Details for Patent: 10,588,901

Which drugs does patent 10,588,901 protect, and when does it expire?

Patent 10,588,901 protects RHOPRESSA and ROCKLATAN and is included in two NDAs.

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

Summary for Patent: 10,588,901

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:	US15/970,635
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,588,901
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 10,588,901: Netarsudil Dimesylate Claims, Exclusivity, Litigation Risk and Patent Landscape

U.S. Patent No. 10,588,901 covers netarsudil dimesylate in three principal forms: as a standalone active compound, as a composition, and as a pharmaceutical composition containing an excipient. It also covers treatment of glaucoma, ocular hypertension, dry eye, neurodegenerative eye disease and reduction of intraocular pressure.

The patent is directed to the active ingredient in Rhopressa, netarsudil ophthalmic solution, and is also relevant to Rocklatan, the fixed combination of netarsudil and latanoprost. The strongest commercial claims are claims 2, 9 and 16, which specifically identify netarsudil dimesylate. Claims 3-8, 10-15 and 17-22 create method-of-use coverage around those formulations.

What drug does U.S. Patent 10,588,901 protect?

The specific compound in claims 2, 9 and 16 is netarsudil dimesylate, also known as netarsudil mesylate or AR-13324 dimesylate. Netarsudil is a Rho-associated coiled-coil-containing protein kinase, or ROCK, inhibitor used in ophthalmic therapy.

FDA approved Rhopressa, netarsudil ophthalmic solution 0.02%, for reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. FDA later approved Rocklatan, a fixed-dose combination of netarsudil and latanoprost, for the same broad pressure-lowering indication.[2][3]

Item	Description
Active ingredient	Netarsudil dimesylate
Development code	AR-13324
Drug class	ROCK inhibitor
Dosage form	Topical ophthalmic solution
Rhopressa strength	Netarsudil ophthalmic solution 0.02%
Rocklatan strength	Netarsudil 0.02% plus latanoprost 0.005%
Primary therapeutic use	Reduction of elevated intraocular pressure
Patent at issue	U.S. Patent No. 10,588,901
Patent grant date	March 10, 2020
Original developer	Aerie Pharmaceuticals
Current commercial rights context	Aerie was acquired by Alcon in 2022

How are the claims of U.S. Patent 10,588,901 structured?

The patent has four functional claim groups.

Claim 1: Broad combination composition claim

Claim 1 covers a composition containing:

1. A dimesylate salt of a compound within a broad formula I genus; and
2. A prostaglandin or prostaglandin analog.

The formula I language is expansive. It allows multiple linkers, substituents, heterocycles, aryl groups, alkyl groups and salt-forming amine structures. The second component is also broad because it includes any compound with a prostanoic acid skeleton and a separately defined prostaglandin analog genus.

The practical significance is that claim 1 is directed to combination therapy rather than netarsudil alone. It is potentially relevant to Rocklatan because latanoprost is a prostaglandin analog. The claim may also reach combinations involving other prostaglandins, depending on the construction of the formula and the applicable written-description and enablement analysis.

Claim 1 is materially broader than claims 2, 9 and 16. Its scope depends on whether the accused compound falls within formula I and whether the second active ingredient satisfies the prostaglandin or prostaglandin-analog limitation.

Claim 2: Specific netarsudil dimesylate compound claim

Claim 2 identifies the active compound by chemical name:

“4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate” in the dimesylate salt form.

This is the principal composition-of-matter claim for the specific salt identified in the patent. It does not require a prostaglandin, excipient, dosage form or particular therapeutic use.

A product containing the same dimesylate salt would face the clearest literal infringement risk under claim 2, subject to claim construction, salt-form characterization, product composition and validity defenses.

Claims 3-8: Methods using the compound of claim 2

These claims cover administering the claim 2 compound to treat:

• An ocular disorder;
• Glaucoma;
• A neurodegenerative eye disease;
• Dry eye;
• Ocular hypertension; or
• Elevated intraocular pressure.

The method claims do not require a particular concentration, dosing frequency, delivery device or ophthalmic formulation. The central limitations are administration of the specified compound and the claimed therapeutic purpose.

Claims 9-15: Composition and treatment claims

Claim 9 recites a composition containing netarsudil dimesylate. Claims 10-15 cover treatment of the same ocular indications using that composition.

These claims overlap commercially with claim 2 and the method claims but differ in claim format. Claim 9 may be relevant where an accused product is characterized as a composition rather than as the isolated compound.

Claims 16-22: Pharmaceutical composition and treatment claims

Claim 16 requires netarsudil dimesylate plus a pharmaceutically acceptable excipient. Claims 17-22 cover use of that pharmaceutical composition for the same indications.

