Details for Patent: 10,695,365

Which drugs does patent 10,695,365 protect, and when does it expire?

Patent 10,695,365 protects LOKELMA and is included in one NDA.

This patent has sixty patent family members in twenty-five countries.

Summary for Patent: 10,695,365

Title:	Microporous zirconium silicate for the treatment of hyperkalemia
Abstract:	The present invention relates to novel microporous zirconium silicate compositions that are formulated to remove toxins, e.g. potassium ions, from the gastrointestinal tract at an elevated rate without causing undesirable side effects. The preferred formulations are designed avoid increase in pH of urine in patients and/or avoid potential entry of particles into the bloodstream of the patient. Also disclosed is a method for preparing high purity crystals of ZS-9 exhibiting an enhanced level of potassium exchange capacity. These compositions are particularly useful in the therapeutic treatment of hyperkalemia.
Inventor(s):	Donald Jeffrey Keyser, Alvaro F. GUILLEM
Assignee:	ZS Pharma Inc
Application Number:	US15/878,120
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,695,365
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 10,695,365: ZS-9 Composition Claims, Lokelma Patent Scope, and Generic Entry Risk

US Patent No. 10,695,365 protects a narrowly defined physical and chemical version of zirconium silicate, commonly identified as ZS-9 and associated with sodium zirconium cyclosilicate, the active ingredient in Lokelma. The claims focus on particle-size distribution, phase purity, sodium content, and potassium-exchange capacity. They do not directly claim a method of treating hyperkalemia, a tablet, a sachet, a dose, or a manufacturing process.

The patent is most relevant to generic manufacturers that intend to reproduce the commercial ZS-9 active pharmaceutical ingredient rather than develop a materially different zirconium silicate composition.

What does US Patent 10,695,365 claim?

Claim 1 is the independent composition claim. It requires every one of the following elements:

Claim element	Requirement
Chemical class	Zirconium silicate composition
Formula	ApMxZr1-xSinGeyOm
Exchangeable cation A	Potassium, sodium, rubidium, cesium, calcium, magnesium, hydronium, or mixtures
Framework metal M	Hafnium, tin, niobium, titanium, cerium, germanium, praseodymium, terbium, or mixtures
Formula ranges	p about 1-20; x from 0 to less than 1; n about 1-12; y 0-12; m about 3-36
Silicate/germanate condition	1 ≤ n+y ≤ 12
Structural phase	ZS-9
Particle size	Median particle size greater than 3 microns
Phase purity	No detectable amounts of ZS-8

The claim uses open-ended language for the composition. A composition may contain additional excipients or components unless another claim limitation or the specification restricts them. It must, however, contain ZS-9 satisfying the claimed physical characteristics.

The claim is narrower than a generic claim to all zirconium silicates. It is also narrower than a claim to all ZS-9 because it requires both a median particle size above 3 microns and the absence of detectable ZS-8.

How broad is the chemical formula in US 10,695,365?

The formula is chemically broad, but the practical scope is constrained by the ZS-9 limitation.

The permitted A ion list covers the principal exchangeable cations used in zirconium silicate ion exchangers. The M list covers multiple tetravalent and pentavalent framework metals. The formula also permits germanium substitution through the y parameter.

Despite that breadth, a competing composition would not necessarily avoid the patent merely by replacing sodium with another cation. Claims 1 and 7-11 can cover compositions in which the claimed ZS-9 has potassium, sodium, or another permitted exchangeable ion, provided the other limitations are satisfied.

The critical limitation is structural identity. A product that is chemically similar to ZS-9 but is a different crystalline phase may avoid literal infringement. A product characterized as ZS-8, an amorphous zirconium silicate, or another framework phase would present a different claim analysis.

What particle-size characteristics are protected?

Claims 1-6 create a tiered particle-size limitation.

Claim	Particle-size requirement
1	Median particle size greater than 3 microns
2	Less than 7% of particles below 3 microns
3	Less than 4% below 3 microns
4	Less than 2% below 3 microns
5	Less than 1% below 3 microns
6	Less than 0.5% below 3 microns

Claims 3-6 are progressively narrower dependent claims. A composition meeting claim 6 would also meet the particle-size limitations of claims 1-5, assuming the other incorporated limitations are satisfied.

