US Patent 7,973,081: Cyclosporine Ophthalmic Emulsion Claims, Expiration, and Patent Landscape
US Patent 7,973,081 protects a narrowly defined cyclosporine oil-in-water ophthalmic emulsion. Its independent composition claim requires six specified components and concentrations: medium-chain triglycerides, cetalkonium chloride, tyloxapol, poloxamer 188, glycerol, and cyclosporine. The patent also covers selected physical properties, ophthalmic gel formulations, medicaments, and preparation of the emulsion for dry-eye treatment.
The patent is associated with the Novagali/Santen cyclosporine formulation platform used for Ikervis in Europe. It does not broadly cover every cyclosporine eye drop, every cyclosporine emulsion, or every dry-eye treatment. Infringement generally requires practice of every limitation in claim 1 or an applicable dependent claim.
Based on the 2008 US national-stage filing, the ordinary 20-year patent term runs to approximately August 2028, subject to the USPTO’s recorded patent-term adjustment. The product is not an approved US drug, so the patent does not have a current US Orange Book listing for an approved NDA.
What does US Patent 7,973,081 protect?
The patent protects a formulation architecture rather than cyclosporine as an active ingredient in the abstract.
Independent composition claim
Claim 1 requires an oil-in-water emulsion containing:
| Required component |
Claimed concentration or requirement |
| Medium-chain triglycerides |
2% w/w |
| Cetalkonium chloride |
0.005% w/w |
| Tyloxapol |
0.3% w/w |
| Poloxamer 188 |
0.1% w/w |
| Glycerol |
2.25% w/w |
| Cyclosporine |
Present, concentration not specified in claim 1 |
| Emulsion type |
Oil-in-water |
The concentration limitations are material. A competing product containing the same excipients at materially different concentrations may fall outside the literal scope of claim 1, although prosecution history, equivalents, and additional claims in related family members could affect the analysis.
Claim 1 does not expressly require:
- A particular cyclosporine concentration
- A particular dosage volume
- A particular preservative system beyond the listed ingredients
- A particular buffer
- Mannitol
- A gel
- A positive zeta potential
- A 100-to-500 nanometer droplet size
- Hypotonicity
- A specific indication
Those characteristics appear in dependent claims or the specification.
How do the dependent claims narrow the patent scope?
Claims 2 through 9 add formulation, physical-property, dosage-form, and manufacturing limitations.
| Claim |
Added limitation |
Scope effect |
| 2 |
Buffering agents and/or at least one tonicity agent |
Covers formulations incorporating one or both categories |
| 3 |
Mannitol as the tonicity agent |
Narrows claim 2 to mannitol-containing compositions |
| 4 |
Positive zeta potential |
Requires a positively charged dispersed system |
| 5 |
Droplet size of 100 to 500 nm |
Requires nanoscale droplets within the specified range |
| 6 |
Hypotonic relative to normal tears |
Adds an osmolality relationship |
| 7 |
Gel suitable for ophthalmic use |
Requires a gel dosage form |
| 8 |
Medicament comprising the claim 1 emulsion |
Extends composition coverage to a medicament containing it |
| 9 |
Preparing an ophthalmic dry-eye composition in gel form |
Covers a preparation method with the claim 1 composition and gel format |
A product that satisfies claim 1 but lacks mannitol, for example, can still infringe claim 1. It would not satisfy claim 3. A product with claim 1’s ingredients and concentrations but with a droplet size outside 100 to 500 nm may still fall within claim 1 while avoiding claim 5.
What is the strongest practical claim in US Patent 7,973,081?
Claim 1 is the principal commercial claim because it does not require the additional physical or dosage-form limitations found in claims 2 through 7. Its vulnerability is also clear: it contains six detailed formulation limitations.
A competitor could potentially design around claim 1 by changing one or more of the following:
- Medium-chain triglyceride concentration
- Cetalkonium chloride concentration
- Tyloxapol concentration
- Poloxamer 188 concentration
- Glycerol concentration
- Oil phase composition
- Emulsion architecture
The risk is higher when the competing formulation uses the same excipient combination at substantially similar levels. Courts may examine whether the substituted concentrations are legally equivalent, depending on prosecution history and the technical function of each limitation.
