Details for Patent: 11,185,538

Which drugs does patent 11,185,538 protect, and when does it expire?

Patent 11,185,538 protects RHOPRESSA and ROCKLATAN and is included in two NDAs.

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

Summary for Patent: 11,185,538

Title:	Compositions for treating glaucoma or reducing intraocular pressure
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:	US17/238,550
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,185,538
Patent Claim Types: see list of patent claims	Composition; Compound;

United States Patent 11,185,538: Netarsudil Dimesylate Formulation Claims and Patent Landscape

U.S. Patent No. 11,185,538 protects pharmaceutical compositions containing netarsudil dimesylate, the active ingredient in Rhopressa ophthalmic solution. Its strongest claims cover a narrow multidose ophthalmic formulation containing netarsudil dimesylate, boric acid, D-mannitol, benzalkonium chloride, and a pH of about 5.0. The patent does not claim netarsudil as a chemical entity or broadly claim every use of the drug.

The commercially important concentration range is approximately 0.02% to less than 0.05% w/v, which encompasses the 0.02% netarsudil ophthalmic solution strength associated with Rhopressa. The patent creates formulation-specific launch risk for an ANDA applicant, but it does not by itself prevent development of every netarsudil product.

What drug and formulation does U.S. Patent 11,185,538 cover?

The claimed active ingredient is the dimesylate salt of netarsudil, chemically identified as:

(S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimesylate.

Netarsudil is a Rho-associated coiled-coil-containing protein kinase, or ROCK, inhibitor used ophthalmically to reduce elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Rhopressa is supplied as a topical ophthalmic solution containing netarsudil dimesylate at 0.02% w/v.[1]

The claims are directed to pharmaceutical compositions rather than to the molecular structure of netarsudil itself.

Patent element	Scope in the claims
Active ingredient	Netarsudil dimesylate
Broad concentration	About 0.01% to about 1.0% w/v
Commercially relevant dependent range	At least about 0.020% to less than about 0.05% w/v
Tonicity agent	Mannitol, specifically D-mannitol in narrower claims
Buffer	Boric acid
Preservative	Benzalkonium chloride
Defined pH	About 5.0
Defined excipient amounts	About 4.7% w/v D-mannitol, about 0.05% w/v boric acid, and about 0.015% w/v benzalkonium chloride
Dosage form expressly stated	Pharmaceutical composition
Ophthalmic route expressly stated in supplied claims	No

The absence of the word “ophthalmic” in the supplied claims is legally significant. The formulation architecture strongly indicates an eye-drop product, but the literal claim language is not expressly limited to ocular administration. Claim construction would depend on the full specification, prosecution history, and the meaning of “pharmaceutical composition” in context.

How many independent claims does Patent 11,185,538 have?

The supplied claims contain three independent claims: claims 1, 19, and 21.

Claim 1: broad composition claim

Claim 1 requires:

1. netarsudil dimesylate;
2. a concentration of about 0.01% to about 1.0% w/v; and
3. at least one excipient.

This is the broadest composition claim in the set. It does not require mannitol, boric acid, benzalkonium chloride, a specific pH, or an ophthalmic route.

A competing product could fall within claim 1 even if it uses a different excipient system, provided it contains the claimed salt in the claimed concentration range and includes at least one excipient.

Claim 19: combination excipient claim

Claim 19 requires netarsudil dimesylate together with:

• boric acid;
• mannitol; and
• benzalkonium chloride.

Unlike claims 5, 8, 11, 14, 17, and 21, claim 19 does not specify amounts for the three excipients. It therefore reaches a broader range of formulations than claim 21, subject to the concentration range for netarsudil.

Claim 21: commercial-formulation claim

Claim 21 is the narrowest independent claim and requires all of the following:

• netarsudil dimesylate at about 0.01% to about 1.0% w/v;
• about 0.05% w/v boric acid;
• about 4.7% w/v D-mannitol;
• about 0.015% w/v benzalkonium chloride; and
• a pH of about 5.0.

This claim is directed to a highly specific formulation. Its infringement analysis will turn on the interpretation of “about,” the measured concentrations in the finished product, and the pH specification.

What formulations are protected by the dependent claims?

