Details for Patent: 10,166,181

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Which drugs does patent 10,166,181 protect, and when does it expire?

Patent 10,166,181 protects TRIPTODUR KIT and TRELSTAR and is included in two NDAs.

This patent has forty-seven patent family members in thirty-two countries.

Summary for Patent: 10,166,181

Title:	Slow release pharmaceutical composition made of microgranules
Abstract:	Pharmaceutical composition made of microparticles for the slow release of an active substance at least during a period covering the 6th month after injection of said composition, said composition comprising a group of microparticles made of a copolymer of the PLGA type which incorporate an active substance in the form of a water insoluble peptide salt; said copolymer furthermore comprising at least 75% of lactic acid and an inherent viscosity between 0.1 and 0.9 dl/g, as measured in chloroform at 25° C. and at a polymer concentration of 0.5 g/dL; said microparticles furthermore having a size distribution defined as follows: —D (v,0.1) is between 10 and 30 micrometers, —D (v,0.5) is between 30 and 70 micrometers, —D (v,0.9) is between 50 and 1 10 micrometers.
Inventor(s):	Bertrand Ducrey, Patrick Garrouste, Catherine Curdy, Marie-Anne Bardet, Herve Porchet, Eija Lundstrom, Frederic Heimgartner
Assignee:	Debiopharm International SA
Application Number:	US12/601,649
Patent Claim Types: see list of patent claims	Composition; Formulation;

US Patent 10,166,181: Triptorelin Pamoate Six-Month Microgranule Patent Scope and Landscape

US Patent 10,166,181 protects a highly specific 22.5 mg triptorelin pamoate depot composition for six-month chemical castration. The independent claim requires two distinct PLGA microgranule populations, specific drug-loading levels, specific lactide-to-glycolide ratios, an immediate initial release, and sustained release for at least 168 days. Claim 2 narrows the product to a 50:50 dose ratio between the two microgranule populations. Claims 3 and 4 link the composition to six-month chemical castration and treatment of advanced prostate cancer.

The patent is materially narrower than a broad claim to triptorelin, triptorelin pamoate, PLGA microspheres, or six-month androgen-deprivation therapy. A competing product would need to avoid at least one required limitation to reduce literal infringement risk. The most commercially important limitations are the dual-microgranule architecture, the 85:15 and 75:25 PLGA compositions, the approximately 20% and 12% drug loadings, and the 50:50 dose allocation.

What does US Patent 10,166,181 protect?

The patent protects a pharmaceutical composition containing 22.5 mg of triptorelin pamoate in two separately formulated microgranule populations:

Claim element	Required limitation
Active ingredient	Triptorelin in the form of triptorelin pamoate
Total dose	22.5 mg
Dosage form	Injectable microgranules
First population	Approximately 20% triptorelin pamoate and 80% PLGA
First PLGA	Approximately 85% lactide and 15% glycolide
Second population	Approximately 12% triptorelin pamoate and 88% PLGA
Second PLGA	Approximately 75% lactide and 25% glycolide
Release profile	Immediate release within hours, followed by substantially constant release
Duration	At least 168 days
Dependent dose ratio	50:50 triptorelin dose ratio
Therapeutic result	Six-month chemical castration
Disease limitation	Advanced prostate cancer

The claim is a composition claim, not merely a method-of-treatment claim. That distinction matters because infringement can arise from making, using, offering for sale, selling, or importing the claimed composition, subject to the applicable statutory and judicial standards.

How does claim 1 define the protected formulation?

Claim 1 uses a product-by-composition-and-performance structure. It combines quantitative formulation limitations with a release-profile limitation.

First microgranule formulation

The first formulation requires:

• Approximately 20% by weight triptorelin pamoate.
• Approximately 80% by weight PLGA.
• PLGA containing approximately 85% lactide and 15% glycolide.

The relatively higher lactide content generally corresponds to slower polymer degradation than formulations with a higher glycolide fraction. The first microgranule population therefore appears designed to contribute to the prolonged phase of the depot release profile.