The particle-size claims create several infringement and invalidity pressure points:

1. The test method must define how particle diameter is measured.
2. The parties may dispute whether the result is based on volume, number, mass, or another distribution.
3. Agglomerated particles may produce different results from primary particles.
4. Sample preparation, dispersion energy, and instrument selection can materially affect the fraction below 3 microns.
5. The term "less than" excludes a result exactly at the stated threshold.

A generic applicant could therefore challenge the claims through analytical evidence showing that its product has a median particle size of 3 microns or less, or that its particle distribution fails another dependent-claim threshold. The patent holder could respond that the applicant’s testing does not measure the relevant particle population or that the product changes during storage, hydration, milling, or dispersion.

What sodium-content limitations are protected?

Claims 2 and 7-10 impose sodium-content limitations.

Claim	Sodium-content requirement
2	Below 12% by weight
7	Below 12% by weight
8	Below 6% by weight
9	Below 3% by weight
10	0.05%-3% by weight

Claim 2 combines the particle-size distribution requirement from claim 2 with sodium content below 12%. Claim 7 separately requires sodium below 12% but does not incorporate the less-than-7% fine-particle limitation.

Claim 10 is particularly narrow. It requires sodium content within a bounded range, rather than merely below an upper limit. A product with sodium content below 0.05% would fall outside the literal range of claim 10, although it could still fall within other claims.

The basis for "sodium content" will matter. Potential measurement issues include:

• Whether the percentage is calculated on an anhydrous basis.
• Whether bound and exchangeable sodium are both counted.
• Whether residual sodium salts from processing are included.
• Whether the result is measured on the active ingredient or the finished drug product.
• Whether normal batch variability causes a product to cross a claim threshold.

What does the potassium-exchange-capacity claim cover?

Claim 11 requires a potassium exchange capacity between 2.7 and 3.7 meq/g.

This limitation provides a functional characterization of the ZS-9 composition. It is independent of the sodium-content limitations in claims 7-10 because claim 11 depends directly on claim 1.

The range is broad enough to cover a substantial operating window but narrow enough to distinguish some lower-capacity or structurally different zirconium silicates. Testing may involve equilibration conditions, potassium concentration, pH, temperature, particle pretreatment, and calculation basis. Those conditions can affect the measured capacity.

A product that falls outside 2.7-3.7 meq/g could avoid claim 11 while remaining exposed under claims 1-10.

What is the likely commercial relevance to Lokelma?

ZS-9 is the zirconium silicate ion-exchange material used in sodium zirconium cyclosilicate products. Lokelma is approved in the United States for treatment of hyperkalemia in adults. It is supplied as an oral suspension powder in single-dose packets, with labeled doses of 5 g and 10 g of sodium zirconium cyclosilicate (FDA, 2024).

The patent’s commercial relevance arises from its focus on the active pharmaceutical ingredient rather than the finished dosage form. A generic company could formulate a different sachet or use different inactive ingredients and still infringe if the supplied active ingredient satisfies the composition claims.

The claims do not require:

• A particular packet size.
• A particular dose.
• A specific excipient.
• A particular indication.
• A particular administration schedule.
• A finished-product concentration.
• A particular manufacturing route.

That makes the patent potentially important against an ANDA applicant that relies on the same or substantially equivalent ZS-9 material.

What other patents may protect sodium zirconium cyclosilicate?

The relevant estate generally divides into five patent groups.

Foundational zirconium silicate patents

Earlier ZS Pharma patents cover zirconium silicate compositions, ion-exchange materials, and uses in removing potassium from biological fluids. These patents are broader in subject matter but generally have earlier expiration dates than later particle-size and formulation patents.

US Patent No. 8,802,152 is widely associated with the early zirconium silicate estate and has an expiration date in the late 2020s based on standard patent-term calculations. Its exact enforceability depends on claim scope, terminal disclaimers, patent-term adjustment, and any court or USPTO proceedings.

