US Patent 9,233,103: Dexlansoprazole and Clopidogrel Patent Scope, Claims, Expiration and Competitive Landscape

US Patent 9,233,103 protects specific methods of administering 60 mg dexlansoprazole to patients receiving clopidogrel for cardiovascular or cerebrovascular disease. The patent does not claim dexlansoprazole, clopidogrel, a formulation, or a pharmaceutical composition. Its protection is limited to treatment conduct involving the selection and administration of dexlansoprazole in the presence of clopidogrel, with the asserted result that clopidogrel pharmacology and CYP2C19-related activity are not inhibited.

The principal commercial risk is a method-of-use challenge involving 60 mg dexlansoprazole, particularly for erosive esophagitis and heartburn in patients treated with clopidogrel. The patent is narrower than a general “PPI plus clopidogrel” patent because it requires dexlansoprazole and a 60 mg dose.

What patent is US 9,233,103?

US Patent 9,233,103 is directed to methods for treating heartburn or erosive esophagitis in a patient who is receiving clopidogrel. The claims distinguish dexlansoprazole from other proton pump inhibitors based on the absence of clinically relevant inhibition of clopidogrel activity or CYP2C19-related interactions.

Item	Details
Patent	US 9,233,103
Patent type	Utility patent
Claim category	Method of treatment
Active drug	Dexlansoprazole
Comparator or concomitant drug	Clopidogrel
Covered dose	60 mg dexlansoprazole
Primary indications	Heartburn and erosive esophagitis
Cardiovascular conditions	Acute coronary syndrome, peripheral artery disease, myocardial infarction and stroke
Key pharmacology limitation	No inhibition of clopidogrel pharmacological activity or CYP2C19 interactions
Grant date	January 12, 2016
Claim status in the supplied text	Claims 1-10

The patent should be analyzed separately from dexlansoprazole formulation patents, including delayed-release and dual delayed-release delivery patents. US 9,233,103 does not require a particular capsule, tablet, release profile, excipient, particle size, or manufacturing process.

What do the independent claims of US 9,233,103 cover?

Claims 1 and 6 are the two independent claims. They overlap in subject matter but impose different limitations.

Claim 1: Selection and concomitant administration method

Claim 1 requires all of the following:

A patient has heartburn or erosive esophagitis.
The patient also has a second disease state.
The patient is being treated, or is about to be treated, with clopidogrel for that second disease state.
Dexlansoprazole is preferentially selected from a group of PPIs.
Separate dosage forms of clopidogrel and dexlansoprazole are administered concomitantly.
The dexlansoprazole dose is 60 mg.

This claim is directed to a treatment decision. The selection of dexlansoprazole over another PPI is an express limitation. A product-only theory of infringement would not fit the claim because the claim requires patient selection and administration in a particular clinical setting.

Claim 6: Treatment without inhibition of clopidogrel activity

Claim 6 requires:

Treatment of heartburn or erosive esophagitis.
Concomitant receipt of clopidogrel.
Preferential administration of dexlansoprazole.
A 60 mg dose.
No inhibition of clopidogrel pharmacological activity.
No inhibition of CYP2C19 interactions between dexlansoprazole and clopidogrel.

Claim 6 does not expressly require “separate dosage forms.” It also does not expressly require that clopidogrel be used for one of the specific cardiovascular diseases listed in dependent claim 8. It is therefore potentially broader than claim 1 in administration format and the required second disease state, but it retains the 60 mg dose and the no-inhibition limitations.

How do claims 1 and 6 differ?

Limitation	Claim 1	Claim 6
Heartburn or erosive esophagitis	Yes	Yes
Patient receiving clopidogrel	Yes	Yes
Second disease state expressly required	Yes	No, except through dependent claim 8
Preferential selection of dexlansoprazole	Yes	Yes
Separate dosage forms	Yes	No
60 mg dexlansoprazole	Yes	Yes
No inhibition of clopidogrel pharmacological activity	Not stated expressly in claim 1	Yes
No inhibition of CYP2C19 interactions	Dependent claim 3	Yes
Cardiovascular or cerebrovascular disease list	Dependent claim 5	Dependent claim 8

The overlap creates a prosecution and enforcement issue. A defendant may argue that “preferentially selecting” and “does not inhibit CYP2C19 interactions” are functional or outcome-based limitations requiring proof of the relevant clinical or pharmacokinetic relationship.

What do the dependent claims add?

Claims 2, 3, 4, 5, 7, 8, 9 and 10 narrow the two independent claims.

