Details for Patent: 8,993,520

Which drugs does patent 8,993,520 protect, and when does it expire?

Patent 8,993,520 protects AXIRON and is included in one NDA.

This patent has twenty patent family members in thirteen countries.

Summary for Patent: 8,993,520

Title:	Method and composition for transdermal drug delivery
Abstract:	The invention is directed to a transdermal drug delivery composition which includes at least one physiologically active agent; and at least one volatile solvent; and at least one viscosity modulating agent. The invention extends to methods of administering such a composition to a subject and treatment of subjects using the composition.
Inventor(s):	Tony DiPietro, Andrew Humberstone, Igor Gonda, Adam Watkinson, Kerrie Setiawan, Nina Wilkins
Assignee:	Acrux DDS Pty Ltd
Application Number:	US12/823,448
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,993,520
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Device;

US Patent 8,993,520: Scope, Claims, Expiration, Orange Book Status, and Patent Landscape for Axillary Testosterone

US Patent 8,993,520 covers a narrow method of raising testosterone blood levels by applying a non-occlusive, alcohol-rich testosterone formulation to the axilla. The independent claims require a testosterone composition, more than 60% alcohol, a specified penetration enhancer, and a viscosity-modifying agent. The patent is associated with the Axiron transdermal testosterone product originally developed by Acrux and commercialized in the United States by Eli Lilly.

The patent’s projected 20-year term ran from the earliest claimed priority date of July 11, 2005, producing a base expiration date of July 11, 2025, subject to any patent-term adjustment. Its commercial importance was concentrated in the Axiron formulation and delivery method rather than in testosterone therapy generally. The claims do not cover oral testosterone, injectable testosterone, testosterone patches, or every topical testosterone gel.

What does US Patent 8,993,520 cover?

US 8,993,520 covers a method of administering testosterone through the skin of at least one axilla without using an occlusive patch. The composition must contain four functional elements:

1. Testosterone in a pharmaceutically effective amount.
2. More than 60% lower alkyl alcohol.
3. A qualifying penetration enhancer.
4. A viscosity-modifying or thickening agent.

The patent has two independent method claims:

• Claim 1 uses a volume-based alcohol limitation: more than 60% v/v.
• Claim 12 uses a weight-based alcohol limitation: more than 60% by weight.

Both claims require axillary application and exclude occlusion by a patch device.

Core claim limitations

Limitation	Claim 1	Claim 12
Testosterone	Required	Required
Adult male subject	Required	Required
Increased testosterone blood level	Required	Required
Axillary application	Required	Required
Patch occlusion excluded	Required	Required
Alcohol concentration	More than 60% v/v	More than 60% by weight
Alcohol type	Lower alkyl alcohols	Ethanol, isopropanol, or mixtures
Penetration enhancer	Broad Markush group	Three specified sunscreen esters
Viscosity modifier	Required	Required
Non-occlusive formulation language	Implied by claim 1	Expressly stated

The claims are method claims, not composition claims. A formulation manufacturer therefore would not necessarily infringe merely by making or selling a chemically similar liquid. Infringement would generally require evidence that the formulation is used, directed, or labeled for the claimed axillary testosterone administration method.

How broad is the scope of claim 1?

Claim 1 is the broadest issued claim, but it is constrained by several cumulative limitations. Every required limitation must be met.

Testosterone requirement

The claim requires a pharmaceutically effective amount of testosterone. It does not specify a particular testosterone concentration, ester, salt, or dosage amount in the independent claim. Claim 11 narrows the formulation to at least 1% w/v testosterone.

The claim is directed to raising blood testosterone in an adult male subject. A product intended only for female patients, pediatric patients, or a non-testosterone indication would fall outside the express patient limitation, although induced-infringement analysis could depend on the product label and actual use.

Axillary administration

Application to at least one axilla is central to the patent. The claims do not cover general application to the arms, shoulders, abdomen, thighs, or scrotum unless the same product is also used on an axilla.

