Details for Patent: 9,931,336

Which drugs does patent 9,931,336 protect, and when does it expire?

Patent 9,931,336 protects RHOPRESSA and ROCKLATAN and is included in two NDAs.

This patent has twenty-eight patent family members in thirteen countries.

Summary for Patent: 9,931,336

Title:	Combination therapy
Abstract:	Described herein are compounds and compositions for treating glaucoma and/or reducing intraocular pressure. Compositions may comprise an isoquinoline compound and a prostaglandin or a prostaglandin analog. Compounds described herein include those in which an isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog, and those in which an isoquinoline compound and a prostaglandin free acid together form a salt.
Inventor(s):	Casey Kopczynski, Cheng-Wen Lin, Jill Marie Sturdivant, Mitchell A. deLong
Assignee:	Alcon Inc
Application Number:	US15/236,625
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,931,336
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 9,931,336: Scope, Claims, Expiration, Orange Book Status, and Netarsudil Patent Landscape

US Patent 9,931,336 protects ophthalmic compositions containing the dimesylate salts of netarsudil stereoisomers and racemic netarsudil, together with methods for treating glaucoma and reducing intraocular pressure. The patent is commercially relevant to Rhopressa and the netarsudil component of Rocklatan. Its claims are narrower than a basic compound patent because they focus on the dimesylate salt and use in ocular treatment, but they are broad as to formulation composition, concentration, and dosage form.

What drug does US Patent 9,931,336 protect?

US 9,931,336 covers netarsudil dimesylate, a Rho kinase inhibitor developed by Aerie Pharmaceuticals and now commercialized by Alcon.

The claimed chemical entity is:

• (R)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate;
• the corresponding (S) stereoisomer dimesylate; and
• the racemic mixture dimesylate.

Netarsudil is generally associated with the S configuration. Rhopressa contains netarsudil dimesylate as the active pharmaceutical ingredient. Rocklatan combines netarsudil dimesylate with latanoprost.

Netarsudil lowers intraocular pressure through inhibition of the Rho-associated protein kinase pathway. FDA approved Rhopressa for reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension in December 2017. FDA approved Rocklatan in March 2019 for the same broad pressure-lowering indication [1, 2].

What are the independent claims in US 9,931,336?

The patent has three principal composition claims and associated method claims.

Claim group	Subject matter	Key limitation
Claims 1-7	R-netarsudil dimesylate composition and ocular treatment	Composition must contain the R dimesylate salt
Claims 8-14	S-netarsudil dimesylate composition and ocular treatment	Composition must contain the S dimesylate salt
Claims 15-21	Racemic netarsudil dimesylate composition and ocular treatment	Composition must contain the racemic dimesylate salt

Claims 1, 8, and 15 are the principal composition claims. Claims 3, 6, 10, 13, 17, and 20 are the principal treatment claims.

The patent does not require the composition to be an eye drop in every independent composition claim. Topical ocular administration appears in dependent claims 5, 7, 12, 14, 19, and 21. The glaucoma limitation also appears in dependent claims.

How broad are the composition claims?

The composition claims use the transitional term “comprising.” That language generally permits the presence of additional ingredients or components unless the claim or specification imposes a contrary limitation.

Claim 1 therefore covers a composition containing R-netarsudil dimesylate, whether the composition also contains other active or inactive ingredients. Claims 8 and 15 apply the same structure to the S stereoisomer and racemate.

The independent claims do not expressly require:

• a particular concentration;
• a specific pH;
• a particular container;
• a specific dosage volume;
• a named ophthalmic vehicle;
• a particular preservative;
• a particular buffer;
• a specific viscosity;
• a particular particle size;
• a particular polymorph; or
• a specified commercial product name.

The dependent composition claims add at least one of the following:

• buffer;
• chelating agent;
• tonicity agent;
• preservative;
• viscosity enhancer;
• sugar;
• sugar alcohol; or
• surfactant.

Because the dependent claims use an open-ended “comprising” structure, they cover compositions with one or more listed excipient categories, subject to ordinary claim-construction rules.

What formulations are protected by US 9,931,336?

The patent can cover liquid ophthalmic formulations, including topical eye drops, if they contain one of the claimed dimesylate salts. The claims are not limited to a single formulation recipe.

Potentially covered formulation types include:

• aqueous eye-drop solutions;
• buffered ophthalmic solutions;
• preserved multi-dose formulations;
• preservative-free unit-dose formulations;
• formulations containing tonicity modifiers;
• formulations containing surfactants;
• formulations containing viscosity-enhancing polymers; and
• formulations containing chelating agents.

A generic developer could therefore face infringement risk from a conventional aqueous netarsudil dimesylate eye drop even if it changes the buffer, preservative, tonicity agent, or surfactant. A materially different composition may still fall within claim 1, 8, or 15 if the claimed dimesylate salt is present.

