Details for Patent: 11,058,677

Which drugs does patent 11,058,677 protect, and when does it expire?

Patent 11,058,677 protects XIIDRA and is included in one NDA.

This patent has thirty patent family members in twenty countries.

Summary for Patent: 11,058,677

Title:	LFA-1 inhibitor formulations
Abstract:	The present invention provides formulations, methods and kits for the treatment of dry eye diseases. In particular, stabilized pharmaceutical compositions comprising the compound of Formula 1 are described herein for a variety of uses including the treatment of dry eye syndrome. In one aspect, methods and ingredients for improving the stability of compositions of the compound of Formula 1 are described.
Inventor(s):	Mary Newman, William HUNKE
Assignee:	Bausch and Lomb Ireland Ltd
Application Number:	US14/650,955
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,058,677
Patent Claim Types: see list of patent claims	Composition; Formulation; Dosage form;

Scope and patent landscape for U.S. Patent 11,058,677: aqueous compositions of Formula 1 with thiosulfate to suppress degradation

Executive summary: U.S. Patent 11,058,677 claims tightly defined aqueous pharmaceutical compositions containing a compound of Formula 1 (or salt) plus a thiosulfate salt (specifically sodium thiosulfate in dependent claims), with explicit degradation-performance limits after accelerated storage at ~40°C. The estate’s core enforceable scope centers on (i) the thiosulfate concentration window (including 0.01% to 0.5% w/v and a specific ~0.3% w/v), (ii) buffering and pH constraints (about 6.0 to 8.5, including about 7.5), (iii) aqueous/topical ophthalmic suitability, (iv) inclusion of sparged inert gas (nitrogen), and (v) specified shelf-life type performance (expiration about 1–5 years at ambient). In practice, competitors that omit thiosulfate, use different antioxidants, run outside the claimed concentration/pH/degradation targets, or avoid inert-gas handling may still have design-around paths, but formulations that maintain thiosulfate-driven stability in aqueous topical systems are at direct risk of infringement under the claim set.

Note: The claims provided show the functional “less than ~1% total degradation products after 40°C for at least one month” constraint, which is often the principal infringement lever in composition/stability patents.

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What does U.S. Patent 11,058,677 claim: the scope of “Formula 1 + thiosulfate + stability” compositions?

Plain-English claim construct: The independent concept is a composition with:

1. a compound of Formula 1 or salt,
2. a pharmaceutically acceptable carrier (dependent claims narrow this to aqueous carrier),
3. a thiosulfate salt (dependent claims specify sodium thiosulfate), and
4. a stability requirement: the composition has < about 1% of total degradation products of the Formula 1 compound after storage at about 40°C for at least one month.

Claim 1 is the core: which product conditions define infringement?

Claim 1 is a composition claim with a stability performance limitation. The infringement analysis will usually focus on whether the accused product:

• contains a Formula 1 compound (or salt),
• contains a thiosulfate salt (not merely “sulfate” or “hypo-sulfite” generically),
• is stored under comparable conditions to the claimed test (about 40°C for at least one month),
• and meets the <1% total degradation products threshold.

Functional limitation as a scope gate

Because the claim ties infringement to the result of storage testing, the claim scope can be defended or attacked using:

• analytical methods used to quantify “total degradation products,”
• choice of stress conditions (time, temperature, potentially container/closure),
• whether the product uses the same test article type (salt form, excipients, headspace).

How do dependent claims narrow to aqueous and specific thiosulfate levels?

• Claim 2: pharmaceutically acceptable carrier is aqueous.
• Claim 3: thiosulfate salt present at ~0.01% to ~0.5% w/v.
• Claim 4: thiosulfate salt present at ~0.3% w/v.

These dependent claims matter for licensing and design-around because they convert Claim 1’s broad “thiosulfate present” concept into quantified formulation parameters.

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Which thiosulfate salts and pH ranges are protected under 11,058,677?

Is sodium thiosulfate required or optional?

• Claim 5 specifies thiosulfate salt is sodium thiosulfate.
• Claim 3 only requires “a thiosulfate salt,” so the specification and litigation record determine whether other thiosulfates (potassium, ammonium, etc.) are within written description and enablement, but the claims show sodium thiosulfate is a clear dependent hook.

What buffering parameters are claimed for eye-drop type aqueous compositions?

• Claim 6: buffered to pH ~6.0 to ~8.5.
• Claim 11: pH ~7.0 to ~8.0 with specified excipients.
• Claim 18: buffered to pH ~7.5 (dependent).

Because ophthalmic formulations often must be near neutral, the claimed 6.0–8.5 window is broad enough to cover typical buffers. In enforcement, the pH reading method and formulation temperature can become contested, but the range itself is straightforward.

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How much compound of Formula 1 is covered: 1%–5% w/v and a 5% point claim?

Concentration ranges

• Claim 7: compound of Formula 1 present at ~1% to ~5% w/v.
• Claim 8: compound at ~5% w/v.

