US Patent 10,124,000: Claim Scope, Exclusivity, Litigation Risk and LFA-1 Patent Landscape

US Patent 10,124,000 protects topical treatment methods using broad classes of LFA-1 antagonists for inflammatory and immune-related disorders. Its strongest commercial relevance is to topical ophthalmic and dermatologic products containing lifitegrast or structurally related LFA-1 inhibitors. The patent does not claim a specific marketed product in claim 1. It claims a treatment method, a formulation route, and a very broad chemical genus.

The patent’s practical value depends on four issues: whether an accused product contains a compound within the Formula I genus, whether the product is administered topically for a listed disorder, whether the relevant patent term remains in force, and whether narrower composition, formulation, or method-of-use patents provide later protection.

What does US Patent 10,124,000 claim?

The independent claim requires all of the following:

A method of treating an inflammatory or immune-related disorder.
A subject in need of treatment.
Topical administration.
A formulation containing:
- an LFA-1 antagonist; and
- a pharmaceutically acceptable excipient.
The antagonist must be a compound of Formula I, or its pharmaceutically acceptable salt or ester.
The disorder must fall within the enumerated disease group.

The listed disorders are:

psoriasis;
inflammatory bowel disease;
adult respiratory distress syndrome;
dermatitis;
meningitis;
uveitis;
eczema;
asthma;
poison ivy;
poison oak;
Sjogren's syndrome;
pulmonary fibrosis; and
rheumatoid arthritis.

The claim therefore combines a broad chemical genus with a restricted delivery route and disease list.

What chemical structures are covered?

Formula I uses a large Markush definition. It permits broad substitution at R1, R2, R3 and R4, including:

alkyl and substituted alkyl groups;
cyclic and heterocyclic groups;
aryl and heteroaryl groups;
oxygen-, sulfur- and nitrogen-containing linkers;
amides, carbamates, ureas and sulfonamides;
phosphonate and phosphate-related groups;
halogens;
nitriles;
hydroxyl, amino and ether substituents; and
fused or linked alicyclic, heteroalicyclic, aryl and heteroaryl systems.

The claim also allows R1 and R2 to form a ring together. That substantially expands the covered chemical space beyond individually substituted acyclic compounds.

The structural definition is constrained by the scaffold represented by Formula I, including:

a ring system in which D is nitrogen;
A, B and E connected by single bonds;
an aryl, heteroaryl, alkylaryl, alkylheteroaryl, alicyclic or heterocyclic AR1 group;
a variable linker L; and
a carboxylate, aldehyde, hydroxymethyl, amide or halomethyl R3 substituent.

The result is a genus claim rather than a simple claim to one active ingredient.

Does the patent cover lifitegrast and Xiidra?

Is lifitegrast the principal commercial compound?

The commercial relevance is lifitegrast, the active ingredient in Xiidra. Lifitegrast is a small-molecule LFA-1 antagonist that inhibits the interaction between LFA-1 on leukocytes and ICAM-1 on ocular surface cells. Xiidra is approved by the FDA for the treatment of signs and symptoms of dry eye disease and is administered as a topical ophthalmic solution [FDA, 2016].

A claim chart for lifitegrast would require a structure-by-structure comparison against Formula I, including:

the core ring system;
the identity and placement of R1 and R2;
the R3 functionality;
the R4 substituents;
the AR1 group;
the identity of L; and
the stereochemical and salt or ester form.

The supplied text does not reproduce the structures referenced in claims 2 and 3. Those claims are important because they appear to narrow Formula I to specific halogenated and lower-alkyl substituted compounds. Exact coverage of lifitegrast under claims 2 and 3 cannot be determined from the text alone.

Does claim 1 require dry eye disease?

No. Claim 1 does not recite dry eye disease. It lists uveitis, but not dry eye disease. Claim 12 limits administration to skin or eyes, but it does not add dry eye disease.

That distinction matters commercially. A patent claim directed to topical treatment of uveitis or another listed disorder is not automatically infringed by Xiidra's approved use for dry eye disease. Patent infringement analysis turns on the elements of the asserted claim and the actual or intended use of the product.

How broad is the patent’s method-of-use scope?

The patent is broad in chemical scope but narrower in therapeutic and administration scope.

Broad elements

The following features expand the claim:

Any compound within the Formula I genus.
Pharmaceutically acceptable salts and esters.
A wide range of topical dosage forms.
A broad list of excipients.
Optional penetration enhancers.
Optional additional therapeutic agents.
Mechanistic language covering modulation of ICAM and CD11/CD18 activity.

