Details for Patent: 12,409,183

Which drugs does patent 12,409,183 protect, and when does it expire?

Patent 12,409,183 protects AURLUMYN and is included in one NDA.

This patent has four patent family members in four countries.

Summary for Patent: 12,409,183

Title:	Method of using iloprost for treating frostbite
Abstract:	The present disclosure generally relates to treatment of frostbite by intravenous injection or intravenous infusion of iloprost or a pharmaceutically acceptable salt thereof.
Inventor(s):	Kevin A. CHRISTAL, Christa-Lynn J. VAMPOLA, Wade W. BENTON
Assignee:	BTG International Inc
Application Number:	US18/776,438
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

Scope & Claims Breakdown of US Patent 12,409,183 (Iloprost for Severe Frostbite) and the U.S. Patent Landscape

US 12,409,183 claims a very specific intravenous (IV) iloprost regimen for severe frostbite that combines (i) a defined iloprost concentration achieved by a 1 mL pre-dilution product diluted into 0.9% sodium chloride to a final 1 µg/mL iloprost, (ii) a three-day repeated titration schedule (Day 1 then repeated Day 2 and Day 3), (iii) a maximum treatment duration of 8 consecutive days, and (iv) a digit-amputation risk reduction outcome versus standard of care. Dependent claims tighten the protocol to specific infusion rates, starting doses, hepatic/renal impairment dosing, infusion modality duration, stage definitions, and formulation/handling attributes (sterility, pH, ethanol, thromethamine, no preservatives, PVC bag).

Core claim 1 is an “IV dosing-and-formulation method” patent. It does not claim iloprost itself, but the method steps and the precise way the concentrated product is prepared for infusion and then titrated across the first three days.

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What are the key elements of US 12,409,183 claim 1 for iloprost IV treatment of severe frostbite?

Claim 1 requires all of the following elements in combination:

1. Indication and patient population

   • “Treating severe frostbite in a subject.”
   • Dependent claim 12 specifies stage 3 or stage 4 frostbite.

2. Pre-dilution composition defined by composition (concentration and excipients)

   • Dilute about 1 mL of a pre-dilution composition comprising a concentrated solution of iloprost.
   • The concentrated solution comprises:
     • ~0.1 mg/mL iloprost (or pharmaceutically acceptable salt or stereoisomer)
     • ~0.24 mg/mL tromethamine
     • sodium chloride
     • ethanol
   • The pre-dilution composition is located in 0.9% sodium chloride as the solution matrix (as written).
   • A later claim specifies the ethanol level precisely as ~8.1 mg/mL (claim 14/15), and the pre-dilution pH as ~8.3 (claim 17).

3. Defined dilution outcome concentration

   • The diluted composition has a final concentration of ~1 µg/mL iloprost (or salt/stereoisomer).

4. Route and administration method

   • IV infusion.
   • Must include a titration step on Day 1.
   • The titration step is repeated on Day 2 and Day 3.

5. Specific titration structure

   • Each day includes:
     • A starting dose and dose increments up to a maximum dose.
   • Day 2 and Day 3 use the same starting dose and increments as Day 1.
   • The maximum dose achieved may differ by day.

6. Treatment duration cap

   • Diluted composition administered for a maximum of 8 consecutive days.

7. Comparative clinical effect requirement

   • The method “reduces the risk of digit amputation” versus standard of care.

Claim 1 scope in plain terms

To practice claim 1, an IV iloprost regimen must replicate the patent’s combination of (a) how the drug is formulated and diluted to 1 µg/mL using a ~1 mL pre-dilution concentrate, (b) three-day repeated titration across Days 1 to 3, (c) ≤8 consecutive days, and (d) the claimed comparative amputation risk reduction.

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What infusion rate and titration dosing limitations are recited in dependent claims?

The patent’s dependent claims add numeric guardrails around dosing.

Rate window (claim 2)

• Administer between ~0.25 ng/kg/min and ~2.0 ng/kg/min.