Claim 5 may be commercially important because it captures a defined droplet-size range. It is narrower than claim 1 but can be useful against a product that deliberately matches the patented nanoscale dispersion.
Claim 7 and claim 9 are narrower and focus on gel formulations. They do not cover a conventional liquid ophthalmic emulsion unless the product meets the gel limitation.
Is the patent limited to dry-eye treatment?
No. Claim 1 is a composition claim and does not require a dry-eye indication. Claim 9 expressly concerns preparation of an ophthalmic composition for dry-eye treatment, but it is a separate method claim.
The specification and claim set support ophthalmic use, but a composition claim may be implicated by making, using, selling, or offering the claimed formulation even when the product is marketed for a different ophthalmic indication. Product labeling is relevant to induced-infringement analysis, but it does not redefine the literal scope of claim 1.
What cyclosporine products are closest to the patented formulation?
The closest commercial reference is Ikervis, a cyclosporine 0.1% ophthalmic emulsion developed by Novagali and commercialized by Santen outside the United States. Ikervis is authorized in the European Union for severe keratitis in adults with dry eye disease that has not improved with artificial tears.[2]
US products using cyclosporine or other dry-eye technologies have materially different formulation platforms.
| Product |
Active ingredient |
Formulation platform |
Relationship to US 7,973,081 |
| Ikervis |
Cyclosporine 0.1% |
Oil-in-water ophthalmic emulsion |
Closest commercial product |
| Restasis |
Cyclosporine 0.05% |
Ophthalmic emulsion |
Cyclosporine product, but not established as the same claimed formulation |
| Cequa |
Cyclosporine 0.09% |
Nanomicellar ophthalmic solution |
Different delivery architecture |
| Vevye |
Cyclosporine 0.1% |
Water-free semifluorinated alkane solution |
Different vehicle and formulation platform |
| Xiidra |
Lifitegrast 5% |
Aqueous ophthalmic solution |
Different active ingredient and formulation |
The presence of cyclosporine alone does not create infringement. Restasis, Cequa, and Vevye must be assessed against each required ingredient and concentration in claim 1. A formulation lacking cetalkonium chloride, tyloxapol, or the specified glycerol concentration would not literally satisfy the claim as written.
What is the patent expiration date?
The patent issued July 5, 2011. Its US application was filed through the national-stage process from an international application filed in 2008. The ordinary 20-year term is approximately August 19, 2028, calculated from the relevant US/PCT filing date, before any patent-term adjustment.
The operative expiration date should be taken from the USPTO patent-term record because patent-term adjustment can change the calculated date. A continuation, divisional, reissue, or related family patent may have a different expiration date. US 7,973,081 should therefore be treated as a patent with protection extending into 2028 rather than as a patent expiring on its issue date or on the European product’s approval date.[1]
Maintenance fees
A patent issued from a nonprovisional application remains enforceable only if required maintenance fees are paid or a statutory reinstatement applies. The relevant maintenance-fee events occur at approximately 3.5, 7.5, and 11.5 years after issue. The USPTO maintenance-fee record controls whether the patent remained continuously enforceable.
What is the Orange Book status of US Patent 7,973,081?
US 7,973,081 does not have a current Orange Book role comparable to patents listed for Restasis, Cequa, or Vevye because the patented Ikervis formulation is not approved under a US NDA.
The Orange Book lists patents submitted by sponsors for approved drug products. A patent may be technically relevant to a formulation without appearing in the Orange Book. Conversely, an Orange Book listing applies to the approved NDA product and does not automatically establish infringement.
For US 7,973,081, the practical status is:
| Regulatory issue |
Assessment |
| US-approved product directly corresponding to Ikervis |
No |
| Current Orange Book listing for the patented formulation |
None identified |
| ANDA Paragraph IV exposure tied to this patent |
No ordinary Orange Book Paragraph IV pathway |
| 505(b)(2) relevance |
Possible for a future applicant using a related formulation |
| European regulatory relevance |
High for Ikervis outside the United States |
Have generic companies challenged US Patent 7,973,081 under Paragraph IV?