Limiting elements

The following features create potential noninfringement positions:

The administration must be topical.
The active compound must be an LFA-1 antagonist within Formula I.
The disorder must be one of the diseases expressly listed.
The formulation must contain a pharmaceutically acceptable excipient.
Claim 1 does not cover systemic, oral, intravenous or subcutaneous administration.
Claim 1 does not cover every LFA-1 antagonist outside the claimed structural genus.

The claim does not require a particular concentration, dosing frequency, treatment duration, particle size, pH, preservative, container, or manufacturing process.

What do dependent claims 2 through 14 add?

Claim	Added limitation	Commercial effect
2	Formula I' with specified halogen substituents and lower-alkyl or hydrogen variables	Narrows the chemical genus
3	Specific compounds represented by additional formulae	Potentially creates the most relevant species claims; exact scope requires the missing structures
4	Amount effective to modulate ICAM-leukocyte integrin adhesion	Adds functional language, but may provide limited practical narrowing
5	Amount effective to antagonize CD11/CD18 receptors	Links the method to the biological mechanism
6	Sodium, potassium, lithium, magnesium or calcium salt	Covers selected salt forms
7	Broad list of topical dosage forms	Extends coverage across creams, gels, solutions, sprays, patches, inhalants and related forms
8	Specified excipients	Covers conventional pharmaceutical excipients and combinations
9	Topical penetration enhancer	Adds a formulation-performance limitation
10	Specified penetration enhancers	Identifies common solvents, fatty acids, polymers and sulfoxides
11	Additional therapeutic agent	Covers combination treatment
12	Topical application to skin or eyes	Narrows claim 1 to dermatologic and ophthalmic administration
13	Sjogren's syndrome	Disease-specific narrowing
14	ICAM-1, ICAM-2 or ICAM-3	Narrows the adhesion mechanism

Claims 7 through 10 are formulation claims in method form. They do not independently claim the formulation as a composition. A competitor could therefore avoid those dependent claims by changing the dosage form, excipient or penetration enhancer, while still potentially facing claim 1.

What formulations are protected by US 10,124,000?

Claim 7 covers an unusually broad set of topical presentations:

ointments;
pastes;
creams;
lotions;
gels;
powders;
solutions;
sprays;
inhalants;
patches;
suspensions;
emulsions;
crystalline forms;
oils;
plasters;
liposomes;
microemulsions; and
buffered solutions.

Claim 8 covers excipients such as glycerine, sorbitol, polyethylene glycols, propylene glycol, cyclodextrins, lecithin, polysorbates, petrolatum, zinc oxide and dimethicone.

Claim 9 requires a penetration enhancer. Claim 10 identifies examples including:

ethanol and isopropanol;
oleic acid;
polyethylene glycol 400;
propylene glycol;
fatty acid esters;
N-methylpyrrolidone;
triglycerides; and
N-decylmethylsulfoxide.

For an ophthalmic product, claims 7 and 8 are more commercially plausible than claims directed to patches, plasters or powders. Xiidra's dosage form is a sterile topical ophthalmic solution, so the relevant analysis would focus on claim 1, claim 7, claim 8 and claim 12, subject to the chemical identity and disease limitations.

Does the patent cover method of use, formulation or manufacturing?

The patent primarily protects method of use.

It does not, based on the supplied claims, provide a standalone composition claim to:

lifitegrast;
a defined ophthalmic solution;
a specific concentration;
a bottle or dispenser;
a preservative system; or
a manufacturing process.

The patent also does not contain a conventional process claim in the supplied claim set. Manufacturing risk would instead arise from separate compound, polymorph, salt, formulation, process or device patents in the family or in related patent estates.

This distinction affects generic strategy. A generic manufacturer may be able to make and sell a formulation that falls within the chemical genus but avoid inducement liability by using a label that omits the patented indications. That strategy is more difficult where the marketed formulation has no realistic use outside the patented method or where a product claim remains in force.

What is the FDA and Orange Book significance?

Xiidra received FDA approval in 2016 as a topical ophthalmic solution containing lifitegrast [FDA, 2016]. It is a small-molecule drug, not a biologic. Biosimilar provisions therefore do not apply.

Does US 10,124,000 automatically block a generic?

No. FDA Orange Book listing and patent infringement are separate issues.

An Orange Book-listed patent can trigger a Hatch-Waxman certification requirement for an abbreviated new drug application. A patent that is not listed may still be asserted in district court, but it generally does not create the same statutory approval stay mechanism.

The relevant regulatory questions are:

whether US 10,124,000 is listed against the Xiidra NDA;
whether it is listed as a drug substance, drug product or method-of-use patent;
whether the listed use corresponds to an approved Xiidra indication; and
whether any unexpired patent remains after a Paragraph IV challenge.

