Details for Patent: 11,738,044

Which drugs does patent 11,738,044 protect, and when does it expire?

Patent 11,738,044 protects LOKELMA and is included in one NDA.

This patent has twenty-six patent family members in twenty countries.

Summary for Patent: 11,738,044

Title:	Extended use zirconium silicate compositions and methods of use thereof
Abstract:	The present invention relates to zirconium silicate compositions having a lead content that is below 0.6 ppm and methods of manufacturing zirconium silicate at reactor volumes exceeding 200-L with a lead content below 1.1 ppm. The lead content of the zirconium silicate of this invention are within the levels that are considered acceptable for extended use given the dose requirements for zirconium silicate.
Inventor(s):	Donald Jeffrey Keyser, Alvaro F. GUILLEM
Assignee:	ZS Pharma Inc
Application Number:	US16/415,550
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,738,044
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 11,738,044: Scope, Claims, Expiration and Patent Landscape for Sodium Zirconium Cyclosilicate

U.S. Patent No. 11,738,044 protects a chronic-treatment method for hyperkalemia using a zirconium-silicate cation exchanger with controlled lead content and, in dependent claims, defined particle-size, sodium-content, crystallographic, pH, and potassium-capacity characteristics. The patent is directed to product quality and clinical-use conditions associated with sodium zirconium cyclosilicate, marketed as Lokelma by AstraZeneca.

The patent does not claim every use of zirconium silicate or every treatment of hyperkalemia. Its enforceable scope depends on proving that the administered composition satisfies the claimed chemical and physical parameters and that treatment continues for more than five consecutive days.

What does U.S. Patent 11,738,044 cover?

U.S. Patent 11,738,044 covers a method of treating hyperkalemia by administering a zirconium-silicate composition for more than five consecutive days. The composition must have lead below 0.6 parts per million.

The core claim has four material elements:

1. A patient in need of hyperkalemia treatment.
2. Administration over a period exceeding five consecutive days.
3. A cation-exchange composition containing a defined zirconium silicate.
4. Lead content below 0.6 ppm.

The claimed zirconium silicate has the formula:

ApMxZr1-xSinGeyOm

The formula permits substantial compositional variation. It covers:

• A as potassium, sodium, rubidium, cesium, calcium, magnesium, hydronium, or mixtures;
• M as hafnium, tin, niobium, titanium, cerium, germanium, praseodymium, terbium, or mixtures;
• p from about 1 to about 20;
• x from 0 to less than 1;
• n from about 0 to about 12;
• y from 0 to about 12;
• m from about 3 to about 36; and
• 1 ≤ n+y ≤ 12.

The formula is broad, but the claim is narrowed by the treatment duration and lead specification.

What is the likely commercial product relationship?

The claim is directed at the same therapeutic and material class as sodium zirconium cyclosilicate, the active ingredient in Lokelma. Lokelma is an orally administered potassium-binding resin approved for treatment of hyperkalemia in adults. The FDA-approved product is supplied as a powder for oral suspension and contains sodium zirconium cyclosilicate as the active moiety. [1]

A claim chart mapping the patent to Lokelma would focus on:

Claim limitation	Lokelma relevance
Hyperkalemia treatment	Express FDA indication
More than five consecutive days	Consistent with chronic maintenance use
Zirconium silicate cation exchanger	Active ingredient is sodium zirconium cyclosilicate
Lead below 0.6 ppm	Requires batch-specific analytical evidence
Particle-size limitations	Requires certificate-of-analysis or testing data
Sodium-content limitations	Requires composition testing
XRD peaks at approximately 15.5 and 28.9	Requires crystallographic comparison
pH 7 to 9	Requires product testing
Potassium capacity of 2.7 to 3.7 mEq/g	Requires analytical testing
ICP-MS lead testing	Controls the analytical method for dependent claim 13

The commercial relevance is strongest where the accused product is intended for chronic use and has a composition matching the patented quality profile.

How broad is independent claim 1?

Independent claim 1 is broad in chemical composition but narrow in use and impurity control.

Chemical breadth

The formula includes sodium zirconium silicate and related framework-substituted materials. It is not limited to a single exact stoichiometry or a single counterion. The language permits mixtures and multiple framework metals.

