United States Patent 7,138,392: Bazedoxifene Claims, Expiration, and Patent Landscape

U.S. Patent No. 7,138,392 covers bazedoxifene, a selective estrogen receptor modulator, as the free-base compound and pharmaceutically acceptable salts. Its claims also cover pharmaceutical compositions and treatment or prevention of bone loss. The patent was assigned to Wyeth Pharmaceuticals and formed part of the original U.S. patent estate for Viviant, the bazedoxifene osteoporosis product.

The patent’s enforceable term has ended. The underlying 20-year term ran from the earliest qualifying nonprovisional filing in 2000, with regulatory patent-term extension carrying protection into March 2023 according to FDA Orange Book records. The patent therefore presents no current U.S. blocking right against a bazedoxifene generic, subject to other patents, regulatory exclusivity, or product-specific intellectual-property rights. [1–3]

What drug does U.S. Patent 7,138,392 protect?

U.S. Patent 7,138,392 protects bazedoxifene, chemically identified as:

1-[4-(2-azepan-1-yl-ethoxy)benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol

Bazedoxifene is also known as bazedoxifene free base. The marketed product is generally supplied as bazedoxifene acetate, a pharmaceutically acceptable salt of the claimed active compound.

Attribute	Information
Active ingredient	Bazedoxifene
Product form	Bazedoxifene acetate
Drug class	Selective estrogen receptor modulator
U.S. brand	Viviant
Original sponsor	Wyeth Pharmaceuticals
FDA indication	Prevention and treatment of postmenopausal osteoporosis
Patent	U.S. 7,138,392
Patent title	Indole compounds
Earliest priority	October 29, 1999
U.S. nonprovisional filing relevant to term	October 27, 2000
Issue date	November 21, 2006
FDA patent-term extension	Extended protection into March 2023
Current status	Expired

Bazedoxifene was approved by the FDA in October 2008 for the prevention of postmenopausal osteoporosis. The FDA later approved the drug in combination with conjugated estrogens as Duavee, formerly known as Duavee or TSEC in development materials. [2,4]

What are the four claims of U.S. Patent 7,138,392?

The patent contains four claims directed to the active molecule, a narrower free-base embodiment, a pharmaceutical composition, and a bone-loss treatment method.

Claim 1: Bazedoxifene and pharmaceutically acceptable salts

Claim 1 covers:

A compound of formula 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol, or a pharmaceutically acceptable salt thereof.

This is the principal chemical claim. It covers:

Bazedoxifene free base.
Bazedoxifene acetate.
Other pharmaceutically acceptable salts, provided the salt contains the claimed bazedoxifene active moiety.
Manufacture, sale, or use of the claimed compound in the United States during the patent term.

The claim is narrow in structural terms. It does not cover every selective estrogen receptor modulator, every indole derivative, or every osteoporosis drug. It is directed to one defined molecular structure and its pharmaceutically acceptable salts.

Claim 2: Bazedoxifene free base

Claim 2 covers the compound itself without the salt alternative in claim 1.

This claim is narrower than claim 1 because it excludes salt forms. A product containing bazedoxifene acetate would be analyzed primarily under claim 1, while the isolated free-base active ingredient would fall within claim 2.

Claim 3: Pharmaceutical composition

Claim 3 covers a pharmaceutical composition containing:

Bazedoxifene or a pharmaceutically acceptable salt; and
A pharmaceutical carrier or excipient.

The claim does not require a particular dosage strength, tablet design, release profile, coating, particle size, or excipient. A conventional oral tablet, capsule, or other dosage form could satisfy the composition limitation if it contains the claimed compound and a pharmaceutical carrier or excipient.

Claim 3 is therefore a broad formulation claim, but it is not a detailed formulation-patent claim. It does not independently protect specific compositions such as:

A defined bazedoxifene acetate polymorph.
A particular tablet coating.
A controlled-release matrix.
A specified dissolution profile.
A fixed combination with conjugated estrogens.
A specific dosage strength.

Those subjects would generally require separate claims and, in many cases, separate patents.

Claim 4: Bone-loss treatment and prevention

Claim 4 covers administering an effective amount of bazedoxifene or a pharmaceutically acceptable salt to a mammal in need of treatment to treat or prevent bone loss.

The claim reaches methods involving:

Postmenopausal osteoporosis.
Osteopenia or reduced bone mineral density.
Prevention of skeletal bone loss.
Treatment of a mammalian patient at risk of bone loss.

