Details for Patent: 11,395,828

Which drugs does patent 11,395,828 protect, and when does it expire?

Patent 11,395,828 protects CAROSPIR and is included in one NDA.

This patent has four patent family members in four countries.

Summary for Patent: 11,395,828

Title:	Spironolactone aqueous compositions
Abstract:	Disclosed herein is a stable, ready-to-use liquid formulation comprising spironolactone and its method of use.
Inventor(s):	Anthony Pipho, Michael Paul DeHart
Assignee:	Mayne Pharma Inc dba Metrics Contract Services , CMP Development LLC
Application Number:	US17/383,761
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,395,828
Patent Claim Types: see list of patent claims	Use; Formulation;

US Patent 11,395,828: Spironolactone Oral Suspension Claims, Patent Scope and Generic-Entry Risk

US Patent 11,395,828 protects specified methods of administering a ready-to-use, micronized spironolactone liquid suspension. The core limitations are a 5 mg/mL spironolactone concentration, defined xanthan-gum viscosity, glycerin concentration, citrate-buffered pH, and, in dependent claims, particle-size and patient-dosing parameters.[1] The patent does not broadly cover all spironolactone products. Its commercial significance depends on whether a competing product is administered with the claimed formulation and dosing instructions.

What does US Patent 11,395,828 protect?

The patent has two substantially parallel independent method claims:

Claim	Independent claim structure	Principal distinction
1	Treatment of an adult with heart failure, hypertension, or edema using a specified ready-to-use liquid formulation	Broad formulation and indication claim
12	Same treatment method and formulation	Glycerin is recited as the sole “dispersing agent”

Both independent claims require all of the following:

1. An adult patient.
2. Heart failure, hypertension, or edema.
3. Administration of a ready-to-use liquid formulation.
4. Micronized spironolactone at about 5 mg/mL.
5. Xanthan gum sufficient to produce viscosity of 100 to 300 cP.
6. Glycerin at 18 to 24 mg/mL.
7. Citrate buffer sufficient to maintain pH at 4.5 to 5.5.
8. Water as the vehicle.

The claims are method claims rather than composition claims. A company generally would not infringe merely by manufacturing or selling a liquid containing the listed ingredients unless the product is made, sold, or promoted for the claimed administration method and the other statutory requirements for infringement are met.

How narrow are the formulation limitations?

The formulation limitations create a relatively defined design space.

Parameter	Independent-claim requirement	Dependent-claim narrowing
Spironolactone concentration	About 5 mg/mL	None
Particle size	Micronized	Median volume particle size ≤9.6 µm; or 3.6 to 9.6 µm
Xanthan gum	Amount producing 100 to 300 cP	1.3 to 3.6 mg/mL; or 1.8 to 3.6 mg/mL
Glycerin	18 to 24 mg/mL	18 to 22 mg/mL
Citrate buffer	pH 4.5 to 5.5	Approximately 10 to 100 mM
Viscosity	100 to 300 cP	120 to 170 cP; or 150 to 170 cP
Vehicle	Water	No further limitation

The independent claims do not expressly require a specific xanthan-gum concentration. They require a resulting viscosity. That distinction matters. A competing formulation could use a different xanthan-gum concentration and still fall within claims 1 or 12 if the resulting viscosity is 100 to 300 cP and all other limitations are satisfied.

The viscosity limitations are functional and measurable. A formulation testing at 150 cP would fall within the narrower 150 to 170 cP range in claims 9 and 20, subject to the other limitations. A product measuring 110 cP could fall within claim 1 but not claims 8, 9, 19, or 20.

What particle-size characteristics are protected?

Claims 2, 3, 13, and 14 protect narrower particle-size embodiments:

• Median volume particle size of not more than about 9.6 µm.
• Median volume particle size of about 3.6 to about 9.6 µm.

The particle-size limitation applies to micronized spironolactone, not to the finished suspension as a whole. “Median volume particle size” is a specific particle-distribution metric. Laser-diffraction results, sampling methodology, dispersion conditions, and analytical parameters could affect whether a product falls within the claimed range.

The broad independent claims require “micronized” spironolactone but do not state a numerical particle-size threshold. A product could therefore present a potential issue under claims 1 or 12 without falling within the narrower numerical claims.

What dosing regimens are covered?

The dosing claims connect the formulation to specific patient populations and volumes.

