Details for Patent: 8,338,395

Which drugs does patent 8,338,395 protect, and when does it expire?

Patent 8,338,395 protects AVEED and is included in one NDA.

This patent has fifty-two patent family members in thirty-eight countries.

Summary for Patent: 8,338,395

Title:	Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
Abstract:	Described are methods for providing prolonged physiologically acceptable steady state serum testosterone levels in a patient deficient in endogenous testosterone levels, methods for male contraception and methods for treating a disease or symptom associated with deficient endogenous levels of testosterone in a man, by intramuscularly administering testosterone esters in a vehicle.
Inventor(s):	Doris Hubler, Sabine Fricke, Jan-Peter Ingwersen, Wilheim Kuhnz
Assignee:	Gruenenthal GmbH
Application Number:	US12/391,655
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,338,395
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 8,338,395: Claim Scope, Exclusivity, Litigation Risk, and Testosterone Undecanoate Patent Landscape

US Patent 8,338,395 protects a specific testosterone undecanoate injection regimen and vehicle composition rather than testosterone undecanoate as a molecule. Its core limitations are intramuscular administration, a castor-oil/Co-solvent vehicle with castor oil at no more than 42% by volume, loading injections, and maintenance dosing every 10 to 14 weeks. The commercially relevant embodiment is 750 mg of testosterone undecanoate in 3 mL, equivalent to 250 mg/mL, administered under the Aveed regimen.

The patent is primarily a method-of-use barrier. A competing product may avoid literal infringement by changing the vehicle, dosing interval, loading schedule, concentration, route, or therapeutic indication. The strongest commercial risk remains a product that duplicates the approved 750 mg/3 mL formulation and the two-dose loading regimen followed by 10-week maintenance injections.

What does US Patent 8,338,395 protect?

US 8,338,395 protects methods for achieving prolonged, physiologically acceptable steady-state testosterone levels through intramuscular testosterone undecanoate administration. The patent does not broadly claim every testosterone undecanoate formulation or every testosterone-replacement method.

The principal claim limitations are:

Limitation	Claims affected	Commercial significance
Testosterone undecanoate administered intramuscularly	1-27	Excludes oral, transdermal and subcutaneous products from literal scope
Vehicle consisting essentially of castor oil and a co-solvent	1-24, 26-27	Targets the long-acting injectable formulation
Castor oil at 42% or less by volume	1-24, 26-27	A key formulation limitation
Benzyl benzoate as co-solvent	10-11, 16-17	Covers the commercially relevant vehicle
2-4 initial doses	1, 24	Defines the loading phase
Initial intervals of 4-8 weeks	1, 24	Limits the induction schedule
Maintenance interval of 10-14 weeks	1, 24	Captures long-interval maintenance dosing
Two initial doses four weeks apart, then 10-week maintenance	6-7, 14-18	Closest claim set to the Aveed regimen
Two initial doses six weeks apart, then 12-week maintenance	8-9	Covers an alternative loading and maintenance schedule
750 mg testosterone undecanoate per dose	13, 18	Matches the approved commercial dose
250 mg/mL testosterone undecanoate	25-27	Matches 750 mg in 3 mL
Testosterone levels of approximately 10-35 nmol/L	12	Adds a pharmacokinetic outcome limitation
Hypogonadism and related causes	2-5, 19-23	Defines therapeutic populations
Male contraception	24	Separate use category with potentially different validity and infringement issues

Claim 27 duplicates claim 26 as supplied. That duplication does not expand the enforceable scope unless the issued patent contains a materially different limitation that is absent from the reproduced text.

How should the independent claims be construed?

Claim 1: broad regimen claim

Claim 1 requires all of the following:

1. A patient deficient in endogenous testosterone.
2. Intramuscular administration.
3. A composition containing testosterone undecanoate.
4. A vehicle consisting essentially of castor oil and a co-solvent.
5. Castor oil at 42% or less by volume.
6. A maintenance dose every 10-14 weeks.
7. Two to four initial doses.
8. Initial doses administered every 4-8 weeks.
9. Prolonged physiologically acceptable steady-state serum testosterone levels.

The claim is broad across dose amount, disease cause and co-solvent identity, but narrow in its combined formulation and schedule requirements. A generic applicant administering testosterone undecanoate every 10 weeks with the same or equivalent vehicle would face a high literal-infringement risk if its formulation contains no more than 42% castor oil.