Because claim 1 does not recite dry eye disease, the patent's Orange Book utility for Xiidra depends heavily on the exact listed indication and the FDA's accepted patent-use correspondence.

When does US Patent 10,124,000 lose exclusivity?

The patent issued on November 13, 2018. The enforceable expiration date depends on:

the earliest effective nonprovisional filing date;
continuity and terminal-disclaimer records;
any patent term adjustment;
any patent term extension; and
the prosecution history.

A patent's issue date is not its expiration date. The relevant date must be taken from the USPTO patent term record and any terminal disclaimer. For a small-molecule product such as lifitegrast, any FDA patent term extension would be governed by 35 U.S.C. §156, while ordinary patent term is governed by 35 U.S.C. §154 [35 U.S.C. §§154, 156].

The commercial exclusivity analysis should separate four dates:

Exclusivity category	Relevance
Patent expiration	Determines the end of enforceable patent rights
FDA new chemical entity exclusivity	Can delay ANDA approval for four years and block approval for five years
FDA three-year exclusivity	Applies to certain supplemental approvals, not necessarily the original active ingredient
Pediatric exclusivity	Can add six months to qualifying FDA exclusivities and certain patent periods

Xiidra's commercial launch protection has been driven by a combination of FDA exclusivity and multiple lifitegrast-related patents, rather than by US 10,124,000 alone.

Which companies are most likely to challenge the patent?

The most likely challengers are generic ophthalmic manufacturers with sterile solution capabilities and established ANDA portfolios. The relevant competitive group includes:

large generic ophthalmic companies;
contract manufacturers with sterile-fill capacity;
companies seeking an authorized generic arrangement; and
branded ophthalmic companies with an LFA-1 or dry-eye pipeline.

A Paragraph IV challenge would likely target one or more of the following:

Lack of anticipation by an earlier LFA-1 compound or topical formulation.
Obviousness based on known LFA-1 antagonists and conventional topical excipients.
Written-description or enablement deficiencies caused by the breadth of Formula I.
Indefiniteness in functional or Markush limitations.
Noninfringement based on the accused compound, indication or route.
Invalidity based on prior clinical, patent or formulation disclosures.

The chemical genus is vulnerable to an enablement challenge if the full scope covers a large number of compounds without adequate guidance or working examples. The method claims may be more durable if the specification provides pharmacological data and representative topical formulations across the claimed genus.

How strong is the patent estate?

US 10,124,000 has mixed strength.

Strengths

The claim combines compound identity, topical administration and disease treatment.
The Formula I genus is broad.
Salt and ester forms are expressly covered.
The dependent claims reach ophthalmic and dermatologic dosage forms.
Functional limitations connect the claimed compounds to LFA-1, CD11/CD18 and ICAM biology.
The claims can cover compounds other than the original development candidate if those compounds fall within the genus.

Weaknesses

Claim 1 is broad enough to invite written-description and enablement scrutiny.
The disease list is heterogeneous and includes conditions with materially different pathophysiology.
The claim does not recite dry eye disease, the principal commercial indication for lifitegrast.
The functional language in claims 4 and 5 may not materially narrow the claims if the compounds are already defined as LFA-1 antagonists.
Claim 7 includes dosage forms with limited relevance to the likely commercial product.
The missing structures for claims 2 and 3 prevent reliable assessment of the most specific chemical coverage.
A generic could pursue a label carve-out for nonclaimed indications if no broader product claim applies.

How does this patent compare with other LFA-1 and dry-eye patents?

Patent category	Typical protection	Relevance to Xiidra
LFA-1 compound patents	Chemical structure, salt, stereochemistry	High for active-ingredient substitution
Topical method patents	Treatment of ocular or inflammatory disease	High if the generic label includes a patented use
Formulation patents	Concentration, pH, viscosity, excipients, sterility or packaging	High for ANDA product matching
Manufacturing patents	Synthesis, purification, crystallization or salt formation	Variable; higher for API suppliers
Device patents	Single-dose containers, dispensers and delivery systems	Product-specific
FDA regulatory exclusivity	Approval-based, not patent-based	Can delay approval independently of patent validity

US 10,124,000 is best understood as a broad topical method patent within a wider LFA-1 and lifitegrast estate. It should not be treated as the sole barrier to generic entry.

What generic launch scenarios exist?

Scenario 1: Full-label generic launch

A generic files a Paragraph IV certification against relevant listed patents and seeks approval for the complete approved indication. This creates the highest litigation exposure and may trigger a 30-month stay if statutory requirements are met.