That breadth creates potential coverage over:

• Sodium zirconium cyclosilicate;
• Potassium- or mixed-cation zirconium silicates;
• Zirconium silicates containing hafnium, tin, niobium, titanium, cerium, germanium, praseodymium, or terbium;
• Materials with variable silicon and germanium content;
• Materials with different degrees of cation loading.

The formula alone therefore reaches well beyond the commercial sodium form. The practical scope is constrained by the requirement that the material be used in the claimed hyperkalemia treatment method and have lead below 0.6 ppm.

Treatment-duration limitation

The phrase "over a period of more than 5 consecutive days" requires treatment extending beyond five consecutive days. In ordinary usage, this means at least six consecutive days.

This limitation is important because it separates chronic or maintenance treatment from short-term correction of serum potassium. A one-time administration, a five-day course, or intermittent dosing that does not extend across more than five consecutive days would present a non-infringement argument unless the patent’s construction or factual record establishes an equivalent treatment period.

The claim does not specify:

• Dose;
• Frequency;
• Route beyond administration of the composition;
• Serum potassium threshold;
• Patient age;
• Renal-disease status;
• Dialysis status;
• Concomitant therapy; or
• The precise number of treatment days after the initial five.

The absence of a dose limitation increases claim breadth for chronic administration.

Lead-content limitation

Lead below 0.6 ppm is a direct composition limitation. Claims 2 through 4 create narrower numerical ranges:

Claim	Lead limitation
1	Below 0.6 ppm
2	0.1 to 0.5 ppm
3	0.3 to 0.5 ppm
4	0.3 to 0.45 ppm
13	Lead determined using ICP-MS

The narrower lead claims provide fallback positions if a court limits claim 1 or if an accused batch falls outside the broad range but inside one of the narrower ranges.

The specification and prosecution history would be important for determining whether "lead content" refers to:

• Total lead in the active pharmaceutical ingredient;
• Lead in the finished composition;
• Lead per unit mass of dry material;
• A release specification; or
• A measured value based on a defined sample-preparation protocol.

Claim 13 gives the patentee a specific analytical method, but it also creates a potential dispute over whether ICP-MS is mandatory for the asserted claim or only a dependent-claim limitation.

What do the dependent claims add?

Claims 5 through 12 impose manufacturing and quality attributes that can materially narrow infringement.

Particle-size limitations

Claims 5 and 6 address fine particles:

• Less than 7% of particles may have a diameter below 3 microns.
• Less than 0.5% of particles may have a diameter below 1 micron.

Claims 7 and 8 combine the particle-size limitation with sodium content:

• Less than 7% below 3 microns and sodium below 12%;
• Less than 7% below 3 microns and sodium at 9% or less.

These claims are directed to particle engineering and composition control. They may be relevant to:

• Powder handling;
• Suspension behavior;
• Dust generation;
• Dose uniformity;
• Gastrointestinal tolerability;
• Manufacturing reproducibility; and
• Commercial release specifications.

Particle-size claims are sensitive to the measurement technique. Laser diffraction, microscopy, sieving, and other methods can produce materially different results, particularly at the sub-3-micron and sub-1-micron thresholds. The relevant evidence would include the measurement instrument, dispersion medium, dispersion energy, sampling method, and calculation model.

X-ray diffraction limitation

Claim 9 requires the two highest X-ray diffraction peaks to occur at approximately 15.5 and 28.9, with the highest peak at 28.9.

This limitation is a structural fingerprint. It can be used to distinguish the claimed crystalline phase from other zirconium-silicate forms. The principal issues in an infringement analysis would include:

• Radiation source and wavelength;
• Peak-position tolerance;
• Sample preparation;
• Hydration state;
• Instrument calibration;
• Relative peak intensity; and
• Whether the accused material contains a mixture of crystalline phases.

The word "approximately" introduces a construction issue. The intrinsic record and examples would likely determine the acceptable deviation from 15.5 and 28.9 degrees two-theta.

pH and potassium-loading capacity

Claim 10 requires pH between 7 and 9. Claims 11 and 12 require potassium-loading capacity of 2.7 to 3.7 mEq/g or approximately 3.5 mEq/g.

These limitations add functional performance specifications:

Claim	Additional requirement
10	pH from 7 to 9
11	Potassium loading capacity from 2.7 to 3.7 mEq/g
12	Potassium loading capacity approximately 3.5 mEq/g

The testing protocol matters. Potassium capacity can vary with pH, ionic strength, equilibration time, particle size, competing cations, and whether the reported value is based on dry or conditioned material.