Claims	Indication	Dose volume	Frequency	Patient criteria
10, 11, 21, 22	Heart failure	4 mL or 7.5 mL	Once daily or every other day	Serum potassium ≤5.0 mEq/L; eGFR >50
23, 24	Heart failure	2 mL	Once daily or every other day	Serum potassium ≤5.0 mEq/L; eGFR 30 to 50
25, 26	Essential hypertension	4 mL	Once daily, single or divided dose	Adult patient
27, 28	Essential hypertension	15 mL	Once daily, single or divided dose	Essential hypertension
29, 30	Edema	15 mL	Once daily	Adult patient

At 5 mg/mL, the claimed volumes correspond to the following nominal spironolactone doses:

Volume	Approximate spironolactone dose
2 mL	10 mg
4 mL	20 mg
7.5 mL	37.5 mg
15 mL	75 mg

Claims 10, 11, and 23 are clinically narrower than the indication language in claims 1 and 12 because they require heart failure, specific kidney-function ranges, and serum-potassium criteria. Claims 25 through 30 do not include the potassium or eGFR limitations.

The eGFR language may create construction and enforcement issues. Claims 10 and 11 require eGFR greater than 50 mL/min/1.73 m². Claims 23 and 24 require eGFR between 30 and 50 mL/min/1.73 m². The boundaries at exactly 50 may require claim construction because the claims use “>50” in one group and “between 30 to 50” in the other.

What is the difference between claims 1 and 12?

Claims 1 and 12 are nearly duplicative, but claim 12 contains a potentially important narrowing phrase:

“a dispersing agent consisting of glycerin”

Claim 1 requires glycerin at 18 to 24 mg/mL but does not expressly state that glycerin is the only dispersing agent. Claim 12 requires the dispersing agent to consist of glycerin. A formulation that uses glycerin plus another ingredient characterized as a dispersing agent may have a stronger noninfringement position against claim 12 while remaining exposed under claim 1.

The phrase “consisting of” generally has a closed transitional effect for the element it modifies. The ultimate scope would depend on how the specification defines “dispersing agent” and whether the additional ingredient performs a different function, such as wetting, suspending, flavoring, buffering, or preservation.

What formulations are most exposed to US 11,395,828?

A competing product has the highest literal exposure where it has the following profile:

• Ready-to-use aqueous spironolactone suspension.
• Approximately 5 mg/mL spironolactone.
• Micronized active ingredient.
• Xanthan gum as the suspending or viscosity-building polymer.
• 100 to 300 cP viscosity.
• Glycerin at 18 to 24 mg/mL.
• Citrate buffer.
• pH of 4.5 to 5.5.
• Labeling for adult heart failure, hypertension, or edema.
• Dosing instructions matching 2, 4, 7.5, or 15 mL regimens.

A product can reduce exposure by changing one or more claim elements, such as:

• Using a concentration materially different from 5 mg/mL.
• Replacing xanthan gum with another suspending polymer.
• Using a non-citrate buffer.
• Moving the pH outside 4.5 to 5.5.
• Using a different vehicle.
• Using a different glycerin concentration.
• Eliminating or changing the claimed dosing instructions.
• Limiting labeling to an indication not recited in the patent.

A design-around must account for the doctrine of equivalents. Changing a component by a nominal amount may not eliminate risk if the substituted formulation performs substantially the same function in substantially the same way to achieve substantially the same result.

How does the patent compare with ordinary spironolactone products?

US 11,395,828 is materially narrower than the basic product category.

Product type	Likely relevance to US 11,395,828
Spironolactone tablets	Low direct exposure because they are not the claimed ready-to-use liquid formulation
Extemporaneously compounded suspension	Depends on formulation and administration; potential method exposure if all limitations are met
Commercial 5 mg/mL suspension	High potential exposure if the excipient, pH, viscosity, particle-size, and labeling limitations align
Different-strength oral suspension	Lower literal exposure to the 5 mg/mL limitation
Capsule or injectable product	Generally outside the claimed dosage form
Product using a non-citrate buffer	Potential design-around, subject to equivalence analysis
Product using a different suspending system	Potential design-around, subject to whether xanthan gum is present and the viscosity limitation is met

The patent therefore targets a liquid formulation platform rather than spironolactone as a molecule. Spironolactone itself is an established small-molecule active ingredient and is not protected by this patent in every dosage form or use.

What is the FDA and Orange Book significance?

CaroSpir is an FDA-approved oral suspension containing spironolactone at 25 mg/5 mL, equivalent to 5 mg/mL.[2] The formulation described in the claims corresponds closely to that commercial strength.

