Details for Patent: 8,466,138

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Which drugs does patent 8,466,138 protect, and when does it expire?

Patent 8,466,138 protects ANDROGEL and is included in one NDA.

This patent has fifty patent family members in thirty countries.

Summary for Patent: 8,466,138

Title:	Testosterone gel and method of use
Abstract:	The present invention relates to an improved transdermal hydroalcoholic testosterone gel formulation that provides, among other things, a desirable pharmacokinetic hormone profile, and methods of use.
Inventor(s):	Ramana Malladi, Jodi Miller
Assignee:	Besins Healthcare Luxembourg SARL , Unimed Pharmaceuticals LLC
Application Number:	US13/253,848
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,466,138
Patent Claim Types: see list of patent claims	Use;

US Patent 8,466,138: Claims, Scope, Expiration, Orange Book Status, and Generic Entry Risk for AndroGel 1.62%

US Patent 8,466,138 protects a specific testosterone transdermal-gel regimen rather than testosterone replacement therapy broadly. Its independent claim requires a hydroalcoholic gel containing 1.62% testosterone, 1.0% isopropyl myristate, 73.5% ethanol, 1.0% polyacrylic acid, 7.0% of 0.1 N sodium hydroxide, and water. The patent also covers use of that formulation to treat male hypogonadism, with dependent claims directed to serum testosterone targets, a 2.5-gram dose, and delivery of 40.5 mg testosterone.

The patent is associated with the AndroGel 1.62% product and its U.S. patent term reached its listed expiration in 2025, subject to any applicable patent-term adjustment or pediatric exclusivity shown in the FDA’s current records. Its commercial blocking power therefore depends primarily on related patents, regulatory exclusivity, settlement terms, and the ability to enforce formulation or method-of-use claims against an approved generic.

What drug and product does US Patent 8,466,138 protect?

US Patent 8,466,138 protects a testosterone gel formulation and a method of treating hypogonadism by applying that formulation to male skin. The patent is closely associated with AndroGel 1.62%, an FDA-approved testosterone replacement product marketed under NDA 022309.

The claimed formulation contains the following components:

Component	Claimed concentration
Testosterone	1.62% w/w
Isopropyl myristate	1.0% w/w
Ethanol	73.5% w/w
Polyacrylic acid	1.0% w/w
0.1 N sodium hydroxide	7.0% w/w
Water	Balance

The formulation is applied to skin as a hydroalcoholic gel. Claim 1 is a method claim, so the claim requires both:

1. A qualifying male patient with hypogonadism; and
2. Application of the specified gel in a therapeutically effective amount.

The patent does not claim every testosterone gel, every transdermal testosterone product, or every treatment of hypogonadism.

What does independent claim 1 require?

Claim 1 contains several cumulative limitations. A product or treatment must satisfy all material limitations to fall within the literal scope of the claim.

Patient and disease limitation

The method must treat “hypogonadism in a human male in need thereof.” This language narrows the claim to male patients diagnosed with, or otherwise falling within the clinical scope of, hypogonadism. Use in women, nontherapeutic cosmetic use, or treatment unrelated to hypogonadism would not satisfy this limitation as written.

Route-of-administration limitation

The gel must be applied to an area of skin. An injectable testosterone product, oral testosterone product, implant, buccal product, or nasal product would not literally meet this limitation.

A competing transdermal product could still present infringement risk if it uses the same formulation and administration method, even if the brand name, pump design, packaging, or dosing instructions differ.

Composition limitation

The formulation must be a hydroalcoholic gel containing the specified ingredients and concentrations. Claim 1 uses “consisting of,” which is materially narrower than “comprising.”

“Consisting of” generally excludes additional unrecited ingredients that materially alter the claimed composition. This creates a meaningful design-around opportunity for a competing manufacturer that changes the formulation architecture, adds a nontrivial excipient, or replaces a listed ingredient. The legal result would depend on claim construction, the function of the added ingredient, and possible infringement under the doctrine of equivalents.

Concentration limitations

The listed percentages are central claim limitations. The claim does not expressly provide broad numerical ranges around the concentrations. A generic formulation with testosterone at 1.60%, 1.65%, or another concentration could contest literal infringement, although the patentee could argue that a small deviation is equivalent depending on prosecution history and technical evidence.

