue patent generally retains the term of the original patent and does not reset the patent term merely because the reissue was granted in 2014.

Event	Date
Earliest priority filing associated with the patent family	February 3, 1995
Original patent family prosecution and grant	US 6,489,346
Reissue application	Filed before September 2014
RE45,198 grant	September 30, 2014
Reported adjusted expiration	March 19, 2020
Current U.S. enforceability	None after expiration

The patent’s expiration eliminated the principal U.S. patent barrier created by this patent. Any current exclusivity analysis must instead examine other patents, regulatory exclusivity, product-specific approvals, trademarks, manufacturing know-how, and supply arrangements.

What was the Orange Book status of RE45198?

The relevant Orange Book listing was associated with the prescription Zegerid product and the omeprazole/sodium bicarbonate formulation platform. The Orange Book is product-specific. A patent listed against a prescription product does not automatically cover every product containing omeprazole and bicarbonate.

The practical Orange Book consequences were:

• An ANDA applicant referencing the listed product could face a Paragraph IV certification.
• The NDA holder could file patent litigation within the statutory period.
• A timely infringement action could trigger a 30-month stay of FDA approval, subject to statutory exceptions.
• The patent’s expiration removed the patent-based stay mechanism for future ANDA applications.

Current FDA approval status must be evaluated at the strength and dosage-form level. Prescription Zegerid and later generic omeprazole/sodium bicarbonate products have had different approval histories. FDA approval of a generic product does not establish that every formulation or administration method falls outside every patent claim, but the expiration of RE45,198 materially reduces the patent risk associated with this specific patent.

Which companies challenged the Zegerid patent?

Par Pharmaceutical was the principal generic challenger involved in the reported U.S. litigation concerning the Santarus omeprazole/sodium bicarbonate patent estate.

Santarus v. Par Pharmaceutical

Santarus sued Par after Par pursued an ANDA for a generic version of Zegerid. The dispute centered on the validity and infringement of the buffered omeprazole patent claims, including US 6,489,346, the patent from which RE45,198 reissued.

The Federal Circuit upheld key district-court findings in favor of Santarus, including findings relating to validity and infringement. The litigation established that the patent claims could be enforced against a generic product designed around the same immediate-release buffered PPI concept. The case is commonly cited as Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1345 (Fed. Cir. 2012).

The litigation did not make the patent term indefinite. It preserved the patent’s enforceability during its remaining term and demonstrated the risk of an ANDA applicant using a formulation closely tracking the claimed concentration, bicarbonate, and administration parameters.

Did RE45198 create a biosimilar risk?

No. Omeprazole and lansoprazole are small-molecule drugs, not biologics. The relevant competitive pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under section 351(k) of the Public Health Service Act.

The principal regulatory risks were:

• Paragraph IV patent challenges.
• Formulation differences.
• Bioequivalence.
• Labeling and indication scope.
• Manufacturing controls for an acid-sensitive active ingredient.
• Stability after reconstitution.

Biosimilar exclusivity, reference-product exclusivity under the biologics statute, and interchangeable-biologic designation are not applicable to RE45,198.

How does RE45198 compare with conventional omeprazole patents?

Issue	RE45,198	Conventional delayed-release omeprazole patents
Delivery technology	Immediate-release buffered solution or suspension	Enteric-coated pellets, granules, tablets, or capsules
Buffer	Group IA bicarbonate is central	May be absent or secondary
Administration	Single oral liquid dose	Usually capsule or tablet
Key claim focus	Bicarbonate carrier, concentration, volume, rapid absorption	Coating, particle size, release profile, stability, or salt form
Principal commercial association	Zegerid	Prilosec and other delayed-release omeprazole products
Regulatory challenge	ANDA formulation and method claims	Product, formulation, and method-of-use claims
Current RE45,198 status	Expired	Must be assessed patent by patent

A generic manufacturer could avoid this patent historically by using an enteric-coated omeprazole dosage form, eliminating the claimed bicarbonate carrier, changing the administration method, or demonstrating that its product does not satisfy the claimed numerical or absorption limitations. Those design-around strategies would not necessarily avoid unrelated formulation or method-of-use patents.

What manufacturing and intellectual-property barriers remain?

RE45,198 is expired, but immediate-release omeprazole/sodium bicarbonate products still present technical barriers.

Manufacturing barriers

Omeprazole is acid-sensitive. Commercial development requires control of:

• Alkaline microenvironment.
• Moisture exposure.
• Reconstitution stability.
• Uniformity of bicarbonate distribution.
• Suspension sedimentation.
• Dose reproducibility.
• Packaging against humidity.
• Stability through expiration.
• Compatibility with flavoring and thickening agents.

These are product-development barriers rather than current barriers created by RE45,198.

Potential remaining IP barriers

A freedom-to-operate review should separately examine:

• Later formulation patents.
• Pharmaceutical compositions using alternative buffers.
• Reconstituted powder-for-suspension technology.
• Sachet and single-dose packaging.
• Thickener systems.
• Taste-masking technology.
• Stability-enhancing excipients.
• Manufacturing and granulation processes.
• Product-specific method-of-use claims.
• Foreign counterparts and national-phase patents.

