US Patent 9,265,762: Macitentan Formulation Claims, Exclusivity and Patent Landscape

US Patent 9,265,762 protects oral pharmaceutical compositions containing macitentan, the active ingredient in Opsumit, together with a narrowly defined excipient system. The core formulation requires lactose monohydrate with microcrystalline cellulose, sodium starch glycolate or sodium starch glycolate plus polyvinylpyrrolidone, a polysorbate surfactant, and magnesium stearate.

The patent is materially narrower than a composition patent covering macitentan itself. It does not cover every macitentan tablet or capsule. Infringement requires practice of the claimed excipient architecture, or a claimed method of treating pulmonary arterial hypertension using that composition.

The patent issued on February 23, 2016, and has a projected ordinary expiration date in October 2032, subject to patent-term adjustment and any applicable terminal disclaimer. It is associated with Actelion Pharmaceuticals Ltd.'s macitentan program and the Opsumit product family.[1][2]

What drug does US Patent 9,265,762 protect?

US 9,265,762 protects formulations of macitentan, an endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension.

Macitentan is marketed in the United States as Opsumit by Actelion Pharmaceuticals US, Inc., a Johnson & Johnson company. The FDA-approved product is an immediate-release oral tablet. Opsumit is available in a 10 mg strength.[3]

The patent claims permit the active pharmaceutical ingredient to be present as:

Macitentan;
A pharmaceutically acceptable salt;
A solvate;
A hydrate; or
A morphological form, including a polymorphic form.

The active-ingredient language is broad, but the excipient limitations substantially narrow the claims.

Patent identification

Item	Data
U.S. patent	US 9,265,762 B2
Issue date	February 23, 2016
Patent subject	Macitentan pharmaceutical compositions
Therapeutic area	Pulmonary arterial hypertension
Dosage forms	Tablets and capsules
Key commercial product	Opsumit
Patent holder or originating company	Actelion-related entity
Earliest priority	October 21, 2011, based on the patent family record
Projected ordinary expiration	October 21, 2032
Principal protection	Formulation and treatment method
Active ingredient	Macitentan

The compound formula in the claims is macitentan, also known as ACT-064992. The formulation patent does not broadly claim the macitentan molecule as a chemical entity. Earlier Actelion patents provide the principal compound-level protection.

What are the independent claims in US 9,265,762?

The patent has four substantive independent claims: claims 1, 8, 9, and 16.

Claim	Claim type	Main scope
1	Composition	Macitentan composition with specified filler, disintegrant, polysorbate and magnesium stearate
8	Method of treatment	Treatment of pulmonary arterial hypertension using a claim 1 composition
9	Composition	More narrowly quantified version of claim 1
16	Method of treatment	Treatment of pulmonary arterial hypertension using a claim 9 composition

Claims 2 through 7 narrow claim 1. Claims 10 through 15 narrow claim 9.

The two composition claims have overlapping structure, but claim 9 adds quantitative limitations for the active ingredient, filler, disintegrant and lubricant. Claim 1 is therefore broader in some respects, while claim 9 provides a more specific formulation profile.

What formulation components are required by the patent?

Filler requirements

The filler must consist of lactose monohydrate with microcrystalline cellulose.

This limitation is important because a formulation using only lactose, only microcrystalline cellulose, or a different filler system would not literally satisfy the filler limitation. A product using mannitol, calcium phosphate, starch, or another diluent would require a doctrine-of-equivalents analysis rather than a straightforward literal-infringement case.

Claim 9 requires the filler system to comprise 10% to 95% by weight of the total composition.

Disintegrant requirements

The disintegrant must be one of the following:

Sodium starch glycolate; or
A combination of sodium starch glycolate and polyvinylpyrrolidone.

Claims 3 and 11 require the combination of sodium starch glycolate and polyvinylpyrrolidone. Claims 4 and 12 require that combination to comprise 2% to 10% by weight.

A formulation using crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, or another disintegrant without sodium starch glycolate presents a strong non-infringement position on the literal claim language.

Surfactant requirements

The surfactant must consist of a polysorbate. Claim 2 and claim 10 specify polysorbate 80.

The required polysorbate range is 0.1% to 3% by weight in both independent composition claims. This is a central limitation. A generic formulation that omits polysorbate, uses sodium lauryl sulfate, or uses another surfactant would not literally meet this element.

Lubricant requirements

The lubricant must consist of magnesium stearate.

Claim 9 requires the lubricant to comprise 0.05% to 10% by weight. Claims 5 and 13 narrow the magnesium stearate amount to 0.1% to 1%.

A formulation using calcium stearate, stearic acid, sodium stearyl fumarate, or another lubricant would avoid literal satisfaction of this element unless the product also contains magnesium stearate.