The same analysis applies to ethanol, isopropyl myristate, carbomer or other polyacrylic acid, sodium hydroxide, and water.

How do claims 2 through 9 expand the patent’s protection?

The dependent claims add narrower limitations. They do not broaden claim 1.

Claim	Added limitation	Commercial significance
2	Ethanol is 95% v/v ethanol	Ties the formulation to a specific ethanol grade or concentration description
3	Polyacrylic acid is neutralized with 7.0% w/w 0.1 N sodium hydroxide	Adds a formulation-process and chemical-state limitation
4	Serum testosterone reaches approximately 298-1,043 ng/dL	Adds a pharmacokinetic or clinical-result limitation
5	Serum testosterone is maintained at approximately 300-1,050 ng/dL	Adds a maintenance-range limitation
6	Polyacrylic acid is a carbomer	Narrows the polymer class
7	Neutralized polyacrylic acid is a carbomer	Combines claims 3 and 6
8	Applied gel dose is 2.5 grams	Matches the standard 2.5-gram application
9	The dose delivers 40.5 mg testosterone	Matches 2.5 grams of 1.62% testosterone

Claims 8 and 9 are commercially important because they align with the standard AndroGel 1.62% dosing configuration. At 1.62% w/w, 2.5 grams of gel contains approximately 40.5 mg of testosterone:

2.5 grams × 1.62% = 0.0405 grams = 40.5 mg.

What formulations are protected by US Patent 8,466,138?

The strongest literal coverage is directed to a formulation materially matching the AndroGel 1.62% composition:

• 1.62% testosterone;
• 1.0% isopropyl myristate;
• 73.5% ethanol;
• 1.0% polyacrylic acid;
• 7.0% of 0.1 N sodium hydroxide; and
• water.

The patent has narrower protection for a carbomer-based formulation and for a formulation in which the polymer is neutralized with sodium hydroxide. The dependent claims create multiple fallback positions if a court rejects broader interpretation of the independent claim.

Why the “consisting of” language matters

The closed transitional phrase limits the claim to the listed composition. A competing formulation may reduce risk by:

• replacing isopropyl myristate with another penetration enhancer;
• using a different polymer;
• using a different neutralizing agent;
• changing the ethanol concentration;
• using a lotion, cream, emulsion, foam, patch, or spray rather than the claimed hydroalcoholic gel; or
• adding an excipient that takes the formulation outside the closed composition.

These changes could affect bioavailability, skin permeation, drying time, tolerability, dose uniformity, and FDA comparability requirements. A formulation design-around may therefore carry development and regulatory costs even when it reduces literal patent risk.

What is the scope of the serum testosterone claims?

Claims 4 and 5 require specified serum testosterone results. Claim 4 recites a range of approximately 298 to 1,043 ng/dL. Claim 5 recites a maintenance range of approximately 300 to 1,050 ng/dL.

These claims raise several enforcement issues:

1. The result may vary among patients.
2. Serum testosterone depends on dose, application site, timing of blood sampling, adherence, skin condition, metabolism, and concomitant therapy.
3. A generic label may recommend the same nominal dose without guaranteeing the same concentration in every patient.
4. The claim may require proof that the accused method produces the claimed result, not merely that the product is capable of doing so.
5. The terms “about,” “achieve,” and “maintained” may require expert testimony and claim construction.

Claims 4 and 5 are therefore narrower than the formulation limitation but may be useful where clinical or pharmacokinetic data show that the accused product produces the specified serum concentrations under the labeled regimen.

What is the patent expiration date for US 8,466,138?

Public patent records identify US 8,466,138 as having a 2025 expiration date associated with the patent family and listed patent term. The patent was granted on June 18, 2013. The relevant term analysis must distinguish:

• the ordinary 20-year term measured from the applicable earliest nonprovisional or international filing date;
• any patent-term adjustment;
• any patent-term extension under 35 U.S.C. § 156; and
• pediatric exclusivity under the Federal Food, Drug, and Cosmetic Act.

The FDA Orange Book, not the grant certificate alone, is the operative commercial reference for the patent information submitted for NDA 022309. The Orange Book records should be checked for the current listed expiration and any pediatric exclusivity adjustment. FDA patent listings can change when patents are delisted, corrected, or superseded by later submissions. (U.S. Food and Drug Administration, 2024a; USPTO, 2024)

What is the Orange Book status of AndroGel 1.62%?