These claims are tailored to a finished drug product. They are more directly aligned with a commercial ophthalmic solution than claim 2, although claim 2 may also read on the active ingredient contained in that product.

What formulations are protected by U.S. Patent 10,588,901?

The patent does not recite a narrow formulation platform such as a specified pH, viscosity range, preservative system or particle size. Claim 16 requires only netarsudil dimesylate and a pharmaceutically acceptable excipient.

Potential excipients could include, depending on the specification and construction:

• Aqueous carriers;
• Buffers;
• Tonicity agents;
• Preservatives;
• Surfactants;
• Solubilizers;
• Chelating agents; and
• Viscosity-adjusting agents.

The broad formulation coverage creates a potential product claim against a generic ophthalmic solution containing the same salt, even if the generic uses a different buffer or preservative system. A generic manufacturer would need to assess whether its formulation falls within the claim construction of “pharmaceutical composition” and “pharmaceutically acceptable excipient.”

The claims supplied do not expressly require:

• A 0.02% concentration;
• A multidose bottle;
• A particular pH;
• Benzalkonium chloride;
• A particular dosing schedule;
• A specific viscosity; or
• A specific delivery device.

Those limitations may appear in the specification, FDA labeling or other patents, but they are not limitations of claim 16 as quoted.

How does the patent cover Rhopressa and Rocklatan?

Rhopressa

Rhopressa contains netarsudil ophthalmic solution. The most relevant claims are:

• Claim 2, directed to netarsudil dimesylate;
• Claim 9, directed to a composition containing netarsudil dimesylate;
• Claim 16, directed to a pharmaceutical composition containing netarsudil dimesylate and an excipient; and
• Claims 3-8, 10-15 and 17-22, directed to therapeutic use.

A netarsudil generic would therefore face multiple overlapping claim categories rather than a single formulation claim.

Rocklatan

Rocklatan contains netarsudil and latanoprost. The most relevant claim is claim 1 because it requires a dimesylate salt of the formula I compound together with a prostaglandin or prostaglandin analog. Latanoprost is a prostaglandin analog used in glaucoma treatment.

Rocklatan may also implicate the specific netarsudil composition and pharmaceutical-composition claims, depending on how the product is characterized and whether the claim is construed to cover the active ingredient in a combination product.

Product	Netarsudil present	Prostaglandin present	Most relevant claim categories
Rhopressa	Yes	No	Claims 2, 9, 16 and related methods
Rocklatan	Yes	Yes, latanoprost	Claim 1, plus claims 2, 9 and 16 depending on construction
Latanoprost-only product	No	Yes	Generally outside the netarsudil-specific claims
Netarsudil generic	Yes	Not required	Claims 2, 9, 16 and method claims
Netarsudil/prostaglandin generic	Yes	Yes	Claim 1 and overlapping composition claims

When does U.S. Patent 10,588,901 lose exclusivity?

The grant date is March 10, 2020, but patent expiration is determined by the patent’s priority chain, effective filing date, patent-term adjustment, terminal disclaimers and any applicable patent-term extension. The claim text alone does not establish the final enforceable expiration date.

The governing baseline is generally 20 years from the earliest effective nonprovisional filing date under 35 U.S.C. § 154, subject to patent-term adjustment and related statutory provisions.[4] FDA-approved products can also receive patent-term extension under 35 U.S.C. § 156, although the extension is product-specific and cannot be assumed from the patent grant alone.[5]

Exclusivity categories

Exclusivity type	Relevance to this patent
Patent term	Depends on priority and USPTO term calculation
FDA new chemical entity exclusivity	Rhopressa received FDA approval in 2017, but the NCE period is separate from this patent
Orphan-drug exclusivity	Not apparent from the stated indications
Pediatric exclusivity	Requires confirmation from FDA regulatory records
Reference-product exclusivity	Relevant to ANDA and 505(b)(2) timing
Patent-term extension	Requires a specific FDA and USPTO determination

FDA approval exclusivity and patent exclusivity are separate. A generic applicant may be blocked by an unexpired patent after FDA exclusivity expires, while an ANDA may be filed before patent expiration if the statutory pathway is satisfied.

What is the Orange Book status of U.S. Patent 10,588,901?

The Orange Book determines whether a patent is listed against a specific approved drug product and whether it is categorized as a drug-substance, drug-product or method-of-use patent.[6]

The patent text does not itself establish Orange Book listing status. A listing must be assessed against the relevant FDA reference listed drug, including:

• Rhopressa;
• Rocklatan;
• The approved NDA holder;
• Patent-use codes;
• Listed expiration dates; and
• Any delisting, correction or dispute history.