Starting dose (claims 3, 4, 5, 6)

• Titration Day 1 starting dose:
  • ~0.25 ng/kg/min or ~0.5 ng/kg/min (claim 3).
• Specific impairment-dependent patterns:
  • Starting dose ~0.5 ng/kg/min if the subject does not have Child-Pugh Class B or C hepatic impairment (claim 4).
  • Starting dose ~0.5 ng/kg/min with renal impairment protocol:
    • dose decreased to ~0.25 ng/kg/min at the beginning of titration if eGFR < 30 mL/min/m² and subject cannot tolerate 0.5 ng/kg/min (claim 5).
  • Starting dose ~0.25 ng/kg/min if subject has Child-Pugh B or C hepatic impairment (claim 6).

Increment and interval (claim 7)

• Dose increased in increments of ~0.5 ng/kg/min every ~30 minutes during titration.

Maximum dose (claims 8, 11)

• Maximum dose:
  • ~2.0 ng/kg/min or the highest tolerated between 0.25 and 2.0 ng/kg/min (claim 8).
• After Day 1–3 titration:
  • Maximum/highest dose maintained for remainder of treatment period (claim 11).

Dose-limiting reaction logic (claim 9)

• Titration includes dose decrease if dose-limiting reaction occurs.

Continuous daily administration duration (claim 10)

• Continuous each day for ~6 hours per day during treatment.

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How do the regimen claims handle Day 2 and Day 3 titration structure?

The claim architecture is built to require a repeat titration schedule:

• Day 1 titration: starting dose + increments to maximum for Day 1.
• Day 2 titration: same starting dose + increments, but maximum may differ.
• Day 3 titration: same starting dose + increments, but maximum may differ.
• After this Day 1–3 period, the regimen supports maintenance of the maximum dose (claim 11) for the remainder of the overall course.
• Whole course must be ≤8 consecutive days (claim 1).

From an infringement perspective, any protocol that uses only a one-time titration, or titration that does not repeat on Days 2 and 3, is outside claim 1’s stated titration structure even if the final doses overlap.

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What formulation and physicochemical constraints appear in the claims?

Claim 1 already locks the “concentrated solution” composition and the final dilution to 1 µg/mL. Dependent claims add specific formulation details that materially narrow or define the protected embodiment.

Ethanol concentration (claims 14/15)

• Concentrated solution includes about 8.1 mg/mL ethanol.

pH constraints (claims 15, 17)

• Diluted method version: composition has pH ~8.3 (claim 15).
• Dependent: pre-dilution composition pH about 8.3 (claim 17).

Sterility and preservative absence (claims 18, 19)

• Pre-dilution composition is a sterile solution (claim 18).
• Pre-dilution composition comprises no preservatives (claim 19).

Specific pre-dilution unit handling (claims 13, 16)

• Pre-dilution composition as a single dose vial about 1 mL (claim 13).
• Tromethamine content:
  • about 0.242 mg/mL (claim 16).

Dilution volume and IV bag configuration (claims 20–23)

• Diluted composition comprises about 100 mL of 0.9% sodium chloride (claim 20).
• Diluting performed in an IV bag (claim 21).
• Infusion bag comprises about 100 mL of 0.9% sodium chloride (claim 22).
• Infusion bag is PVC (claim 23).

These operational details matter because some iloprost administration workflows use different diluent volumes, different container materials (e.g., non-PVC), or different pre-dilution presentations. Such changes may fall outside the literal claim scope depending on construction.

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What clinical outcome language is claimed, and how is it quantified?

Claim 1 includes an effect statement: reduction in digit amputation risk versus standard of care.

Dependent claims specify magnitude:

• At least 15% / 20% / 25% / 30% reduction options (claim 24).
• About 35% to about 50% reduction (claim 25).
• About 40% reduction (claim 26).

From a claim scope perspective, the quantified language is tethered to “when compared with standard of care treatments for frostbite.” That language supports a narrower subset of regimens that achieve those efficacy deltas under the claimed administration framework.

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How do the claims define stage 3 and stage 4 frostbite?

Claim 12 restricts the severe frostbite to:

• Stage 3 or Stage 4 (claim 12).