The patent’s Orange Book significance depends on whether it is listed against the relevant approved drug product and whether the listing covers the approved labeling. FDA Orange Book listings can include drug-substance, drug-product, and method-of-use patents. A method-of-use patent is most relevant where the approved labeling contains the patented indication or dosing method.[3]

A Paragraph IV challenger to an approved generic application would need to address any listed patent by asserting that the patent is invalid, unenforceable, or not infringed. A Paragraph IV notice can trigger Hatch-Waxman litigation and, for an applicable listed patent, a statutory stay of approval of up to 30 months under the conditions specified in the statute.[4]

The supplied claim text does not establish:

• Whether US 11,395,828 is currently listed in the Orange Book.
• The exact NDA or ANDA to which it is listed.
• The patent’s terminal disclaimer or patent-term-adjustment calculation.
• Whether a Paragraph IV notice has been served.
• Whether litigation or a settlement agreement exists.

Those issues must be determined from the current USPTO, FDA Orange Book, and federal court records. The patent number and claims alone do not establish current enforceability, listing status, or litigation status.

When does US 11,395,828 lose exclusivity?

The patent expires at the end of its adjusted or disclaimed patent term, not necessarily on the date suggested by the 20-year filing rule alone. The relevant calculation requires:

• Earliest effective nonprovisional priority date.
• Patent-term adjustment.
• Patent-term extension, if any.
• Terminal disclaimer, if any.
• Any post-grant or litigation-related changes affecting enforceability.

Patent term is governed primarily by 35 U.S.C. §§ 154 and 156.[5] FDA regulatory exclusivity is separate from patent protection. For an established active ingredient such as spironolactone, the key barrier for an oral-suspension competitor is likely to be patent scope and listing status rather than new-molecular-entity exclusivity.

Are biosimilars a risk for spironolactone?

No. Spironolactone is a chemically synthesized small molecule, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply. Competitive entry would proceed through an abbreviated new drug application or another applicable small-molecule pathway, not a biosimilar application.

The principal competitive questions are:

• Whether an ANDA applicant can demonstrate pharmaceutical equivalence.
• Whether the proposed product uses the same or a non-infringing formulation.
• Whether listed method-of-use patents must be carved out.
• Whether the applicant submits Paragraph III or Paragraph IV certifications.
• Whether the FDA-approved label contains indications covered by the patent.

Which companies are likely to challenge the patent estate?

Generic competition in spironolactone tablets is broad because multiple manufacturers market conventional solid oral products. That does not establish that those companies are challenging US 11,395,828. A liquid-suspension challenge would most likely come from a company developing a pharmaceutically equivalent oral suspension or an alternative liquid product.

Publicly identifying a challenger requires a confirmed Paragraph IV notice, ANDA litigation complaint, or court docket. Generic tablet manufacturers should not be treated as patent challengers solely because they sell spironolactone.

How strong is the patent estate?

Strengths

• The claims identify a commercially useful 5 mg/mL liquid suspension.
• The formulation includes several measurable parameters, complicating superficial design-around attempts.
• The dependent claims cover particle size, viscosity, excipient ranges, pH, and dosing.
• Method claims may cover use of an otherwise similar product when the label directs the claimed indications and dosing.

Weaknesses

• The independent claims are method claims, not composition claims.
• A competitor may be able to change the buffer, suspending agent, concentration, or dosing label.
• “About” ranges can create uncertainty at the boundaries.
• The claims rely on clinical administration facts that may not be present in every use.
• Claims 1 and 12 substantially overlap, which may limit the practical benefit of the second independent claim.
• The patent does not prevent use of spironolactone tablets or unrelated liquid formulations outside the recited parameters.

Validity pressure points

Potential validity issues would likely focus on:

• Obviousness based on known spironolactone suspensions and conventional excipients.
• Whether the claimed particle-size and viscosity combination produces an unexpected result.
• Written description and enablement for the full numerical ranges.
• Definiteness of “about,” “sufficient amount,” “ready-to-use,” and the viscosity measurement conditions.
• Support for the specific patient-dose combinations and renal-function thresholds.

A full validity opinion requires review of the specification, prosecution history, cited prior art, examiner amendments, and any terminal disclaimer or post-grant proceedings. The claim text alone supports scope analysis but not a final validity conclusion.

What generic launch scenarios exist?

