US Patent 6,465,477: Scope, Claim Analysis, Expiration, and Pitavastatin Patent Landscape

US Patent 6,465,477 protects pharmaceutical compositions containing pitavastatin, pitavastatin calcium, or related salts and esters, subject to a defined aqueous pH range and, in most dependent claims, specified alkaline or organic stabilizing agents and solid-dose excipients. It does not claim pitavastatin as a chemical compound by itself. The patent was assigned to Kowa Co., Ltd. and is an expired composition patent relevant to historical Livalo and pitavastatin generic-exclusivity analysis.[1]

The patent’s commercial importance came from formulation protection for pitavastatin calcium, particularly oral solid formulations containing basic substances and conventional tablet excipients. Its claims are narrower than the foundational compound claims covering pitavastatin.

What drug and active ingredient does US Patent 6,465,477 cover?

The claimed active ingredient is pitavastatin, also known as NK-104 and pitavastatin calcium when formulated as its calcium salt. Pitavastatin is an HMG-CoA reductase inhibitor used to reduce LDL cholesterol.

The structural name in the claims contains typographical variations, including “flurophenyl.” The intended compound is generally identified as the pitavastatin acid structure:

(E)-3,5-dihydroxy-7-[4-(4-fluorophenyl)-2-cyclopropylquinolin-3-yl]-6-heptenoic acid
Pitavastatin free acid
Pitavastatin calcium, the marketed pharmaceutical form

The patent is directed to a pharmaceutical composition rather than the active molecule in isolation. A product containing pitavastatin could infringe only if its composition satisfied the relevant formulation limitations.

What are the independent claims in US Patent 6,465,477?

Claims 1 and 15 are the principal composition claims.

Claim	Principal subject matter	Key limitation
1	Composition containing pitavastatin acid, salt, or ester	Aqueous solution or dispersion has pH 6.8 to 7.8
15	Composition containing pitavastatin acid, salt, or ester	Contains a vehicle, disintegrator, binder, or lubricant

Claim 1 is the broadest claim in the patent by subject matter, but its pH limitation materially narrows the scope. Claim 15 does not expressly include the pH requirement because it depends directly from claim 1 as reproduced in the user-provided claim set. As a result, the claim dependency must be read carefully. If the issued patent contains the same dependency, claim 15 incorporates claim 1’s limitations and adds the excipient requirement.

The claim set therefore has two central protection theories:

A pitavastatin composition with a near-neutral aqueous pH.
A pitavastatin composition containing conventional pharmaceutical excipients, particularly in an oral solid dosage form.

How broad is claim 1 of US Patent 6,465,477?

Claim 1 has four material elements:

A pharmaceutical composition.
Pitavastatin free acid, a salt, or an ester.
A pharmaceutically acceptable carrier.
An aqueous solution or dispersion of the composition with pH from 6.8 to 7.8.

The chemical component is drafted broadly enough to include pitavastatin acid and its salts and esters. Claim 2 narrows that scope to the calcium salt. The practical commercial focus is pitavastatin calcium because that is the active ingredient used in Livalo.

The pH limitation is the principal narrowing feature. A composition that contains pitavastatin calcium but produces an aqueous solution or dispersion outside pH 6.8 to 7.8 would have a potential non-infringement position under claim 1, subject to how the court interprets “aqueous solution or dispersion” and the testing method.

What does the pH limitation mean?

The claim does not simply require the finished tablet to have a measured surface pH. It refers to the pH of an aqueous solution or dispersion of the pharmaceutical composition. In a litigation context, the relevant questions would include:

The concentration used for testing.
Whether the composition fully dissolves or remains a dispersion.
The temperature and testing protocol.
Whether pH is measured before or after equilibration.
Whether the claim requires the pH of the marketed dosage form or a prepared sample.
Whether a formulation’s excipients materially alter the measured pH.

The pH limitation can create testing and claim-construction issues. It also creates design-around potential if a competing formulation does not fall within the specified range.

What do claims 2 through 9 protect?

Claims 2 through 9 narrow claim 1 by specifying the salt or the basic substance used in the composition.

Claim	Limitation	Commercial relevance
2	Pitavastatin calcium salt	Directly targets the marketed active form
3	Composition contains a basic substance	Broad stabilizer or pH-control limitation
4	Basic substance is an organic base compound	Covers organic alkalizing agents
5	Basic substance is an alkaline earth metal silicate	Covers inorganic silicate materials
6	Basic substance is an aluminum compound	Potential textual inconsistency with claim 5
7	Alkaline earth metal silicate is a magnesium salt	Narrows to magnesium-containing materials
8	Magnesium aluminometasilicate, magnesium aluminosilicate, or magnesium aluminum silicate	Targets specific tablet excipients
9	Basic substance is L-arginine	Targets a defined organic amino-acid base

Claims 3 through 9 are formulation-dependent claims. They are narrower than claim 1 because they require a particular class or species of basic substance.

What is the significance of the magnesium silicate claims?

Claims 5, 7, and 8 are directed to inorganic excipients used for alkalinity, stabilization, adsorption, or processing. Magnesium aluminometasilicate and related materials are common pharmaceutical excipient categories. A generic formulation using one of the specifically named materials would face a greater literal-infringement risk than a formulation using a different alkalizing agent.