This is critical for generic or reformulation strategies. If an applicant uses a materially different concentration outside the range (for example, lower strength drops or different dosing concentration), they may avoid concentration-limited dependent claims, but still face risk under Claim 1 if “1% to 5% w/v” is not required in Claim 1 itself. Here, Claim 1 as provided does not specify the concentration of Formula 1, while the dependent claims do. So a competitor using a Formula 1 formulation with thiosulfate and meeting the stability performance could still map to Claim 1 even if it avoids the exact 1%–5% dependent range.

Stability timepoints expand in dependent Claim 9

• Claim 9: further limits that at 40°C the composition has < about 1% total degradation products for storage time selected from 2, 3, 4, 5, or 6 months.

This expands the enforceability surface for long-stability holds. Products that only meet the “at least one month” condition may be outside Claim 9 but still potentially within Claim 1.

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What manufacturing/handling steps are claimed: sparged inert gas and nitrogen?

Inert gas is present in two different ways

• Claim 10: composition further comprising sparged nitrogen gas.
• Claim 16–17: further comprising a sparged inert gas, where inert gas is nitrogen.

Does “sparged inert gas” apply to any antioxidant system or only thiosulfate formulations?

• Claim 19: composition of claim 1 comprising one or more antioxidants and a sparged inert gas.

Claim 19 is broader in that it does not state the antioxidant is thiosulfate in the text you provided; instead, it references claim 1’s composition (which includes thiosulfate in Claim 1). So Claim 19 likely remains tied to thiosulfate via incorporation-by-reference to claim 1, while adding that additional antioxidants and sparged inert gas can coexist.

Litigation impact: If a formulation uses thiosulfate but is manufactured without inert-gas sparging, the claim coverage may hinge on whether Claim 1 stands alone without sparging (it does) and whether the accused product’s stability performance still meets the degradation limit.

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What “expiration 1–5 years at ambient temperature” claims exist?

• Claim 20: Claim 1 formulation expires in about 1–5 years at or below ambient temperature.
• Claim 21: Claim 14 formulation expires in about 1–5 years at or below ambient temperature.

How can expiration-based limitations affect enforcement?

Shelf-life expressed as “expires in about 1–5 years” is typically supported by stability studies. For infringement, the practical question becomes whether the accused product’s stability and dating meet the claimed expiration window under relevant storage conditions.

These claims often become evidentiary anchors in litigation:

• stability reports,
• accelerated vs real-time extrapolation,
• container-closure system match.

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How specific are the ophthalmic topical eye formulations in Claims 13–18?

Claims 13–18 narrow the scope to topical administration to the eye and define antioxidant identity as sodium thiosulfate.

Claim 13: key ophthalmic composition definition

• about 4 to 10% w/v compound of Formula 1 (or salt),
• 0.2 to 0.4% antioxidant, where the antioxidant is sodium thiosulfate,
• aqueous solution,
• suitable for topical administration to the eye.

Claim 14: more explicit buffer and isotonicity

• about 5% w/v compound of Formula 1,
• 0.3% w/v antioxidant (sodium thiosulfate),
• sodium phosphate buffering at pH ~6.0 to 8.0,
• sodium chloride for isotonicity,
• aqueous solution for eye topical administration.

Claim 15: thiosulfate as primary antioxidant

• “said thiosulfate salt is the primary antioxidant.”

This can matter for design-arounds using mixed antioxidants. If the formulation includes thiosulfate but a different antioxidant is dominant in the total antioxidant system, a challenger could argue that thiosulfate is not “primary” depending on how “primary” is construed.

Claim 16–18: inert gas and pH ~7.5

• sparged inert gas (nitrogen),
• buffered to pH ~7.5.

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What is the practical patent claim hierarchy: which claims create the strongest enforcement hooks?

Highest-leverage claim set (based on clarity + quantified limits)

1. Claim 1: thiosulfate + performance test (<1% degradation at 40°C for ≥1 month).
2. Claim 3–4: thiosulfate concentration windows (0.01–0.5% w/v; 0.3% w/v).
3. Claim 6: pH 6.0–8.5.
4. Claim 9: extends performance to 2–6 months.
5. Claim 13–14: ophthalmic topical framework with explicit antioxidant identity and isotonic buffer system.
6. Claim 10 / 16–17 / 19: sparged nitrogen/inert gas.
7. Claims 20–21: shelf-life expressed as about 1–5 years.

What design-arounds are most likely to avoid literal coverage?

• Remove thiosulfate entirely or substitute a non-thiosulfate antioxidant system (risk remains under Claim 1 if thiosulfate is still present).
• Use thiosulfate outside the claimed concentration windows (though exact mapping depends on whether the accused product satisfies claim 1 without relying on dependent claim limitations).
• Adjust pH to fall outside 6.0–8.5 (or outside the narrower pH windows in dependent claims).
• Avoid sparged inert gas (helps against dependent claims 10/16/19; less helpful against Claim 1).
• Achieve acceptable degradation but outside the time-window claims (avoid Claim 9 performance length; may still face Claim 1 if it meets ≥1 month).
• Use different formulation type (not topical ophthalmic) to target claims 13–14; again, Claim 1 still applies if it remains a composition claim without the topical limitation.

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How many patent angles does the estate likely cover: compound, salts, formulations, and stability?