The claim does not recite a specific dose, route, dosing interval, disease stage, patient age, or formulation. The central limitations are the administration of the claimed compound and the treatment or prevention of bone loss.

How broad is the scope of the bazedoxifene patent claims?

The patent has strong historical coverage of the original bazedoxifene product but limited structural breadth.

Claim	Subject matter	Relative breadth	Commercial significance
1	Bazedoxifene and pharmaceutically acceptable salts	High within one molecule	Main product claim; reaches bazedoxifene acetate
2	Bazedoxifene free base	Narrower	Protects the active free-base compound
3	Composition containing bazedoxifene and carrier or excipient	Broad but generic	Covers ordinary dosage forms, subject to claim construction
4	Treatment or prevention of bone loss	Broad method claim	Covers osteoporosis-related administration during the term

Chemical claim scope

Claim 1 is a species claim rather than a broad Markush claim. A structurally different SERM would not infringe merely because it has similar estrogen-receptor activity. A generic product containing the same bazedoxifene active ingredient, however, would have presented direct infringement risk while the claim remained in force.

Salt coverage

The salt language was commercially important because the marketed form is bazedoxifene acetate. A generic manufacturer could not avoid claim 1 simply by using the acetate salt instead of the free base.

A different salt would also have been within the literal scope of claim 1 if it qualified as a pharmaceutically acceptable salt of bazedoxifene. Salt selection, crystal form, hydration state, and formulation design would not ordinarily defeat the molecule claim unless the resulting product no longer contained the claimed compound or a covered salt.

Composition claim scope

Claim 3 is not limited to Viviant’s precise commercial formulation. It covers a composition containing the active ingredient and a pharmaceutical carrier or excipient. The absence of a specific excipient list increases the claim’s potential reach, but the claim’s practical value ended with the expiration of the underlying patent.

Method-of-use scope

Claim 4 is limited to bone loss. It does not expressly cover every clinical use of bazedoxifene, including all potential breast-cancer, endometrial, menopausal-symptom, or estrogen-receptor indications.

A product label directed to osteoporosis would have created direct method-of-use concerns during the patent term. A generic company could have pursued a section viii label carve-out for nonprotected uses only if the remaining label and regulatory pathway permitted that approach. Because the patent is expired, claim 4 no longer creates a current U.S. launch barrier.

When did U.S. Patent 7,138,392 expire?

The patent’s ordinary 20-year term was calculated from the relevant 2000 nonprovisional filing date and would have ended in October 2020. The FDA granted patent-term extension associated with the approved bazedoxifene product, extending the effective expiration into March 2023. FDA Orange Book records identify the patent as having expired after that extended term. [1,3]

Exclusivity timeline

Event	Date
Earliest priority filing	October 29, 1999
Relevant U.S. nonprovisional filing	October 27, 2000
FDA approval of Viviant	October 3, 2008
Patent issuance	November 21, 2006
Original 20-year patent term	October 27, 2020
Regulatory patent-term extension	Into March 2023
Current patent status	Expired

The patent-term extension applied to the approved product and regulatory review period. It did not create a new patent claim set or extend protection indefinitely.

FDA regulatory exclusivity

Bazedoxifene’s FDA exclusivity was separate from patent protection. The original Viviant approval included statutory regulatory exclusivity associated with the new drug approval, but that period expired well before the patent-term extension ended.

Patent expiration and FDA exclusivity operate independently:

FDA exclusivity restricts certain approval submissions for a defined statutory period.
Patent protection restricts activity that falls within an enforceable patent claim.
Expiration of the patent does not erase prior infringement exposure.
Expiration does remove the patent as a current barrier to generic commercialization.

What is the Orange Book status of U.S. Patent 7,138,392?

U.S. Patent 7,138,392 was listed in the FDA Orange Book for the bazedoxifene product and was associated with the approved Viviant drug application. The listing reflected the patent’s relevance to the active ingredient and approved use. [1]

The Orange Book listing did not mean that every bazedoxifene formulation or use was protected indefinitely. Its relevance depended on:

The patent’s claim scope.
The listed expiration date.
Any patent-term extension.
The approved product and indication.
The ANDA applicant’s certification or labeling strategy.

After expiration, the listing remains a historical record but does not support a current Paragraph IV litigation threat.

Were Paragraph IV challenges possible against this patent?

Yes. Before expiration, an ANDA applicant seeking approval for bazedoxifene could have challenged the patent through a Paragraph IV certification, asserting that the patent was invalid, unenforceable, or would not be infringed.