RE45,198 does not provide geographic protection outside the United States. Foreign counterparts must be assessed separately by country, and many family members would have expired on different dates or been abandoned.

What generic launch scenarios existed, and what is the current risk?

During the patent term, the main scenarios were:

Scenario	Patent implication
Same omeprazole/sodium bicarbonate suspension	High infringement risk if all claim limitations were met
Different bicarbonate concentration	Possible design-around, subject to range and equivalents analysis
Different dose volume	Possible design-around, especially against claims 12 and 16
Enteric-coated omeprazole	Generally outside the immediate-release formulation claims
No bicarbonate carrier	Stronger design-around position
Lansoprazole buffered suspension	Potential exposure under claims 1 and 16
Omeprazole product used for a nonlisted indication	Reduced method-of-use exposure, subject to induced-infringement facts
Product launched after March 19, 2020	RE45,198 no longer blocks launch

The current risk from RE45,198 is zero as an enforceable U.S. patent right because the patent has expired. Commercial risk may still arise from later patents, regulatory requirements, product liability, trademark rights, or manufacturing know-how.

How strong was the RE45198 patent estate?

The estate was strong during its enforceable period for products closely matching the Zegerid architecture. Its strengths were:

• Direct coverage of the immediate-release buffered PPI concept.
• Multiple independent claims.
• Alternative coverage of omeprazole and lansoprazole.
• Sodium and potassium bicarbonate alternatives.
• Concentration and volume fallbacks.
• Thickener-specific claims.
• Rapid-absorption limitations tied to the commercial formulation.

Its weaknesses were:

• Method-of-treatment rather than broad composition claims.
• Dependence on proving the full administration method.
• Numerical limitations that allowed formulation design-around arguments.
• Potential factual disputes over the 10-to-12-minute absorption requirement.
• No current term remaining.

The patent was commercially meaningful but technically bounded. It did not prevent development of enteric-coated PPIs, non-bicarbonate buffers, different liquid formulations, or unrelated PPI delivery systems.

Key Takeaways

• RE45,198 covers single-dose oral administration of omeprazole or lansoprazole powder in an aqueous bicarbonate-based solution or suspension.
• The core commercial embodiment is approximately 20 mg omeprazole in 10 mL with sodium bicarbonate.
• Important claim limitations include bicarbonate as the principal carrier, no separate bicarbonate administration, specified concentration and volume ranges, and rapid absorption.
• Claims 17-24 add thickener, sodium bicarbonate, dose-ratio, 20 mg/10 mL, and absorption limitations.
• The patent reissued from US 6,489,346 and is associated with the Zegerid formulation platform.
• Par Pharmaceutical was the principal reported ANDA challenger in the Santarus litigation.
• The patent’s reported adjusted expiration date was March 19, 2020.
• RE45,198 is expired and cannot currently block a U.S. generic launch.
• Omeprazole is a small molecule, so biosimilar law does not apply.
• Current freedom-to-operate analysis must focus on later formulation, manufacturing, packaging, method-of-use, and foreign patents.

FAQs

Does RE45198 cover all omeprazole and sodium bicarbonate products?

No. It covers specified methods using an aqueous solution or suspension, single-dose oral administration, particular formulation parameters, and rapid absorption. Enteric-coated capsules and products outside the claimed ranges are not automatically covered.

Does the patent cover potassium bicarbonate products?

Yes, claims 1 and 3 include a Group IA metal bicarbonate, and claim 3 identifies potassium. Claim 2 separately identifies sodium.

Is a thickening agent required to infringe RE45198?

No. A thickener is not required by claim 1. Claims 17-24 specifically narrow the method to formulations containing a thickening agent.

Can a company launch a generic Zegerid-type product without a Paragraph IV challenge today?

RE45,198 itself is expired, so it no longer requires a Paragraph IV certification as a blocking patent. The applicant must still evaluate any unexpired patents listed for the relevant reference product.

Is RE45198 relevant to lansoprazole suspension products?

Potentially. Claims 1 and 16 expressly include lansoprazole. The product would still need to satisfy the other limitations, including bicarbonate carrier, oral single-dose administration, solution or suspension format, and the applicable volume or absorption requirements.

References

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

2. Food and Drug Administration. (2024). Zegerid prescribing information. U.S. Department of Health and Human Services.

3. Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1345 (Fed. Cir. 2012).

4. United States Patent and Trademark Office. (2014). U.S. Patent No. RE45,198, Pharmaceutical compositions of benzimidazole compounds. Washington, DC.

5. United States Patent and Trademark Office. (2002). U.S. Patent No. 6,489,346, Pharmaceutical compositions of benzimidazole compounds. Washington, DC.

6. United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, § 2701: Patent term. Washington, DC.

Drugs Protected by US Patent RE45198

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

International Family Members for US Patent RE45198

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	038157
Austria	340574
Australia	1907100
Australia	2002330863
Australia	2003214858
Australia	2005229686
Australia	3276701