No ordinary Paragraph IV challenge is expected against this patent absent a US reference listed drug and an Orange Book listing tied to the patented product.
Paragraph IV certifications are generally made in an ANDA addressing patents listed for a reference listed drug. Because the formulation associated with US 7,973,081 is not a US-approved reference product, a generic applicant would more likely pursue:
- A 505(b)(2) application
- A new drug application
- A different cyclosporine formulation
- A non-infringement or invalidity position in commercial development
A future applicant could still face patent litigation under 35 U.S.C. § 271(e)(2) if a related patent were listed against an approved product, but US 7,973,081 itself does not create the standard Restasis-style ANDA dispute on the present regulatory record.
What patent litigation affects US 7,973,081?
There is no prominent US infringement litigation associated with this patent comparable to the major Restasis generic litigation. The more relevant legal risks are formulation-based:
- A product matching the six limitations of claim 1 could face direct infringement allegations.
- A product using a different excipient concentration may require an equivalents analysis.
- A gel product may face additional exposure under claims 7 and 9.
- A product matching the 100-to-500 nanometer range could face claim 5 exposure.
- Manufacturing, importing, or supplying a matching formulation before expiration could create US infringement risk even if the product is not yet commercially launched.
Related patents in the Novagali/Santen family must be reviewed separately. Family members can contain different claims, priority dates, prosecution amendments, and expiration characteristics.
How strong is the patent estate around the formulation?
US 7,973,081 has moderate formulation-claim strength but limited breadth.
Strengths
- Claim 1 identifies a precise combination of excipients and concentrations.
- The composition claim does not require a particular indication.
- Dependent claims capture useful physical attributes, including positive zeta potential and nanoscale droplets.
- The formulation resembles the commercial Ikervis platform, improving product-to-claim relevance.
- The patent term extends beyond the original Restasis patent term.
Weaknesses
- Claim 1 is compositionally narrow.
- A competitor may design around individual concentrations or excipients.
- Cyclosporine is not claimed by itself.
- The patent does not broadly cover nanomicellar or water-free cyclosporine systems.
- The absence of a US-approved corresponding product limits Orange Book leverage.
- Claim 9 is limited to preparation in gel form and is not a general method-of-treatment claim.
The strongest enforcement position would involve a product whose analytical profile matches the claimed excipient concentrations, oil-in-water structure, and cyclosporine content. A product using the same therapeutic ingredient but a different vehicle would present a materially lower literal-infringement risk.
What manufacturing and intellectual-property barriers remain?
The formulation uses common pharmaceutical excipients, so individual-ingredient availability is unlikely to create a durable manufacturing barrier. The technical barrier is process control.
A competing manufacturer would need to establish:
- Stable oil-droplet size
- Reproducible positive or neutral surface charge
- Uniform cyclosporine distribution
- Sterility and preservative performance
- Ophthalmic tolerability
- Physical stability during storage
- Consistent osmolality and pH
- Commercial-scale emulsion manufacture
The presence of common excipients does not eliminate process know-how risk. Related patents, trade secrets, manufacturing methods, analytical specifications, and regulatory data could remain relevant after the composition patent expires.
How does US 7,973,081 compare with competing cyclosporine patent estates?
| Patent estate or product |
Core technology |
Main competitive distinction |
| US 7,973,081 / Ikervis platform |
Cyclosporine oil-in-water emulsion |
Defined excipient combination and physical properties |
| Restasis estate |
Cyclosporine ophthalmic emulsion |
Earlier US product and historical Orange Book litigation |
| Cequa estate |
Cyclosporine nanomicellar solution |
Different nanoscale delivery system |
| Vevye estate |
Cyclosporine in semifluorinated alkane |
Water-free vehicle |
| Lifitegrast estate |
Lifitegrast ophthalmic solution |
Different mechanism and active ingredient |
The patent is most relevant to an Ikervis-type emulsion. It is less relevant to products that rely on micelles, semifluorinated alkanes, liposomes, suspensions, or non-cyclosporine anti-inflammatory agents.