This limitation distinguishes the patent from many conventional testosterone gels. Axiron’s delivery system used an underarm applicator and was designed for once-daily application to the axilla. The FDA label instructed patients to apply the product to the axillary area and prohibited application to other body parts.[2]

No patch occlusion

The phrase “without occlusion by a patch device” excludes a conventional testosterone patch method. The patent instead targets a non-occlusive liquid or semisolid formulation that is applied directly to the skin.

A product could potentially remain within the claim even if a patient wears clothing over the application site. The limitation is directed to occlusion by a patch device, not necessarily to every form of covering or physical contact after application.

Alcohol concentration

Claim 1 requires more than 60% v/v combined lower alkyl alcohol. Claim 12 requires more than 60% by weight of ethanol, isopropanol, or a mixture.

This is a high-alcohol formulation requirement. It narrows the claim against low-alcohol gels, creams, emulsions, lotions, and nonalcoholic delivery systems. The distinction between volume and weight is material. A formulation may satisfy one measurement basis but not the other, depending on density and the identity of the nonalcohol components.

What penetration enhancers are protected?

Claim 1 contains a broad Markush group covering multiple penetration-enhancer classes:

• Oleic acid
• Fatty acid esters
• Fatty alcohols
• Glycols
• Glycol esters
• 1,3-dioxolanes
• 1,3-dioxanes
• Macrocyclic ketones with at least 12 carbon atoms
• Oxazolidinones
• Alkyl-2-(N,N-disubstituted amino)-alkanoate esters
• (N,N-disubstituted amino)-alkanol alkanoates
• Sunscreen esters
• Mixtures of these materials

Claims 2 and 12 narrow the relevant enhancer group to three sunscreen esters:

• Octyl dimethyl para-aminobenzoate
• Octyl para-methoxycinnamate
• Octyl salicylate

Claim 3 and claim 13 further narrow the formulation to octyl salicylate. Claims 4 and 14 specify a penetration-enhancer concentration of 0.01% to 15% w/v.

Commercial significance of octyl salicylate

Octyl salicylate is the most commercially important enhancer limitation in the issued claims because the Axiron formulation used a sunscreen ester-based penetration-enhancement approach. A competing product using a different enhancer could avoid claims 3, 13, and the corresponding dependent claims while still requiring analysis under the broader Markush language of claims 1 or 12.

The risk analysis would depend on whether the alternative enhancer falls within one of the expressly listed chemical classes and whether the remaining alcohol, viscosity, dosage, and axillary-use requirements are met.

What viscosity and formulation limitations apply?

The independent claims require a viscosity-modifying agent. Claim 8 limits the viscosity to greater than water and no more than 300 centipoise. Claim 9 identifies polyvinylpyrrolidone, or PVP, at 1% to 3% w/v.

Claim 12 and its dependents contain equivalent limitations:

• Claim 15: viscosity from the viscosity of water to 300 cps.
• Claim 16: polyvinylpyrrolidone.
• Claim 17: PVP at 1% to 3% w/v.

These limitations perform two legal functions. First, they require more than the presence of testosterone and alcohol. Second, they tie the claims to a liquid formulation with enough viscosity to improve dosing control and reduce run-off from the axilla.

A formulation with no viscosity modifier would not meet the literal language of the independent claims. A formulation using a different thickener could still raise infringement issues under the broader claims, but it would not meet the narrower PVP claims unless the alternative agent were legally equivalent under the applicable doctrine-of-equivalents analysis.

How do claims 1 and 12 differ?

Claims 1 and 12 overlap substantially but are not identical.

Issue	Claim 1	Claim 12
Alcohol measurement	More than 60% v/v	More than 60% by weight
Alcohol definition	One or more lower alkyl alcohols	Ethanol, isopropanol, or mixtures
Enhancer scope	Broad chemical classes	Three named sunscreen esters
Non-occlusive wording	“Without occlusion by a patch device”	“Non-occlusive” and without patch occlusion
Strategic function	Broader formulation coverage	More specific Axiron-like coverage

Claim 1 is broader as to the penetration enhancer and alcohol identity. Claim 12 is narrower as to the enhancer but may capture formulations that meet the weight-based alcohol threshold even if they do not meet the volume-based threshold in claim 1.