AndroGel 1.62% is an FDA-approved prescription testosterone product under NDA 022309. The product is regulated as a testosterone replacement therapy for males with conditions associated with a deficiency or absence of endogenous testosterone.

The Orange Book is relevant because it identifies patents submitted by the NDA holder for the listed drug. For a generic applicant, listed patents can trigger:

• a Paragraph III certification stating that approval will await patent expiration;
• a Paragraph IV certification asserting that a listed patent is invalid, unenforceable, or not infringed; or
• a section viii statement carving out a patented method of use from the proposed labeling.

A formulation patent with a method-of-treatment claim can present a Paragraph IV issue, while a method-of-use patent may sometimes be addressed through a label carveout. The feasibility of a section viii strategy depends on whether the proposed generic label can omit the patented use without making the product misbranded or creating induced-infringement risk.

Which companies have challenged testosterone gel patents?

Generic testosterone gel applicants have had commercial incentives to challenge AndroGel patents because testosterone gel is a mature, high-volume small-molecule product with no biosimilar requirement. Public litigation and FDA records have associated generic competition with applicants including Teva Pharmaceuticals and Perrigo-related entities, among others.

The relevant legal path is an abbreviated new drug application under section 505(j), not a biosimilar application under the Public Health Service Act. The applicant may challenge Orange Book patents through Paragraph IV certifications. A timely Paragraph IV notice can trigger a 30-month stay of FDA approval under 21 U.S.C. § 355(j)(5)(B)(iii), unless the litigation is resolved earlier or the stay is otherwise terminated.

The commercial effect of a challenge depends on:

• the exact ANDA formulation;
• the proposed label;
• the patents listed for NDA 022309;
• the timing of notice;
• whether the NDA holder files suit within 45 days;
• the asserted patent claims;
• any preliminary injunction or judgment; and
• the terms of any settlement.

What patent litigation affects AndroGel 1.62%?

The principal litigation risk arises from ANDA litigation under 35 U.S.C. § 271(e)(2), which treats submission of an ANDA containing a Paragraph IV certification as a technical act of infringement for purposes of adjudicating patent rights before commercial launch.

A litigation assessment should separate three questions:

Was the patent listed?

The FDA Orange Book determines whether the patent was submitted for the approved drug and remains listed against the relevant dosage form or strength.

Was the patent asserted?

A patent may be listed but not asserted against every ANDA applicant. Complaint filings and docket records determine whether US 8,466,138 was included in a particular case.

Was the patent adjudicated?

A judgment of invalidity, unenforceability, or noninfringement can remove the patent’s practical blocking effect against the litigated applicant. The result may not automatically bind unrelated applicants or eliminate all risk under different formulations and labels.

A complete diligence review should examine the complaint, answer, claim-construction order, summary-judgment decisions, trial judgment, Federal Circuit proceedings, and any settlement or consent judgment. A settlement can permit an agreed launch date before the nominal patent expiration and may include a license, authorized-generic arrangement, or restrictions on formulation and labeling.

When does generic testosterone gel lose patent protection?

The principal patent-specific barrier associated with US 8,466,138 reached its listed term in 2025. Generic entry can occur earlier if:

• the generic applicant prevails in Paragraph IV litigation;
• the NDA holder settles for an earlier license date;
• the patent is disclaimed or delisted;
• the patent is held invalid or unenforceable; or
• the generic uses a noninfringing formulation and label.

Generic approval does not always equal immediate commercial launch. A manufacturer may delay launch because of manufacturing transfer, supply constraints, controlled-substance compliance, reimbursement contracting, product liability exposure, or an agreement with the innovator.

Testosterone is a controlled substance in the United States. Commercial launch therefore also requires compliance with Drug Enforcement Administration requirements, including controlled-substance registration, quota, security, recordkeeping, and distribution controls.

Is there biosimilar risk for AndroGel 1.62%?

There is no biosimilar pathway risk for AndroGel 1.62%. Testosterone is a chemically synthesized small molecule, so competing products proceed through the ANDA pathway as generics.

The relevant competitive risks are:

• an identical or near-identical testosterone gel;
• a formulation that designs around the 8,466,138 composition;
• a different topical testosterone dosage form;
• nasal, buccal, injectable, or oral testosterone products; and
• nonprescription or compounded products, subject to applicable regulatory restrictions.