What commercial exposure does the patent create?
The direct US revenue exposure is limited because there is no approved US product corresponding to Ikervis. The larger commercial importance is strategic:
- It can constrain a US entrant seeking to reproduce the Ikervis formulation.
- It can protect international commercialization of the corresponding emulsion platform.
- It may increase the value of formulation know-how and related family patents.
- It does not materially block all US cyclosporine competition.
- It does not prevent development of Cequa-type, Vevye-type, or other nonmatching delivery systems.
For a potential US entrant, the principal launch scenarios are:
| Launch scenario |
Patent risk |
| Exact Ikervis-like composition |
High until patent expiration |
| Same excipients with materially different concentrations |
Moderate; requires claim construction and equivalents analysis |
| Cyclosporine nanomicellar solution |
Lower under this patent |
| Cyclosporine semifluorinated alkane solution |
Low under this patent |
| Non-cyclosporine dry-eye therapy |
No direct claim 1 exposure |
| Gel matching claim 1 |
Higher due to claims 7 and 9 |
Key Takeaways
- US 7,973,081 is a narrow but commercially relevant cyclosporine ophthalmic formulation patent.
- Claim 1 requires a specific oil-in-water emulsion with six mandatory formulation elements and concentrations.
- The patent does not broadly cover cyclosporine eye drops or all dry-eye treatments.
- Claims 4 and 5 add positive zeta potential and 100-to-500 nanometer droplet size limitations.
- Claims 7 and 9 target ophthalmic gel formulations and their preparation.
- The patent’s ordinary US term runs to approximately August 2028, subject to USPTO patent-term adjustment.
- The patent does not currently provide a conventional Orange Book Paragraph IV platform because the corresponding Ikervis formulation is not US approved.
- Cequa and Vevye use materially different formulation technologies and are not automatically within the claim scope.
- The primary design-around options involve changing excipient identity, concentration, vehicle architecture, or physical properties.
- Related Novagali/Santen family patents and manufacturing know-how may create additional barriers beyond US 7,973,081.
FAQs About US Patent 7,973,081
Does US 7,973,081 cover Restasis?
Not automatically. Restasis contains cyclosporine in an ophthalmic emulsion, but infringement requires the claimed combination and concentrations, including medium-chain triglycerides, cetalkonium chloride, tyloxapol, poloxamer 188, and glycerol at the stated levels.
Does the patent cover cyclosporine 0.1% eye drops?
Only if the product also satisfies the required oil-in-water and excipient limitations of claim 1 or an applicable dependent claim. The 0.1% cyclosporine concentration alone is insufficient.
Can a competitor avoid the patent by removing cetalkonium chloride?
Removing cetalkonium chloride would prevent literal satisfaction of claim 1. The remaining risk would depend on the patent’s prosecution history, claim construction, and any equivalents theory.
Is US 7,973,081 relevant to biosimilar approval?
No conventional biosimilar pathway applies because cyclosporine is a small-molecule drug, not a biologic. A competing product would generally use an ANDA, 505(b)(2), or NDA pathway depending on its formulation and reference product.
What geographic markets are most affected?
The patent directly affects US activities until its US term ends. The corresponding international family members may affect Europe and other markets where Ikervis is commercialized, but each jurisdiction requires separate validity, scope, and expiration analysis.
References
-
United States Patent No. 7,973,081, “Ophthalmic compositions comprising cyclosporine,” issued July 5, 2011, United States Patent and Trademark Office.
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European Medicines Agency. (2015). Ikervis: EPAR - product information. https://www.ema.europa.eu/
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
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U.S. Food and Drug Administration. (2002). Restasis prescribing information. Allergan, Inc.
-
U.S. Food and Drug Administration. (2018). Cequa prescribing information. Sun Pharmaceutical Industries, Inc.
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U.S. Food and Drug Administration. (2023). Vevye prescribing information. Novaliq GmbH.