The two independent claims create alternative infringement pathways. A design-around must be evaluated against both, not only against claim 1.

What dependent claims add?

Claims	Added limitation
2, 12	Selected sunscreen-ester penetration enhancers
3, 13	Octyl salicylate
4, 14	Enhancer concentration of 0.01% to 15% w/v
5	Ethanol, isopropanol, or mixtures
6	More than 80% v/v alcohol
7, 19	Adult male suffers from androgen deficiency
8, 15	Viscosity greater than water and up to 300 cps
9, 16	Polyvinylpyrrolidone
10	Once-daily administration
11, 18	Testosterone at least 1% w/v

Claims 6, 9, 10, and 11 are particularly relevant to product comparisons. A once-daily, 1% or higher testosterone formulation using more than 80% ethanol or isopropanol and PVP would present a close claim profile.

When did US Patent 8,993,520 expire?

The patent’s earliest claimed priority date is July 11, 2005. Under the standard U.S. patent-term calculation, the base expiration date is July 11, 2025, subject to any patent-term adjustment shown on the issued patent record.[1]

Event	Date
Earliest claimed priority	July 11, 2005
U.S. patent grant	March 31, 2015
Base 20-year expiration	July 11, 2025
Patent-term adjustment	Must be taken from the patent certificate and USPTO record

The 2015 issue date did not create a new 20-year term. U.S. utility patent term generally runs from the earliest effective nonprovisional filing date, not from issuance.[3]

Any patent-term adjustment could extend the expiration date beyond July 11, 2025. Patent-term extension under 35 U.S.C. § 156 is a separate issue and generally depends on regulatory-review eligibility. The patent’s commercial relevance should therefore be separated into two periods:

• Pre-expiration: potential blocking value against covered Axiron-like products.
• Post-expiration: reduced direct blocking value, subject to other unexpired patents in the Axiron family and any continuing regulatory exclusivity.

What was the Orange Book status of US 8,993,520?

US 8,993,520 was associated with the Axiron testosterone topical solution patent estate and was eligible for consideration as a method-of-use or drug-product patent listing under FDA Orange Book procedures. The relevant reference product was Axiron, NDA 022504, approved by FDA in November 2010.[2][4]

Orange Book significance depends on three separate questions:

1. Whether the patent was listed for the reference product.
2. Whether the listed claims covered the approved indication or use.
3. Whether the patent remained unexpired when an ANDA applicant filed a Paragraph IV certification.

A listing does not establish patent validity or infringement. It can, however, trigger the Hatch-Waxman 30-month stay if the NDA holder or patent owner timely files an infringement action after receiving a Paragraph IV notice.[5]

The Axiron commercial product was later discontinued in the United States. Discontinuation of sales does not automatically eliminate all patent or regulatory consequences, but it can affect the commercial value of an Orange Book listing and the availability of an active reference product for generic development.

Which companies challenged Axiron-related exclusivity?

Generic testosterone topical products have been developed by multiple companies, including firms operating through ANDA filings and later abbreviated approvals. Publicly reported Axiron patent disputes and Paragraph IV activity involved generic-drug companies seeking approval for testosterone topical solutions or comparable products.

The most relevant competitor categories were:

• Generic topical testosterone solution developers.
• Companies seeking an Axiron-equivalent axillary delivery method.
• Manufacturers using different skin sites or different delivery vehicles.
• Products relying on alternative alcohol levels, penetration enhancers, or viscosity agents.

The precise patent claims implicated depended on each ANDA’s formulation and proposed labeling. A generic applicant could challenge validity, noninfringement, or both. A formulation materially different from the Axiron composition might avoid the narrower octyl-salicylate and PVP claims while still facing the broader independent claims.

What patent litigation affected the Axiron estate?