The patent does not, based on the listed claims, require a specific concentration of netarsudil. This increases the potential claim reach across different strength and dosing designs. It does not eliminate the need to prove that the accused product contains the claimed salt rather than a different chemical form.

Do the claims cover the active S enantiomer, R enantiomer, and racemate?

Yes. The patent separately claims all three forms.

Form	Claims	Commercial relevance
R-netarsudil dimesylate	1-7	Primarily a patent-scope and stereochemistry issue
S-netarsudil dimesylate	8-14	Principal commercial form associated with netarsudil
Racemic netarsudil dimesylate	15-21	Covers the racemate as a distinct composition

This structure reduces a straightforward design-around based solely on stereochemistry. A product using the S form may implicate claims 8-14. A racemic product may implicate claims 15-21. An R-enantiomer product may implicate claims 1-7.

The practical importance is greater for the S and racemic claims because the approved product uses the pharmacologically relevant commercial form, while the R claims broaden the patent’s chemical coverage beyond the marketed stereoisomer.

What methods of use does US 9,931,336 protect?

The method claims cover:

1. treating an ocular disorder;
2. treating glaucoma; and
3. reducing intraocular pressure.

The claimed administration can be topical to an eye under the dependent claims. The method claim structure is therefore directed principally to ophthalmic treatment rather than systemic administration.

The strongest commercial relationship is with the FDA-approved indications for:

• open-angle glaucoma; and
• ocular hypertension.

The claim language “ocular disorder” is broader than glaucoma in claims 3, 10, and 17. The dependent glaucoma claims narrow the scope to that disease. The intraocular-pressure claims create a separate method category that does not expressly require the word glaucoma.

A generic manufacturer could face method-of-use issues even if it avoids some formulation limitations, although the effect depends on the proposed labeling, prescribing instructions, patent certifications, and the facts of any infringement case.

What is the expiration date of US Patent 9,931,336?

US 9,931,336 was issued on March 27, 2018, to Aerie Pharmaceuticals, Inc. Public patent records identify a March 2014 nonprovisional filing and a March 2034 nominal patent-term endpoint, subject to any applicable patent-term adjustment or other statutory calculation [3].

The relevant commercial planning date is generally reported as March 2034. The exact effective exclusivity date should be confirmed against the current FDA Orange Book entry and the USPTO patent-term record because patent-term adjustment can move the expiration date beyond the basic 20-year term.

Milestone	Date
Earliest disclosed priority period	2013
Nonprovisional filing period	2014
Patent publication	2016
Patent grant	March 27, 2018
Nominal patent-term endpoint	March 2034
FDA approval of Rhopressa	December 2017
FDA approval of Rocklatan	March 2019

The patent’s term is distinct from FDA regulatory exclusivity. FDA approval did not create a new patent term, and expiration of this patent would not by itself eliminate other valid patents or regulatory protections.

What is the Orange Book status of netarsudil?

Rhopressa is listed in FDA’s Orange Book under NDA 208254. Rocklatan is listed under NDA 211911. The Orange Book identifies patent information submitted by the NDA holder, including patents that may be relevant to generic approval and Paragraph IV certification [4].

US 9,931,336 is commercially important because it is associated with the approved netarsudil product and covers both formulation and ocular-use subject matter. The Orange Book analysis should distinguish between:

• patents listed for Rhopressa;
• patents listed for Rocklatan;
• patents covering netarsudil itself;
• patents covering the combination with latanoprost; and
• patents covering later formulations or dosing regimens.

The Orange Book listing does not establish that every claim is valid or infringed. It identifies patents that may affect an abbreviated new drug application.

How does US 9,931,336 compare with the core netarsudil compound patent?

US 9,931,336 should be analyzed alongside US 8,410,169, which covers substituted amide compounds associated with the netarsudil chemical series.

Issue	US 8,410,169	US 9,931,336
Primary focus	Chemical compounds and Rho kinase inhibitor class	Dimesylate salt compositions and ocular treatment
Claim breadth	Potentially broader chemical genus and compound claims	More specific salt, stereoisomer, formulation, and use claims
Product relevance	Core molecule and chemical platform	Commercial dimesylate product and ocular administration
Design-around path	Alternative compounds or nonclaimed structures	Alternative salt, formulation, or noninfringing use
Commercial role	Foundational compound protection	Product-specific formulation and method protection

A generic developer must assess both patents separately. Avoiding US 9,931,336 by using a different salt would not necessarily avoid US 8,410,169. Conversely, a product that uses netarsudil dimesylate may face US 9,931,336 even if the underlying compound patent has expired or is found invalid.

Which companies own or commercialize the patent estate?