The presence of a listed excipient alone would not establish infringement. The accused product would still need to meet all incorporated limitations of the parent claim, including the active ingredient and any pH requirement.

Is claim 6 internally inconsistent?

The claim language supplied contains a technical inconsistency. Claim 5 identifies an “alkaline earth metal silicate,” while claim 6 states that the basic substance is “an aluminum compound.” Aluminum is not an alkaline earth metal. Claim 8 also uses magnesium-aluminum silicate terminology.

A court could address this through ordinary claim construction, correction of an obvious drafting error, prosecution-history review, or a validity challenge based on indefiniteness. The practical effect depends on the exact issued claim text, prosecution record, and any certificate of correction. The inconsistency reduces the predictability of claim 6 compared with claims 2, 7, and 8.

What do claims 10 through 15 protect?

Claims 10 through 15 cover conventional pharmaceutical formulation components and oral solid dosage forms.

Claim	Formulation subject matter
10	Vehicle, disintegrator, binder, or lubricant
11	Peroral solid preparation
12	Lactose vehicle
13	Low-substitution hydroxypropyl cellulose
14	Hydroxypropylmethyl cellulose binder
15	Vehicle, disintegrator, binder, or lubricant

These claims are directed primarily to tablets or other oral solid preparations. They are not limited to a particular tablet strength, release profile, coating, or commercial brand presentation based on the supplied language.

Potentially relevant excipients include:

Lactose
Low-substitution hydroxypropyl cellulose
Hydroxypropylmethyl cellulose
Lubricants
Disintegrants
Conventional tablet vehicles

The claims may be difficult to enforce against a generic product if the generic uses a different excipient system, a different binder, or a non-solid dosage form. They are stronger against formulations that reproduce the listed excipient combinations.

When did US Patent 6,465,477 expire?

US Patent 6,465,477 was granted on October 15, 2002. Its term was governed by the 20-year patent-term framework applicable to the underlying US filing. Public patent records identify a February 24, 2019 expiration date for the patent, subject to any recorded patent-term adjustment or correction.[1][2]

Event	Date
US filing	February 24, 1999
Grant	October 15, 2002
Expected statutory expiration	February 24, 2019
Current status	Expired

The patent is therefore no longer an enforceable US exclusion right. Historical infringement exposure remains relevant for conduct occurring before expiration, but the patent cannot block a current generic launch based solely on this patent.

What is the Orange Book status of pitavastatin patents?

The FDA Orange Book historically listed multiple patents associated with Livalo, including patents directed to pitavastatin compounds and formulations. US Patent 6,465,477 was relevant to the product’s formulation patent estate.[3]

Orange Book-listed patent issues include:

Whether the patent was listed against the approved Livalo product.
Whether the listed patent covered the active ingredient, formulation, or method of use.
Whether an abbreviated new drug application required a Paragraph IV certification.
Whether the patent had expired by the time of generic approval.
Whether any pediatric exclusivity or other statutory extension affected the listing.

Because US Patent 6,465,477 has expired, it does not presently create a live Orange Book blocking period. A current applicant would need to analyze the remaining listed patents, applicable exclusivity, and any litigation certification associated with other Livalo patents.

Which patents form the broader pitavastatin landscape?

The major US patent families historically relevant to pitavastatin include the following.

Patent	General subject matter	Relevance
US 5,856,336	Quinoline-based HMG-CoA reductase inhibitors, including pitavastatin-related compounds	Foundational chemical patent family
US 6,465,477	Pharmaceutical compositions containing pitavastatin	Formulation and pH protection
US 7,799,789	Later pitavastatin formulation technology	Potential follow-on formulation protection
Livalo Orange Book listings	Product-specific patents and regulatory certifications	Generic entry analysis

US Patent 5,856,336 is materially broader from a molecule perspective because it belongs to the compound patent estate. US Patent 6,465,477 is narrower but more directly relevant to a finished dosage form using particular pH and excipient characteristics.

The later formulation families may have provided residual commercial protection after expiration of the foundational compound patent. Their relevance depends on the exact claims, Orange Book listing status, and whether a generic product practices the claimed formulation.

What patent litigation affected pitavastatin generic entry?

Pitavastatin generic-entry litigation historically centered on Paragraph IV challenges to patents listed for Livalo. The key litigation questions were:

Whether the generic applicant challenged the validity or enforceability of listed patents.
Whether the applicant certified that its product would not infringe.
Whether Kowa or another patent holder filed suit within the statutory period.
Whether litigation triggered a 30-month stay.
Whether the parties entered into a settlement with a permitted launch date.

US Patent 6,465,477 itself is now expired and should not be treated as a current litigation barrier. Any present diligence should focus on still-active continuation, divisional, or later-filed formulation patents rather than the expired patent.

No biosimilar pathway applies. Pitavastatin is a small-molecule drug, so generic applicants proceed under section 505(j) of the Federal Food, Drug, and Cosmetic Act using an ANDA, not under the biosimilar pathway under section 351(k) of the Public Health Service Act.[4]

What generic launch risks did this patent create?

