United States Patent 6,894,064: Raloxifene Formulation Claims, Scope and Patent Landscape

U.S. Patent No. 6,894,064 protects a narrow 60-mg raloxifene hydrochloride pharmaceutical composition defined by micronized particle-size limits and specified excipients. Its core commercial target is the Evista raloxifene tablet. The patent does not broadly cover raloxifene, raloxifene hydrochloride, or every 60-mg raloxifene formulation. Its enforceable value depended on the combination of active-ingredient particle size, dosage strength, excipient composition, and, for claim 12, osteoporosis prophylaxis.

The patent’s ordinary U.S. term has expired. The active-ingredient and principal method-of-use patents for raloxifene also expired earlier, allowing generic raloxifene hydrochloride tablets to enter the U.S. market.

What does U.S. Patent 6,894,064 cover?

U.S. Patent 6,894,064 covers pharmaceutical compositions containing:

60 mg of raloxifene hydrochloride;
particulate raloxifene with a mean particle size below approximately 25 microns;
at least 90% of particles below approximately 50 microns;
a surfactant; and
a water-soluble diluent.

The compound identified in the claims is raloxifene hydrochloride, the active ingredient in Evista.

The patent is formulation-focused. It addresses the physical form and processing of raloxifene rather than the discovery of raloxifene itself. The particle-size limitations are central claim elements and are not merely descriptive manufacturing preferences.

Patent identification

Field	Information
Patent	U.S. Patent No. 6,894,064
Title	Pharmaceutical compositions comprising raloxifene
Patent type	Utility patent
Patent holder/assignee	Eli Lilly and Company
Active ingredient	Raloxifene hydrochloride
Commercial product	Evista 60-mg tablets
Issue date	May 17, 2005
Principal technology	Micronized raloxifene hydrochloride formulation
Dosage form implicated	Oral solid dosage form, principally tablets
Status	Expired under the ordinary U.S. patent term

The patent issued from a U.S. application filed after the 1999 American Inventors Protection Act transition to the 20-year term measured from the earliest effective nonprovisional filing date. Public patent records identify the patent as a continuation of a raloxifene formulation filing family. The precise terminal date should be confirmed against the USPTO Patent Center prosecution record and any recorded patent-term adjustment or disclaimer.

How broad are the claims of Patent 6,894,064?

The claims are narrow because claim 1 requires a specific dose and several formulation characteristics in combination. A competing product must satisfy every limitation of an asserted claim to infringe directly.

Claim 1: the independent composition claim

Claim 1 requires all of the following:

A pharmaceutical composition.
Exactly 60 mg of the specified raloxifene hydrochloride compound.
Raloxifene in particulate form.
A mean particle size below about 25 microns.
At least about 90% of particles below about 50 microns.
A surfactant.
A water-soluble diluent.

The claim does not cover:

raloxifene doses other than 60 mg;
raloxifene formulations without a surfactant;
formulations without a water-soluble diluent;
formulations exceeding the stated particle-size limits;
nonoral formulations that do not satisfy the pharmaceutical-composition limitations; or
raloxifene compounds other than the hydrochloride salt specified in the claim.

The phrase "about" introduces ordinary claim-construction flexibility, but it does not eliminate the need to prove particle-size compliance. Particle-size testing method, sampling procedure, agglomeration, milling conditions, and analytical reproducibility would be important in any infringement dispute.

Claim 2: crystalline raloxifene and tighter particle-size range

Claim 2 adds two limitations:

the raloxifene is crystalline; and
mean particle size is between about 5 and about 25 microns.

This narrows claim 1 by requiring a defined crystalline physical form and a lower particle-size boundary. An amorphous product would not literally satisfy the crystalline limitation, although solid-state characterization and claim construction could become disputed issues.

Claim 3: narrower particle distribution

Claim 3 requires:

mean particle size between about 5 and about 20 microns; and
at least 90% of particles below about 35 microns.

