US Patent 9,387,249: Scope, Claim Construction, Expiration and Patent Landscape for Azilsartan Medoxomil-Chlorthalidone

US Patent 9,387,249 protects a narrow combination-treatment method for hypertension using azilsartan medoxomil potassium salt with chlorthalidone. The independent claim requires specific daily dose options for both drugs and requires a reduction in hypokalemia relative to chlorthalidone monotherapy. The patent does not broadly cover azilsartan, chlorthalidone, or all antihypertensive combinations.

The principal commercial relevance is Edarbyclor, the fixed-dose combination of azilsartan medoxomil and chlorthalidone. The patent creates method-of-use risk for an ANDA applicant seeking approval for the same active ingredients, dosage strengths, and hypokalemia-related indication.

What drug and combination does US Patent 9,387,249 cover?

The benzimidazole derivative identified in claim 1 is azilsartan medoxomil, administered as its potassium salt. The required second active ingredient is chlorthalidone.

Claim element	Required limitation
Angiotensin receptor blocker	Azilsartan medoxomil potassium salt
Diuretic	Chlorthalidone
Azilsartan dose	About 40 mg/day or about 80 mg/day
Chlorthalidone dose	About 12.5 mg/day or about 25 mg/day
Treatment objective	Treat hypertension and reduce hypokalemia incidence
Comparator	Chlorthalidone at 12.5 mg/day or 25 mg/day alone
Administration	Separate dosage forms or one combined dosage form
Dosage-form limitation	Tablets for the dependent claims

Azilsartan medoxomil is an angiotensin II receptor blocker, or ARB. Chlorthalidone is a thiazide-like diuretic. The combination is intended to provide antihypertensive activity while limiting the potassium-lowering effect associated with chlorthalidone.

What is the scope of independent claim 1?

Claim 1 is a treatment-method claim with four material requirements:

A patient must require treatment for hypertension.
The patient must receive azilsartan medoxomil potassium salt.
The patient must receive chlorthalidone at one of the specified dose levels.
The combination must reduce the incidence of hypokalemia compared with the relevant chlorthalidone monotherapy regimen.

The claim covers four principal dose combinations:

Azilsartan medoxomil	Chlorthalidone
About 40 mg/day	About 12.5 mg/day
About 40 mg/day	About 25 mg/day
About 80 mg/day	About 12.5 mg/day
About 80 mg/day	About 25 mg/day

The phrase “about” introduces a claim-construction issue. Courts generally assess the term in light of the specification, prosecution history, formulation tolerances, dosing practice, and whether a proposed dose remains within the invention’s technical teaching. A product labeled at exactly 40/12.5 mg or 80/25 mg presents materially higher infringement exposure than a product using substantially different doses.

The claim is not limited to essential hypertension. Claim 2 expressly includes essential hypertension, secondary hypertension, arterial hypertension, pulmonary arterial hypertension, and portal vein hypertension.

Does the supplied claim contain a drafting or transcription defect?

Yes. The final clause of claim 1, as supplied, reads:

“wherein the hypokalemia is greater than the reduction in incidence of hypokalemia is lower than the incidence of hypokalemia provided by 12.5 mg or 25.0 mg per day of chlorthalidone alone.”

That wording is grammatically and logically defective. “The hypokalemia is greater than the reduction in incidence” does not establish a coherent therapeutic comparison. The apparent intended meaning is:

“wherein the incidence of hypokalemia is lower than the incidence of hypokalemia provided by 12.5 mg or 25.0 mg per day of chlorthalidone alone.”

The official issued patent should control over a transcription. If the issued patent contains the same defect, claim construction, correction, prosecution history, and written-description evidence become central. A court may construe the language if the intended meaning is reasonably certain, but it will not rewrite a claim merely to cure an unfavorable drafting error.

What do claims 2 through 7 add?