Second microgranule formulation

The second formulation requires:

• Approximately 12% by weight triptorelin pamoate.
• Approximately 88% by weight PLGA.
• PLGA containing approximately 75% lactide and 25% glycolide.

The higher glycolide content generally increases polymer hydrophilicity and can accelerate erosion or drug release relative to an 85:15 PLGA system. The second population appears intended to contribute to the initial and intermediate release phases.

Combined release behavior

The composition must release triptorelin:

1. In an immediate amount within hours after injection; and
2. Then continuously or substantially constantly for at least 168 days.

This release limitation gives the claim technical breadth beyond a purely compositional claim, but it also creates an infringement and validity issue. The parties would likely dispute:

• The meaning of "immediate amount."
• Whether "constantly released" requires a mathematically uniform release rate.
• Whether the release must remain constant for the full 168 days.
• Whether in vitro and in vivo release data should control.
• Whether the claim permits a clinically insignificant terminal tail after the principal six-month release period.

What does claim 2 add to the patent scope?

Claim 2 requires the two microgranule formulations to be mixed so that the triptorelin dose is divided in a 50:50 ratio.

This limitation is narrower than a 50:50 mass ratio of the finished microgranules. Because the two populations have different drug loadings, an equal triptorelin dose ratio would generally require unequal amounts of the two microgranule masses.

For example, ignoring manufacturing overages and assay variation:

Formulation	Drug loading	Microgranule mass needed for 11.25 mg triptorelin pamoate
First population	20%	Approximately 56.25 mg
Second population	12%	Approximately 93.75 mg
Combined microgranule mass	Not specified	Approximately 150 mg

The claim therefore does not require a 50:50 weight ratio of the two microgranule populations. It requires a 50:50 allocation of the triptorelin dose.

What do claims 3 and 4 protect?

Claim 3: Six-month chemical castration

Claim 3 requires the composition to induce chemical castration over six months. It adds a therapeutic-performance limitation to the formulation.

The wording may generate claim-construction disputes. A patent challenger could argue that "induces chemical castration" describes the intended use or expected pharmacology rather than a measurable structural limitation. The patent owner would likely argue that the limitation distinguishes compositions that fail to maintain sufficient gonadotropin suppression or testosterone suppression for the claimed period.

Claim 4: Advanced prostate cancer

Claim 4 limits the composition to inducing chemical castration in patients with advanced prostate cancer. It is narrower than claim 3 and is directed to the primary commercial use of long-acting triptorelin in androgen-deprivation therapy.

Because claim 4 depends on claim 2, a product must satisfy all of the following:

• 22.5 mg triptorelin pamoate;
• The two specified microgranule formulations;
• The specified PLGA ratios and drug loadings;
• A 50:50 triptorelin dose ratio;
• Six-month chemical castration; and
• Use in advanced prostate cancer.

How strong is the patent scope of US 10,166,181?

The patent has a narrow literal scope but potentially meaningful commercial significance if the marketed product uses the claimed architecture.

Scope factor	Assessment
Active ingredient	Narrow because the claim requires triptorelin pamoate
Dose	Narrow because the claim requires 22.5 mg
Polymer	Moderately narrow because PLGA is required
Polymer composition	Narrow because both 85:15 and 75:25 systems are specified
Drug loading	Narrow because approximately 20% and approximately 12% are required
Formulation architecture	Narrow because two microgranule populations are required
Release profile	Potentially broad in theory, but fact-intensive to prove
Treatment period	At least 168 days
Disease	Claims 3 and 4 are narrower than claim 1
Design-around potential	Material, through changing polymer ratio, loading, dose, or population structure

The claim does not appear to cover every six-month triptorelin depot. A competing formulation could potentially avoid the claim by using:

• A single microgranule population;
• Different PLGA ratios;
• A different triptorelin loading;
• A different total dose;
• A different ratio between the two populations;
• A non-PLGA polymer;
• A different release profile;
• A different delivery system, such as an implant or in situ gel.