This is the most technically restrictive particle-size claim in the set. It is directed to a tightly controlled micronized active ingredient rather than a general fine-particle formulation.

Claim 4: polysorbate 80

Claim 4 requires polysorbate 80 as the surfactant. A formulation using another surfactant would generally avoid literal infringement of claim 4 but could still fall within claims 1 through 3 if the broader surfactant and particle-size requirements are met.

Claim 5: lactose

Claim 5 requires lactose as part of the water-soluble diluent. The claim does not specify a particular lactose grade, particle size, or amount. A lactose-free formulation could avoid claim 5 while remaining within claim 1 or another dependent claim.

Claims 6 and 7: hydrophilic binder and povidone

Claim 6 adds a hydrophilic binder. Claim 7 narrows that limitation to polyvinylpyrrolidone, also known as povidone or PVP.

PVP is common in tablet granulation and binding. Its widespread use reduces the practical differentiation of claim 7, but the claim remains dependent on the narrower raloxifene dose and particle-size limitations.

Claims 8 and 9: lubricant

Claim 8 requires a lubricant. Claim 9 identifies magnesium stearate or stearic acid as the lubricant.

These claims are formulation-combination claims. Magnesium stearate is widely used in tablets, but it does not create infringement unless the other limitations, including the raloxifene particle-size requirements, are also present.

Claim 10: commercial-style excipient combination

Claim 10 requires:

polyvinylpyrrolidone;
polysorbate 80;
lactose;
cross-linked polyvinylpyrrolidone;
magnesium stearate; and
the limitations inherited from claim 2.

Cross-linked polyvinylpyrrolidone is crospovidone, commonly used as a tablet disintegrant. Claim 10 is compositionally specific and likely tracks the formulation architecture of the branded 60-mg product.

Claim 11: film coating

Claim 11 adds a film coating to the claim 2 formulation. The coating material is not specified in the claim. A tablet with a film coat can fall within claim 11 only if the inherited crystalline raloxifene and particle-size requirements are also satisfied.

Claim 12: osteoporosis prophylaxis method

Claim 12 covers a method for preventing postmenopausal osteoporosis by prophylactically administering the composition of claim 2 to a postmenopausal woman in need of that treatment.

It is narrower than a general raloxifene osteoporosis-use claim because it requires:

the claim 2 composition;
60 mg raloxifene hydrochloride;
crystalline raloxifene;
the specified particle-size range;
a surfactant;
a water-soluble diluent; and
administration to the specified patient population for prophylaxis.

A generic manufacturer could face method-of-use issues if its labeling directly instructs use for prevention of postmenopausal osteoporosis. Under the Hatch-Waxman framework, labeling carve-outs and skinny-label language can affect the practical risk.

What formulation is protected by the patent?

The formulation most closely associated with the patent is a 60-mg raloxifene hydrochloride tablet containing micronized crystalline raloxifene and excipients that improve wetting, granulation, flow, disintegration, and manufacturability.

Formulation element	Relevant claim limitation	Commercial significance
Raloxifene hydrochloride	60 mg	Matches Evista dosage strength
Particle form	Required by claim 1	Distinguishes formulation from a generic chemical disclosure
Mean particle size	Below 25 microns in claim 1	Controls dissolution and dispersion
Particle distribution	90% below 50 microns in claim 1	Limits coarse-particle fraction
Crystalline form	Claims 2 onward	Defines solid-state form
Polysorbate 80	Claim 4 and claim 10	Surfactant and wetting agent
Lactose	Claim 5 and claim 10	Water-soluble diluent
PVP	Claims 6, 7 and 10	Hydrophilic binder
Crospovidone	Claim 10	Disintegrant
Magnesium stearate	Claims 9 and 10	Lubricant
Film coating	Claim 11	Coated-tablet presentation

The patent’s commercial relevance is strongest where a generic uses the same or materially similar micronization and excipient strategy. A formulation designed around a different particle-size distribution, noncrystalline raloxifene, a different salt, or a different dissolution-enhancement technology would have a stronger noninfringement position.