Claim 2: covered hypertension indications

Claim 2 expands the disease categories to:

Essential hypertension
Secondary hypertension
Arterial hypertension
Pulmonary arterial hypertension
Portal vein hypertension

This claim does not expand the active ingredients or dosing requirements. It remains dependent on all limitations of claim 1.

The inclusion of pulmonary arterial hypertension and portal vein hypertension is commercially less important than essential hypertension because azilsartan medoxomil and chlorthalidone are principally commercialized for systemic hypertension. The broader disease wording may still affect literal infringement where the labeled or prescribed use falls within one of those categories.

Claims 3 through 5: separate dosage forms

Claims 3 through 5 cover coadministration in separate dosage forms. Claims 4 and 5 specify tablets for azilsartan medoxomil and chlorthalidone, respectively.

These claims are relevant to a regimen involving:

An azilsartan medoxomil tablet; and
A separate chlorthalidone tablet.

A generic applicant could attempt to avoid these claims by using a different dosage form, but that strategy would not necessarily avoid claim 1, which does not require separate products.

Claims 6 and 7: single dosage form

Claims 6 and 7 cover administration in one dosage form, with claim 7 specifying a tablet.

These claims are directed to a fixed-dose combination, including the commercial configuration associated with Edarbyclor. The claims do not require a particular tablet-release profile, excipient, manufacturing process, tablet shape, coating, or package configuration.

What formulations are protected by US 9,387,249?

The patent protects the therapeutic use of the active ingredients rather than a detailed formulation architecture.

Product configuration	Claim exposure
Separate azilsartan and chlorthalidone tablets	Claims 1, 3, 4 and 5
Single fixed-dose tablet	Claims 1, 6 and 7
Azilsartan 40 mg plus chlorthalidone 12.5 mg	Within claim 1 if the efficacy limitation is met
Azilsartan 40 mg plus chlorthalidone 25 mg	Within claim 1 if the efficacy limitation is met
Azilsartan 80 mg plus chlorthalidone 12.5 mg	Within claim 1 if the efficacy limitation is met
Azilsartan 80 mg plus chlorthalidone 25 mg	Within claim 1 if the efficacy limitation is met

The patent does not, on the face of the supplied claims, protect:

Azilsartan monotherapy;
Chlorthalidone monotherapy;
Other ARB-diuretic combinations;
Azilsartan doses outside the claimed ranges;
Chlorthalidone doses outside the claimed ranges;
A formulation absent the claimed therapeutic comparison; or
A manufacturing process for either active ingredient.

When does US Patent 9,387,249 expire?

The patent issued on July 12, 2016. Public patent-family records associate it with a priority date in December 2010. On that basis, the nominal 20-year patent term runs into December 2031, subject to patent-term adjustment, terminal disclaimers, and any applicable regulatory patent-term extension.

Event	Date
Earliest reported priority period	December 2010
Patent issued	July 12, 2016
Nominal 20-year term	December 2031
Relevant statutory framework	35 U.S.C. § 154

The operative expiration date must be taken from the USPTO patent-term information and any applicable terminal disclaimer. An Orange Book listing may remain relevant to an ANDA even when the patent has different litigation or enforcement characteristics.

What is the Orange Book status of the patent?

The commercial product associated with this patent is Edarbyclor, FDA-approved as a combination of azilsartan medoxomil and chlorthalidone. FDA Orange Book treatment of a patent depends on whether the patent is listed against the approved drug, its formulation, or its method of use.

An Orange Book-listed method-of-use patent can support a Paragraph IV challenge. A generic applicant may also use a section viii statement to carve out a patented method of use if the remaining label does not instruct use within the protected indication. The feasibility of a carve-out depends on the exact approved labeling and whether the claimed therapeutic benefit is inseparable from the core combination use.

The patent is not a biologic patent and does not create biosimilar exclusivity. The relevant abbreviated 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.

How does the patent compare with the underlying azilsartan patent estate?

US 9,387,249 should be separated from patents covering azilsartan or azilsartan medoxomil as chemical entities.

