US Patent 9,169,238: Claim Scope, Exclusivity, and Patent Landscape for Azilsartan Medoxomil/Chlorthalidone

US Patent 9,169,238 protects a pharmaceutical formulation that combines azilsartan medoxomil potassium with chlorthalidone through separate granulation. Its core limitation is not the active ingredients alone. The patent requires a pH-control agent in the azilsartan-containing granule, a defined aqueous pH range of 2 to 5, and separate granulation of the azilsartan and chlorthalidone portions. The patent is directed to formulation stability and azilsartan dissolution rather than to the underlying compounds.

The protected product is associated with the Edarbyclor fixed-dose combination, marketed by Takeda Pharmaceuticals for hypertension. FDA-approved Edarbyclor strengths contain azilsartan medoxomil and chlorthalidone at 40/12.5 mg, 40/25 mg, 80/12.5 mg, and 80/25 mg doses.[1]

What drug and formulation does US Patent 9,169,238 protect?

The unusually long chemical name in the claims is azilsartan medoxomil potassium, the active pharmaceutical ingredient related to azilsartan medoxomil. The claimed preparation combines it with chlorthalidone.

The patent protects a solid dosage form with these required elements:

Claim element	Required by independent claim 1
Azilsartan medoxomil potassium	Yes
Chlorthalidone	Yes
pH-control agent associated with the azilsartan portion	Yes
pH of 1% aqueous solution or suspension	2 to 5
Separate granulation of the two portions	Yes
Solid preparation	Yes
Tablet form	No, unless claim 4 or 5 applies
Specific active-ingredient ratio	No
Specific tablet strength	No
Specific excipient other than the pH-control agent	No

The formulation architecture separates the two actives during granulation. The first part contains azilsartan medoxomil potassium and the pH-control agent. The second part contains chlorthalidone. The separately granulated parts may then be compressed as a single-layer tablet or retained as separate layers in a bilayer tablet.

How do claims 1 through 8 operate?

What does independent claim 1 cover?

Claim 1 is the principal composition claim. A potentially infringing product must satisfy all of the following conditions:

It contains azilsartan medoxomil potassium.
It contains chlorthalidone.
It contains a pH-control agent in the first, azilsartan-containing part.
A 1% w/v aqueous solution or suspension of that pH-control agent has a pH of 2 to 5 at 25°C.
The first and second parts are obtained by separate granulation.
The resulting article is a solid preparation.

The claim does not require a multilayer tablet. A conventional single-layer tablet can fall within the claim if the two granulated parts are mixed before compression.

The claim also does not require the final dosage form to retain physically identifiable first and second portions. Separate granulation is a process limitation, but the finished product may be a mixed single-layer tablet under claim 1 and claim 4.

What does claim 2 add?

Claim 2 narrows the pH-control agent to an acidic substance or a salt or solvate of that substance. The listed acids are:

Tartaric acid
Citric acid
Lactic acid
Fumaric acid
Succinic acid
Phosphoric acid
Malic acid
Ascorbic acid
Acetic acid
Acidic amino acids

The claim creates a broad acidic-excipient genus. It does not require fumaric acid specifically.

What does claim 3 add?

Claim 3 is narrower. It covers:

Monosodium fumarate; or
A combination of fumaric acid and a sodium-ion donor.

This claim is commercially important because it identifies the preferred pH-control chemistry more narrowly than claim 2. A formulation using a different listed acid may avoid claim 3 but remain within claim 2 or claim 1.

What do claims 4 and 5 cover?

Claim 4 covers a single-layer tablet made by mixing the separately granulated first and second parts and compressing the mixture.

Claim 5 covers a multilayer tablet in which:

The first layer contains the azilsartan portion.
The second layer contains the chlorthalidone portion.

The claims therefore cover both physical segregation and post-granulation mixing. A manufacturer cannot necessarily avoid the patent by converting a bilayer design into a conventional single-layer tablet.

What does claim 6 add?

Claim 6 requires the pH-control agent to represent 0.01% to 20% by weight of the total preparation. This is a wide concentration range. It is likely to capture routine commercial use of acidic excipients, while leaving a potential design-around path below 0.01% or above 20%, subject to practical formulation constraints and infringement analysis.

What do claims 7 and 8 cover?

Claims 7 and 8 are method claims.

Claim 7 covers a method of stabilizing azilsartan medoxomil potassium and chlorthalidone by separately granulating:

A first part containing azilsartan medoxomil potassium and the pH-control agent; and
A second part containing chlorthalidone.

Claim 8 covers a method of improving azilsartan dissolution using the same separate-granulation structure.