Claim	Added limitation
2	Heartburn associated with symptomatic non-erosive GERD
3	Dexlansoprazole administration does not inhibit CYP2C19 interactions between dexlansoprazole and clopidogrel
4	Clopidogrel retains pharmacological activity while treating the second disease state
5	Second disease state is acute coronary syndrome, peripheral artery disease, myocardial infarction, stroke or a combination
7	Heartburn associated with symptomatic non-erosive GERD
8	Acute coronary syndrome, peripheral artery disease, myocardial infarction, stroke or a combination
9	Erosive esophagitis treatment includes healing
10	Erosive esophagitis treatment includes healing

Claims 2 and 7 are particularly relevant to non-erosive GERD. Claims 9 and 10 are relevant to a healing indication rather than symptom control alone.

What is the core scope of US 9,233,103?

The core scope is the following clinical scenario:

A patient receiving clopidogrel is treated for heartburn or erosive esophagitis with 60 mg dexlansoprazole instead of another PPI, on the basis that dexlansoprazole does not inhibit clopidogrel activity or CYP2C19-related interactions.

The patent does not cover:

Dexlansoprazole used without clopidogrel.
Clopidogrel used without dexlansoprazole.
Dexlansoprazole at 30 mg under these claims.
A generic PPI selected without dexlansoprazole.
A composition containing both active ingredients.
A fixed-dose combination product.
The manufacture of dexlansoprazole.
A delayed-release formulation independent of the clopidogrel treatment method.
Treatment of reflux disease in a patient not receiving clopidogrel.

The claims also do not appear to require a particular timing interval between the two drugs. “Concomitantly” generally creates a temporal overlap requirement, but the claim text supplied does not specify simultaneous administration, same-day administration, morning dosing, or a defined number of hours between doses.

How strong are the patent claims?

The patent has meaningful commercial specificity but several potential vulnerability points.

Strengths

The claims contain multiple limiting elements:

Named active ingredient: dexlansoprazole.
Named concomitant drug: clopidogrel.
Defined dose: 60 mg.
Defined gastrointestinal indications.
Express selection over other PPIs.
Cardiovascular and cerebrovascular disease limitations in dependent claims.
Functional distinction based on clopidogrel activity and CYP2C19 interaction.

These limitations make a broad anticipation reference less likely to disclose every element in combination. A prior-art reference showing that dexlansoprazole treats GERD would not, by itself, anticipate the claims. A separate reference describing clopidogrel and PPI coadministration would also need to disclose the required dexlansoprazole selection, 60 mg dose and pharmacological relationship.

Vulnerabilities

The most significant issues are claim construction and enablement.

“Preferentially selecting” may be disputed because it describes a clinical choice rather than a conventional structural limitation. The phrase may require proof that dexlansoprazole was selected because of its interaction profile, rather than merely prescribed to a patient who happened to be taking clopidogrel.

The CYP2C19 language may also create evidentiary complexity. Clopidogrel is a prodrug whose activation involves CYP enzymes, including CYP2C19. The patent’s negative limitation requires showing that dexlansoprazole does not inhibit the relevant interaction or clopidogrel activity. FDA labeling for dexlansoprazole has described the absence of a clinically important interaction with clopidogrel, while FDA labeling for omeprazole and esomeprazole has contained stronger warnings regarding clopidogrel activation and CYP2C19 inhibition. The clinical and pharmacokinetic meaning of “does not inhibit CYP2C19 interactions” would be central to claim construction. [1, 2]

The 60 mg requirement is both a strength and a limitation. It narrows literal infringement, but it reduces the patent’s ability to reach 30 mg dexlansoprazole regimens or uses outside the claimed dosage.

What FDA and Orange Book issues affect the patent?

US 9,233,103 is a method-of-treatment patent, not a composition patent. Its Orange Book relevance depends on whether the patent was submitted for listing against an approved dexlansoprazole product and whether FDA accepted the listing under the applicable Orange Book rules.

The relevant FDA product is Dexilant, which contains dexlansoprazole in delayed-release dosage forms. FDA-approved labeling identifies 30 mg and 60 mg dosing regimens for different indications, including healing and maintenance of erosive esophagitis and treatment of symptomatic non-erosive GERD. [1]

Regulatory issue	Relevance to US 9,233,103
New chemical entity exclusivity	Separate from the patent and generally expired well before the current period
Formulation protection	Separate from the method claims
Orange Book listing	Must be confirmed in the current FDA Orange Book record
Paragraph IV risk	Applies if an ANDA applicant certifies that a listed patent is invalid, unenforceable or not infringed
Label carve-out	Potentially relevant if a generic label omits the clopidogrel-related use
60 mg dosage	Directly relevant to the claimed method
Drug interaction labeling	Important to induced or divided infringement theories

A generic applicant could seek to avoid the patent through a section viii statement that omits the patented use, if the relevant use is listed as a protected method and the remaining label supports approval. If the applicant files a Paragraph IV certification, litigation exposure would depend on Orange Book listing, the filing date of the notice, and the NDA holder’s response under the Hatch-Waxman framework. [3]

The patent does not automatically block approval of every dexlansoprazole generic. The practical impact depends on whether the generic label encourages the claimed 60 mg use in patients receiving clopidogrel.