Axiron-related litigation was driven by Paragraph IV certifications against patents listed for the product. The major litigation issues in this field typically included:

• Obviousness of axillary testosterone delivery.
• Written description and enablement for the claimed concentration ranges.
• Inherency or anticipation based on earlier testosterone gels.
• Claim construction for “non-occlusive,” “viscosity modulating agent,” and alcohol concentration.
• Whether an ANDA label induced use on the axilla.
• Whether the generic formulation contained a listed penetration enhancer or equivalent excipient system.

A patent challenge to one Axiron patent did not automatically eliminate the entire estate. Axiron-related protection was distributed across formulation, delivery-device, method-of-use, and related continuation patents. A generic applicant therefore had to address each relevant listed patent independently.

What other patents protected Axiron and related testosterone products?

The broader estate included more than US 8,993,520. Axiron protection was built around several overlapping categories:

Formulation patents

These patents addressed high-alcohol testosterone solutions, penetration enhancement, viscosity control, testosterone concentration, and dosing characteristics.

Delivery-device patents

Axiron used a metered applicator designed to dispense a controlled amount of solution while reducing direct hand contact. Device claims can remain relevant even when formulation claims expire.

Method-of-use patents

These patents addressed axillary administration, testosterone replacement in androgen-deficient men, once-daily dosing, and blood-level improvement.

Regulatory exclusivity

FDA approval exclusivity is distinct from patent protection. New-drug exclusivity, pediatric exclusivity, and patent-term adjustments can alter the timing of generic approval even where a patent’s ordinary term is approaching expiration.[4][5]

How strong is the patent estate for an Axiron-like product?

US 8,993,520 had moderate claim strength against close copies and weaker reach against substantially redesigned products.

Stronger infringement positions

Risk was highest where a competing product had:

• Axillary administration.
• A non-occlusive liquid.
• More than 60% ethanol or isopropanol.
• Octyl salicylate or another listed sunscreen ester.
• PVP or a similar viscosity-control system.
• Testosterone at 1% w/v or higher.
• Once-daily dosing.

Stronger design-around positions

Risk was lower where a competing product used:

• A patch or occlusive delivery system.
• A non-axillary application site.
• A low-alcohol or alcohol-free formulation.
• A different penetration-enhancement strategy.
• A cream, emulsion, foam, or hydroalcoholic system outside the claimed viscosity profile.
• A non-PVP thickener.
• A materially different dosing schedule.

The principal weakness is that the claims are cumulative. A competitor can reduce risk by changing one required limitation, although the broader claim 1 and claim 12 must both be assessed.

How does US 8,993,520 compare with competing testosterone delivery systems?

Product type	Axillary-use risk under US 8,993,520	Main distinction
Axiron-type solution	High before expiration	Matches site and formulation architecture
Conventional testosterone gel	Moderate to low	Usually applied to shoulders or upper arms
Testosterone patch	Low under the no-patch limitation	Uses occlusive delivery
Injectable testosterone	None under these claims	No transdermal administration
Oral testosterone undecanoate	None under these claims	Non-transdermal route
Nasal testosterone	None under these claims	Different administration route
Alternative axillary liquid	Variable	Depends on alcohol, enhancer, and viscosity

The patent is therefore more relevant to an axillary testosterone solution than to the testosterone market as a whole.

What generic entry risks exist for Axiron-like products?

A generic launch strategy would generally involve one of four paths:

1. Wait for expiration of the relevant listed patents and regulatory exclusivities.
2. File a Paragraph IV certification and litigate.
3. Use a formulation or label design-around.
4. Launch after a settlement date agreed with the patent holder.

A Paragraph IV challenge could trigger a 30-month FDA approval stay if the patent owner filed suit within the statutory period. The commercial outcome would depend on the remaining patent term, the number of unexpired listed patents, the strength of invalidity arguments, and the economics of the reference product.

Because US 8,993,520 reached its base expiration date in 2025, its standalone blocking value is materially lower after that date. The principal remaining risk would come from patent-term adjustment, related unexpired continuation patents, device rights, and any settlement restrictions applicable to a particular ANDA applicant.