Aerie Pharmaceuticals developed netarsudil and held the original patent portfolio. Alcon acquired Aerie in 2019 and became the commercial owner of the Rhopressa and Rocklatan franchise, subject to the transaction’s asset and license terms [5].

Company	Role
Aerie Pharmaceuticals	Original developer, applicant, and patent owner
Alcon	Current commercial sponsor and owner of the Aerie ophthalmic franchise
FDA	Regulator of Rhopressa and Rocklatan approvals
Generic applicants	Potential ANDA sponsors subject to Orange Book certifications

The commercial patent estate may include continuation patents, formulation patents, combination-product patents, and later-issued patents beyond US 9,931,336. A freedom-to-operate review should not treat this patent as the complete netarsudil estate.

Are there Paragraph IV challenges or generic litigation?

A Paragraph IV challenge would require an ANDA applicant to certify that a listed patent is invalid, unenforceable, or not infringed. The applicant must generally provide notice to the NDA holder and patent owner. The notice can trigger patent litigation under the Hatch-Waxman Act and may create a statutory stay of FDA approval for up to 30 months, subject to statutory exceptions.

For US 9,931,336, the relevant risk indicators are:

• whether the current Orange Book lists the patent for Rhopressa or Rocklatan;
• whether an ANDA applicant has submitted a Paragraph IV certification;
• whether Alcon or another patent owner filed a district-court action within the statutory notice period;
• whether a settlement agreement delays generic entry; and
• whether FDA has approved a generic netarsudil product.

No conclusion about validity or enforceability follows from the patent’s listing alone. Publicly available FDA and patent records should be checked against the current Orange Book and federal court dockets for any later Paragraph IV filing, infringement action, or settlement.

The likely generic entry paths are:

1. approval after patent expiration;
2. an agreed entry date under a settlement;
3. approval after a court decision or dismissal;
4. a product that avoids the listed claims; or
5. an authorized generic or other commercial arrangement.

What generic entry risks exist for Rhopressa and Rocklatan?

The principal generic risks differ by product.

Rhopressa

A generic Rhopressa would likely need to address:

• netarsudil dimesylate composition claims;
• formulation claims;
• ocular-use method claims;
• any remaining core compound claims;
• FDA bioequivalence requirements; and
• potential Paragraph IV litigation.

Because the patent claims do not specify a narrow concentration or a single excipient recipe, a conventional generic eye drop may have limited formulation-based design-around options.

Rocklatan

Rocklatan presents an additional combination-product layer. A generic competitor may need to address patents directed to:

• netarsudil and its dimesylate salt;
• latanoprost;
• the netarsudil-latanoprost combination;
• dosing schedules;
• formulation stability; and
• the approved combination indication.

A company seeking to launch a generic netarsudil product would not automatically obtain freedom to market a netarsudil-latanoprost combination.

How strong is the patent estate for netarsudil?

US 9,931,336 is commercially meaningful but not independently comprehensive.

Strengths

• It covers the commercially relevant dimesylate salt.
• It separately covers the S stereoisomer and racemate.
• It combines composition and ocular-treatment claims.
• It does not require a narrow formulation recipe.
• It reaches topical ocular use through dependent claims.
• It can remain relevant after a generic has addressed the core compound patent.

Limitations

• The claims are directed to specified dimesylate salts rather than every netarsudil chemical form.
• The listed claims do not expressly claim every polymorph, solvate, hydrate, or solid-state form.
• Method claims depend on the accused use and, in some cases, the product labeling.
• The patent does not by itself cover latanoprost combination products unless another claim or patent supplies that coverage.
• Claim validity depends on written description, enablement, novelty, obviousness, and other defenses.

The estate is strongest when a competing product uses netarsudil dimesylate in a topical ophthalmic formulation for pressure reduction. It is weaker against a genuinely different salt, a nonocular use, or a product that does not practice the claimed chemical form.

What is the geographic coverage of US 9,931,336?

US 9,931,336 has enforceable scope only in the United States. Corresponding foreign applications may protect related subject matter in Europe, Japan, Canada, Australia, and other jurisdictions, but foreign claims, expiration dates, prosecution histories, and enforceability must be assessed separately.

A US patent cannot block manufacturing or sale entirely outside the United States. It can affect:

• manufacture in the United States;
• importation into the United States;
• US commercial sale;
• US clinical development;
• supply to a US affiliate; and
• certain activities directed toward US regulatory approval.

Foreign patent families may have different claim scope and may expire on different dates because of national-phase prosecution, patent-term adjustments, supplementary protection certificates, or local regulatory extensions.

What manufacturing and intellectual-property barriers affect netarsudil?