Then claims 27–28 provide lesion-characterization descriptors:

• Stage 3: lesion extends just beyond a proximal phalanx (claim 27).
• Stage 4: lesion extends proximal to a metacarpal joint or metatarsal joint (claim 28).

This staging language can be decisive for coverage in mixed populations where the protocol is used for earlier or different lesion extents.

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What exactly is protected: method claims vs. composition claims?

US 12,409,183 is drafted as method-of-treatment with embedded formulation and administration preparation steps. There is no claim text here indicating standalone product composition claims (e.g., “a pharmaceutical composition comprising…”). Instead, the protected activity is a specific sequence:

1. Use a defined pre-dilution iloprost concentrate (composition and container presentation).
2. Dilute it to a defined final concentration in a defined diluent volume.
3. Administer by IV infusion using a specific titration plan over Days 1–3, with defined dose range and increment logic.
4. Limit total course to ≤8 consecutive days.
5. Achieve digit-amputation risk reduction vs standard of care.

This structure makes the patent susceptible to a “protocol-design” workaround: changing the titration days, starting/increment rules, dilution concentration, or the container/dilution setup can potentially avoid literal infringement.

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How does US 12,409,183 compare with typical iloprost frostbite use patterns?

Typical iloprost regimens for frostbite in practice (where used) often include IV iloprost in a titration-like or scheduled infusion format across multiple days, but not necessarily with the exact combination locked in claim 1:

• Many regimens focus on clinical dosing schedules but do not always specify:
  • a particular pre-dilution concentrate volume (1 mL),
  • dilution to exactly 1 µg/mL,
  • repeated titration on Days 2 and 3 using the same starting dose and increments,
  • the container material (PVC),
  • a “no preservatives” sterile single-dose vial,
  • and a defined pH of ~8.3.

Claim 1 is built to close those “implementation gaps.”

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Patent landscape for US 12,409,183: what categories of other patents typically matter for freedom to operate?

US 12,409,183 is a U.S. method patent that is likely part of a broader U.S. and international portfolio around:

1. Iloprost product formulation and presentation
   • Solutions, excipients (tromethamine, ethanol), pH targets, preservative status.
2. IV preparation and administration
   • Dilution instructions, final concentration targets, diluent composition and volumes.
3. Dosing and titration protocols
   • Dose ranges, starting doses, increments, infusion duration per day, treatment course length.
4. Clinical staging and indication definitions
   • Stage 3 vs stage 4 frostbite criteria.
5. Comparative efficacy framing
   • Digit amputation endpoints vs standard of care.

In litigation or licensing, these portfolios often split into:

• earlier/compound-level patents (iloprost use and/or formulation),
• later regimen patents (titration schedules and duration),
• and specific manufacturing or container constraints.

US 12,409,183 is squarely in the later regimen + formulation-handling bucket.

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Which design-arounds are most plausible against claim 1’s elements?

Because claim 1 is conjunctive, avoiding a single required element can remove literal coverage. Candidate workarounds, conceptually, include changing:

• Final iloprost concentration away from ~1 µg/mL.
• Pre-dilution volume/presentation away from ~1 mL single-dose vial.
• Titration schedule so that titration is not repeated on Day 2 and Day 3.
• Starting dose and increment interval away from the claimed starting dose options and ~0.5 ng/kg/min every ~30 minutes increment structure (where dependent claims apply).
• Max treatment duration beyond 8 consecutive days or using a different course structure.
• IV container material away from PVC (dependent claim 23).
• pH ~8.3 target, ethanol level (claims 14/15), or preservative-free status (claims 18/19).

Practical viability depends on whether alternative embodiments are still clinically used and whether other patents cover those alternative regimens.

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How strong is the patent estate’s claim scope based on wording density?

US 12,409,183 uses high-density, parameterized limitations across:

• formulation concentration levels (iloprost, tromethamine, ethanol),
• buffer/excipient system (tromethamine + sodium chloride + ethanol in 0.9% NaCl matrix),
• pH,
• dilution setup (1 mL into ~100 mL 0.9% NaCl),
• dosing kinetics (dose range, starting dose, increments every 30 minutes),
• clinical structure (titration Day 1 and repeated Day 2/Day 3),
• duration (max 8 consecutive days, ~6 hours/day continuous),
• patient subsets (Child-Pugh and eGFR triggers),
• and staging descriptors for frostbite.