Based on the claims you provided, the estate’s angle is not a method-of-synthesis or a broad therapeutic use claim. It is a formulation stability portfolio:

Claim categories

• Composition with specific stabilizer class: thiosulfate.
• Concentration limitations: 0.01%–0.5% and 0.2%–0.4% and 0.3% specific point claims.
• Buffer/pH: 6.0–8.5, 7.0–8.0, 7.5.
• Carrier and dosage form orientation: aqueous; eye drop/topical.
• Manufacturing handling: sparged nitrogen/inert gas.
• Functional stability property: <1% total degradation products after defined stress.
• Shelf-life framing: 1–5 years ambient.

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What generic entry risks exist for a thiosulfate-stabilized ophthalmic Formula 1 product?

Risk drivers for Paragraph IV or 505(b)(2) reformulations

• If the generic uses the same Formula 1 and includes sodium thiosulfate at ~0.3% w/v with pH near neutral and meets the stability threshold, exposure to Claim 1 and multiple dependent claims is high.
• If the generic changes antioxidants but retains thiosulfate at the claimed levels, risk persists because the claims are not limited to “only thiosulfate” unless “primary antioxidant” language is invoked (Claims 13–15).

What would lower infringement risk most

• Omit thiosulfate or use a thiosulfate amount outside the concentration windows and show the product does not meet the <1% degradation threshold under 40°C storage.
• Use a different buffer system that pushes pH outside the claimed ranges (and demonstrate stability results accordingly).
• Avoid sparged inert gas and show stability is achieved without the claimed handling (relevant mostly to dependent claims).

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Regulatory signaling: how these claims may interact with Orange Book listings

Claim structure suggests the patent is a drug product/formulation stability patent rather than a method patent. In Orange Book terms, this typically maps to patents listed for the approved drug product with:

• a specific active ingredient (Formula 1 or salt),
• a dosage form (likely aqueous ophthalmic solution),
• and a patent type that corresponds to formulation/composition and stability.

Practical outcome: If the patent is listed in the Orange Book for the relevant NDA/BLA, it can drive:

• 30-month stay exposure in Paragraph IV,
• settlement leverage for brand,
• and tight design constraints for generics planning an approval route that depends on referencing the brand’s formulation claims.

(Orange Book listing details are not provided in the prompt, so enforcement mapping by application number cannot be performed here.)

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Key takeaways

• U.S. Patent 11,058,677 is built around a thiosulfate-stabilized aqueous composition of a Formula 1 compound (or salt) with a quantifiable stability performance limit at 40°C.
• Strongest claim anchors are the <1% total degradation products at defined durations, the thiosulfate concentration (including ~0.3% w/v), and the pH/buffering ranges (including pH ~7.5).
• Ophthalmic topical claims (Claims 13–18) add explicit sodium thiosulfate identity, antioxidant concentration, and sodium phosphate/sodium chloride buffering and isotonicity.
• Sparged nitrogen/inert gas supports additional dependent coverage, but Claim 1’s stability limitation creates risk even without inert-gas handling if the product still contains thiosulfate and meets the degradation threshold.
• Expiration framed as about 1–5 years at ambient creates an additional evidentiary target for shelf-life and stability study alignment.

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FAQs

1) What makes Claim 1 enforceable in practice?
A composition is defined not only by ingredients (Formula 1 + thiosulfate + aqueous carrier) but also by a functional performance metric: < about 1% total degradation products after ~40°C for at least one month.

2) Can a product infringe if it contains thiosulfate but at a different concentration than 0.3% w/v?
Yes. The claim set includes ranges (e.g., 0.01% to 0.5% w/v). Changing concentration may avoid some dependent claims but can still meet Claim 1 if the performance/stability test and ingredient requirements are met.

3) Does sparged nitrogen matter if the product meets the stability threshold?
Sparged nitrogen is required only in certain dependent claims (and Claim 19 incorporates Claim 1 plus inert gas). Even without inert gas, Claim 1 can still be implicated if the product still meets the degradation criteria with thiosulfate present.

4) Are ophthalmic eye-drop formulations treated differently than general aqueous solutions?
Yes. Claims 13–18 explicitly require suitability for topical administration to the eye and specify ophthalmic-compatible excipients (phosphate buffer, sodium chloride isotonicity) and sodium thiosulfate as antioxidant.

5) How do “expiration 1–5 years” limitations affect a design-around?
They increase the relevance of shelf-life testing and dating. A competitor may try to meet degradation thresholds at shorter timepoints but still face risk if the overall ambient stability and expiration fall within the claimed window.

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References

No external sources were cited because the prompt provided only the claim text for U.S. Patent 11,058,677 and did not include bibliographic details, specification passages, prosecution history, Orange Book identifiers, or litigation records.

Drugs Protected by US Patent 11,058,677

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bausch And Lomb Inc	XIIDRA	lifitegrast	SOLUTION/DROPS;OPHTHALMIC	208073-001	Jul 11, 2016		RX	Yes	Yes			Y

International Family Members for US Patent 11,058,677

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013361579
Brazil	112015014367
Canada	2894170
China	104955453
Denmark	2934510
Eurasian Patent Organization	028008