US Patent 8,829,186: Pitavastatin Magnesium Claims, Scope, Expiration and Competitive Patent Landscape

US Patent No. 8,829,186 protects pitavastatin magnesium in defined crystalline, amorphous, hydrated, purity-controlled and process-defined forms. Its broadest commercial significance is the combination of solid-state protection and a manufacturing route that converts an alkali-metal pitavastatin salt into the magnesium salt. The patent does not claim pitavastatin calcium, the marketed Livalo product, or every pharmaceutical use of pitavastatin.

The strongest infringement positions are likely to arise where a manufacturer produces or sells:

Crystalline pitavastatin magnesium with the specified powder X-ray diffraction peaks;
Amorphous pitavastatin magnesium having the claimed diffraction profile;
Material within the claimed water-content, optical-rotation or purity ranges;
A pharmaceutical composition containing the claimed magnesium compound; or
Pitavastatin magnesium made through the claimed protected intermediate and salt-conversion process.

The patent issued on September 9, 2014. Its precise expiration date depends on the earliest effective nonprovisional or international filing date and any patent-term adjustment. A 20-year term measured from an ordinary 2012 effective filing date would ordinarily place expiration in 2032, subject to the official USPTO term calculation.[1]

What does US Patent 8,829,186 protect?

US 8,829,186 contains 30 claims directed to four related subject-matter groups:

Claim group	Claims	Protected subject matter
Compound claims	1-11	Pitavastatin magnesium, hydrates, amorphous material, water content, optical rotation and purity
Process claims	12-21	Preparation from protected pitavastatin intermediates through an alkali-metal salt and magnesium conversion
Consolidated compound claims	22-28	Crystalline or amorphous forms with analytical and purity characteristics
Composition claims	9 and 29	Pharmaceutical compositions containing the claimed pitavastatin magnesium

The patent is centered on Formula (IB), which is the magnesium salt of pitavastatin. Claim interpretation must therefore begin with the identity of the claimed magnesium compound, its salt stoichiometry, and whether the claimed “hydrate thereof” includes a defined magnesium-containing hydrate or a broader hydrated solid form.

What is the broadest compound claim?

Claim 1 covers:

An isolated pitavastatin magnesium compound of Formula (IB) or a hydrate thereof.

This is the broadest product claim in the patent. It does not require crystallinity, amorphousness, a particular water content, a particular diffraction pattern, or a purity threshold. If valid and properly construed, claim 1 can reach isolated pitavastatin magnesium regardless of whether the material is crystalline, amorphous or hydrated.

The principal limitations are:

The product must be pitavastatin magnesium of the specified Formula (IB).
It must be isolated.
A hydrate is expressly included.

The claim does not expressly require a pharmaceutical composition or a particular use. A manufacturer making the active pharmaceutical ingredient would face greater exposure under claim 1 than a party merely practicing a use of pitavastatin.

How do the crystalline and amorphous claims differ?

The patent protects two distinct solid-state categories.

Crystalline pitavastatin magnesium

Claims 3, 4, 22, 23 and 24 cover crystalline material identified by an XRPD pattern having characteristic peaks at approximately:

10.1° 2θ;
13.2° 2θ;
19.3° 2θ; and
27.2° 2θ.

The permitted deviation is ±0.2° 2θ. Claim 4 also refers to a pattern substantially the same as Figure 1.

The crystalline claims are not limited solely to the four listed peaks. Claim 3 requires a crystalline compound having those characteristic peaks, while claim 4 adds a figure-based “substantially same” limitation. Claim 22 supplements the XRPD requirement with at least one of the following:

Specific optical rotation of approximately +22.0 to +22.5;
HPLC purity above approximately 99% by area; or
Diastereomeric impurity below approximately 0.3% by area.

Claim 24 adds a water-content range of approximately 7% to 12% by weight.

Amorphous pitavastatin magnesium

Claims 5, 6, 7, 8, 9, 10, 11 and 25-30 address the amorphous material. These claims require, directly or by dependency:

An amorphous pitavastatin magnesium compound;
An XRPD pattern substantially the same as Figure 2;
Water content below approximately 5% by weight;
Specific optical rotation of approximately +22.0 to +22.5;
HPLC purity greater than approximately 99% by area; or
Diastereomeric impurity below approximately 0.3% by area.

The amorphous form is therefore protected through a combination of physical characterization and analytical parameters. The XRPD limitation is particularly important because an amorphous solid typically lacks the sharp diffraction peaks associated with a crystalline polymorph.

What formulations are protected by US 8,829,186?

Claims 9 and 29 cover a pharmaceutical composition comprising the claimed pitavastatin magnesium and one or more pharmaceutically acceptable carriers or excipients.