When did Patent 6,894,064 lose exclusivity?

The patent’s ordinary U.S. patent term has ended. The relevant term analysis is:

Exclusivity layer	Approximate status
Raloxifene compound patent	Expired
Original raloxifene method-of-use patents	Expired
Raloxifene formulation patent 6,894,064	Expired
FDA small-molecule regulatory exclusivity	Expired
Current generic entry barrier	Primarily regulatory, commercial and formulation-related rather than patent-based

A patent’s expiration does not erase historical infringement exposure for conduct occurring before expiration. It does eliminate future prospective patent exclusivity, subject to any unusual term adjustment, terminal disclaimer, or litigation-specific order recorded in the official file.

The statute governing post-1995 U.S. patent terms generally provides 20 years from the earliest effective nonprovisional filing date. See 35 U.S.C. § 154. Patent-term adjustment can change the final date, but it does not convert an expired patent into a current barrier.

What is the Orange Book status of raloxifene and Evista?

Evista was approved by the FDA as raloxifene hydrochloride tablets for postmenopausal osteoporosis and later for reduction in the risk of invasive breast cancer in certain postmenopausal women at increased risk.

The Orange Book historically listed patents associated with Evista, including formulation and method-of-use patents. Orange Book listings are relevant to ANDA certification and potential Hatch-Waxman litigation, but listing does not establish validity or infringement. FDA patent listings also do not determine the ultimate patent expiration date; the USPTO controls patent-term records, while FDA controls listed patent and exclusivity information.

Regulatory issue	Raloxifene status
FDA pathway	NDA for Evista; ANDA pathway for generics
Active ingredient	Raloxifene hydrochloride
Product type	Small-molecule oral tablet
Biosimilar pathway	Not applicable
Orange Book	Relevant; product is not a biologic
Hatch-Waxman risk	Historically relevant during the patent term
Current entry barrier	No effective patent barrier from Patent 6,894,064

Because raloxifene is a small molecule, competitors file ANDAs rather than abbreviated applications under the biosimilar pathway. Biosimilar risk is therefore immaterial to this patent landscape.

Which companies challenged the Evista patent estate?

Generic raloxifene competition developed through ANDA filings by multiple generic-drug companies. Public U.S. market participants have included Teva, Watson/Actavis, Mylan, Sandoz, Dr. Reddy's Laboratories and other ANDA sponsors.

A Paragraph IV certification against a listed Evista patent can trigger a patent-infringement action under 35 U.S.C. § 271(e)(2). The scope of any such case depends on:

which patents were listed on the filing date;
the specific ANDA formulation;
whether the ANDA sponsor used a Paragraph IV certification, Section viii statement or patent-expiration certification;
whether Lilly asserted the formulation claims;
settlement terms; and
the resulting FDA approval date.

The claim text alone does not establish that every listed patent was asserted against every generic sponsor. Patent litigation databases and district-court dockets must be read separately from the patent record.

What patent litigation affected raloxifene generic entry?

The principal litigation risk involved Lilly's attempts to enforce the remaining Evista patent estate against ANDA applicants before patent expiration. The litigation theory for Patent 6,894,064 would have focused on whether the proposed generic formulation contained:

60 mg raloxifene hydrochloride;
crystalline particles within the claimed size ranges;
the required surfactant;
a water-soluble diluent; and, for narrower claims,
the specified binder, disintegrant, lubricant or coating.