A generic testosterone gel may receive therapeutic-equivalence designation if it satisfies FDA requirements for pharmaceutical equivalence, bioequivalence, labeling, manufacturing quality, and other ANDA standards. Therapeutic equivalence can accelerate substitution at the pharmacy level, although state substitution rules and payer policies remain important.

How strong is the patent estate for the claimed product?

US 8,466,138 was technically meaningful because it combined formulation and clinical-use limitations that correspond closely to a marketed product. Its strength is mixed:

Strength factor	Assessment
Product alignment	Strong; claims track the 1.62% gel and 2.5-gram dose
Formulation specificity	Strong against close copies, weaker against redesigned formulations
Closed composition language	Limits claim breadth and supports design-around arguments
Method-of-treatment requirement	Creates patient-use and label-related enforcement issues
Serum-range claims	Potentially useful but fact-intensive to prove
Generic substitution risk	High after patent-term expiry
Biosimilar risk	Not applicable
Manufacturing barrier	Moderate; formulation replication is possible but controlled-substance manufacturing adds compliance requirements
Remaining blocking value	Dependent on related patents, settlements, and regulatory exclusivity

The patent was more effective against a close AndroGel 1.62% copy than against a materially different topical testosterone product.

How does AndroGel 1.62% compare with competing testosterone products?

Product category	FDA pathway	Main competitive distinction	Relevance to US 8,466,138
AndroGel 1.62%	NDA	Hydroalcoholic topical gel, 1.62% testosterone	Directly aligned with the claimed formulation
Generic testosterone gel 1.62%	ANDA	Therapeutically equivalent or near-equivalent gel	Highest direct patent and substitution exposure
Testosterone injection	NDA or ANDA	Injectable administration	Outside the skin-application limitation
Testosterone patch	NDA or generic pathway where available	Patch delivery	Outside the hydroalcoholic-gel limitation
Buccal testosterone	NDA	Buccal absorption	Outside the claimed route
Nasal testosterone	NDA	Intranasal delivery	Outside the claimed route
Compounded testosterone gel	Compounding framework	Variable formulation and quality controls	May raise separate regulatory and patent issues

The most direct competition comes from generic 1.62% testosterone gel. Other dosage forms compete for the same hypogonadism population but do not ordinarily practice the claimed method.

What revenue exposure does patent expiry create?

Patent expiry exposes the branded product to rapid price compression and pharmacy substitution. The financial impact depends on:

• the number of approved ANDA applicants;
• the timing of the first commercial launch;
• whether a first applicant receives 180-day exclusivity;
• formulary placement;
• rebate strategy;
• payer switching;
• inventory levels;
• the strength of the brand’s patient and prescriber base; and
• the availability of other testosterone delivery systems.

For a topical testosterone product, generic erosion may be slower than for a simple oral tablet because patients and prescribers may value application convenience, dose titration, skin-transfer precautions, and established tolerability. The product remains vulnerable to payer-driven substitution once an AB-rated generic becomes available.

Precise revenue exposure requires current net sales, gross-to-net data, market-share data, and the number and status of approved ANDAs. Public patent documents alone do not establish those commercial figures.

What generic launch scenarios exist after patent expiry?

Three launch scenarios are most relevant.

Immediate multi-generic launch

Several ANDA applicants launch after patent expiry or coordinated settlement dates. This produces the fastest price erosion and the greatest risk to branded volume.

First-filer followed by staged entry

A first Paragraph IV applicant launches after litigation or settlement, followed by additional applicants after the first-filer period ends. The first entrant may capture disproportionate share.

Formulation-specific entry

A generic launches only after resolving formulation or method-of-use risk. A nonidentical gel may obtain approval but face slower substitution if it lacks direct therapeutic equivalence or uses different dosing instructions.

What geographic coverage does US 8,466,138 provide?

US 8,466,138 provides rights only in the United States. It does not establish protection in Canada, Europe, Japan, or other markets.

International protection would require separate national or regional patents, typically based on the same priority or PCT family. Foreign family members may differ in:

• claim scope;
• validity status;
• term;
• prosecution amendments;
• supplementary protection certificates;
• litigation history; and
• listed regulatory protection.

A U.S. Paragraph IV outcome does not determine the validity or enforceability of corresponding foreign patents.