What is the patent’s likely expiration date?

The patent was granted on August 29, 2023. Its enforceable term is governed by the earliest effective nonprovisional priority date in the family, adjusted for any patent-term adjustment and subject to any applicable patent-term extension. [2]

The relevant commercial analysis should distinguish three dates:

Date type	Business significance
Patent grant date	Date on which the issued claims became enforceable, subject to statutory limits
Nominal patent expiration	Twenty years from the applicable earliest nonprovisional filing date
Adjusted expiration	Nominal expiration plus any USPTO patent-term adjustment, less any applicable terminal disclaimer

The patent is part of the broader Lokelma patent estate. A generic applicant cannot assume that expiration of one patent permits launch if another listed patent remains enforceable.

FDA Orange Book patent listings, rather than the patent number alone, determine the principal Hatch-Waxman significance for an ANDA applicant. The Orange Book identifies patents submitted for approved drug products and their use codes, but it does not decide validity, infringement, or enforceability. [3]

What is the Orange Book status of U.S. Patent 11,738,044?

The patent’s commercial significance depends on whether AstraZeneca submitted it to FDA for listing against NDA 207954 for Lokelma and, if listed, the applicable use code.

An Orange Book listing can trigger the statutory certification framework for an ANDA applicant:

• Paragraph I: no patent information has been submitted;
• Paragraph II: the patent has expired;
• Paragraph III: the applicant will wait until patent expiration; or
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV notice creates litigation risk for the generic applicant. If the NDA holder files suit within the statutory period, FDA approval may be stayed for up to 30 months, subject to statutory exceptions and court action. [4]

For this patent, the relevant infringement question is narrower than whether a generic product contains sodium zirconium cyclosilicate. The analysis must address whether the proposed label directs administration for more than five consecutive days and whether the product meets the claimed lead, particle, XRD, pH, or capacity limitations.

Which companies are likely to challenge the Lokelma patent estate?

The relevant challengers are generic manufacturers pursuing ANDAs for sodium zirconium cyclosilicate or products with a therapeutically equivalent claim to Lokelma.

Potential challenger categories include:

• Large generic manufacturers;
• Specialty pharmaceutical companies;
• Contract manufacturers supplying an ANDA sponsor;
• Companies using a non-infringing zirconium-silicate formulation; and
• Companies seeking approval after patent expiry under a Paragraph III certification.

A Paragraph IV challenge would likely focus on one or more of the following:

1. Anticipation by earlier zirconium-silicate composition patents.
2. Obviousness based on known zirconium-silicate potassium binders and routine impurity control.
3. Indefiniteness of terms such as "approximately," "below," or "over a period."
4. Lack of written description or enablement across the full formula.
5. Non-infringement based on lead content, particle-size distribution, XRD profile, or treatment duration.
6. Lack of inducement where the proposed label does not direct chronic treatment exceeding five days.

The patent’s method-of-use format may allow a generic company to pursue a narrower label, depending on FDA labeling requirements and the scope of any listed use code.

How does this patent compare with earlier Lokelma patents?

The Lokelma estate generally divides into several technical groups.

Patent-estate category	Typical subject matter	Relevance to generic entry
Core zirconium-silicate composition patents	Chemical structure and ion-exchange materials	Can block manufacture or use of the active ingredient
Crystalline-form patents	XRD-defined phases and structural characteristics	Can block a specific solid form
Formulation patents	Powder, suspension, sachet, excipients, and delivery characteristics	Can require design-around of the finished product
Manufacturing patents	Synthesis, purification, particle control, and impurity reduction	Can create process or supply-chain barriers
Method-of-use patents	Chronic hyperkalemia treatment and dosing	Can create induced-infringement risk under a labeled-use theory
Quality-control patents	Lead, particle size, sodium level, pH, and exchange capacity	Can cover commercial release specifications

U.S. Patent 11,738,044 is most significant as a quality-control and chronic-use patent. It does not require a particular commercial name, sachet size, excipient system, or dose. Its broadest practical reach arises from the combination of a zirconium-silicate class with a low-lead specification and chronic hyperkalemia treatment.

What manufacturing and intellectual-property barriers does the patent create?

The lead limitation is the principal manufacturing barrier. Zirconium-silicate production requires control over raw materials, reaction conditions, washing, drying, milling, storage, and packaging. Lead may enter through:

• Mineral or inorganic raw materials;
• Process water;
• Reactor or milling equipment;
• Contaminated excipients;
• Packaging components; or
• Cross-contamination in a shared facility.