These claims are composition claims, not detailed dosage-form claims. They do not expressly identify:

Tablets;
Capsules;
Oral suspensions;
Specific excipients;
A particular dose;
A release profile;
A dissolution threshold; or
A specific therapeutic indication.

A formulation containing the claimed amorphous or crystalline pitavastatin magnesium could fall within the composition claims if the active ingredient satisfies the relevant dependent limitations. The composition claims are narrower than claim 1 because they require both the protected active ingredient and a pharmaceutical composition.

The claims do not appear to protect a formulation technology independently of the active ingredient. A tablet containing an unclaimed pitavastatin salt would not, on the supplied claim language alone, satisfy claims 9 or 29.

What manufacturing process is protected?

Claim 12 is the principal process claim. It requires all of the following stages:

Reaction of a Formula-IV phosphonium bromide with a Formula-III aldehyde;
Use of an alkali or alkaline-earth metal base;
Use of one or more polar aprotic solvents;
Formation of the protected tert-butyl ester, Formula-II;
Acidic hydrolysis to remove the acetonide protecting group and form a diol;
In-situ treatment with an alkali-metal hydroxide to form an alkali-metal pitavastatin salt;
Treatment of that alkali-metal salt with a magnesium source; and
Isolation of pitavastatin magnesium.

The process is structured as a sequence. A competing process that omits a required stage, uses a materially different intermediate, or forms magnesium pitavastatin through a different salt-conversion route may avoid literal infringement of claim 12, although the product claims remain independently relevant.

Which bases and solvents are claimed?

Claims 13 and 14 narrow the process by listing permitted reagents.

Claim 13 identifies bases including:

Sodium hydroxide;
Potassium hydroxide;
Lithium hydroxide;
Potassium carbonate;
Sodium carbonate;
Lithium carbonate; and
Cesium carbonate.

Claim 14 identifies polar aprotic solvents including:

Dimethylformamide;
Dimethyl sulfoxide;
Dimethylacetamide;
Tetrahydrofuran;
N-methylpyrrolidone; and
Mixtures of those solvents.

These dependent claims create narrower fallback positions. They also provide a practical screening list for process-risk review of a generic API route.

Which magnesium sources are claimed?

Claim 20 identifies:

Magnesium chloride;
Magnesium methoxide;
Magnesium acetate; and
Hydrates of those sources.

The claim set therefore reaches a conventional salt-conversion operation in which an alkali-metal pitavastatin salt is converted to pitavastatin magnesium using a listed magnesium reagent.

What analytical specifications matter for infringement?

The patent relies on four principal analytical controls.

Parameter	Claimed range or characteristic
XRPD crystalline peaks	10.1°, 13.2°, 19.3° and 27.2° 2θ, ±0.2°
Crystalline water content	Approximately 7%-12% wt/wt
Amorphous water content	Less than approximately 5% wt/wt
Specific optical rotation	Approximately +22.0 to +22.5 in 1% DMSO at 20 ±0.5°C
HPLC purity	Greater than approximately 99% by area
Diastereomeric impurity	Less than approximately 0.3% by area

The XRPD limitations are likely to carry the greatest product-identification value. Water content alone is less discriminating because hydration can change during drying, storage and handling. Optical rotation and HPLC measurements also require defined analytical methods, sample preparation and instrument conditions.

Claims using “about” and “substantially the same” create interpretation issues. The ±0.2° XRPD tolerance is comparatively specific. By contrast, “substantially the same as” a figure may require comparison of the overall pattern, peak positions, relative intensities and baseline rather than a simple four-peak test.

How strong is the patent estate?

The patent has a layered structure, but its practical strength differs by claim category.

Claim category	Relative strength	Main vulnerability
Claim 1 isolated compound	High breadth if valid	Prior-art disclosure of pitavastatin magnesium or a hydrate
Crystalline-form claims	Moderate to high	Anticipation or obviousness from prior solid forms; XRPD reproducibility
Amorphous-form claims	Moderate	Enablement, characterization and prior-art amorphous material
Purity and optical-rotation claims	Moderate	Inherent disclosure and routine purification arguments
Composition claims	Moderate	Dependence on infringement of the active-ingredient claims
Process claim 12	Moderate	Design-around using a different route or reagents
Dependent process claims	Narrower	Easy avoidance by changing a listed reagent or solvent

The strongest commercial protection comes from the combination of claim 1 and the solid-state claims. A challenger that defeats only the process claims may still face direct product claims. Conversely, a challenger that develops a different pitavastatin magnesium form may avoid some XRPD-specific claims but still need to address claim 1.

When does US 8,829,186 lose exclusivity?