How broad are the claims to tablets and capsules?

Claims 6, 7, 14 and 15 expressly cover capsules and tablets.

The independent claims are not limited to one dosage form. A tablet or capsule may fall within claim 1 or claim 9 if it contains the required macitentan and excipient system. The express dependent claims remove potential ambiguity and make both dosage forms separately claimable.

The claims do not expressly require:

Immediate release;
A particular tablet weight;
A particular macitentan dose;
Film coating;
A particular manufacturing process;
A specific dissolution profile;
A particular particle-size distribution; or
A particular polymorph.

The claims do require the specified ingredients. A product with a materially different formulation may avoid the patent even if it has the same strength and dosage form.

What quantitative ranges does claim 9 impose?

Claim 9 provides the most commercially relevant quantitative limitations.

Component	Claim 9 range
Macitentan or permitted form	Up to 50% by weight
Lactose monohydrate plus microcrystalline cellulose	10% to 95%
Sodium starch glycolate, alone or with PVP	1% to 20%
Polysorbate	0.1% to 3%
Magnesium stearate	0.05% to 10%

Dependent claims impose narrower ranges:

Limitation	Narrower range
Sodium starch glycolate plus PVP	2% to 10%
Magnesium stearate	0.1% to 1%
Polysorbate	Polysorbate 80

The use of “consisting of” for the identified excipient categories creates a meaningful prosecution and infringement issue. The phrase generally excludes additional materials within the claimed category, although it does not necessarily prohibit other ingredients that perform unrelated functions. The total formulation must be analyzed ingredient by ingredient, including coating materials and processing aids.

What is the patent scope compared with the Opsumit product?

The FDA label for Opsumit identifies macitentan and inactive ingredients including lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, povidone, polysorbate 80 and magnesium stearate.[3] Those ingredients substantially correspond to the claimed formulation architecture.

Opsumit and claim limitations

Opsumit characteristic	Relationship to US 9,265,762
Macitentan active ingredient	Satisfies active-ingredient limitation
Lactose monohydrate	Part of required filler system
Microcrystalline cellulose	Part of required filler system
Sodium starch glycolate	Satisfies disintegrant alternative
Povidone	Supports combination disintegrant limitation if within the claimed PVP definition
Polysorbate 80	Satisfies dependent polysorbate limitation
Magnesium stearate	Satisfies lubricant limitation
Tablet dosage form	Expressly covered by claims 7 and 15

The exact infringement analysis depends on the quantitative composition of the commercial product and the identity of the povidone used. The public label establishes ingredient overlap but does not alone establish every weight-percentage limitation in claim 9.

When does US Patent 9,265,762 expire?

The patent has an earliest priority date of October 21, 2011. Applying the standard 20-year term from the earliest effective nonprovisional filing date produces an ordinary expiration in October 2032.[1][2]

The effective date can change because of:

Patent-term adjustment;
Patent-term extension;
Terminal disclaimers;
Corrected priority data; or
Relevant continuation or divisional relationships.

The patent is not the principal molecule patent for macitentan. Its commercial value arises from the later formulation expiry. The formulation patent can therefore remain relevant after earlier chemical-entity patents expire.

What FDA exclusivity protects Opsumit?

FDA regulatory exclusivity and patent protection are separate rights.

Protection	Relevance to Opsumit
New chemical entity exclusivity	Initially protected Opsumit from ANDA approval for five years after approval
Orphan-drug exclusivity	Pulmonary arterial hypertension indication received orphan-drug protection
Patent protection	Covers macitentan, formulations, and related methods across separate patent families
Orange Book listing	Determines which listed patents an ANDA applicant must address
Pediatric exclusivity	Applies only if FDA awarded the additional six-month period for qualifying pediatric work

Opsumit was approved by FDA on October 18, 2013.[3] Its five-year new chemical entity exclusivity therefore expired in October 2018, subject to the statutory rules governing submission and approval timing. Any orphan exclusivity attached to the approved indication is separate from NCE exclusivity and does not replace patent protection.

Is US 9,265,762 listed in the Orange Book?

The Orange Book is the controlling source for current listed-patent status, expiration dates, and use codes. A formulation patent may be listed if it claims the approved drug, an approved formulation, or an approved method of use and meets FDA listing requirements.[4]

US 9,265,762 is commercially relevant to the Opsumit Orange Book estate because its claims correspond to the approved macitentan tablet formulation. The practical significance of the listing is that an ANDA applicant may need to submit a Paragraph IV certification if the patent is listed and has not expired.

An Orange Book listing does not establish infringement. It determines the patent-certification framework and can trigger the statutory 30-month stay if the patent holder timely files an infringement action after receiving a Paragraph IV notice.[5]

What Paragraph IV challenges and generic-entry risks exist?