The term "approximately" reduces the practical value of small numerical changes as a design-around strategy. A modest departure from 85:15, 75:25, 20%, or 12% may still fall within the court's construction of the term, depending on the intrinsic evidence and prosecution history.

What are the principal validity risks?

The main validity issues are likely to involve obviousness and claim construction rather than simple anticipation.

Anticipation risk

A reference would need to disclose all material elements in a single publication or product disclosure, including:

• The 22.5 mg triptorelin pamoate dose;
• Two distinct microgranule populations;
• Both specified drug-loading levels;
• Both specified PLGA compositions;
• The release profile;
• At least 168 days of release.

Earlier triptorelin depot products may disclose the active ingredient, dose, PLGA microspheres, and prolonged release without disclosing the claimed dual-population combination.

Obviousness risk

The claim combines known formulation variables:

• PLGA lactide:glycolide ratios;
• Drug loading;
• Microsphere particle populations;
• Initial burst release;
• Sustained release;
• A six-month dosing interval.

A challenger could argue that a skilled formulator would have combined different PLGA grades or loadings to tune the initial burst and six-month duration. The patent owner would likely rely on the specific release behavior and the 50:50 dose allocation as evidence that the combination was not a routine optimization.

The strongest patentability position would depend on comparative data showing that the claimed combination achieved a release profile or clinical suppression duration not reasonably predictable from the individual formulations.

Written description and enablement

The patent must support the claimed ranges implied by "approximately," the claimed 168-day duration, and the clinical effects in claims 3 and 4. If the specification discloses only a single formulation example, a challenger could argue that the claims extend beyond the technical teaching.

The risk is higher for the functional release language if the patent claims a broad class of formulations but provides limited release testing across the relevant variables.

What Orange Book and FDA issues affect this patent?

The commercial significance of US 10,166,181 depends on whether it is listed for the relevant approved drug product in the FDA Orange Book. A patent can be commercially important without being listed, but an Orange Book listing can create the statutory framework for notice and a potential 30-month stay following a Paragraph IV certification.

For an NDA-listed triptorelin product, the relevant FDA issues include:

• Whether US 10,166,181 is listed against the 22.5 mg dosage form;
• Whether the listing is categorized as a drug substance, drug product, or method-of-use patent;
• Whether the claims correspond to the approved formulation;
• The patent expiration date recorded by FDA;
• Whether pediatric exclusivity extends the listed patent term;
• Whether a later-expiring patent or regulatory exclusivity is also present.

The patent itself does not create FDA exclusivity. Patent rights and FDA regulatory exclusivity are separate. A generic applicant could face an ANDA patent certification obligation even where the NDA has no remaining regulatory exclusivity.

Triptorelin is a peptide drug regulated through the NDA framework. A conventional generic applicant would ordinarily use an ANDA rather than the biosimilar pathway. The 351(k) biosimilar pathway applies to biological products and is not the standard pathway for an ANDA product containing triptorelin pamoate.

When does US Patent 10,166,181 lose exclusivity?

The exact expiration date should be taken from the patent front page, the USPTO patent-term record, and the FDA Orange Book entry if the patent is listed. The effective term may be affected by:

• The earliest effective nonprovisional or international priority filing;
• Patent term adjustment;
• Patent term extension;
• Terminal disclaimer;
• Pediatric exclusivity;
• Any correction or reissue.

The grant date of US 10,166,181 is January 1, 2019. The grant date does not determine expiration. For a patent filed after the Uruguay Round transition, the ordinary term is generally 20 years from the earliest effective nonprovisional filing date, subject to statutory adjustments.[1]

Because the claim text alone does not establish the priority chain or term-adjustment calculation, an exact expiration date cannot be stated reliably from the supplied information.

What Paragraph IV challenges could target this patent?