The patent issued in 2014 and is subject to the ordinary US patent term framework under 35 U.S.C. §154.[2] The expected expiration is approximately 20 years from the earliest effective nonprovisional filing date, not 20 years from the issue date.

Because the supplied claim text does not identify the patent’s priority chain, the enforceable expiration date cannot be calculated from the claims alone. The relevant record is the USPTO patent-term data and the patent’s priority statement. Any term adjustment, terminal disclaimer or disclaimer tied to a related patent can change the result.[1]

The patent appears to be a small-molecule API and solid-state patent. It is not a biologic patent and does not create a biosimilar exclusivity period. Any FDA exclusivity associated with pitavastatin products would arise separately from this patent.

What is the FDA and Orange Book status?

Pitavastatin is an FDA-approved statin active ingredient. The reference product Livalo contains pitavastatin calcium, not pitavastatin magnesium.[3] The supplied claims are directed to pitavastatin magnesium and therefore do not automatically correspond to the FDA-listed active ingredient in Livalo.

The Orange Book analysis is consequently product-specific:

An Orange Book listing for pitavastatin calcium would not, by itself, establish an Orange Book listing for pitavastatin magnesium.
A patent covering pitavastatin magnesium may be commercially important without being listed for a particular reference product.
Paragraph IV certification risk depends on whether a generic applicant seeks approval for an FDA product whose listed patents cover the proposed product or method of use.
A manufacturer seeking approval for a pitavastatin magnesium product would need to assess the applicable FDA product-specific guidance, reference product designation and any listed patents for the relevant application.[3]

The patent itself does not claim a method of treating hypercholesterolemia, cardiovascular disease or any other indication. It is therefore not, on the supplied claims, a method-of-use patent.

Are Paragraph IV challenges or litigation identified?

No Paragraph IV notice, district-court case, settlement agreement or PTAB proceeding is established by the claim text supplied. The patent’s claim structure indicates potential litigation theories, but not that a challenge has occurred.

A Paragraph IV dispute would most likely focus on:

Anticipation by an earlier disclosure of pitavastatin magnesium;
Obviousness based on pitavastatin salts, magnesium salts and routine solid-form screening;
Indefiniteness of “substantially the same” XRPD language;
Enablement of the claimed crystalline and amorphous forms;
Inherent anticipation of water-content or purity limitations;
Noninfringement based on a different polymorph, solvate or amorphous profile; and
Process noninfringement based on a different synthesis or magnesium-conversion step.

A generic applicant could also pursue an alternative formulation, a different salt, or a route that produces pitavastatin magnesium without the claimed protected intermediate sequence. Product claim 1 would remain the primary barrier if the final isolated API is the same claimed compound.

Which companies are challenging the patent?

The supplied information does not identify a challenger, ANDA filer, licensee, settlement party or litigation defendant. No company should be characterized as a challenger based solely on the patent claims.

The relevant competitive set would include:

The patent owner and its authorized API or finished-dose licensees;
Generic manufacturers developing pitavastatin products;
Companies pursuing pitavastatin calcium rather than magnesium;
API manufacturers using alternative salt-formation processes; and
Formulation companies using a non-infringing crystalline, amorphous or hydrated form.

Pitavastatin calcium products may compete commercially without directly practicing the claimed pitavastatin magnesium subject matter.

How does this patent compare with pitavastatin calcium protection?

Issue	Pitavastatin magnesium under US 8,829,186	Pitavastatin calcium products
Active salt	Magnesium	Calcium
Main protection	Compound, solid form, purity and process	Product-specific compound, formulation and use patents
FDA reference relevance	Separate from Livalo unless specifically approved	Directly relevant to Livalo and related products
Biosimilar risk	None; small molecule	None; small molecule
Solid-state risk	Crystalline and amorphous forms expressly claimed	Depends on separate calcium-form patents
Process risk	Alkali-metal salt to magnesium conversion route	Depends on the relevant calcium synthesis and salt process
Orange Book analysis	Must be tied to the specific approved magnesium product	Tied to the applicable calcium reference product

Changing the counterion from calcium to magnesium is a potentially meaningful design choice, but it does not remove risk if the marketed product is pitavastatin magnesium. The patent claims the magnesium salt as a chemical entity, not merely a formulation use.

What generic launch scenarios exist?

Scenario 1: Launch with pitavastatin magnesium before patent expiry

This would require a successful invalidity, noninfringement or license position. The principal arguments would concern prior art, claim construction, solid-form differentiation and process design-around.

Scenario 2: Launch with pitavastatin calcium

A calcium product could avoid the literal magnesium-salt claims, but it would face a separate patent and regulatory analysis. The product would also compete with established pitavastatin calcium products rather than directly enter the magnesium-salt market.