Scenario	Commercial effect	Patent risk
Generic tablets launch	Competes with solid oral products	Generally low under this patent
Generic liquid uses a different strength	May compete for pediatric or swallowing-impaired patients	Lower literal risk, but market substitution may be limited
Generic liquid uses non-xanthan suspension system	Avoids a central express limitation if label and formulation differ	Moderate design-around potential
Generic liquid matches CaroSpir formulation and label	Closest commercial substitute	Highest infringement and litigation risk
Generic obtains indication carve-out	May avoid selected method claims	Depends on remaining label language and induced-infringement theory
Generic uses same formulation but different dosing instructions	May avoid some dependent claims	Claims 1 and 12 remain relevant

The strongest entry strategy is likely a formulation design-around combined with a label that omits patented use where legally and regulatorily permissible. A label-only strategy may not avoid the independent claims because claims 1 and 12 broadly recite heart failure, hypertension, or edema without requiring the narrower dose volumes.

Key Takeaways

• US 11,395,828 protects methods of treating adults with a specific ready-to-use spironolactone suspension.
• The central formulation is approximately 5 mg/mL spironolactone with xanthan gum, glycerin, citrate buffer, water, pH 4.5 to 5.5, and viscosity of 100 to 300 cP.
• Dependent claims add particle-size, excipient-concentration, viscosity, renal-function, potassium, indication, and dose-volume limitations.
• A 5 mg/mL commercial oral suspension aligned with the claimed excipients and labeling has the highest exposure.
• Conventional spironolactone tablets are generally outside the direct formulation scope.
• The patent does not create biosimilar risk because spironolactone is a small molecule.
• Orange Book listing, patent expiration, Paragraph IV activity, litigation, and settlement status cannot be established from the supplied claims alone.
• The most credible design-around paths involve changing the suspending system, buffer, concentration, pH, or approved labeling.

FAQs About US Patent 11,395,828

Does US Patent 11,395,828 cover all spironolactone oral suspensions?

No. It covers methods using a formulation with the specified concentration, excipient, pH, viscosity, and water-vehicle limitations, together with the claimed patient treatment.

Is a 25 mg/5 mL spironolactone suspension within the claimed concentration?

Yes, 25 mg/5 mL equals 5 mg/mL. The remaining formulation and method limitations must also be satisfied.

Can a generic avoid the patent by using a different xanthan-gum concentration?

Potentially. The independent claims focus on resulting viscosity rather than a specific xanthan-gum concentration. A different xanthan level does not avoid the claims if the product still satisfies the 100 to 300 cP viscosity range and all other limitations.

Do the claims cover pediatric use?

No express pediatric use is claimed. Every independent claim requires treatment of an adult patient.

Does a formulation with 150 cP viscosity fall within the patent?

Yes. It falls within the independent 100 to 300 cP viscosity range and the narrower 150 to 170 cP dependent range, assuming the other claim elements are met.

References

1. United States Patent No. 11,395,828, claims 1-30. United States Patent and Trademark Office.
2. U.S. Food and Drug Administration. (2017). CaroSpir (spironolactone) oral suspension prescribing information. FDA.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA, Orange Book.
4. Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
5. Patent Act, 35 U.S.C. §§ 154, 156.

Drugs Protected by US Patent 11,395,828

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cmp Dev Llc	CAROSPIR	spironolactone	SUSPENSION;ORAL	209478-001	Aug 4, 2017	AB	RX	Yes	Yes						CAROSPIR IS INDICATED FOR TREATMENT OF NYHA CLASS III-IV HEART FAILURE AND REDUCED EJECTION FRACTION TO INCREASE SURVIVAL, MANAGE EDEMA, AND TO REDUCE THE NEED FOR HOSPITALIZATION FOR HEART FAILURE
Cmp Dev Llc	CAROSPIR	spironolactone	SUSPENSION;ORAL	209478-001	Aug 4, 2017	AB	RX	Yes	Yes						CAROSPIR IS INDICATED AS AN ADD-ON THERAPY FOR THE TREATMENT OF HYPERTENSION, TO LOWER BLOOD PRESSURE IN ADULT PATIENTS WHO ARE NOT ADEQUATELY CONTROLLED ON OTHER AGENTS
Cmp Dev Llc	CAROSPIR	spironolactone	SUSPENSION;ORAL	209478-001	Aug 4, 2017	AB	RX	Yes	Yes						CAROSPIR IS INDICATED FOR THE MANAGEMENT OF EDEMA IN ADULT CIRRHOTIC PATIENTS WHEN EDEMA IS NOT RESPONSIVE TO FLUID AND SODIUM RESTRICTION

International Family Members for US Patent 11,395,828

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	3003028
European Patent Office	3368045
Morocco	43132