When does US 9,233,103 lose exclusivity?

The patent was granted on January 12, 2016. The statutory term for a modern US utility patent generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension and terminal disclaimers. The exact expiration date cannot be established from the claim text alone and should not be equated with the grant date.

Timing event	Date or rule
Patent grant	January 12, 2016
Statutory term framework	20 years from applicable earliest nonprovisional filing date
Patent-term adjustment	May extend the term
Patent-term extension	Potentially available for qualifying regulatory delay, subject to statutory limits
Terminal disclaimer	Could shorten the term if applicable
Regulatory exclusivity	Separate from patent duration

For diligence, the controlling sources are the patent front page, USPTO Patent Center transaction history, assignment records, maintenance-fee status, and the current FDA Orange Book listing. A patent can remain unexpired while not being listed in the Orange Book, and an Orange Book listing does not establish validity or infringement.

What Paragraph IV challenges and generic entry risks exist?

The highest-risk generic entry scenario is a 60 mg dexlansoprazole product whose proposed labeling expressly or implicitly directs use in patients taking clopidogrel for heartburn or erosive esophagitis.

Potential scenarios include:

Generic scenario	Patent risk
30 mg product only	Low literal risk under the supplied claims because each independent claim requires 60 mg
60 mg product with broad GERD labeling	Moderate to high method-of-use risk if clopidogrel use is encouraged
60 mg product with a section viii carve-out	Lower risk, subject to label content and induced-infringement analysis
Product labeled for erosive esophagitis healing	Directly relevant to claims 9 and 10
Product with no clopidogrel reference	Lower inducement risk, but physician and patient use may remain relevant
Fixed-dose dexlansoprazole/clopidogrel product	Potentially higher exposure, although the claims require separate dosage forms in claim 1 but not claim 6

A Paragraph IV challenge could target invalidity based on obviousness. The likely theory would combine prior art teaching PPI gastroesophageal treatment, clopidogrel coadministration and known CYP2C19 interaction concerns. The patentee would argue that the prior art did not establish dexlansoprazole as the preferred PPI at 60 mg with the claimed non-inhibition result.

What competing drugs and patent estates matter?

The commercial comparison is not limited to dexlansoprazole. The relevant market includes other PPIs prescribed to patients receiving antiplatelet therapy.

PPI	Relevance to clopidogrel interaction analysis
Dexlansoprazole	Drug specifically selected by US 9,233,103
Omeprazole	Historically associated with CYP2C19 and clopidogrel interaction warnings
Esomeprazole	Similar interaction concern because of its relationship to omeprazole
Pantoprazole	Often considered a lower-interaction alternative in clinical practice
Lansoprazole	Interaction profile differs from dexlansoprazole and is not covered by these claims
Rabeprazole	Not covered by the patent’s dexlansoprazole limitation

The patent therefore creates product differentiation for dexlansoprazole rather than a general PPI exclusivity position. A competing PPI manufacturer does not literally practice the claims merely by marketing a PPI for a clopidogrel-treated patient.

What formulation and manufacturing patents are separate from US 9,233,103?

Dexlansoprazole has historically been protected by separate patent categories:

Formulation patents

These may cover:

Dual delayed-release dosage forms.
Multiple populations of drug particles.
Enteric coatings with different dissolution profiles.
Capsule or tablet architecture.
Release timing and plasma concentration characteristics.

Those patents can present a different barrier to generic entry. A generic applicant may avoid a formulation patent by using a different release system while still facing a method-of-use patent.

Manufacturing patents

Potential manufacturing protection may concern:

Preparation of dexlansoprazole stereoisomers.
Resolution or stereoselective synthesis.
Crystalline forms.
Salt or solvate forms.
Particle processing and encapsulation.

US 9,233,103 does not claim any of those technologies. It cannot be used as a direct manufacturing-process patent.

What litigation and licensing issues affect the patent?

A patent number alone does not establish a pending infringement case, settlement agreement or license. Method-of-treatment patents are often enforced through Hatch-Waxman litigation when listed in the Orange Book and challenged in an ANDA certification.

The main litigation questions are:

Was US 9,233,103 listed against the relevant dexlansoprazole NDA?
Did an ANDA applicant submit a Paragraph IV certification?
Did the NDA holder file a timely infringement action?
Was a 30-month stay triggered?
Did the parties enter a settlement with a launch date or license?
Did the generic label carve out the clopidogrel-related method?
Does the label induce performance of the claimed method?