Before expiration, the patent created several potential generic risks:

Direct formulation infringement

A generic could have faced risk if it used:

Pitavastatin calcium.
A pharmaceutical carrier.
A pH-adjusted composition within pH 6.8 to 7.8.
A listed basic substance.
The specified magnesium-aluminum silicate excipients.
The listed lactose, cellulose, or binder system.

Design-around opportunities

A generic applicant could seek to avoid the claims by:

Using a different alkalizing agent.
Selecting an excipient outside the listed species.
Modifying the aqueous pH outside the claimed range.
Using a formulation that does not produce the claimed aqueous dispersion characteristics.
Changing the solid dosage-form architecture.
Demonstrating that the accused excipient is not within the claimed chemical category.

Invalidity positions

Potential validity arguments could have included:

Lack of written description for the full range of salts, esters, bases, and excipient combinations.
Obviousness over earlier pitavastatin formulations or conventional stabilizer systems.
Indefiniteness arising from the pH testing language.
Indefiniteness or claim-construction problems arising from the aluminum and alkaline-earth-metal terminology.
Lack of enablement across the breadth of the Markush language.

The strength of these arguments would depend on the prosecution history and cited prior art, not on the claim text alone.

How strong is the patent estate for US Patent 6,465,477?

The patent was commercially meaningful but technically narrow.

Strength factor	Assessment
Active compound coverage	Limited; the patent does not claim pitavastatin alone
Calcium-salt coverage	Direct through claim 2
pH coverage	Important but creates a measurable design-around limitation
Excipient coverage	Meaningful for products using named materials
Oral tablet coverage	Relevant to conventional generic dosage forms
Manufacturing coverage	None apparent from the supplied claims
Method-of-use coverage	None
Biologic or biosimilar relevance	None
Current enforceability	None because the patent has expired

The strongest historical claims were likely claims 1, 2, 3, 8, and 9. Claim 2 directly addressed pitavastatin calcium. Claims 8 and 9 identified specific basic substances that could have been used in a commercial tablet. Claims 4 through 7 were narrower and more dependent on chemical classification and claim construction.

What licensing and commercial issues are associated with this patent?

Kowa was the principal commercial stakeholder associated with pitavastatin and Livalo. The relevant commercial arrangements historically included product development, marketing, and regional commercialization relationships rather than a standalone license centered only on US Patent 6,465,477.

Patent diligence should separate:

Ownership of the patent.
Ownership of Livalo regulatory rights.
Regional marketing arrangements.
Any settlement license granted to an ANDA applicant.
Any right to launch before patent expiration.
Any obligations relating to supply of pitavastatin calcium.

An expired patent cannot support a new exclusionary license in the United States, although historical licenses, settlement terms, royalty audits, and representations concerning past conduct may remain commercially relevant.

Key Takeaways

US Patent 6,465,477 is a formulation patent for pitavastatin compositions.
Its central claim requires pitavastatin acid, a salt, or an ester in a composition whose aqueous solution or dispersion has pH 6.8 to 7.8.
Claim 2 specifically covers pitavastatin calcium.
Claims 3 through 9 cover basic substances, including L-arginine and magnesium-aluminum silicate materials.
Claims 10 through 15 address conventional oral solid dosage-form excipients.
The patent does not claim pitavastatin as a chemical compound by itself.
The patent expired on or about February 24, 2019, based on public patent-term records.
It presents no current US generic-launch barrier by itself.
Historical infringement analysis would turn on pH testing, excipient identity, claim dependency, and the composition of the accused product.
Current pitavastatin diligence should focus on later formulation patents, Orange Book listings, FDA exclusivity, and Paragraph IV litigation involving other patents.

FAQs About US Patent 6,465,477 and Pitavastatin

Does US Patent 6,465,477 cover Livalo?

Historically, it covered certain Livalo-type pharmaceutical compositions containing pitavastatin, particularly pitavastatin calcium formulations meeting the claimed pH and excipient limitations. It does not cover every formulation of Livalo.

Can a generic pitavastatin product infringe this patent today?

No current US product can be enjoined solely on the basis of this expired patent. Historical damages or pre-expiration conduct would require a separate infringement analysis.

Does the patent cover pitavastatin calcium tablets with lactose?

Potentially, if the formulation satisfies all incorporated limitations, including the applicable pH requirement and claim-specific excipient limitations. Lactose alone does not establish infringement.

Is US Patent 6,465,477 a method-of-use patent?

No. The supplied claims are composition claims. They do not recite treating hypercholesterolemia, reducing LDL cholesterol, or administering pitavastatin to a patient.

Does pitavastatin have biosimilar risk?

No. Pitavastatin is a small-molecule drug regulated through the ANDA generic pathway. The relevant competitive risks are generic substitution, formulation design-arounds, Paragraph IV certifications, and remaining Orange Book patents.

References

United States Patent and Trademark Office. (2002). US Patent No. 6,465,477, Pharmaceutical composition.
Google Patents. (n.d.). US6465477B1: Pharmaceutical composition.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA) process and generic drugs.

Details for Patent: 6,465,477

Summary for Patent: 6,465,477