A manufacturer seeking to design around the patent could attempt to use a product with lead at or above the claimed threshold. That strategy would create obvious regulatory and commercial problems because lead is a toxic-element impurity and drug manufacturers must control elemental impurities under applicable quality standards. [5]

Other design-around paths could include:

• A different crystalline phase;
• A particle distribution outside the claimed thresholds;
• A sodium content outside claims 7 and 8;
• Potassium capacity outside claims 11 and 12;
• pH outside claim 10; or
• A label that does not direct treatment for more than five consecutive days.

Each path must be assessed against the broader claim 1 and other patents in the estate. Avoiding a dependent claim does not avoid claim 1.

What is the biosimilar risk for Lokelma?

Lokelma is a small-molecule or inorganic ion-exchange drug product, not a biological product. Biosimilar approval under the Public Health Service Act is therefore not the principal competitive pathway. [6]

The relevant competitors are ANDA applicants, 505(b)(2) applicants, or products using a different potassium-binding technology. The principal branded alternative is Veltassa, which contains patiromer sorbitex and has a separate patent estate, formulation, and regulatory profile. [7]

Product	Active ingredient	FDA pathway for conventional generic competition	Key patent issue
Lokelma	Sodium zirconium cyclosilicate	ANDA or 505(b)(2), depending on product and equivalence	Zirconium-silicate composition, quality, formulation, and use patents
Veltassa	Patiromer sorbitex	ANDA or 505(b)(2), depending on product and equivalence	Polymer composition, formulation, and method-of-use patents

What patent litigation and settlement issues matter?

A generic challenge to a listed Lokelma patent would normally produce one of three outcomes:

1. Litigation continues through claim construction, validity, and infringement rulings.
2. The parties settle with a license, agreed launch date, or other restrictions.
3. The challenger obtains a judgment or settlement permitting earlier launch.

Settlement analysis should examine:

• Authorized-generic rights;
• Licensed manufacturing rights;
• Royalty obligations;
• Launch date;
• Geographic restrictions;
• Product-form restrictions;
• Covenants not to sue;
• Acceleration clauses; and
• Treatment of patents not included in the original case.

A settlement involving one patent does not necessarily clear the full Lokelma estate. Orange Book patents, unlisted process patents, trade secrets, regulatory exclusivity, and supply agreements may remain relevant.

How strong is the patent estate around U.S. Patent 11,738,044?

The patent has meaningful commercial value but a narrower litigation profile than a patent claiming the active ingredient itself.

Strengths

• The lead threshold is objective and analytically testable.
• The claim reaches chronic treatment, which corresponds to Lokelma’s maintenance use.
• Claim 1 covers a broad zirconium-silicate formula.
• Dependent claims provide multiple fallback positions.
• Particle size, XRD, pH, and potassium capacity are measurable product attributes.
• A generic product designed to match Lokelma may naturally satisfy several limitations.

Vulnerabilities

• The treatment-duration requirement may support a label-based non-infringement defense.
• The exact meaning of lead content may be disputed.
• "Approximately" and "below" may create claim-construction issues.
• The broad formula may face written-description and enablement challenges.
• Particle-size and potassium-capacity results can vary by test method.
• Prior-art zirconium-silicate disclosures may be relevant to obviousness.
• A generic manufacturer may alter the crystalline form or quality profile while retaining potassium-binding activity.

The strongest asserted claims are likely to be claim 1, claims 2 through 4 for specific lead ranges, and claim 9 if the accused product has the same XRD signature. Claims 5 through 8 and 10 through 12 are more dependent on batch testing and standardized analytical methods.

What generic launch scenarios exist for Lokelma?

Scenario	Effect
No Paragraph IV challenge	Launch generally follows patent and regulatory exclusivity dates
Paragraph III certification	Approval is deferred until the relevant patent expires
Paragraph IV with no timely suit	FDA approval may proceed under the statutory framework
Paragraph IV followed by timely suit	FDA approval may be stayed for up to 30 months, subject to statutory exceptions
Successful invalidity or non-infringement decision	Earlier approval or launch may become available
Settlement with licensed entry	Launch occurs on the negotiated date and terms
Carve-out or restricted label	Potential approval without some patented use, if FDA accepts the carve-out

For this patent, a narrow label carve-out could be commercially difficult if chronic use is central to the approved product’s value. The feasibility of a carve-out depends on the Orange Book use code and the exact language of the proposed generic label.