The dependent claims progressively narrow the formulation.

Claims	Additional limitation	Commercial significance
2-5	Tonicity agent is mannitol, specifically D-mannitol at about 4.7% w/v	Captures the principal tonicity system
6-8	Boric acid buffer at about 0.05% w/v and pH about 5.0	Adds the defined buffering system
12-14	Benzalkonium chloride at about 0.015% w/v	Adds the multidose preservative
9-11	Boric acid and pH about 5.0 to the D-mannitol branch	Links tonicity and buffering limitations
15-17	Benzalkonium chloride to the boric-acid/D-mannitol branch	Approaches the full commercial formulation
18	Netarsudil dimesylate from at least about 0.020% to less than about 0.05% w/v	Targets the 0.02% commercial strength
20	Claim 19 plus the 0.020% to less than 0.05% range	Narrows the combination excipient claim
22	Claim 21 plus the 0.020% to less than 0.05% range	Closest claim to the commercial product

Claims 21 and 22 are particularly important because they combine the exact excipient system with the commercially relevant drug concentration. Claim 22 requires the 0.020% to less than 0.05% active range, while claim 21 permits a much wider active concentration range.

Does Patent 11,185,538 cover Rhopressa?

The supplied claims appear to read directly on the core formulation of Rhopressa if the marketed product contains the claimed ingredients and concentrations. The FDA-approved Rhopressa labeling identifies netarsudil ophthalmic solution as 0.02% and identifies inactive ingredients that include boric acid, mannitol, and benzalkonium chloride.[1]

A product-by-product infringement analysis would compare the approved or proposed formulation against:

• netarsudil salt identity;
• netarsudil concentration;
• mannitol identity and concentration;
• boric acid concentration;
• benzalkonium chloride concentration;
• finished-product pH; and
• any formulation changes made by the applicant.

The claims use approximate numerical language. “About 4.7%,” “about 0.05%,” “about 0.015%,” and “about 5.0” may cover manufacturing tolerances or an evidentiary range broader than the stated nominal value. The specification and prosecution history would be important in defining those boundaries.

When does U.S. Patent 11,185,538 lose exclusivity?

The patent issued on November 30, 2021. Its effective expiration date depends on the earliest applicable nonprovisional priority or filing date, patent-term adjustment, terminal disclaimers, and any patent-term extension. Based on the reported family chronology, the ordinary 20-year term is expected to run into approximately 2036, before any patent-term adjustment.

Event	Date or status
Patent issued	November 30, 2021
Patent type	Utility patent
Patent term framework	20 years from the applicable earliest nonprovisional filing date
Expected ordinary term endpoint	Approximately 2036, subject to USPTO term calculation
Patent-term adjustment	Must be confirmed from the issued patent and USPTO records
Patent-term extension under 35 U.S.C. § 156	No extension is established by the supplied information
Regulatory exclusivity	Separate from patent protection

Patent expiration does not necessarily equal the end of all netarsudil exclusivity. Other patents may cover the active ingredient, methods of treatment, salts, polymorphs, manufacturing processes, or alternative formulations. FDA regulatory exclusivity also operates independently of patent term.[2][3]

What is the Orange Book status of Patent 11,185,538?

A patent is relevant to an ANDA only if it is listed for the reference drug or otherwise creates an applicable patent dispute. The FDA Orange Book identifies patents submitted by an NDA holder for approved products, together with use codes for method-of-use patents.[2]

For a formulation patent such as U.S. Patent 11,185,538, the key Orange Book issues are:

• whether it is listed against Rhopressa;
• whether the listing is classified as a drug-substance, drug-product, or method-of-use patent;
• whether the listing includes an expiration date;
• whether the product label corresponds to the claimed formulation; and
• whether the patent has been delisted, corrected, or challenged.

The supplied claims are drug-product claims. They do not depend on a particular treatment indication. If listed against Rhopressa, they would present a formulation patent obstacle to an ANDA applicant seeking approval for a product that uses the same active concentration and excipient system.

What Paragraph IV challenges could target this patent?