The phrase "consisting essentially of" is important. It generally permits additional ingredients that do not materially alter the basic and novel characteristics of the vehicle, while excluding ingredients that materially change those characteristics. The scope is broader than "consisting of," but narrower than "comprising." The infringement analysis would turn on the identity and function of any additional excipients.

Claim 14: narrower commercial regimen

Claim 14 requires:

• two initial intramuscular injections;
• four weeks between those injections;
• each dose containing 500-1,000 mg of testosterone undecanoate;
• subsequent injections every 10 weeks;
• the same castor-oil/co-solvent vehicle;
• castor oil at 42% or less by volume.

This claim is narrower than claim 1 because it fixes the loading schedule at two injections four weeks apart and the maintenance interval at 10 weeks. It is also narrower because it defines a dose range.

The claim is commercially significant because it tracks the approved Aveed loading regimen: an initial injection, a second injection four weeks later, followed by injections every 10 weeks. Claim 18 narrows the dose to 750 mg, and claims 15-17 narrow the vehicle to 25-42% castor oil and 58-75% benzyl benzoate.

Claim 24: male contraception

Claim 24 applies the same formulation and schedule to male contraception. Its practical scope is narrower than the hypogonadism claims because the method must be used for contraception. A testosterone undecanoate product used solely for testosterone replacement would not ordinarily satisfy the contraception-purpose limitation.

The claim could nevertheless create risk where a product label includes male contraception, suppression of gonadotropins or a contraception-related clinical indication. Label language, promotional activity and physician-directed use would be relevant to induced or contributory infringement theories.

What formulations are protected by US 8,338,395?

The most concentrated formulation protection appears in claims 10, 11 and 15-18.

Formulation limitation	Claim coverage
Castor oil at 42% or less by volume	1-24, 26-27
Castor oil at 25-42% by volume	15
Benzyl benzoate as co-solvent	10, 16
Castor oil:benzyl benzoate ratio of 1:1 to 1:1.6 v/v	11
Benzyl benzoate at 58-75% by volume	17
Testosterone undecanoate at 750 mg per dose	13, 18
Testosterone undecanoate at 250 mg/mL	25-27

The 750 mg/3 mL presentation contains 250 mg/mL of testosterone undecanoate. The concentration claims therefore focus on the commercial presentation rather than a theoretical formulation range.

A formulation containing more than 42% castor oil could avoid literal infringement of the claims containing that limitation, although it would need to be assessed against other patents, regulatory requirements and the doctrine of equivalents. A vehicle using a different co-solvent may also avoid claims 10, 11, 16 and 17, but not necessarily the broader claims that do not specify benzyl benzoate.

When does US Patent 8,338,395 lose exclusivity?

The patent appears to have a 2006 nonprovisional filing date and a projected 20-year term extending to approximately May 2026, subject to the official USPTO patent-term calculation, any patent-term adjustment, terminal disclaimer and post-grant legal events. The patent issued on December 25, 2012. Patent expiration is distinct from FDA regulatory exclusivity.

Exclusivity event	Approximate date or status
Earliest relevant priority period	2005
US nonprovisional filing	2006
Patent grant	December 25, 2012
Aveed FDA approval	March 5, 2014
Five-year new chemical entity exclusivity	Expired in 2019
Projected US patent expiration	Approximately May 2026
Post-expiration generic entry	Subject to ANDA approval, patent litigation and settlement terms

The FDA's five-year new chemical entity exclusivity for Aveed did not replace or extend the patent term. A Paragraph IV ANDA challenge could have been filed after the statutory restriction period, even while the patent remained in force.

Patent-term restoration under 35 U.S.C. § 156 is generally unavailable for method claims where the product received an earlier regulatory approval outside the relevant statutory framework, and the public patent record does not establish a material extension beyond the ordinary patent term. The controlling expiration date should be taken from the USPTO Patent Center record and current Orange Book listing.

What is the Orange Book status of testosterone undecanoate injection?

Aveed is the US reference product for testosterone undecanoate injection. It was approved under NDA 021463 for testosterone replacement therapy in adult males with conditions associated with a deficiency or absence of endogenous testosterone. The FDA label specifies 750 mg/3 mL administered intramuscularly, with a second injection four weeks later and subsequent injections every 10 weeks. The product must be administered in a certified health-care setting because of the risk of serious pulmonary oil microembolism and anaphylaxis. (FDA, 2024)

The Orange Book status of any particular patent listing can change through delisting, expiration, correction or FDA publication updates. US 8,338,395 is the patent most directly aligned with the Aveed formulation and dosing regimen described in the supplied claims. Orange Book-listed method patents can support a regulatory patent certification even when they do not claim the active ingredient itself.