A Paragraph IV challenge could attack the patent through several theories:

1. The accused generic does not contain the claimed two-population formulation.
2. The generic uses a PLGA ratio outside the proper construction of "approximately."
3. The generic has a different drug-loading profile.
4. The product does not produce the claimed immediate and substantially constant release.
5. The claims are anticipated by an earlier triptorelin depot disclosure.
6. The claimed combination would have been obvious.
7. The functional release limitation lacks adequate written-description or enablement support.
8. Claims 3 and 4 improperly rely on treatment results that do not meaningfully limit the composition.

A generic applicant could file a Paragraph III certification and defer launch until patent expiration, or file a Paragraph IV certification and challenge validity or infringement. The commercial value of the challenge would depend on whether the patent is listed for the exact 22.5 mg product and whether other patents independently block launch.

What generic launch scenarios exist?

Scenario	Product strategy	Patent risk
Direct formulation copy	Uses both claimed microgranule populations and similar release profile	High literal infringement risk
Single-population depot	Uses one PLGA microsphere population	Lower risk under claim 1, subject to equivalents
Different PLGA grades	Changes one or both lactide:glycolide ratios	Potentially lower risk, but "approximately" must be assessed
Different drug loading	Changes 20% or 12% loading	Potentially lower risk, depending on claim construction
Different dose	Uses a dose other than 22.5 mg	Avoids the express dose limitation, but may not be commercially substitutable
Alternative delivery system	Uses implant, gel, or another depot technology	Generally outside the literal formulation claim
Non-infringing ANDA	Demonstrates pharmaceutical equivalence through a different formulation	Requires careful formulation and release testing

A product that avoids claim 1 may still face other patents covering triptorelin, PLGA depot manufacture, particle-size control, injectable compositions, or methods of androgen deprivation.

What manufacturing and technical barriers remain?

The patent's commercial value is supported by technical manufacturing complexity even where the claim can be designed around.

Key manufacturing controls include:

• Separate manufacture of the 85:15 and 75:25 PLGA microgranules;
• Control of triptorelin pamoate loading;
• Particle-size distribution;
• Residual solvent limits;
• Encapsulation efficiency;
• Polymer molecular weight and inherent viscosity;
• Sterility and endotoxin control;
• Suspension uniformity;
• Syringeability and reconstitution;
• Initial burst control;
• Six-month in vitro and in vivo release correlation.

A generic company may avoid literal infringement but still face development risk because a change in polymer ratio or loading can alter burst release, depot persistence, injection performance, and testosterone suppression.

How does this patent compare with earlier triptorelin depot patents?

US 10,166,181 should be distinguished from earlier patent categories:

Earlier patent category	Typical subject matter	Relationship to US 10,166,181
Triptorelin composition patents	Triptorelin salts, formulations, or dosage forms	May disclose the active ingredient but not the claimed dual-population architecture
PLGA microsphere patents	General peptide encapsulation and sustained release	May supply broad technical prior art
Depot manufacturing patents	Solvent evaporation, particle formation, drying, or sterilization	May cover manufacturing processes rather than the final composition
Earlier triptorelin products	One-, three-, or six-month depot products	May create anticipation or obviousness risk depending on disclosure
Method-of-treatment patents	Androgen deprivation or prostate cancer treatment	May overlap clinically without covering the same formulation

The relevant freedom-to-operate analysis must therefore examine both product claims and process claims. Avoiding US 10,166,181 does not establish freedom to operate across the full triptorelin depot landscape.

Which companies are commercially relevant?

The commercial landscape includes:

• The NDA holder and manufacturer of the relevant 22.5 mg triptorelin pamoate depot;
• Generic injectable-depot developers;
• Contract manufacturers with PLGA microsphere capabilities;
• Companies holding alternative GnRH agonist or antagonist products;
• Developers of six-month androgen-deprivation systems.

Competitive products include other triptorelin presentations and alternative prostate-cancer androgen-deprivation products. The closest technical competitors are long-acting GnRH agonist depots, especially products using leuprolide or goserelin. GnRH antagonists such as degarelix and relugolix compete clinically but do not generally create direct formulation overlap with this patent.