Patent category	Typical protected subject matter	Relevance to Edarbyclor
Compound patents	Azilsartan or azilsartan medoxomil chemical structure	May affect the active ingredient itself
Combination patents	Azilsartan medoxomil plus chlorthalidone	Directly relevant to the fixed-dose product
Method-of-use patents	Hypertension treatment and potassium effects	Relevant to labeled use and Paragraph IV risk
Formulation patents	Tablets, release properties, excipients, stability	Relevant to a specific dosage form
Manufacturing patents	Synthesis, salt formation, crystallization	May affect API sourcing
Regulatory exclusivity	New drug, pediatric, or other FDA exclusivity	Blocks approval independently of patent infringement

US 9,387,249 is strongest when asserted against a product that matches the commercial regimen and label: azilsartan medoxomil at 40 mg or 80 mg with chlorthalidone at 12.5 mg or 25 mg, particularly where the labeling describes reduced hypokalemia relative to chlorthalidone alone.

It is weaker against a product that uses different doses, omits the hypokalemia comparison from the label, or is marketed for a carved-out indication, although physician prescribing and induced-infringement theories remain relevant.

Which companies are challenging the patent?

Publicly reported litigation and FDA Paragraph IV information should be checked against the current Orange Book and federal court dockets before relying on a specific challenger, filing date, or settlement status. The supplied record does not identify a Paragraph IV notice letter, ANDA filer, district-court action, or settlement agreement.

No biosimilar challenge is applicable because the product is a small-molecule combination. Generic competition would proceed through ANDA litigation, typically involving:

The patent holder or NDA holder;
An ANDA applicant;
The FDA’s 30-month stay framework under Hatch-Waxman;
Paragraph IV allegations of invalidity, unenforceability, or noninfringement; and
Potential label carve-out arguments under section viii.

A generic company could challenge claim 1 by arguing that the hypokalemia limitation is indefinite, unsupported, not enabled across the full dose range, anticipated by combination therapy data, or obvious over ARB-diuretic prior art. It could also argue noninfringement based on dose, labeling, dosage form, or the absence of an instruction to reduce hypokalemia.

How strong is the patent estate?

US 9,387,249 has a focused but commercially meaningful claim set.

Strength factor	Assessment
Chemical-entity coverage	Low under the supplied claims
Combination coverage	High for the specified active ingredients and doses
Fixed-dose tablet coverage	High under claims 6 and 7
Separate-tablet coverage	High under claims 3 through 5
Dose breadth	Moderate to narrow
Therapeutic-result limitation	Creates infringement proof and validity issues
Formulation design-around	Potentially available
Biosimilar relevance	None
ANDA relevance	High
Litigation sensitivity	High because of the comparative hypokalemia limitation

The patent’s central vulnerability is also its central limitation: the claimed reduction in hypokalemia must be established and connected to the accused regimen. A generic label that omits the hypokalemia benefit may reduce direct infringement exposure, but it does not automatically eliminate inducement risk if the combination regimen is otherwise promoted or prescribed for the claimed result.

What generic launch scenarios exist?

Scenario 1: No Paragraph IV challenge

The generic applicant waits until relevant listed patents and regulatory exclusivity expire. This produces the lowest litigation risk but delays entry.

Scenario 2: Paragraph IV challenge to the combination patent

The applicant certifies that US 9,387,249 is invalid, unenforceable, or not infringed. A timely patent lawsuit can trigger a statutory stay of FDA approval for up to 30 months, subject to statutory exceptions and court rulings.

Scenario 3: Section viii carve-out

The applicant removes the patented hypokalemia-related use from labeling. This strategy is more plausible if the remaining label can support hypertension treatment without encouraging the patented comparative benefit.

Scenario 4: Dose or formulation design-around

The applicant uses a nonclaimed dose or dosage form. This approach must account for other patents, the approved reference-product strengths, FDA substitutability requirements, and potential induced-infringement theories.