These claims are narrower in practical enforcement than a product claim because they require proof of the accused manufacturing process or claimed method. A generic manufacturer may face greater discovery exposure if batch records, master manufacturing instructions, or validation documents show separate granulation.

How strong is the patent estate for the claimed formulation?

US Patent 9,169,238 has a focused but commercially relevant scope. Its strength rests on the combination of several limitations that target a known compatibility and dissolution problem:

A specific active-ingredient pair.
A defined acidic pH range.
Separate granulation.
A pH agent located in the azilsartan portion.
Coverage of both single-layer and multilayer tablets.
Separate method claims for stability and dissolution.

The estate is stronger against a formulation that reproduces the same manufacturing concept than against a product that uses a materially different formulation platform.

Claim-strength assessment

Issue	Assessment
Active ingredients	Narrow and product-specific
pH-agent requirement	Provides a measurable infringement limitation
pH range	Supports objective testing
Separate granulation	Creates a process-sensitive limitation
Single-layer coverage	Broadens commercial relevance
Bilayer coverage	Captures an alternative tablet architecture
Active ratio limitation	None in claim 1
Manufacturing flexibility	Moderate; different granulation or excipient systems may create design-around options
Stability/dissolution rationale	Technically aligned with the claimed formulation structure
Small-molecule generic vulnerability	Higher than a biologic formulation patent because ANDA applicants can develop alternative formulations

The most material weakness is the requirement that the accused formulation use separate granulation. A generic developer could investigate direct blending, co-granulation, dry blending, spray drying, hot-melt processing, or a different pH-modifying system. Whether any alternative avoids the claims depends on the actual process and the doctrine of equivalents.

What patents protect Edarbyclor and related azilsartan products?

Edarbyclor is a small-molecule fixed-dose combination. Its relevant patent landscape normally divides into four groups:

Patent category	Subject matter	Relevance to generic entry
Azilsartan compound patents	Azilsartan, azilsartan medoxomil, salts, and related intermediates	May protect the active ingredient or its manufacture
Combination patents	Azilsartan plus chlorthalidone	May cover the therapeutic combination independent of formulation
Formulation patents	Separate granulation, pH control, stability, and dissolution	May block a particular generic formulation
Method-of-use patents	Treatment of hypertension and related dosing regimens	May affect labeling and paragraph IV strategy

US Patent 9,169,238 is a formulation patent. It does not, on its face, claim azilsartan medoxomil potassium as a chemical compound in isolation. It also does not claim chlorthalidone by itself.

The commercial product’s patent exposure must therefore be assessed against the full FDA Orange Book listing for the relevant NDA, not against US 9,169,238 alone.[2]

What is the Orange Book status of US Patent 9,169,238?

The Orange Book question is product-specific. A patent may be technically relevant to an approved product but have no current Orange Book listing, or it may be listed with a use code that limits the scope of a paragraph IV notice.

For Edarbyclor, the relevant reference product is NDA 202810. The FDA Orange Book identifies patents and exclusivity information associated with approved products, while FDA’s electronic patent-submission rules govern patent listing and use-code information.[2][3]

US 9,169,238 should be evaluated across four separate questions:

Was it submitted for listing against NDA 202810?
Was it accepted by FDA for Orange Book listing?
Does the listing remain active?
What expiration date and use code does the listing report?

The patent number alone does not establish all four facts. A listed formulation patent can create a paragraph IV exposure even when compound-patent protection has expired. Conversely, an unlisted formulation patent may remain enforceable under ordinary patent law but generally will not create the same ANDA certification mechanism.

When does US Patent 9,169,238 lose exclusivity?

The patent issued on October 27, 2015. Its term is generally measured from the earliest effective US nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable prosecution history.[4]

The patent belongs to the 2010s formulation-patent generation and has a nominal term extending into the early 2030s. A precise expiration date should be taken from the USPTO Patent Center record and the Orange Book listing, if listed. The issue date itself is not the expiration date.

Exclusivity timeline

Event	Timing
Underlying Edarbyclor FDA approval	2012
US Patent 9,169,238 issuance	October 27, 2015
Nominal patent-term period	Extends into the early 2030s
Small-molecule ANDA pathway	Available when statutory and patent barriers are satisfied
Biosimilar pathway	Not applicable

FDA approval exclusivity and patent exclusivity are separate. Edarbyclor is a small-molecule product, so it does not receive biologic reference-product exclusivity under the Biologics Price Competition and Innovation Act. Generic applicants proceed through section 505(j) ANDAs rather than biosimilar applications.[5]

Are paragraph IV challenges likely against this patent?