A Paragraph IV certification could have targeted:

The chemical claim covering bazedoxifene.
The salt coverage relevant to bazedoxifene acetate.
The pharmaceutical composition claim.
The bone-loss method claim.

The principal commercial risk for a generic challenger would have been claim 1. A successful challenge to the compound-and-salt claim would have materially reduced the patent estate’s ability to block a standard bazedoxifene acetate product.

The Hatch-Waxman framework could have produced a 30-month stay of FDA approval if the NDA holder or patent owner timely filed infringement litigation. That mechanism was relevant only while a listed patent remained unexpired and litigation was timely initiated. [5]

No current Paragraph IV risk arises from U.S. 7,138,392 because the patent has expired.

What other patents protected bazedoxifene and Viviant?

The bazedoxifene estate was broader than U.S. 7,138,392. Relevant patent categories included the following.

Core compound patents

The core family included patents directed to indole compounds and specific bazedoxifene compounds. U.S. 7,138,392 is the most important patent for the precise claims supplied because it expressly names bazedoxifene and its salts.

Related family members and continuation or divisional patents could have contained overlapping or differently drafted claims. Their legal status had to be assessed separately because expiration, terminal disclaimers, prosecution history, and claim scope can differ.

Formulation patents

Formulation patents may cover:

Bazedoxifene acetate solid forms.
Polymorphs or crystalline forms.
Tablet compositions.
Stability-enhancing excipients.
Dissolution or bioavailability characteristics.
Combination products containing bazedoxifene.

Claim 3 of U.S. 7,138,392 is not a substitute for a narrowly drafted formulation patent. A later formulation patent could have created a separate barrier even after the core compound patent expired, but it would not necessarily block every bazedoxifene product.

Combination-product patents

Duavee combines bazedoxifene with conjugated estrogens. Combination patents may cover:

Bazedoxifene plus conjugated estrogens.
Menopausal vasomotor symptom treatment.
Endometrial protection.
Specific estrogen-to-bazedoxifene ratios.
Dosage regimens and patient populations.

Those patents are commercially distinct from the monotherapy osteoporosis claims in U.S. 7,138,392.

Method-of-use patents

Separate patents may cover uses beyond the bone-loss indication, including:

Menopausal symptoms.
Prevention of endometrial hyperplasia.
Breast-cancer risk reduction.
Hormone therapy combinations.
Specific patient subgroups.

A generic bazedoxifene product could face different patent questions depending on whether it seeks approval for monotherapy, combination therapy, osteoporosis, or menopausal indications.

How strong was the patent estate for bazedoxifene?

Historically, the estate had high product protection because claim 1 directly covered the active molecule and its salts. That type of claim is usually more difficult to design around than a formulation or method claim.

Its principal strengths were:

Direct coverage of bazedoxifene.
Express inclusion of pharmaceutically acceptable salts.
Composition coverage.
A bone-loss method claim aligned with the initial product indication.

Its limitations were:

Claim 1 covered one specific chemical entity rather than a broad chemical genus.
Claim 3 lacked detailed formulation limitations.
Claim 4 was limited to bone loss.
The patent had a finite term and is now expired.
Later products, including Duavee, could rely on separate combination or use patents.

Patent strength therefore changed over time. Before March 2023, U.S. 7,138,392 was a meaningful Hatch-Waxman barrier. After expiration, it became a freedom-to-operate reference rather than an active exclusion right.

Which companies challenged or competed with bazedoxifene?

The relevant competitive groups were:

Wyeth, later part of Pfizer, as the original innovator sponsor.
Generic manufacturers seeking ANDA approval for bazedoxifene acetate.
Manufacturers of alternative SERMs, including raloxifene.
Suppliers of bisphosphonates and denosumab for postmenopausal osteoporosis.
Hormone-therapy companies competing with Duavee.

Bazedoxifene competes pharmacologically with raloxifene, but the patents are separate. Raloxifene does not infringe U.S. 7,138,392 because it has a different chemical structure.

What generic launch risks existed?

During the patent term, a generic bazedoxifene applicant faced four principal risks:

Infringement of claim 1 through the active ingredient or acetate salt.
Infringement of claim 3 through an ordinary pharmaceutical dosage form.
Infringement of claim 4 through an osteoporosis label or use.
Additional risk from separate formulation, polymorph, combination, or method-of-use patents.