An ANDA applicant could challenge Patent 11,185,538 through a Paragraph IV certification under the Hatch-Waxman Act. The principal challenge theories would be:

Noninfringement

An applicant may design around the claims by changing one or more required elements, such as:

• using a different preservative;
• eliminating benzalkonium chloride;
• replacing mannitol with another tonicity agent;
• using a different buffer;
• changing the finished-product pH;
• selecting an active concentration outside the claimed range; or
• using a non-dimesylate form, if pharmaceutically and regulatorily acceptable.

A formulation that omits one required element of claim 19 or claim 21 may avoid that claim, but claim 1 could remain relevant because it requires only an excipient.

Invalidity for anticipation or obviousness

A challenger would search earlier patents and publications for:

• netarsudil dimesylate ophthalmic solutions;
• the 0.02% concentration;
• boric acid and mannitol combinations;
• benzalkonium chloride-preserved eye drops;
• a pH near 5.0; and
• stability or solubility data for netarsudil.

The narrower claims may have greater validity vulnerability if a single reference discloses the complete combination or if the claimed excipient selection is viewed as an obvious optimization. The patent holder would likely rely on formulation stability, solubility, tolerability, preservative performance, or other unexpected results.

Written description and enablement

The broad 0.01% to 1.0% concentration range could receive greater scrutiny than the narrow commercial range. A challenger could argue that the specification does not adequately support the full range or enable every composition within it. The strength of that defense depends on the examples and disclosure across the full range.

Which companies are challenging Rhopressa or netarsudil patents?

The principal generic-entry pathway is an ANDA for netarsudil ophthalmic solution. Generic applicants may submit Paragraph IV certifications against listed Rhopressa patents and may face patent litigation under 21 U.S.C. § 355(j)(5)(B)(iii).

The supplied patent number alone does not establish:

• the identity of any current ANDA applicant;
• the date of a Paragraph IV notice;
• the existence of a district-court case;
• the status of any appeal;
• a settlement agreement; or
• an authorized generic arrangement.

Those facts must be established from FDA Orange Book records, FDA Paragraph IV notices, PACER litigation records, and relevant docket filings. A patent-family analysis should distinguish between challenges to the active ingredient patents and challenges to formulation patents. A dismissal or settlement involving one patent does not necessarily remove the remaining estate.

How strong is the patent estate for netarsudil?

The patent strength assessment is claim-specific.

Estate segment	Protection type	Strategic value
Core molecule	Composition-of-matter claims	Usually the strongest barrier if unexpired and valid
Netarsudil salt	Salt or solid-state claims	Can restrict alternative active forms
Ophthalmic formulation	Excipient, concentration, pH, and stability claims	Directly relevant to ANDA product design
Method of treatment	Reduction of intraocular pressure or glaucoma treatment	Relevant if listed with a use code
Manufacturing	Synthetic intermediates, processes, purification	Can restrict supply chains but may be difficult to assert against finished-product applicants
Commercial product	Formulation claims such as Patent 11,185,538	Strongest where the proposed generic copies the reference formulation

Patent 11,185,538 has a mixed profile. Claim 1 is broad in excipient selection but limited to a netarsudil concentration range. Claim 21 is narrow and easier to map to a commercial product, but it has more individual limitations that a challenger can avoid or attack. Claims 18, 20, and 22 increase relevance to a 0.02% product while reducing coverage of higher or lower strengths.

Are biosimilar risks relevant to netarsudil?

No. Netarsudil is a chemically synthesized small-molecule drug, not a biologic. Competitive products would generally use the ANDA pathway rather than the abbreviated pathway for biosimilars under the Public Health Service Act.

The principal regulatory risks are therefore:

• ANDA approval;
• Paragraph IV litigation;
• formulation design-around;
• therapeutic-equivalence requirements; and
• possible authorized-generic competition.

A generic applicant does not need to reproduce every inactive ingredient, but it must satisfy FDA requirements for pharmaceutical equivalence, bioequivalence, quality, and product performance.[3]

What generic launch scenarios exist?

Scenario 1: Same formulation

A generic applicant uses 0.02% netarsudil dimesylate with boric acid, mannitol, benzalkonium chloride, and a pH near 5.0. This creates the highest direct infringement risk under claims 19, 21, and 22, subject to claim construction and the Orange Book listing.