Scenario 5: Settlement or licensed entry

The patent holder and ANDA applicant may resolve the dispute through a settlement providing delayed entry, a license, or another commercial arrangement. No settlement agreement is identified in the supplied record.

What revenue exposure does this patent create?

The revenue exposure is tied to the US market for Edarbyclor and to the extent that the product’s value depends on the combination’s potassium-sparing clinical positioning. A generic entrant could attack the entire fixed-dose combination market if it obtains approval for the same strengths.

The patent does not independently block generic azilsartan or generic chlorthalidone used outside the claimed combination. Its economic importance is therefore concentrated in:

Fixed-dose combination tablets;
The 40/12.5 mg, 40/25 mg, 80/12.5 mg, and 80/25 mg regimens;
Labeling that discusses hypokalemia reduction; and
Prescribing patterns involving chlorthalidone-associated potassium loss.

Key Takeaways

US 9,387,249 is a method-of-treatment patent, not a broad compound patent.
It covers azilsartan medoxomil potassium salt combined with chlorthalidone.
Claim 1 requires azilsartan doses of about 40 mg or 80 mg per day and chlorthalidone doses of about 12.5 mg or 25 mg per day.
The claim requires a lower incidence of hypokalemia than with chlorthalidone alone.
Claims 3 through 5 cover separate dosage forms; claims 6 and 7 cover a single tablet.
The supplied text contains a material grammatical defect in the final hypokalemia limitation.
The reported nominal patent term extends into December 2031, subject to USPTO term calculations.
Generic competition would proceed through an ANDA, Paragraph IV challenge, section viii carve-out, or post-expiration entry.
Biosimilar competition is irrelevant because azilsartan medoxomil/chlorthalidone is a small-molecule combination.
The patent is commercially strongest against an Edarbyclor-equivalent product using the same strengths and hypokalemia-related labeling.

FAQs About US Patent 9,387,249

Does US 9,387,249 cover Edarbi alone?

No. The supplied claims require both azilsartan medoxomil potassium salt and chlorthalidone. Azilsartan monotherapy is outside claim 1.

Does the patent cover any dose of chlorthalidone?

No. Claim 1 specifies about 12.5 mg per day or about 25 mg per day. Other doses may fall outside the literal claim, subject to construction of “about” and potential equivalents analysis.

Is a fixed-dose combination tablet required?

No. Claim 1 is not limited to one dosage form. Claims 3 through 5 cover separate dosage forms, while claims 6 and 7 cover a single dosage form.

Can an ANDA applicant omit the hypokalemia statement from its label?

A label carve-out may reduce infringement exposure, but its effectiveness depends on the remaining label, promotional conduct, prescribing evidence, and the precise scope of the issued claims.

Does the patent protect the manufacturing process for Edarbyclor?

Not under the supplied claims. The claims are directed to administering the two active ingredients for hypertension treatment and hypokalemia reduction.

References

U.S. Patent No. 9,387,249. (2016). United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2016). Edarbyclor prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug product list and patent and exclusivity information.
35 U.S.C. § 154. Patent term.
21 U.S.C. § 355. New drugs.
21 C.F.R. § 314.94. Content and format of an abbreviated application.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	EDARBYCLOR	azilsartan kamedoxomil; chlorthalidone	TABLET;ORAL	202331-001	Dec 20, 2011	AB	RX	Yes	No	9,387,249	⤷ Start Trial				TREATMENT OF HYPERTENSION	⤷ Start Trial
Azurity	EDARBYCLOR	azilsartan kamedoxomil; chlorthalidone	TABLET;ORAL	202331-002	Dec 20, 2011	AB	RX	Yes	Yes	9,387,249	⤷ Start Trial				TREATMENT OF HYPERTENSION	⤷ 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)	2010075347	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,387,249

Which drugs does patent 9,387,249 protect, and when does it expire?

Summary for Patent: 9,387,249