After patent expiration, the principal barriers shifted from patent enforcement to:

FDA approval requirements.
Bioequivalence.
Manufacturing scale-up.
Product quality and stability.
Commercial demand.
Remaining patents covering specific combinations or formulations.

A standard bazedoxifene acetate generic is not exposed to biosimilar litigation because bazedoxifene is a small-molecule drug, not a biologic. The applicable pathway is generally an ANDA under section 505(j), not a biosimilar application under the Public Health Service Act. [2,5]

What manufacturing and geographic IP barriers applied?

The core patent was a U.S. right. It did not automatically block manufacture or sale outside the United States. Foreign family members required separate country-by-country analysis.

Potential manufacturing barriers included:

Synthesis of the indole core.
Control of regioisomers and impurities.
Formation of bazedoxifene acetate.
Crystallization and polymorph control.
Reproducible tablet manufacture.
Stability under commercial storage conditions.

Those technical barriers are not necessarily patent barriers. A manufacturer could face process patents, solid-form patents, trade secrets, regulatory requirements, or supplier constraints even after U.S. 7,138,392 expired.

What is the commercial impact of patent expiration?

Expiration removes the strongest product-level exclusion right for bazedoxifene. The commercial consequences include:

Greater feasibility of ANDA entry.
Reduced value of the expired patent in licensing negotiations.
Lower litigation leverage for the original sponsor.
Increased substitution risk for the branded product.
Greater importance of manufacturing cost and distribution access.
Continued relevance of unexpired combination or formulation patents.

Revenue exposure depends on the product being evaluated. Viviant monotherapy and Duavee combination therapy require separate analyses because Duavee may have had distinct Orange Book-listed patents and exclusivity dates. A license or acquisition based solely on U.S. 7,138,392 would not provide current U.S. exclusivity.

Key Takeaways

U.S. Patent 7,138,392 covers bazedoxifene, including pharmaceutically acceptable salts such as bazedoxifene acetate.
Claim 1 is the principal product claim and historically presented the largest barrier to generic bazedoxifene.
Claim 2 covers bazedoxifene free base.
Claim 3 covers pharmaceutical compositions containing bazedoxifene and a carrier or excipient.
Claim 4 covers treatment or prevention of bone loss in mammals.
The patent’s ordinary term ended in 2020, with FDA patent-term extension into March 2023.
The patent is expired and does not create a current U.S. blocking right.
Bazedoxifene is a small molecule, so biosimilar rules do not apply.
Separate patents for formulations, solid forms, combination products, or other methods of use must be reviewed independently.
Duavee and Viviant cannot be treated as having identical patent estates.

FAQs About U.S. Patent 7,138,392 and Bazedoxifene

Does U.S. 7,138,392 cover bazedoxifene acetate?

Yes. Claim 1 covers bazedoxifene and pharmaceutically acceptable salts. Bazedoxifene acetate is the commercially relevant salt form.

Can a generic manufacturer design around claim 1 by using a different bazedoxifene salt?

Historically, no. The claim expressly covers pharmaceutically acceptable salts of bazedoxifene. The patent is now expired, so salt selection is no longer needed to avoid this patent.

Does claim 3 cover every bazedoxifene tablet?

During the patent term, claim 3 could cover a pharmaceutical composition containing bazedoxifene or a covered salt and a pharmaceutical carrier or excipient. Its application depended on the product’s composition and claim construction.

Is bazedoxifene subject to biosimilar approval?

No. Bazedoxifene is a chemically synthesized small molecule. Generic versions generally proceed through the ANDA pathway rather than the biosimilar pathway.

Does expiration of U.S. 7,138,392 clear all Duavee patent risk?

No. Duavee combines bazedoxifene with conjugated estrogens and may be protected by separate combination, formulation, and method-of-use patents. Expiration of the core bazedoxifene patent does not establish freedom to market every bazedoxifene-containing product.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (2008). Viviant (bazedoxifene acetate) prescribing information. FDA.
United States Patent and Trademark Office. (2006). U.S. Patent No. 7,138,392: Indole compounds. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2013). Duavee (conjugated estrogens/bazedoxifene) prescribing information. FDA.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity information. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0802183	⤷ Start Trial	PA2009007	Lithuania	⤷ Start Trial
European Patent Office	0802183	⤷ Start Trial	CA 2009 00035	Denmark	⤷ Start Trial
European Patent Office	0802183	⤷ Start Trial	91608	Luxembourg	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,138,392

Summary for Patent: 7,138,392