No license or settlement right is created by the patent itself. Any license, covenant not to sue, authorized generic arrangement or reverse-payment agreement would have to be established from a separate agreement, court docket or Federal Trade Commission filing.

What is the geographic coverage of US 9,233,103?

US 9,233,103 provides rights only in the United States. It does not directly block:

Use of dexlansoprazole in Canada, Europe or Japan.
Manufacturing outside the United States, unless the conduct falls within US infringement provisions.
Foreign sales that do not involve US importation.
Foreign method-of-treatment activity.

The same invention may have corresponding PCT, European, Canadian or other national filings, but foreign patent scope, prosecution history and expiration dates must be analyzed separately. US claim construction does not control foreign counterparts.

What is the commercial exposure?

Commercial exposure is concentrated in the 60 mg dexlansoprazole segment, especially:

Erosive esophagitis healing.
Patients with acute coronary syndrome or prior myocardial infarction.
Patients receiving long-term antiplatelet therapy.
Patients with symptomatic non-erosive GERD who are considered unsuitable for omeprazole or esomeprazole because of interaction concerns.

The patent does not cover all Dexilant revenue. Revenue attributable to 30 mg use, non-clopidogrel patients, pediatric or maintenance uses outside the claim language, and unrelated formulation features falls outside the supplied claims unless covered by other patents.

Key Takeaways

US 9,233,103 is a narrow method-of-treatment patent focused on 60 mg dexlansoprazole administered with clopidogrel.
Claims 1 and 6 are the key independent claims.
Claim 1 requires separate dosage forms and a second disease state.
Claim 6 omits the separate-dosage-form limitation but expressly requires no inhibition of clopidogrel activity or CYP2C19 interactions.
The patent does not claim dexlansoprazole, clopidogrel, a fixed-dose combination or a formulation.
A 30 mg-only generic strategy has a strong non-infringement position against the supplied claims.
A 60 mg generic label that references or encourages use with clopidogrel creates the highest method-of-use risk.
Orange Book listing, Paragraph IV certifications, label carve-outs and any Hatch-Waxman litigation determine practical entry exposure.
Formulation, crystal-form and manufacturing patents must be analyzed separately.
US rights do not establish exclusivity in foreign markets.
The exact patent expiration date depends on the applicable filing date, patent-term adjustment, terminal disclaimers and any patent-term extension.

FAQs About US 9,233,103

Does US 9,233,103 cover all patients taking Dexilant?

No. The supplied claims require concomitant clopidogrel treatment and a 60 mg dexlansoprazole dose, along with heartburn or erosive esophagitis treatment.

Does the patent cover omeprazole or pantoprazole with clopidogrel?

No. The claims specifically require preferential selection or administration of dexlansoprazole.

Can a generic avoid the patent by selling only 30 mg dexlansoprazole?

The supplied claims each require a 60 mg dose. A 30 mg-only product would have a strong literal non-infringement position against these claims, although separate patents could remain relevant.

Is US 9,233,103 a patent on the Dexilant formulation?

No. It is a method patent. Delayed-release and dual delayed-release formulation patents are separate patent assets.

Can a physician’s use create infringement exposure?

Potentially. Method claims may be implicated by performance of the claimed treatment, and a manufacturer can face induced-infringement allegations if its labeling or promotional conduct encourages the claimed combination and dose.

References

U.S. Food and Drug Administration. (2022). Dexilant (dexlansoprazole) delayed-release capsules: Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2011). Plavix (clopidogrel bisulfate) tablets: Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Patent and Trademark Office. (2016). U.S. Patent No. 9,233,103: Methods of treating heartburn in patients taking clopidogrel. https://patents.google.com/patent/US9233103B2/en
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension resources. https://www.uspto.gov/patents/laws/patent-term-adjustment-patent-term-extension-recovery-methods-terms-extensions

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Takeda Pharms Usa	DEXILANT	dexlansoprazole	CAPSULE, DELAYED RELEASE;ORAL	022287-001	Jan 30, 2009	AB	RX	Yes	No	9,233,103	⤷ Start Trial				USE OF DEXLANSOPRAZOLE IN PATIENTS TAKING CLOPIDOGREL WITHOUT MEANINGFUL CYP2C19 INTERACTIONS	⤷ Start Trial
Takeda Pharms Usa	DEXILANT	dexlansoprazole	CAPSULE, DELAYED RELEASE;ORAL	022287-002	Jan 30, 2009	AB	RX	Yes	Yes	9,233,103	⤷ Start Trial				USE OF DEXLANSOPRAZOLE IN PATIENTS TAKING CLOPIDOGREL WITHOUT MEANINGFUL CYP2C19 INTERACTIONS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
World Intellectual Property Organization (WIPO)	2012134828	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,233,103

Which drugs does patent 9,233,103 protect, and when does it expire?

Summary for Patent: 9,233,103