Scenario 2: Skinny-label launch

The generic omits patented methods of use from its labeling. This approach is strongest when the patent claims do not cover the FDA-approved indication or when substantial noninfringing uses remain.

Scenario 3: At-risk launch

The generic launches before final resolution of patent litigation. Exposure includes damages, an injunction, possible willfulness findings and disruption of supply contracts.

Scenario 4: Settlement or license

The parties agree to a delayed entry date, authorized generic supply arrangement, royalty-bearing license or other commercial resolution. Any settlement involving a branded and generic drug company may be subject to FTC review under the Medicare Modernization Act [FTC, 2024].

Scenario 5: Non-infringing alternative LFA-1 compound

A competitor develops an LFA-1 antagonist outside Formula I. This avoids literal infringement but may create doctrine-of-equivalents risk and requires separate freedom-to-operate analysis against compound and formulation patents.

What patent litigation and settlement issues matter?

The key litigation question is claim construction, particularly:

the meaning of "LFA-1 antagonist";
the boundaries of the Formula I Markush groups;
whether the accused compound falls within the claimed scaffold;
whether topical administration includes the accused dosage form;
whether the disease must be the purpose stated in labeling;
whether "amount effective" imposes a measurable limitation; and
whether the claimed genus is adequately enabled.

Induced infringement risk is particularly relevant for a generic product label. A label that instructs treatment of a listed disorder can provide evidence of intent, even where the generic product itself is structurally identical to the reference product.

No settlement agreement should be assumed from patent-family or Orange Book data alone. A reliable settlement analysis requires a court docket, FTC filing or public transaction disclosure.

What is the geographic coverage?

US Patent 10,124,000 has territorial effect only in the United States. Parallel protection may exist in:

Canada;
Europe;
Japan;
Australia;
China;
South Korea; and
other jurisdictions entered through national-phase filings.

Foreign claims may differ materially in:

chemical scope;
disease limitations;
topical-use limitations;
patent term;
validity;
prosecution amendments; and
regulatory linkage.

A US noninfringement position does not establish freedom to operate in Europe or other markets.

Key Takeaways

US 10,124,000 is primarily a broad topical method-of-treatment patent.
Claim 1 requires a Formula I LFA-1 antagonist, topical administration, an excipient and treatment of a listed inflammatory or immune disorder.
The patent does not expressly claim dry eye disease in the supplied claims.
Claims 7 through 10 extend protection to topical dosage forms, excipients and penetration enhancers.
Claims 2 and 3 may provide more commercially important species coverage, but their structural drawings are required for exact compound mapping.
Lifitegrast and Xiidra are the principal commercial reference points.
Biosimilar risk is irrelevant because lifitegrast is a small molecule.
Generic risk depends on the full patent estate, Orange Book listings, indication-specific labeling and the expiration of compound and formulation patents.
The broad Markush genus creates both substantial coverage and potential enablement, written-description and obviousness vulnerabilities.
Patent term must be confirmed from the USPTO term record, continuity documents and any terminal disclaimer or patent term extension.

FAQs About US Patent 10,124,000

Does US Patent 10,124,000 claim lifitegrast by name?

No. The supplied claims define a chemical genus through Formula I rather than naming lifitegrast expressly. Coverage requires a structural comparison.

Can a generic avoid US 10,124,000 by changing the excipient?

Changing the excipient may avoid claims 8 or 10, but it will not necessarily avoid claim 1. Claim 1 requires only a pharmaceutically acceptable excipient.

Does the patent cover oral LFA-1 inhibitors?

No. The independent claim requires topical administration. Oral, intravenous and other systemic uses fall outside claim 1 as written.

Is a topical ophthalmic solution necessarily covered?

Not necessarily. The solution must contain an LFA-1 antagonist within Formula I and be used for a listed disorder. Claim 12 further limits the method to topical application to skin or eyes.

Does expiration of this patent permit immediate generic Xiidra entry?

No. Other lifitegrast compound, formulation, method-of-use, manufacturing or device patents, along with FDA exclusivity, may independently affect approval and launch timing.

References

Food and Drug Administration. (2016). FDA approves Xiidra for dry eye disease. U.S. Department of Health and Human Services.
Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
Federal Trade Commission. (2024). Agreement filings under the Medicare Modernization Act. Federal Trade Commission.
United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
United States Code. (2024). 35 U.S.C. § 156: Extension of patent term.
U.S. Patent No. 10,124,000. (2018). Methods and compositions for treating inflammatory and immune-related disorders. United States Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	551339	⤷ Start Trial
Australia	2004287875	⤷ Start Trial
Canada	2544678	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,124,000