Scenario 3: Use a nonclaimed magnesium form

A manufacturer could attempt to produce a magnesium solvate, polymorph or amorphous material outside the claimed XRPD and analytical parameters. Claim 1 creates the central obstacle because it is not limited to the specific crystalline peaks or water-content ranges.

Scenario 4: Use an alternative manufacturing route

A different route may avoid claims 12-21. It would not necessarily avoid claims 1-11 or 22-30 if the resulting API has the claimed identity or solid-state properties.

What geographic coverage does the patent provide?

US 8,829,186 provides enforceable rights in the United States only. Corresponding protection in India, Europe, China, Japan or other jurisdictions would require separate national or regional patent rights. The process, crystalline-form and amorphous-form claims may have materially different outcomes across jurisdictions because of differences in:

Patentable subject-matter standards;
Treatment of polymorphs and salts;
Sufficiency and enablement requirements;
Markush claim interpretation;
Patent-term rules; and
Regulatory-linkage mechanisms.

A global freedom-to-operate review cannot infer foreign coverage from the US grant alone.

What manufacturing and intellectual-property barriers remain after expiration?

After expiration of the relevant US patent claims, the compound and process claims generally cease to block US practice, subject to any separate, unexpired patents. Commercial barriers may remain in:

API process validation;
Control of hydration state;
Reproducible amorphous or crystalline material;
Diastereomer control;
HPLC impurity limits;
Scale-up of the magnesium conversion;
Stability and packaging;
FDA filing requirements; and
Separate formulation or method-of-use patents.

The patent’s process claims also indicate potential manufacturing know-how around isolating a reproducible solid form. Patent expiration does not eliminate the need to reproduce the claimed physical and analytical quality attributes.

Key Takeaways

US 8,829,186 is primarily a pitavastatin magnesium compound, solid-form and manufacturing-process patent.
Claim 1 is the broadest product claim and covers isolated pitavastatin magnesium and hydrates without requiring a specified polymorph.
Crystalline claims require XRPD peaks near 10.1°, 13.2°, 19.3° and 27.2° 2θ.
Amorphous claims rely on a Figure 2 XRPD profile and may include water content below approximately 5% by weight.
Purity, diastereomer content and optical rotation operate as additional claim limitations.
The main process route converts an alkali-metal pitavastatin salt into pitavastatin magnesium using a magnesium source.
The patent does not claim pitavastatin calcium, a method of treating disease, or a biologic.
Livalo’s pitavastatin calcium status cannot be treated as an automatic Orange Book listing for pitavastatin magnesium.
Alternative synthesis routes may avoid the process claims but do not necessarily avoid the compound claims.
The expected patent term is approximately 20 years from the earliest effective filing date, subject to USPTO term calculations.
No challenger, Paragraph IV notice, litigation or settlement is established by the supplied claim text.

FAQs

Does US 8,829,186 cover pitavastatin calcium?

No. The supplied claims specifically cover pitavastatin magnesium and its hydrates, forms, compositions and preparation processes.

Does the patent cover any pitavastatin magnesium hydrate?

Claim 1 expressly includes a pitavastatin magnesium hydrate. The scope of particular hydrates may depend on claim construction and whether the hydrate is materially the claimed Formula (IB) compound.

Can a generic manufacturer avoid the patent by using a different magnesium source?

A different magnesium source may avoid a dependent process claim such as claim 20. It would not automatically avoid claim 12 or the compound claims.

Is an amorphous pitavastatin magnesium product outside the crystalline claims?

It may be outside claims limited to the specified crystalline XRPD peaks. It can still fall within the separate amorphous claims or the broader compound claim.

Does FDA approval of pitavastatin calcium invalidate this patent?

No. FDA approval and patent validity are separate issues. Approval of pitavastatin calcium does not establish invalidity of claims directed to pitavastatin magnesium.

References

United States Patent and Trademark Office. (n.d.). US8829186B2: Patent term and bibliographic record. USPTO Patent Center.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Medicure	ZYPITAMAG	pitavastatin magnesium	TABLET;ORAL	208379-001	Jul 14, 2017		DISCN	Yes	No	⤷ Start Trial	⤷ Start Trial	Y	Y			⤷ Start Trial
Medicure	ZYPITAMAG	pitavastatin magnesium	TABLET;ORAL	208379-002	Jul 14, 2017		RX	Yes	No	⤷ Start Trial	⤷ Start Trial	Y	Y			⤷ Start Trial
Medicure	ZYPITAMAG	pitavastatin magnesium	TABLET;ORAL	208379-003	Jul 14, 2017		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y	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

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
India	159/MUM/2010	Jan 20, 2010

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Japan	2013516459	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2011089623	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,829,186

Which drugs does patent 8,829,186 protect, and when does it expire?

Summary for Patent: 8,829,186