If listed against Rhopressa, the claims most likely to matter are the netarsudil compound, composition and method-of-use claims. If listed against Rocklatan, claim 1’s combination coverage would be particularly relevant.

Method-of-use listings can be narrower than the full patent claims because FDA patent-use codes identify the approved use covered by the listed patent. A generic applicant can attempt a section viii statement to omit a patented use where the product label can be carved out, but that strategy is more difficult when the patent claims the active compound or the finished composition itself.

What Paragraph IV challenges could target this patent?

An ANDA applicant challenging a listed patent can submit a Paragraph IV certification asserting that the patent is invalid, unenforceable or will not be infringed.[7]

For this patent, the principal challenge theories would be:

Anticipation

A challenger could argue that a prior-art reference discloses:

• The specific netarsudil dimesylate salt;
• A pharmaceutical composition containing it;
• The claimed ophthalmic use; or
• The claimed combination with a prostaglandin.

Claim 2 is most exposed to a direct anticipation challenge if an earlier publication discloses the identical salt and chemical identity.

Obviousness

Potential obviousness theories could combine:

• A known ROCK inhibitor;
• Known netarsudil free base or related salts;
• Conventional dimesylate salt formation;
• Known ophthalmic excipients; and
• Existing prostaglandin glaucoma therapy.

Salt-selection obviousness would depend on evidence concerning crystallinity, stability, solubility, manufacturability, bioavailability and unexpected properties.

Written description and enablement

Claim 1 is substantially broader than the specific compound claims. A challenger could argue that the specification does not adequately support the full genus of formula I compounds combined with the full scope of prostaglandins and prostaglandin analogs.

The neurodegenerative eye disease and dry-eye method claims may also face written-description or enablement scrutiny if the specification provides limited examples outside glaucoma and ocular hypertension.

Indefiniteness and claim construction

The broad definitions of substituted groups, optional substitution and multiple linker structures may create claim-construction disputes. The scope of “prostaglandin analog” and the relationship between formula I and the specific netarsudil structure would be central issues.

Which companies are challenging netarsudil patents?

The supplied claim text does not identify a Paragraph IV filer, ANDA applicant or litigation docket. Patent ownership and product commercialization do not establish that a particular generic company has filed a challenge.

A current competitive review should distinguish among:

1. An ANDA filing;
2. A Paragraph IV notice letter;
3. District-court litigation;
4. Inter partes review;
5. A tentative FDA approval; and
6. A final FDA approval.

Those events have different commercial consequences. A patent litigation complaint alone does not establish that a generic can launch, and a Paragraph IV certification does not invalidate the patent.

What patent litigation affects U.S. Patent 10,588,901?

The patent’s practical litigation significance depends on whether it has been asserted against an ANDA applicant and whether the patent is listed against Rhopressa or Rocklatan.

A conventional Hatch-Waxman case could produce:

• A 30-month FDA approval stay;
• Claim-construction proceedings;
• Invalidity and noninfringement defenses;
• A settlement with a deferred generic entry date;
• An authorized-generic arrangement; or
• A judgment permitting earlier launch.

The patent can also be challenged at the Patent Trial and Appeal Board through inter partes review if a challenger identifies qualifying patents or printed publications. IPR cannot be used to challenge every issue, particularly certain written-description, enablement and infringement questions.

No settlement terms can be inferred from the claim language. Any settlement would require review of the litigation docket, FTC reporting, FDA records and public company disclosures.

How strong is the patent estate for netarsudil?

The estate is commercially meaningful because the supplied patent uses overlapping claim formats:

• Compound claim;
• Composition claim;
• Pharmaceutical-composition claim;
• Treatment claims;
• Intraocular-pressure claims; and
• Combination claim with a prostaglandin.

That structure creates several enforcement routes. The compound claim is the most direct against a product containing the same salt. The pharmaceutical-composition claim is important for finished dosage forms. The method claims may provide additional protection but are more vulnerable to label carve-outs and divided-infringement arguments.

The principal weakness is breadth. Claim 1 covers a large chemical and therapeutic space, and several method claims extend beyond the core approved glaucoma use. Broad claims generally attract greater written-description, enablement and obviousness scrutiny than claims limited to the demonstrated commercial compound and indication.

What generic launch scenarios exist?