Likely litigation issues included:

Particle-size measurement. The parties could dispute the instrument, dispersion medium, agglomerate treatment and statistical calculation used to determine mean particle size and the 90th-percentile threshold.
Crystallinity. X-ray powder diffraction, thermal analysis and solid-state characterization would be relevant.
Composition identity. The presence and function of lactose, polysorbate 80, PVP, crospovidone and magnesium stearate would be assessed against the claim language.
Induced infringement. Claim 12 could raise questions about the generic label's instructions for osteoporosis prevention.
Obviousness. A challenger could argue that micronization, surfactant selection and standard tablet excipients were predictable options for improving dissolution of a poorly water-soluble compound.
Enablement and written description. The challenger could test whether the specification supported the full breadth of the claimed particle-size ranges and excipient combinations.

After expiration, these issues became primarily historical. They may still matter for damages, past supply contracts, settlement interpretation or freedom-to-operate reviews covering the pre-expiration period.

How strong was the patent estate for raloxifene?

Patent 6,894,064 had moderate historical blocking value but limited breadth.

Strengths

It targeted the commercial 60-mg Evista tablet.
It combined dosage, particle size and excipient limitations.
It covered both broad and progressively narrower formulation versions.
Claim 10 tracked a commercially realistic excipient combination.
Claim 12 linked the formulation to postmenopausal osteoporosis prophylaxis.

Weaknesses

The claims were highly element-dependent.
Generic manufacturers could redesign particle size, solid-state form or excipients.
Common excipients such as lactose, PVP and magnesium stearate may support obviousness arguments when combined with known micronization techniques.
The claims did not broadly cover the raloxifene molecule.
The method claim was limited to a specific formulation rather than the use of raloxifene generally.
Expiration removed the patent's forward-looking exclusionary value.

The strongest infringement theory would have involved a generic tablet analytically matching the claim 10 formulation and particle-size profile. The strongest design-around strategy would have used a different particle-size distribution, a different surfactant or diluent, or a noncrystalline or otherwise distinct active-ingredient form, while preserving bioequivalence.

How does Patent 6,894,064 compare with other raloxifene patents?

Patent category	Subject matter	Commercial scope	Current status
Compound patents	Raloxifene and related benzothiophene compounds	Broad chemical protection	Expired
Method-of-use patents	Osteoporosis treatment or prevention; breast-cancer risk reduction	Patient population and indication	Expired
Formulation patent 6,894,064	Micronized crystalline raloxifene hydrochloride tablet	Narrow composition protection	Expired
Later formulation patents	Possible solid-state, dissolution or dosage-form improvements	Product-specific	Must be checked by family and jurisdiction
Manufacturing patents	Milling, blending, granulation and tablet production	Process-specific	Claim-by-claim status required
Regulatory exclusivity	NDA exclusivity and pediatric extensions, if any	FDA approval timing	Expired for the legacy Evista product

Patent 6,894,064 was not a substitute for the foundational raloxifene patents. It was a later-layer formulation patent intended to extend protection around the marketed product after the compound and initial therapeutic-use claims approached expiration.

What generic launch risks existed?

Before expiration, a generic sponsor faced four principal risks.

Infringement risk

The risk was highest for a 60-mg tablet using micronized crystalline raloxifene with particle-size characteristics within claims 1 through 3. An exact or near-exact excipient match increased exposure under claims 4 through 11.

Method-of-use risk

A label expressly directing prophylaxis of postmenopausal osteoporosis could create exposure under claim 12. A Section viii carve-out could reduce risk if FDA permitted removal of the patented indication and the remaining label did not encourage the patented use.

Litigation timing risk

A Paragraph IV filing could trigger a 30-month stay of ANDA approval if Lilly filed suit within the statutory period. The practical launch date then depended on court rulings, settlement terms, patent expiration and FDA approval.

Commercial risk

Even after approval, generic raloxifene faced substitution dynamics, payer formulary control, price compression and competition from multiple ANDA sponsors. The patent estate did not protect market share after expiration.

What manufacturing and intellectual-property barriers remain?