What licensing deals supported Axiron?

Acrux developed the transdermal delivery technology and entered into a North American commercialization arrangement with Eli Lilly. Lilly obtained rights to commercialize Axiron in the United States and Canada, while Acrux retained economic participation through milestone payments, royalties, and related commercial arrangements.[6]

The deal structure mattered because patent enforcement and Orange Book strategy were divided between the technology owner and the commercial NDA holder. For Hatch-Waxman purposes, the relevant parties could include the NDA holder, patent owner, exclusive licensee, and other parties with enforcement rights.

Key Takeaways

• US 8,993,520 is a method-of-use patent for non-occlusive axillary testosterone delivery.
• Claims 1 and 12 are independent and use different alcohol measurement standards.
• The core formulation requires testosterone, more than 60% alcohol, a qualifying penetration enhancer, and a viscosity modifier.
• Octyl salicylate, PVP, 1% or higher testosterone, and once-daily axillary dosing create the closest Axiron-like profile.
• The patent does not cover injectable, oral, nasal, patch-based, or ordinary non-axillary testosterone products.
• The base patent-term expiration date was July 11, 2025, subject to patent-term adjustment.
• The patent estate was broader than this single patent and included formulation, device, method-of-use, and continuation patents.
• Generic risk was highest for an Axiron-equivalent axillary solution and lower for products changing the administration site, delivery route, alcohol system, enhancer, or viscosity architecture.
• Acrux was the technology originator; Eli Lilly commercialized Axiron in North America.
• Orange Book and Paragraph IV consequences depended on the patent’s listing status, the ANDA’s proposed formulation and labeling, and the timing of any infringement action.

FAQs

Does US 8,993,520 cover all testosterone gels?

No. It covers a specific transdermal method involving axillary application, non-occlusive administration, high alcohol content, penetration enhancement, and viscosity modification.

Can a testosterone product avoid the patent by changing only the application site?

Potentially. A product labeled solely for the shoulders, upper arms, abdomen, or another non-axillary site would not meet the express axilla limitation, subject to the product’s actual labeling and use.

Is octyl salicylate required in every claim?

No. It is required only in narrower dependent claims such as claims 3 and 13. Claim 1 covers a broader group of penetration enhancers, while claim 12 covers three named sunscreen esters.

Does patent expiration eliminate FDA approval requirements for generic testosterone?

No. Patent expiration removes one potential exclusivity barrier. An ANDA applicant must still satisfy FDA requirements for pharmaceutical equivalence, bioequivalence, labeling, manufacturing quality, and other regulatory conditions.

Could an alternative thickener still infringe?

Yes, potentially under the broader independent claims if all other limitations are met. The narrower PVP claims would present a separate and more limited issue.

References

1. United States Patent and Trademark Office. (2015). U.S. Patent No. 8,993,520, Transdermal drug delivery compositions and methods of use.
2. U.S. Food and Drug Administration. (2010). Axiron testosterone topical solution prescribing information, NDA 022504.
3. United States Code, 35 U.S.C. §§ 154, 156.
4. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
5. United States Code, 21 U.S.C. § 355(j).
6. Acrux Limited. (2010). Annual report and commercialization disclosures for Axiron and the Eli Lilly agreement.

Drugs Protected by US Patent 8,993,520

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Eli Lilly And Co	AXIRON	testosterone	SOLUTION, METERED;TRANSDERMAL	022504-001	Nov 23, 2010		DISCN	Yes	No	8,993,520					A METHOD OF INCREASING THE TESTOSTERONE BLOOD LEVEL OF AN ADULT MALE SUBJECT IN NEED THEREOF

Foreign Priority and PCT Information for Patent: 8,993,520

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	2005902902	Jun 3, 2005

International Family Members for US Patent 8,993,520

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006254742
Australia	2011202787
Brazil	PI0611134
Canada	2610708
China	101212975