Scenario	Commercial consequence
No Paragraph IV challenge	Generic entry normally waits for patent and regulatory barriers to expire
Paragraph IV followed by litigation	Entry may be delayed by the 30-month stay and court proceedings
Successful invalidity or noninfringement decision	Potential launch before patent expiration
Settlement with licensed entry	Entry occurs on an agreed date, often with other conditions
Section viii carve-out	Possible only if the patented use can be removed from labeling
Authorized generic	Earlier competitive pricing pressure without an independent ANDA launch
505(b)(2) product	May face different patent certifications and clinical requirements

For netarsudil, a section viii strategy is less useful against claims 2, 9 and 16 because those claims are directed to the compound or composition rather than only to a particular indication. A carve-out may be more relevant to method-of-use claims if the FDA label can omit the patented use.

Does biosimilar risk apply to netarsudil?

No. Netarsudil is a chemically synthesized small molecule, not a biologic. A competing product would ordinarily proceed through the ANDA pathway under section 505(j), or potentially a 505(b)(2) pathway, rather than through the biosimilar pathway under section 351(k).

The relevant competitive risks are generic substitution, Paragraph IV litigation, formulation design-around and authorized-generic entry. Biosimilar interchangeability and Purple Book listing are not the governing issues.

What manufacturing and geographic barriers remain?

The patent covers the specified dimesylate salt and compositions containing it. A manufacturer cannot avoid the compound claims merely by changing the bottle, preservative or manufacturing site if the resulting product contains the claimed salt.

Potential design-around strategies include:

• Using a different pharmaceutically acceptable salt, if clinically and technically viable;
• Using a different solid-state form, where legally distinct and therapeutically acceptable;
• Developing a different active ingredient;
• Pursuing a noninfringing combination or label strategy; or
• Contesting the patent’s validity or claim scope.

A different salt may create regulatory, stability and bioequivalence problems. Geographic protection must be analyzed separately in each jurisdiction. A U.S. patent does not block manufacture, sale or use outside the United States unless a corresponding foreign patent exists.

Key Takeaways

• U.S. Patent 10,588,901 specifically covers netarsudil dimesylate in claims 2, 9 and 16.
• Claims 3-8, 10-15 and 17-22 cover ocular treatment and intraocular-pressure reduction.
• Claim 1 is a broad combination claim covering a formula I dimesylate salt with a prostaglandin or prostaglandin analog.
• The patent is directly relevant to Rhopressa and potentially relevant to Rocklatan.
• The claims do not require a specific 0.02% concentration, bottle, preservative, pH or dosing schedule.
• Netarsudil is a small molecule, so generic rather than biosimilar competition is expected.
• Final patent expiration cannot be calculated from the claim text alone because the priority chain, PTA, terminal disclaimers and any PTE must be confirmed.
• Paragraph IV exposure is highest for the specific compound and pharmaceutical-composition claims.
• Broad combination and method claims may face greater written-description, enablement, obviousness and label-carve-out challenges.
• The strongest commercial barrier is the overlap of compound, composition and finished-product claim formats.

FAQs

Is netarsudil dimesylate the same active ingredient as netarsudil?

Yes. Netarsudil is administered as the dimesylate salt in approved ophthalmic products. The salt form is the form expressly identified in the patent claims.

Does claim 1 cover Rhopressa alone?

Claim 1 requires a prostaglandin or prostaglandin analog in addition to the formula I dimesylate compound. Rhopressa alone is more directly implicated by claims 2, 9 and 16.

Does U.S. Patent 10,588,901 cover latanoprost by itself?

No. The claims require netarsudil or a covered formula I dimesylate compound. Latanoprost alone does not satisfy those netarsudil limitations.

Can a generic avoid the patent by using a different preservative?

Changing the preservative would not avoid claims directed to the netarsudil dimesylate compound. It may affect formulation-claim analysis only if the revised product no longer satisfies a specific limitation.

Is a dry-eye indication commercially important to the patent?

The dry-eye claims broaden the method-of-use scope beyond the core glaucoma and ocular-hypertension market. Their commercial value depends on FDA labeling, clinical development and whether an accused product is marketed for that use.

References

1. United States Patent No. 10,588,901, claims 1-22. U.S. Patent and Trademark Office. (2020, March 10).
2. U.S. Food and Drug Administration. (2017). Rhopressa (netarsudil ophthalmic solution) prescribing information.
3. U.S. Food and Drug Administration. (2019). Rocklatan (netarsudil and latanoprost ophthalmic solution) prescribing information.
4. 35 U.S.C. § 154. Patent term.
5. 35 U.S.C. § 156. Extension of patent term.
6. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
7. 21 U.S.C. § 355(j)(2)(A)(vii)(IV). Paragraph IV patent certification.

Drugs Protected by US Patent 10,588,901

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 10,588,901

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