Composition and purity patents

US 10,695,365 belongs to the later composition-focused group. Its distinguishing limitations are:

• ZS-9 phase identity.
• No detectable ZS-8.
• Median particle size above 3 microns.
• Low fine-particle content.
• Controlled sodium content.
• Defined potassium-exchange capacity.

These limitations appear directed to reproducibility, handling, performance, and product quality rather than merely the existence of zirconium silicate.

Formulation patents

Separate patents may cover oral powder formulations, packet presentation, excipient systems, suspension behavior, dosing, stability, and administration. A generic applicant could avoid a formulation patent by changing inactive ingredients while remaining exposed to an active-ingredient composition patent such as US 10,695,365.

Method-of-use patents

Other patents may cover treatment of hyperkalemia, dosing schedules, chronic maintenance therapy, acute reduction of serum potassium, or use in particular patient populations. Method-of-use claims can present separate Paragraph IV or section viii certification issues under the Hatch-Waxman framework.

Manufacturing patents

Manufacturing patents may cover crystallization, ion exchange, drying, particle classification, phase control, and removal of ZS-8. A process can avoid a manufacturing patent while still producing an active ingredient that infringes a composition claim. Conversely, a noninfringing composition made by a patented process may create a separate process-infringement issue.

What is the Orange Book status of US 10,695,365?

US 10,695,365 should be assessed against the current FDA Orange Book patent listing for Lokelma. An Orange Book listing can create statutory notice and automatic-stay consequences if an ANDA applicant submits a Paragraph IV certification and the patent holder files suit within the statutory period (FDA, 2024; 21 U.S.C. § 355).

The practical questions are:

1. Is US 10,695,365 listed against Lokelma?
2. Which approved strength or dosage form is linked to the listing?
3. What expiration date does the Orange Book report?
4. Has the patent been delisted, corrected, or subject to a listing dispute?
5. Does the listed claim actually read on the approved product?

Patent listing does not establish validity or infringement. It affects the timing and procedural posture of generic entry.

When does US 10,695,365 lose exclusivity?

The patent’s nominal term is determined by the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any disclaimer or reexamination outcome. The priority date alone does not establish the final expiration date.

The patent appears to belong to the later-generation Lokelma estate, with a nominal expiration in the mid-2030s rather than the late 2020s. The Orange Book expiration date, USPTO patent-term data, and any terminal disclaimer should control commercial launch modeling.

FDA regulatory exclusivity is separate. Lokelma’s new-drug exclusivity period does not extend the patent term. A generic applicant may face patent barriers after FDA exclusivity has expired.

Which companies are likely to challenge the patent?

A sodium zirconium cyclosilicate generic would normally be developed through an ANDA because the reference product is a small-molecule drug product, not a biologic. Potential applicants would evaluate Paragraph IV certifications against listed patents and may use a section viii statement for patents directed only to methods of use that are not included in the proposed labeling.

A biosimilar pathway is not applicable. Sodium zirconium cyclosilicate is an inorganic ion-exchange material and is regulated as a drug, not as a protein biologic.

Publicly attributing a Paragraph IV challenge requires a filed ANDA notice, litigation complaint, settlement document, or other identifiable record. Patent-number analysis alone does not establish that a particular generic company has challenged US 10,695,365.

What generic launch scenarios exist?

Scenario	Commercial consequence
No Paragraph IV challenge	Entry generally waits for patent and regulatory barriers to expire
Paragraph IV notice with no timely suit	FDA approval may proceed after the applicable notice period
Paragraph IV notice followed by suit	Approval may be delayed by the statutory 30-month stay, subject to court action
Noninfringement design-around	Applicant develops ZS-9 outside one or more claim limitations
Invalidity challenge	Applicant contests written description, enablement, anticipation, obviousness, or indefiniteness
Section viii strategy	Applicant omits patented methods from labeling where legally available
Settlement	Entry date depends on the agreement and antitrust constraints

The most practical design-around options would involve a different crystalline phase, a median particle size at or below the threshold, a particle distribution with a higher fine fraction, sodium content outside the claimed ranges, or potassium-exchange capacity outside claim 11. Each approach must be evaluated against the remaining claims and other patents in the estate.