A paragraph IV challenge would be commercially credible if US 9,169,238 is listed for Edarbyclor and remains unexpired. An ANDA applicant could assert that the patent is:

Not infringed because its product does not use separate granulation.
Not infringed because its pH agent does not produce a pH of 2 to 5 at 1% w/v.
Not infringed because the pH agent is not in the azilsartan-containing part.
Invalid for lack of anticipation or obviousness.
Invalid for inadequate written description or enablement, depending on the asserted claim and evidentiary record.

The most direct noninfringement strategy would be a formulation design that avoids separate granulation or uses a pH-control system outside the claimed parameters. The strongest validity challenge would likely focus on prior-art combinations involving azilsartan formulations, acidic excipients, separate granulation, and dissolution improvement.

Potential generic certification positions

Certification	Strategic effect
Paragraph I	No patent information listed
Paragraph II	Listed patent expired
Paragraph III	Generic waits for listed patent expiration
Paragraph IV	Patent is invalid, unenforceable, or not infringed
Section viii statement	Generic omits a patented method of use from labeling

A section viii strategy could be relevant to method-of-use patents, but it would not ordinarily remove a formulation patent that claims the generic product itself.

What litigation and settlement risks affect generic launch?

The principal litigation risk depends on whether the patent is Orange Book-listed and whether the generic product reproduces the claimed process. If a paragraph IV notice is served for a listed patent, the NDA holder generally has 45 days to file an infringement action. Timely litigation can trigger a 30-month stay of ANDA approval under the Hatch-Waxman framework, subject to statutory exceptions and court orders.[6]

A settlement could permit launch before patent expiration through:

A negotiated entry date.
A license to use the formulation.
A no-challenge agreement.
A supply or authorized-generic arrangement.
A covenant not to sue limited to a noninfringing formulation.

No settlement terms should be inferred from the existence of US 9,169,238. Settlement analysis requires the specific case docket, ANDA filer, patent assertions, and agreement terms.

What generic entry risks exist for Edarbyclor?

Edarbyclor faces the standard small-molecule generic-entry sequence:

Expiration or removal of relevant compound and combination patents.
Paragraph IV challenges to remaining listed patents.
Litigation over formulation and manufacturing limitations.
FDA review of bioequivalence and pharmaceutical equivalence.
Potential first-filer exclusivity under section 505(j), if available.
Commercial launch after final approval or permitted settlement entry.

The formulation claim may delay an exact copy while leaving room for an alternative formulation. This distinction matters because a generic applicant does not need to reproduce Takeda’s formulation if it can demonstrate bioequivalence using a different excipient and manufacturing design.

Generic launch scenarios

Scenario	Commercial result
No listed patent remains	FDA approval can proceed after regulatory review
Claim 1 is listed and generic uses separate granulation	High litigation exposure
Generic avoids separate granulation	Lower direct infringement risk
Generic uses acidic excipient outside pH 2-5	Potential claim-avoidance route
Generic uses a different dosage form	Risk depends on whether claim 1 remains satisfied
Patent challenge succeeds	Earlier approval or settlement leverage
Patent challenge fails	Launch generally waits for expiry or licensed entry

Does this patent create biosimilar risk?

No. Azilsartan medoxomil and chlorthalidone are chemically synthesized small molecules. US 9,169,238 is not a biologic patent and does not create biosimilar litigation under the BPCIA.

The relevant competitors are generic ANDA applicants, not biosimilar developers. Manufacturing confidentiality, formulation know-how, and bioequivalence testing remain important, but the regulatory pathway is abbreviated new drug approval.

What manufacturing and IP barriers does the patent create?

The patent creates three practical barriers.

First, the generic manufacturer must determine whether the reference product uses separate granulation and whether its proposed process falls within that limitation.

Second, the manufacturer must characterize the pH-control agent under the claim’s test condition: 1% w/v in water at 25°C. The relevant pH is not necessarily the final tablet’s dissolution-medium pH or the finished product’s microenvironmental pH.

Third, the manufacturer must separate formulation development from legal analysis. A product may be bioequivalent while still infringing a process-limited formulation claim. Conversely, a formulation may avoid the patent while requiring additional development to meet dissolution and bioequivalence specifications.

How does US 9,169,238 compare with compound and method-of-use patents?