An ANDA applicant seeking approval of generic macitentan tablets must address each relevant listed patent through one of four certifications:

Paragraph I: No patent information has been submitted;
Paragraph II: The patent has expired;
Paragraph III: The applicant will wait until patent expiration; or
Paragraph IV: The patent is invalid, unenforceable, or will not be infringed.

For US 9,265,762, a Paragraph IV challenge would likely focus on formulation design-around and claim validity.

Likely design-around options

A generic applicant could attempt to avoid the claims by:

Omitting polysorbate;
Replacing polysorbate 80 with a non-polysorbate surfactant;
Replacing sodium starch glycolate with croscarmellose sodium or crospovidone;
Omitting polyvinylpyrrolidone where claims 3, 4, 11 and 12 are at issue;
Using a filler other than lactose monohydrate plus microcrystalline cellulose;
Using a lubricant other than magnesium stearate;
Selecting excipient quantities outside claim 9 ranges; or
Developing a different dosage form or release profile.

The main commercial risk is that Opsumit-like formulations may reproduce the claimed excipient system because those excipients may support dissolution, content uniformity, manufacturability and stability. A design-around may therefore create formulation-development and bioequivalence risks.

Paragraph IV litigation analysis

A Paragraph IV case would likely address:

Whether the ANDA formulation contains polysorbate;
Whether the active ingredient is macitentan or a covered salt, solvate, hydrate or morphology;
Whether the lactose and microcrystalline cellulose combination is present;
Whether the disintegrant includes sodium starch glycolate;
Whether magnesium stearate is present;
Whether the claimed percentage ranges are met; and
Whether the claims are invalid for anticipation or obviousness.

A generic applicant could also contest the patent based on written description, enablement, indefiniteness or obviousness. The strongest invalidity theory would likely require prior art disclosing a macitentan oral solid dosage form with the same or closely overlapping excipient combination and percentages.

How strong is the patent estate for macitentan?

The macitentan estate has multiple protection layers:

Layer	Function
Chemical-entity patents	Protect macitentan and related compounds
Formulation patents	Protect excipient combinations and dosage forms
Polymorph or morphology patents	Protect selected solid forms
Method-of-use patents	Protect treatment of pulmonary hypertension or related indications
Regulatory exclusivity	Delays generic approval independently of patent validity
Manufacturing patents	May protect synthesis, purification or solid-form production

US 9,265,762 is strongest against an Opsumit-copying formulation. It is weaker against a product that uses a different surfactant, disintegrant, filler or lubricant.

Its claim breadth is mixed:

Claim 1 is broad on component quantities but narrow on ingredient identity.
Claim 9 is narrower because it imposes multiple percentage ranges.
Claims 8 and 16 depend on use of the claimed formulation, which limits them to treatment with the specified composition.
Claims 2, 4, 5, 10, 12 and 13 provide commercially useful fallback positions around polysorbate 80, disintegrant levels and magnesium stearate levels.

The patent is therefore a formulation barrier rather than a complete generic barrier. A generic applicant that successfully designs around the excipient requirements may avoid the principal infringement risk while still confronting separate macitentan patents.

What litigation and settlement issues affect generic macitentan?

The principal litigation exposure depends on the current ANDA filing record and the patents listed for Opsumit at the time of filing. A Paragraph IV notice directed to US 9,265,762 could create a 30-month stay if Actelion or the relevant patent owner files a timely infringement action.[5]

A settlement agreement could establish:

An agreed generic launch date;
A license to the formulation patent;
A no-launch period tied to other patents;
An authorized-generic arrangement;
A covenant not to sue; or
A permitted formulation design-around.

Settlement terms are often confidential. A lack of a publicly reported case specific to this patent would not establish that no Paragraph IV notice has been served. ANDA notices and private settlement arrangements are not all publicly available.

What revenue exposure does the patent create?

The patent's revenue exposure is linked to the Opsumit franchise rather than to the full macitentan market.

A generic entrant that avoids US 9,265,762 may still be blocked by:

Unexpired compound patents;
Method-of-use patents;
Other formulation patents;
Regulatory exclusivity;
Patent litigation stays;
Supply-chain or manufacturing constraints; and
FDA approval timing.

A formulation patent expiring in 2032 can protect branded pricing after earlier compound patents expire, but its actual economic value depends on whether competitors can launch non-infringing formulations. The narrower the generic formulation, the greater the design-around risk for the patent holder.

How does US 9,265,762 compare with a compound patent?