How strong is the patent estate for US 10,695,365?

The patent has meaningful commercial leverage because it claims the active material itself and uses multiple measurable quality attributes. It is stronger against a product that copies the reference ZS-9 specification than against a deliberately engineered alternative.

Its principal vulnerabilities are claim construction and proof:

• "No detectable amounts" may raise detection-limit and analytical-method disputes.
• "Median particle size" requires a defined measurement protocol.
• The formula includes broad numerical ranges that may face prior-art and enablement scrutiny.
• The claims depend on distinguishing ZS-9 from ZS-8 and other zirconium silicate phases.
• Functional capacity testing may produce variable results across laboratories.

The estate should therefore be modeled as a layered barrier. US 10,695,365 may block one active-ingredient pathway, but generic entry will depend on the combined status of composition, formulation, method-of-use, manufacturing, and regulatory protections.

Key Takeaways

• US 10,695,365 is a composition patent directed to ZS-9 zirconium silicate.
• Claim 1 requires ZS-9, median particle size above 3 microns, and no detectable ZS-8.
• Claims 2-6 progressively tighten the fraction of particles below 3 microns.
• Claims 7-10 impose sodium-content limitations, with claim 10 requiring 0.05%-3% sodium by weight.
• Claim 11 requires potassium exchange capacity of 2.7-3.7 meq/g.
• The patent does not directly claim a treatment method, dose, packet, or excipient system.
• The main generic risk is reproduction of the reference ZS-9 active ingredient.
• A design-around based on particle size, phase identity, sodium content, or exchange capacity remains possible but must be tested against the full Lokelma patent estate.
• Biosimilar risk is not applicable; the relevant pathway is an ANDA with Paragraph IV or section viii certifications.
• Final launch timing depends on the current Orange Book listing, patent-term data, litigation, settlements, and other Lokelma patents.

FAQs About US Patent 10,695,365

Does US 10,695,365 claim Lokelma by name?

No. The claims recite zirconium silicate compositions and technical properties. They do not name Lokelma or require a particular commercial label.

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

Not necessarily. Potassium is expressly included among the permitted A ions. The generic would need to avoid the complete combination of claim limitations.

Does a product containing ZS-8 infringe US 10,695,365?

A product with detectable ZS-8 would face a potential noninfringement position against claim 1 because claim 1 requires that the composition lack detectable ZS-8. It could remain exposed to other patents or other claims if those do not contain the same limitation.

Is particle size measured on the finished Lokelma packet?

The claim analysis generally concerns the claimed composition, not automatically the entire finished packet. The relevant testing basis depends on the patent specification, product composition, and infringement theory.

Does expiration of the earliest Lokelma patent permit immediate generic launch?

No. Later-expiring composition, formulation, method-of-use, or manufacturing patents may continue to delay or increase the risk of generic entry.

References

1. AstraZeneca. (2024). Lokelma (sodium zirconium cyclosilicate) prescribing information. U.S. Food and Drug Administration.

2. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

3. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance. U.S. Department of Commerce.

4. U.S. Patent No. 8,802,152. (2014). Zirconium silicate compositions and methods of use. U.S. Patent and Trademark Office.

5. U.S. Patent No. 10,695,365. (2020). Zirconium silicate composition. U.S. Patent and Trademark Office.

6. 21 U.S.C. § 355. Abbreviated applications and patent certifications under the Federal Food, Drug, and Cosmetic Act.

Drugs Protected by US Patent 10,695,365

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		RX	Yes	No				Y
Astrazeneca	LOKELMA	sodium zirconium cyclosilicate	FOR SUSPENSION;ORAL	207078-002	May 18, 2018		RX	Yes	Yes				Y

International Family Members for US Patent 10,695,365

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	093106
Argentina	095600
Argentina	098365
Argentina	098367
Australia	2013334776