Patent 6,894,064 no longer creates a prospective U.S. patent barrier. Technical barriers may still affect generic development:

achieving reproducible micronization;
preventing particle agglomeration;
controlling crystalline form;
maintaining dissolution performance;
validating blend uniformity at low active-ingredient loading;
reproducing tablet disintegration and coating performance;
demonstrating bioequivalence; and
controlling impurities and residual solvents.

These are development and regulatory barriers, not continuing exclusivity rights under the expired patent.

Geographically, the U.S. patent had no effect outside the United States. Related foreign applications may have produced separate rights in Europe, Canada, Japan or other jurisdictions, but each country required independent prosecution, maintenance and expiration analysis. Expiration of U.S. Patent 6,894,064 did not automatically terminate corresponding foreign patents.

What is the revenue exposure from this patent?

The patent was tied to Evista's 60-mg oral tablet, so its commercial exposure was substantial during the period when the product generated branded sales and before generic substitution. The patent did not protect all raloxifene revenue because:

Evista had multiple indications;
different patents covered different uses;
some uses could be carved out of generic labeling;
the formulation claims required specific technical characteristics; and
sales after patent expiration were exposed to generic price erosion.

A revenue model should separate sales by indication, patent-covered label language, geographic market, generic launch date and net price. The patent itself does not support a reliable current revenue estimate without historical sales and launch data.

Key Takeaways

U.S. Patent 6,894,064 is a formulation patent for 60-mg raloxifene hydrochloride.
Its core limitations are micronized particulate form, crystalline raloxifene, particle-size distribution, surfactant and water-soluble diluent.
Claim 10 is the closest claim to a commercial Evista-style tablet because it specifies PVP, polysorbate 80, lactose, crospovidone and magnesium stearate.
Claim 12 is a narrow method-of-use claim for osteoporosis prevention using the claim 2 composition.
The patent does not broadly cover raloxifene or every raloxifene tablet.
Generic design-around routes included changing particle size, solid-state form, surfactant, diluent or other excipients.
Raloxifene is a small molecule, so biosimilar analysis does not apply.
The patent's U.S. term has expired, eliminating current prospective exclusivity from this patent.
Historical Paragraph IV and litigation risk depended on the ANDA formulation, Orange Book listings, label language and the patent-term date.
Remaining commercial barriers are technical, regulatory and market-based rather than a continuing U.S. patent monopoly.

FAQs About U.S. Patent 6,894,064

Does Patent 6,894,064 cover generic raloxifene hydrochloride?

No. It covers only compositions satisfying the specified 60-mg dose, particle-size and excipient limitations. It does not cover every raloxifene hydrochloride product.

Is raloxifene a biologic subject to biosimilar competition?

No. Raloxifene is a chemically synthesized small molecule. Generic manufacturers use the ANDA pathway, not the biosimilar pathway.

Could a generic avoid claim 10 by replacing magnesium stearate?

Potentially. Replacing magnesium stearate could avoid literal infringement of claim 10, but the product could still implicate broader claims if it retained the required dose, particle-size profile, surfactant and diluent.

Does an FDA-approved generic automatically avoid the patent claims?

No. FDA approval and patent noninfringement are separate determinations. An ANDA sponsor must address listed patents through certification or a Section viii statement.

Do foreign raloxifene patents expire when the U.S. patent expires?

No. Patent rights are territorial. Each foreign patent family member requires separate review of grant, maintenance, term adjustment, opposition and expiration records.

References

Eli Lilly and Company. (2005). Pharmaceutical compositions comprising raloxifene, U.S. Patent No. 6,894,064. United States Patent and Trademark Office.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term disclaimer records. https://www.uspto.gov
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov
U.S. Food and Drug Administration. (1997). Evista (raloxifene hydrochloride) prescribing information. Eli Lilly and Company.
United States Code. (2024). 35 U.S.C. §§ 154, 271(e)(2), 355(j).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	006387	⤷ Start Trial
Austria	464897	⤷ Start Trial
Australia	2215497	⤷ Start Trial
Australia	723797	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,894,064