Issue	Compound patent	US 9,265,762
Protected subject	Macitentan molecule or close analogues	Macitentan oral composition
Design-around difficulty	High if active molecule is required	Moderate if alternative excipients work
Product dependence	Applies to the active ingredient	Applies to formulation architecture
Dosage-form limitation	Usually none or limited	Tablet and capsule claims
Expiry profile	Earlier Actelion chemical patents	Later formulation expiry in 2032
Generic challenge	Chemical invalidity or non-infringement	Formulation non-infringement and obviousness
Commercial effect	Can block all macitentan products	Can block only covered formulations

The patent should be evaluated together with the complete Orange Book and worldwide family, not as a standalone right.

What geographic coverage does the patent family provide?

US 9,265,762 provides protection only in the United States. Parallel national patents may exist in Europe, Canada, Japan, Australia and other jurisdictions based on the same international application.

Foreign rights can differ materially because of:

Different claim amendments;
National examination outcomes;
Patent-term rules;
Supplementary protection certificates;
Validity challenges;
Orange Book equivalents; and
Local rules for formulation and method-of-use claims.

The US patent does not itself create protection in other countries. Each national family member must be checked independently through WIPO PATENTSCOPE, Espacenet and the relevant national register.[6][7]

What manufacturing and intellectual-property barriers remain after the patent expires?

Expiration of US 9,265,762 would remove the ordinary US patent barrier created by its claims. It would not eliminate:

Other unexpired US patents;
Regulatory requirements for ANDA approval;
Bioequivalence obligations;
Controlled manufacturing specifications;
Macitentan active-ingredient supply constraints;
Trade secrets involving granulation, blending or coating;
Foreign patent rights; or
Patent rights covering other indications or formulations.

Because the patent claims ingredients rather than a specific manufacturing process, a competitor can potentially avoid it through formulation redesign. Process patents and trade secrets may still affect cost, yield and scale-up.

Key Takeaways

US 9,265,762 is a macitentan formulation patent associated with Opsumit.
The core formulation requires lactose monohydrate plus microcrystalline cellulose, sodium starch glycolate or sodium starch glycolate with PVP, a polysorbate, and magnesium stearate.
Claims 2 and 10 specifically cover polysorbate 80.
Claims 9 through 13 add important weight-percentage limitations.
Claims 8 and 16 cover treatment of pulmonary arterial hypertension using the claimed compositions.
The patent is materially narrower than a macitentan compound patent.
The projected ordinary expiration is in October 2032, subject to patent-term adjustment and other statutory modifications.
A generic applicant can pursue a formulation design-around using a different surfactant, disintegrant, filler or lubricant.
Opsumit regulatory exclusivity expired years before the projected formulation-patent expiry.
The patent must be assessed with the broader Orange Book estate, compound patents, method-of-use patents and any Paragraph IV litigation or settlements.

FAQs

Can a generic macitentan tablet avoid US 9,265,762?

Yes. A product may avoid literal infringement by omitting polysorbate, replacing sodium starch glycolate, using a different filler system, or omitting magnesium stearate. The complete formulation and applicable doctrine of equivalents would control.

Does the patent cover macitentan as a chemical compound?

No. The patent claims pharmaceutical compositions and treatment methods. Separate Actelion patent families provide the principal chemical-entity protection for macitentan.

Does using polysorbate 80 automatically infringe?

No. Polysorbate 80 is only one required element. The product must also contain the claimed macitentan form, filler, disintegrant and magnesium stearate limitations.

Are capsules covered by the patent?

Yes. Claims 6 and 14 expressly cover capsules. Claims 1 and 9 are composition claims that are not inherently limited to tablets.

Can a Paragraph IV filer challenge only the formulation patent?

Yes. An ANDA applicant may challenge US 9,265,762 while certifying Paragraph III or taking another position on separate listed patents. Approval and launch still depend on the complete Orange Book estate.

Sources

United States Patent and Trademark Office. (2016). US Patent No. 9,265,762 B2, Pharmaceutical compositions.
WIPO. (2013). International patent publication and family records for pharmaceutical compositions comprising macitentan. PATENTSCOPE.
U.S. Food and Drug Administration. (2024). Opsumit (macitentan) prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
U.S. Code, 21 U.S.C. § 355(j).
European Patent Office. (2024). Espacenet patent family and legal-status records.
World Intellectual Property Organization. (2024). PATENTSCOPE international patent records.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Actelion	OPSUMIT	macitentan	TABLET;ORAL	204410-001	Oct 18, 2013	AB	RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial			Y		⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	PCT/EP2005/009775	Sep 12, 2005

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006290309	⤷ Start Trial
Brazil	PI0615898	⤷ Start Trial
Canada	2621273	⤷ Start Trial
China	101262847	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,265,762

Which drugs does patent 9,265,762 protect, and when does it expire?

Summary for Patent: 9,265,762