What is the revenue exposure from this patent?

The patent’s revenue exposure is tied to Lokelma’s chronic-use market rather than to every zirconium-silicate product. The highest-value exposure is in:

• Long-term maintenance treatment;
• Patients with chronic kidney disease;
• Patients receiving renin-angiotensin-aldosterone-system inhibitors;
• Hospital-discharge continuation therapy; and
• Recurrent hyperkalemia management.

The patent may have limited relevance to acute or short-course treatment if the treatment does not exceed five consecutive days. Its commercial impact increases if the Orange Book listing covers the primary approved use and if the product’s release specifications consistently fall within the claimed ranges.

Key Takeaways

• U.S. Patent 11,738,044 claims chronic hyperkalemia treatment using a low-lead zirconium-silicate cation exchanger.
• Claim 1 requires administration for more than five consecutive days and lead content below 0.6 ppm.
• Dependent claims cover narrower lead ranges, particle-size distributions, sodium content, XRD peaks, pH, potassium capacity, and ICP-MS testing.
• The patent is closely associated with the commercial quality and chronic-use profile of sodium zirconium cyclosilicate, including Lokelma.
• The main generic defenses are non-infringement based on treatment duration or analytical properties, and invalidity based on prior art, indefiniteness, written description, or obviousness.
• Lokelma does not face biosimilar competition. The relevant challenges are ANDA or 505(b)(2) programs.
• A complete launch assessment requires review of all Orange Book-listed Lokelma patents, use codes, terminal disclaimers, patent-term adjustment, and any Paragraph IV litigation or settlement.
• The patent is a meaningful secondary barrier in the Lokelma estate, particularly for manufacturers attempting to reproduce the branded product’s material specifications.

FAQs

Does U.S. Patent 11,738,044 claim sodium zirconium cyclosilicate itself?

No. Its independent claim is a method-of-treatment claim. It requires administration of a qualifying zirconium-silicate composition for more than five consecutive days and requires lead below 0.6 ppm.

Can a generic avoid the patent by using potassium zirconium silicate instead of sodium zirconium silicate?

Not necessarily. Claim 1 permits A to be potassium, sodium, rubidium, cesium, calcium, magnesium, hydronium, or mixtures. A potassium-based material may still fall within the claim if the other limitations are satisfied.

Does avoiding the XRD peak limitation avoid all patent risk?

No. Claim 9 would not necessarily be infringed, but claim 1 and other patents in the Lokelma estate could remain relevant.

Is lead content tested in the finished dosage form or active ingredient?

The answer depends on the patent’s construction, specification, prosecution history, and testing evidence. Claim 13 specifically identifies ICP-MS, while the broader claims require proof of the claimed lead content in the relevant composition.

Does a five-day treatment course infringe the patent?

Claim 1 requires administration over more than five consecutive days. A course limited to five days does not satisfy that express duration limitation, subject to claim construction and the facts of the accused labeling and use.

References

1. U.S. Food and Drug Administration. (2018). Lokelma (sodium zirconium cyclosilicate) prescribing information.
2. United States Patent and Trademark Office. (2023). U.S. Patent No. 11,738,044, zirconium silicate compositions and methods of use thereof.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.
5. United States Pharmacopeia. (2024). General chapter <232>: Elemental impurities: Limits.
6. 42 U.S.C. § 262. Regulation of biological products.
7. U.S. Food and Drug Administration. (2015). Veltassa (patiromer) prescribing information.

Drugs Protected by US Patent 11,738,044

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca	LOKELMA	sodium zirconium cyclosilicate	FOR SUSPENSION;ORAL	207078-001	May 18, 2018	AB	RX	Yes	No	11,738,044					TREATMENT OF HYPERKALEMIA IN ADULTS
Astrazeneca	LOKELMA	sodium zirconium cyclosilicate	FOR SUSPENSION;ORAL	207078-002	May 18, 2018	AB	RX	Yes	Yes	11,738,044					TREATMENT OF HYPERKALEMIA IN ADULTS

International Family Members for US Patent 11,738,044

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	106369
Australia	2016338753
Brazil	112018007189
Canada	3000950
Chile	2018000916