A generic applicant may seek a label carve-out for patented indications or dosing methods under the skinny-label provisions. That strategy is difficult where the patented regimen is the same regimen required for safe and effective use of the reference product. A carve-out that removes the only commercially viable dosing instructions may not provide a practical design-around.

Which companies are challenging the testosterone undecanoate patent estate?

The principal commercial parties are:

Company	Role
Endo Pharmaceuticals and related entities	US commercial interests associated with Aveed
Bayer and predecessor organizations	Historical development and international rights associated with testosterone undecanoate products
Generic ANDA applicants	Potential challengers through Paragraph IV certifications
FDA-approved generic manufacturers	Potential post-expiration entrants, subject to ANDA approval and patent status

Public litigation around pharmaceutical patents can involve multiple related entities, licensees and manufacturing affiliates. A litigation docket must be matched to the asserted patent, ANDA number, product formulation and settlement terms. The claim text alone does not establish whether a particular ANDA applicant has resolved its challenge through a license, covenant not to sue or launch-date settlement.

A Paragraph IV certification would create a statutory basis for patent litigation. If the patent owner filed suit within 45 days, FDA approval could be stayed for up to 30 months, subject to court decisions and statutory exceptions. A first-filer could receive 180-day generic exclusivity if the statutory requirements were satisfied, although that outcome would depend on the specific ANDA and certification history. (FDA, 2023)

How strong is the patent estate for Aveed?

The estate is strongest when a competitor copies the entire commercial package:

• testosterone undecanoate;
• intramuscular delivery;
• castor oil and benzyl benzoate;
• castor oil at 42% or less;
• 750 mg in 3 mL;
• two loading injections four weeks apart;
• maintenance injections every 10 weeks.

The estate is weaker against products that change multiple variables simultaneously. Potential design-around vectors include:

Design-around vector	Likely effect
Different oil vehicle	May avoid the central formulation limitation
Castor oil above 42%	May avoid claims requiring the upper concentration limit
Different co-solvent	May avoid benzyl-benzoate-specific claims
Oral testosterone undecanoate	Avoids intramuscular administration claims
Transdermal or nasal testosterone	Avoids both formulation and injection claims
Subcutaneous administration	May avoid literal intramuscular limitations
Different loading interval	Could avoid claims 6, 8 and 14
Maintenance interval outside 10-14 weeks	Could avoid the principal regimen claims
Different dose concentration	Could avoid claims 13, 18 and 25-27

The doctrine of equivalents could narrow the practical value of some design-arounds, particularly where the altered ingredient or concentration performs substantially the same function in substantially the same way. Prosecution history estoppel and the express numerical ranges may limit that theory.

How does the patent compare with competing testosterone products?

US 8,338,395 has a narrower commercial focus than patents covering oral testosterone undecanoate, transdermal testosterone or other injectable esters.

Product category	Active ingredient or delivery	Relationship to US 8,338,395
Aveed	Testosterone undecanoate, intramuscular	Directly aligned with the claims
Oral testosterone undecanoate	Testosterone undecanoate, oral	Outside the intramuscular limitation
Testosterone cypionate	Injectable testosterone ester	Different active ingredient
Testosterone enanthate	Injectable testosterone ester	Different active ingredient
Transdermal gel or patch	Testosterone, transdermal	Outside the claimed route and vehicle
Nasal testosterone	Testosterone, intranasal	Outside the claimed route and vehicle
Subcutaneous autoinjector	Testosterone enanthate or another ester	Generally outside literal intramuscular scope

This patent does not block all testosterone replacement therapy. Its value depends on the long-acting testosterone undecanoate injection market and the ability of a generic competitor to reproduce the approved regimen.

What generic entry risks exist?

The most probable launch scenarios are:

1. A generic copies the approved 750 mg/3 mL formulation and dosing schedule, creating substantial infringement risk until patent expiry or settlement.
2. A generic modifies the vehicle or administration schedule and accepts clinical-development and regulatory risk.
3. A generic obtains approval with a narrow label carve-out, if the FDA permits the relevant indication or regimen to be omitted.
4. A post-expiration generic launches after the patent term ends, subject to FDA approval and any surviving patents.
5. A competitor launches an alternative testosterone product that does not require testosterone undecanoate or the claimed vehicle.