Scenario 2: Preservative or buffer design-around

The applicant changes benzalkonium chloride or boric acid. This may avoid claims requiring those ingredients, but claim 1 could remain relevant because it requires only one excipient.

Scenario 3: Tonicity-agent design-around

The applicant replaces mannitol with another tonicity agent. Claims 2-5, 9-11, 19-22 may become less relevant, while claim 1 remains a potential obstacle.

Scenario 4: Concentration design-around

A strength below 0.020% or at least 0.05% may avoid claims 18, 20, and 22. It could still fall within claim 1 or claim 19, which use the broader 0.01% to 1.0% range.

Scenario 5: Post-expiration launch

The applicant delays commercial launch until the relevant formulation and core-product patents expire or are otherwise removed as barriers. This minimizes litigation risk but sacrifices market-entry time.

What geographic coverage does the patent provide?

U.S. Patent 11,185,538 provides protection only in the United States. It does not automatically protect the formulation in Canada, Europe, Japan, China, or other jurisdictions.

International protection would require separate national or regional patents claiming the same formulation or related subject matter. A complete freedom-to-operate review should map the patent family across:

• United States;
• European Patent Office member states;
• Canada;
• Japan;
• China;
• Australia; and
• other markets where netarsudil products are commercialized.

Patent term, prosecution history, claim scope, and enforceability can differ by jurisdiction.

Key Takeaways

• U.S. Patent 11,185,538 is a netarsudil dimesylate formulation patent.
• The broadest supplied claim covers 0.01% to 1.0% w/v netarsudil dimesylate with at least one excipient.
• The most commercially important claims cover approximately 0.02% netarsudil with boric acid, D-mannitol, benzalkonium chloride, and pH about 5.0.
• Claim 21 is the principal exact-formulation claim; claim 22 narrows it to the commercial-strength range.
• The patent does not claim netarsudil’s chemical structure as such.
• An ANDA applicant can pursue noninfringement through excipient, pH, preservative, tonicity-agent, or concentration changes.
• Netarsudil is a small molecule, so generic rather than biosimilar competition is expected.
• The patent issued November 30, 2021, with an ordinary term expected to extend into approximately 2036, subject to the official USPTO term calculation.
• Orange Book listing, Paragraph IV activity, litigation, and settlement status must be evaluated across the entire Rhopressa patent estate, not from Patent 11,185,538 alone.

FAQs About U.S. Patent 11,185,538

Does Patent 11,185,538 cover all netarsudil eye drops?

No. It covers compositions meeting the stated active-ingredient, concentration, and excipient limitations. A netarsudil product outside those limitations may avoid some or all claims, although other patents may apply.

Can a generic use a different preservative?

Potentially. A different preservative may avoid claims requiring benzalkonium chloride, but the generic must still evaluate claim 1 and any other active-ingredient, formulation, or method patents.

Is a 0.02% netarsudil product automatically infringing?

No. The concentration alone is insufficient. Infringement depends on the full formulation and whether the product contains the claimed active salt, excipients, amounts, and pH.

Does this patent protect a netarsudil manufacturing process?

The supplied claims do not. They are composition claims. Manufacturing protection would require separate process, intermediate, or purification claims.

What is the primary legal risk for an ANDA applicant?

The primary risk is a Paragraph IV patent dispute if the proposed generic matches the claimed netarsudil formulation and the patent is listed against the reference product. The risk depends on the patent’s listing status, remaining term, validity, claim construction, and the applicant’s formulation design.

References

1. U.S. Food and Drug Administration. (2017). Rhopressa (netarsudil ophthalmic solution) prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations [Orange Book].
3. U.S. Code, 21 U.S.C. § 355. Abbreviated new drug applications and patent certifications.
4. U.S. Code, 35 U.S.C. §§ 154, 156. Patent term and patent-term extension.
5. United States Patent and Trademark Office. (2021). U.S. Patent No. 11,185,538.

Drugs Protected by US Patent 11,185,538

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
Alcon Labs Inc	ROCKLATAN	latanoprost; netarsudil dimesylate	SOLUTION/DROPS;OPHTHALMIC	208259-001	Mar 12, 2019		RX	Yes	Yes			Y

International Family Members for US Patent 11,185,538

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