What is the revenue exposure from this patent?

The revenue exposure depends on the sales of the covered 22.5 mg six-month product rather than the entire triptorelin market. A successful Paragraph IV launch could affect:

• Six-month depot sales;
• Prescriber preference for less frequent injections;
• Urology and oncology purchasing contracts;
• Product switching among GnRH agonists;
• Net price and rebate levels;
• Patient adherence and administration revenue.

A six-month product may retain commercial value even after a patent challenge because manufacturing complexity, FDA approval requirements, clinical release testing, and limited qualified suppliers can delay effective competition.

Key Takeaways

• US 10,166,181 is a narrow formulation patent directed to a 22.5 mg triptorelin pamoate six-month depot.
• Claim 1 requires two separate PLGA microgranule populations with specific loadings and polymer compositions.
• Claim 2 requires a 50:50 allocation of the triptorelin dose, not necessarily a 50:50 weight ratio of microgranules.
• Claims 3 and 4 narrow the scope to six-month chemical castration and advanced prostate cancer.
• The principal design-around routes are changing the microgranule architecture, PLGA ratios, drug loadings, dose, or delivery technology.
• The main validity risks are obviousness, interpretation of "approximately," and the meaning and support of the release-profile limitations.
• Triptorelin is generally addressed through the NDA and ANDA framework, not the biosimilar pathway.
• An exact patent expiration date requires the complete priority chain, USPTO term adjustment, and any Orange Book data.
• The patent may create substantial launch risk for a formulation copy but does not by itself block every alternative six-month triptorelin depot.

FAQs About US Patent 10,166,181

Does US 10,166,181 cover all triptorelin injections?

No. The claims require a 22.5 mg triptorelin pamoate microgranule composition with two specified PLGA formulations and a defined release profile.

Can a generic avoid the patent by using a 50:50 mixture of microgranules?

Not necessarily. Claim 2 concerns a 50:50 triptorelin dose ratio. A generic using a different drug loading, polymer composition, or release profile may avoid the claim, but the full formulation must be assessed.

Does the patent cover triptorelin acetate?

The supplied claims require triptorelin in the form of triptorelin pamoate. Triptorelin acetate is outside the express active-ingredient limitation, although other patents or regulatory requirements could apply.

Is a six-month triptorelin product automatically infringing?

No. Six-month duration alone is insufficient. The product must satisfy every limitation of at least one asserted claim, including the two microgranule populations and specified PLGA formulations.

Does US 10,166,181 prevent a biosimilar launch?

No conventional biosimilar analysis is generally applicable to triptorelin as a peptide drug. A competing product would more commonly proceed through the ANDA pathway, with patent certifications determined by the Orange Book listing and the applicant's formulation.

References

1. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. https://www.uspto.gov
2. United States Patent and Trademark Office. (2019). U.S. Patent No. 10,166,181.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
4. U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions and patent certifications. https://www.fda.gov
5. U.S. Food and Drug Administration. (n.d.). Purple Book: Lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations. https://purplebooksearch.fda.gov/

Drugs Protected by US Patent 10,166,181

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	TRIPTODUR KIT	triptorelin pamoate	FOR SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	208956-001	Jun 29, 2017		RX	Yes	Yes			Y
Verity	TRELSTAR	triptorelin pamoate	INJECTABLE;INTRAMUSCULAR	022437-001	Mar 10, 2010		RX	Yes	Yes			Y

Foreign Priority and PCT Information for Patent: 10,166,181

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	07109767	Jun 6, 2007
	PCT/IB2007/054372	Oct 27, 2007

PCT Information
PCT Filed	June 06, 2008	PCT Application Number:	PCT/IB2008/052241
PCT Publication Date:	December 11, 2008	PCT Publication Number:	WO2008/149320

International Family Members for US Patent 10,166,181

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3000
Australia	2008259411
Brazil	PI0812250
Canada	2688478
China	101677959
Colombia	6251234
Cyprus	1118434