The formulation limitations raise manufacturing barriers beyond patent law. Long-acting oil injections require control of viscosity, solubility, particle-free sterilization, container compatibility, injection volume and pharmacokinetic reproducibility. The FDA label's pulmonary oil microembolism warning also creates administration and risk-management requirements. These factors can delay entry even after the principal patent expires.

What is the revenue exposure from this patent?

The patent's revenue exposure is concentrated in Aveed sales and in any US license or royalty stream tied to testosterone undecanoate injection. It does not cover the broader testosterone replacement market.

Revenue risk increases as the patent approaches expiration because:

• generic applicants can challenge the patent before expiry;
• the product's 10-week dosing interval can support a differentiated price;
• physician and patient switching may be limited by administration requirements;
• competing testosterone products are already available;
• a successful formulation design-around could reduce the patent's effective market protection before formal expiration.

Precise revenue exposure requires current Aveed net sales, product-level margin data, licensing terms and the status of any approved or pending ANDAs. Those figures are not contained in the claim set.

Key Takeaways

• US 8,338,395 is a method patent covering a defined long-acting testosterone undecanoate injection regimen.
• Its central combination is testosterone undecanoate, intramuscular delivery, a castor-oil/co-solvent vehicle, castor oil at no more than 42% by volume, loading injections and 10-14 week maintenance dosing.
• Claims 14-18 most closely track the commercial Aveed regimen.
• Claims 25-27 cover the 250 mg/mL concentration associated with 750 mg in 3 mL; claim 27 duplicates claim 26 in the supplied text.
• The patent does not block oral, transdermal, nasal or other testosterone products that do not satisfy the claim limitations.
• The projected patent term appears to extend to approximately May 2026, subject to the official USPTO term calculation.
• FDA new chemical entity exclusivity expired years earlier and is separate from patent protection.
• The strongest generic challenge would target the vehicle, numerical castor-oil limitation, loading schedule, maintenance interval and 750 mg/3 mL presentation.
• Manufacturing, safety-monitoring and injection-administration requirements may remain commercial barriers after patent expiry.

FAQs about US Patent 8,338,395

Does US 8,338,395 claim testosterone undecanoate itself?

No. The claims require a method of administering testosterone undecanoate in a specified vehicle and dosing regimen. They do not claim the molecule in the abstract.

Can a testosterone undecanoate product avoid the patent by using a different oil?

Potentially. A product using an oil other than castor oil may avoid literal infringement of the vehicle limitations, but the complete patent family and doctrine-of-equivalents issues would still require analysis.

Does a 12-week testosterone undecanoate regimen infringe?

It may fall within claim 1 or claim 24 because those claims cover maintenance dosing every 10-14 weeks. Claims 8 and 9 specifically address two loading doses six weeks apart followed by 12-week maintenance.

Is 750 mg of testosterone undecanoate the only dose covered?

No. Claim 14 covers 500-1,000 mg per dose, while claim 1 does not state a dose amount. Claims 13 and 18 narrow the coverage to 750 mg.

Does patent expiry automatically permit a generic Aveed product to launch?

No. Launch still requires FDA approval, compliance with applicable Orange Book certifications, resolution of other unexpired patents and satisfaction of manufacturing and safety requirements.

References

1. U.S. Patent and Trademark Office. (2012). U.S. Patent No. 8,338,395, testosterone undecanoate formulations and methods of use.
2. U.S. Food and Drug Administration. (2024). Aveed (testosterone undecanoate) injection prescribing information. Endo Pharmaceuticals Inc.
3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations, 45th ed. [Orange Book].
4. U.S. Food and Drug Administration. (2019). Approved drug product label: Aveed testosterone undecanoate injection.
5. United States Code. (2024). 35 U.S.C. §§ 154, 156, 271, 355(j).

Drugs Protected by US Patent 8,338,395

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Endo Operations	AVEED	testosterone undecanoate	INJECTABLE;INTRAMUSCULAR	022219-001	Mar 5, 2014		RX	Yes	Yes						TESTOSTERONE REPLACEMENT THERAPY IN ADULT MALES FOR CONDITIONS ASSOCIATED WITH A DEFICIENCY OR ABSENCE OF ENDOGENOUS TESTOSTERONE; PRIMARY HYPOGONADISM (CONGENITAL OR ACQUIRED); HYPOGONADOTROPIC HYPOGONADISM (CONGENITAL OR ACQUIRED).

International Family Members for US Patent 8,338,395

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	043603
Austria	336251
Australia	2004218893
Brazil	PI0400214