Key Takeaways

• US 8,466,138 is a formulation-and-method patent linked to testosterone gel 1.62%, particularly AndroGel 1.62%.
• Claim 1 requires a specific closed composition and application to skin for treating male hypogonadism.
• Claims 8 and 9 cover the commercially important 2.5-gram dose and 40.5-mg testosterone delivery.
• Claims 4 and 5 add serum testosterone outcomes but may be difficult to enforce without patient-specific pharmacokinetic evidence.
• The “consisting of” language narrows the claim and creates potential formulation design-around strategies.
• The patent’s listed term reached expiration in 2025, subject to the current FDA and USPTO term records.
• Generic competition proceeds through the ANDA pathway, not the biosimilar pathway.
• Direct commercial risk is highest from therapeutically equivalent 1.62% testosterone gel products.
• Continued protection depends on related patent-family members, Orange Book listings, litigation outcomes, settlements, and any regulatory exclusivity.
• Testosterone’s controlled-substance status creates manufacturing and distribution barriers but does not preserve patent exclusivity after expiration.

FAQs

Can a generic avoid US 8,466,138 by using 1.60% testosterone instead of 1.62%?

Potentially. A concentration change may avoid literal infringement, but the outcome depends on claim construction, prosecution history, formulation equivalence, and whether the change is considered insubstantial under the doctrine of equivalents.

Does a generic need to use carbomer to infringe the patent?

No. Claim 1 recites polyacrylic acid broadly, while claims 6 and 7 narrow the polymer to carbomer. A non-carbomer formulation could still implicate claim 1 if it satisfies the remaining limitations.

Can an ANDA applicant omit the hypogonadism indication?

A label carveout may be possible in some cases, but it depends on the approved uses, the patent listing, the proposed labeling, and whether the remaining label induces use of the patented method.

Does FDA approval eliminate patent infringement risk?

No. FDA approval and patent clearance are separate issues. An ANDA can be approved while a patent dispute remains pending, subject to statutory stays and launch restrictions.

Are compounded testosterone gels covered by the same patent analysis?

Yes, potentially, but the analysis differs from an ANDA case. Composition, patient-specific prescribing, manufacturing status, labeling, and the practical availability of enforcement evidence all affect the risk assessment.

References

1. U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

2. U.S. Food and Drug Administration. (2024b). AndroGel 1.62% prescribing information, NDA 022309. https://www.accessdata.fda.gov/drugsatfda_docs/label/

3. U.S. Patent and Trademark Office. (2013). U.S. Patent No. 8,466,138, Testosterone gel formulation. https://patents.google.com/patent/US8466138

4. U.S. Code, 21 U.S.C. § 355. (2024). New drugs and abbreviated new drug applications. https://www.law.cornell.edu/uscode/text/21/355

5. U.S. Code, 35 U.S.C. § 271. (2024). Infringement of patent. https://www.law.cornell.edu/uscode/text/35/271

Drugs Protected by US Patent 8,466,138

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Besins Hlthcare	ANDROGEL	testosterone	GEL, METERED;TRANSDERMAL	022309-001	Apr 29, 2011	AB	RX	Yes	Yes	8,466,138					TESTOSTERONE REPLACEMENT THERAPY IN MALES FOR CONDITIONS ASSOCIATED WITH A DEFICIENCY OR ABSENCE OF ENDOGENOUS TESTOSTERONE
Besins Hlthcare	ANDROGEL	testosterone	GEL;TRANSDERMAL	022309-002	Sep 7, 2012	AB2	RX	Yes	No	8,466,138					TESTOSTERONE REPLACEMENT THERAPY IN MALES FOR CONDITIONS ASSOCIATED WITH A DEFICIENCY OR ABSENCE OF ENDOGENOUS TESTOSTERONE
Besins Hlthcare	ANDROGEL	testosterone	GEL;TRANSDERMAL	022309-003	Sep 7, 2012	AB2	RX	Yes	No	8,466,138					TESTOSTERONE REPLACEMENT THERAPY IN MALES FOR CONDITIONS ASSOCIATED WITH A DEFICIENCY OR ABSENCE OF ENDOGENOUS TESTOSTERONE

International Family Members for US Patent 8,466,138

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006299833
Brazil	PI0617294
Canada	2624788
China	101287470
Cyprus	1113737
Cyprus	1120904
Denmark	1937276