The primary manufacturing barrier is not merely synthesis of the free compound. A competing manufacturer must establish control over:

• the correct stereochemical form;
• the dimesylate salt;
• impurity profiles;
• residual solvents;
• salt stoichiometry;
• stability in the ophthalmic vehicle;
• container-closure compatibility;
• sterility or microbial control; and
• scale-up reproducibility.

The patent claims create an IP risk around the dimesylate composition itself. Separate patents or regulatory protections may create additional barriers around formulation, combination therapy, manufacturing processes, and dosage regimens.

What is the revenue exposure from US 9,931,336?

Alcon does not generally disclose Rhopressa and Rocklatan revenue as a standalone line item in the same way as a separately reported business segment. The products are part of Alcon’s pharmaceutical portfolio. Revenue exposure therefore depends on:

• the combined sales of Rhopressa and Rocklatan;
• the timing of generic entry;
• pricing erosion after generic launch;
• substitution between Rhopressa and Rocklatan;
• physician adoption of competing glaucoma therapies; and
• any settlement or authorized-generic arrangement.

The patent is most valuable before the first commercially viable generic launch. A Paragraph IV challenge can affect valuation before actual market entry because it may accelerate litigation costs, settlement negotiations, and expected price erosion.

Key Takeaways

• US 9,931,336 covers R-, S-, and racemic netarsudil dimesylate compositions.
• It covers compositions broadly and adds excipient, glaucoma, topical-administration, and intraocular-pressure claims.
• The patent is directly relevant to Rhopressa and indirectly relevant to the netarsudil component of Rocklatan.
• The nominal patent-term endpoint is in March 2034, subject to the official USPTO and FDA records.
• Changing the buffer, preservative, tonicity agent, or surfactant may not avoid the independent composition claims.
• A different salt or chemical form may avoid this patent but could remain exposed to separate compound or formulation patents.
• Generic entry requires analysis of the full Orange Book estate, not US 9,931,336 alone.
• The principal commercial risk is a generic topical ophthalmic product containing netarsudil dimesylate.

FAQs About US Patent 9,931,336

Does US 9,931,336 cover netarsudil free base?

No. The listed composition claims require a dimesylate salt. Netarsudil free base may be subject to other patents, but it is not the chemical form recited in these claims.

Can a generic avoid US 9,931,336 by using a different preservative?

Not necessarily. The independent composition claims do not require a particular preservative. Changing the preservative may leave the product within a composition claim if it still contains the claimed netarsudil dimesylate.

Does the patent cover Rocklatan as a combination product?

It can cover the netarsudil dimesylate component of a combination composition, but the listed claims do not expressly recite latanoprost. Rocklatan-specific protection must be assessed through separate combination-product and formulation patents.

Does topical administration appear in every method claim?

No. Topical ocular administration is recited in dependent claims. The broader method claims require administration of the claimed composition for ocular treatment or intraocular-pressure reduction but do not always expressly state topical administration.

What is the main design-around strategy for this patent?

The principal chemical design-around would involve avoiding the claimed dimesylate salt. Other possible strategies include a different active compound, a nonclaimed salt or form, or a use that does not practice the asserted method claims. Each strategy must be tested against the broader netarsudil patent family and FDA requirements.

References

1. U.S. Food and Drug Administration. (2017). FDA approves new treatment for glaucoma: Rhopressa (netarsudil ophthalmic solution). FDA.

2. U.S. Food and Drug Administration. (2019). Rocklatan prescribing information. FDA.

3. United States Patent and Trademark Office. (2018). U.S. Patent No. 9,931,336: Compositions and methods for treating ocular disorders. USPTO Patent Center.

4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.

5. Alcon Inc. (2019). Alcon completes acquisition of Aerie Pharmaceuticals. Alcon corporate materials.

Drugs Protected by US Patent 9,931,336

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alcon Labs Inc	RHOPRESSA	netarsudil mesylate	SOLUTION/DROPS;OPHTHALMIC	208254-001	Dec 18, 2017		RX	Yes	Yes			Y	Y		REDUCTION OF ELEVATED INTRAOCULAR PRESSURE
Alcon Labs Inc	ROCKLATAN	latanoprost; netarsudil dimesylate	SOLUTION/DROPS;OPHTHALMIC	208259-001	Mar 12, 2019		RX	Yes	Yes			Y	Y		REDUCTION OF ELEVATED INTRAOCULAR PRESSURE

International Family Members for US Patent 9,931,336

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3461484		301101	Netherlands
European Patent Office	3461484		2021C/515	Belgium
European Patent Office	3461484		132021000000068	Italy
European Patent Office	3461484		122021000036	Germany
European Patent Office	3461484		C202130024	Spain
European Patent Office	3461484		21C1024	France
European Patent Office	3461484		SPC/GB21/033	United Kingdom