Patent type	What it protects	Design-around potential
Compound patent	Chemical entity or salt	Low if active ingredient is required
Combination patent	Azilsartan plus chlorthalidone	Moderate, depending on claim language
Formulation patent	Excipient system and manufacturing process	Often higher
Method-of-use patent	Treatment, patient group, or dosing regimen	Moderate through labeling strategy
Manufacturing patent	API synthesis or intermediate	Moderate to high if alternate route exists

US 9,169,238 is narrower than a compound patent but can be commercially important because it targets the final dosage form sold to patients. Its infringement analysis is more fact-intensive than a claim directed simply to azilsartan medoxomil or chlorthalidone.

What is the revenue exposure from this patent?

The patent’s revenue exposure is tied to Edarbyclor sales, not to all azilsartan or all chlorthalidone sales. A successful design-around could preserve generic entry while avoiding direct infringement. A successful patent challenge could accelerate competition in a fixed-dose hypertension product, but it would not necessarily affect Edarbi monotherapy or standalone chlorthalidone products.

The financial impact depends on:

Edarbyclor net sales before generic entry.
The number of ANDA filers.
First-filer status.
Settlement timing.
Price erosion after launch.
Whether the generic launches all four strengths.
The survival of separate compound, combination, and method-of-use patents.

Key Takeaways

US Patent 9,169,238 is a formulation patent for azilsartan medoxomil potassium plus chlorthalidone.
Claim 1 requires separate granulation, an azilsartan-containing first part, a chlorthalidone-containing second part, and a pH-control agent meeting the 2-to-5 pH test.
Claims 4 and 5 cover both single-layer and multilayer tablets.
Claim 6 adds a 0.01% to 20% pH-agent concentration range.
Claims 7 and 8 cover stabilization and dissolution-improvement methods using the same manufacturing architecture.
The patent does not claim azilsartan medoxomil potassium or chlorthalidone in isolation.
Generic developers may pursue direct blending, alternative granulation, different pH systems, or other formulation designs.
The commercial significance depends on Orange Book listing status, remaining patent term, related Edarbyclor patents, and any Hatch-Waxman litigation.
Biosimilar risk is not applicable because the product contains small-molecule active ingredients.
The patent’s nominal term extends into the early 2030s, subject to the official USPTO term calculation and any Orange Book listing data.

FAQs

Is US Patent 9,169,238 a patent on Edarbyclor itself?

It is a patent on a particular azilsartan medoxomil potassium/chlorthalidone solid formulation and its manufacture. It is not a broad patent on every formulation or every use of the two active ingredients.

Can a generic avoid US 9,169,238 by using a bilayer tablet?

No. Claim 5 expressly covers a multilayer tablet with separate azilsartan and chlorthalidone layers.

Can a generic avoid the patent by using a single-layer tablet?

Not necessarily. Claim 4 covers a single-layer tablet made by mixing the separately granulated parts before compression.

Does the patent cover any acidic excipient at any concentration?

No. The independent claim requires a pH-control agent producing a pH of 2 to 5 under the specified 1% w/v aqueous test. Claim 6 further limits the agent to 0.01% to 20% by weight of the preparation.

Is a patent challenge required before a generic can enter?

Only if an unexpired, relevant patent creates a regulatory or infringement barrier. A generic applicant may wait for expiration, certify under paragraph IV, use a section viii statement for an appropriately limited method-of-use patent, or develop a formulation that does not infringe.

References

U.S. Food and Drug Administration. (2023). Edarbyclor (azilsartan medoxomil and chlorthalidone) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2016). Listing of patent information in the Orange Book. 21 C.F.R. § 314.53.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process.
Hatch-Waxman Amendments, 21 U.S.C. § 355(j).
United States Patent and Trademark Office. (2015). U.S. Patent No. 9,169,238: Solid preparation comprising azilsartan medoxomil potassium and chlorthalidone.

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	9,169,238	⤷ Start Trial	Y				⤷ Start Trial
Azurity	EDARBYCLOR	azilsartan kamedoxomil; chlorthalidone	TABLET;ORAL	202331-002	Dec 20, 2011	AB	RX	Yes	Yes	9,169,238	⤷ Start Trial	Y				⤷ 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

PCT Information
PCT Filed	July 29, 2009	PCT Application Number:	PCT/JP2009/063833
PCT Publication Date:	February 04, 2010	PCT Publication Number:	WO2010/013835

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	072883	⤷ Start Trial
Australia	2009277455	⤷ Start Trial
Brazil	PI0916847	⤷ Start Trial
Canada	2732018	⤷ Start Trial
Chile	2011000187	⤷ Start Trial
China	102164918	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,169,238

Which drugs does patent 9,169,238 protect, and when does it expire?

Summary for Patent: 9,169,238