That combination narrows literal infringement but strengthens the patent’s ability to control specific commercial administration practices.

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Where are the most commercially relevant claim choke points?

The most commercially sensitive “choke points” are those likely to vary between institutions, vendors, and product labels:

1. Titration cadence: Day 1 with repeated titration on Day 2 and Day 3
2. Final concentration target: ~1 µg/mL iloprost
3. Dilution math: ~1 mL pre-dilution into ~100 mL 0.9% NaCl
4. Pre-dilution composition: tromethamine ~0.24–0.242 mg/mL and ethanol ~8.1 mg/mL
5. Administration modality: continuous infusion ~6 hours/day
6. Course length: ≤8 consecutive days
7. Container: PVC bag

Regulatory-labeled dosing that does not match these exact parameters is the first place to test non-infringement.

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What does the claims set imply about the protected “product + protocol” packaging?

The dependent claims strongly suggest the inventors intended protection not only for “how to dose,” but also for “how to prepare” the iloprost concentrate in a particular way that aligns with a specific marketed or planned supply format:

• single-dose vial about 1 mL,
• preservative-free sterile solution,
• no preservatives,
• ethanol and tromethamine included at specific levels,
• pre-dilution pH targeted at ~8.3,
• diluted in PVC IV bag with ~100 mL 0.9% NaCl,
• and yields a final 1 µg/mL concentration.

That “linked” structure can reduce the risk that a competitor avoids infringement purely by sourcing iloprost from the same chemical entity while using different excipient or preparation choices.

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Does the patent create biosimilar/generic-like issues?

This is a small-molecule branded regimen pattern, not a biologics-centered patent. The “generic” risk is more about:

• whether an alternative sponsor’s IV preparation steps and titration protocol match the claim’s parameters, and
• whether the alternative product/formulation used for IV infusion is the claimed pre-dilution composition and dilution setup.

So the functional analog to “bioequivalence” is whether the alternative administration achieves the claimed concentration and schedule while avoiding defined formulation/container/pH elements.

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Key Takeaways

• US 12,409,183 protects a narrow, parameterized IV iloprost regimen for severe frostbite that combines a defined 1 mL pre-dilution concentrate with a dilution to ~1 µg/mL final iloprost, and a three-day repeated titration structure (Day 1 titration repeated on Days 2 and 3).
• Dependent claims lock dosing ranges, increment logic, hepatic/renal-based starting adjustments, infusion duration (~6 hours/day), and course duration (≤8 consecutive days).
• Formulation and handling dependencies are material: ethanol level (~8.1 mg/mL), pH (~8.3), tromethamine (~0.24–0.242 mg/mL), preservative-free sterile single-dose vial, and PVC infusion bag are all specifically claimed.
• Clinical effect language is quantified (digit amputation risk reduction ranges and thresholds), strengthening the patent’s linkage to demonstrated comparative outcomes.
• Most actionable infringement leverage points are the claim’s conjunctive requirements: titration schedule (Days 1–3), final concentration (1 µg/mL), and the formulation/dilution preparation (including pH and excipient levels, and in some dependents the PVC bag).

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FAQs

1) What elements must match to infringe US 12,409,183 claim 1?
All claim 1 steps must be met together: severe frostbite treatment; use of the defined pre-dilution iloprost concentrate (including tromethamine and ethanol in the specified system); dilution of ~1 mL to a final ~1 µg/mL iloprost in 0.9% NaCl; IV infusion with titration on Day 1 repeated on Days 2 and 3; ≤8 consecutive days; and the claimed digit amputation risk reduction versus standard of care.

2) How does the patent handle patients with hepatic impairment and renal impairment?
It adds dependent dosing rules: Child-Pugh B/C use a lower starting dose (~0.25 ng/kg/min), and eGFR <30 mL/min/m² triggers a decreased starting/titration dose (~0.25 ng/kg/min) if the subject cannot tolerate ~0.5 ng/kg/min.

3) Are staging definitions part of the core protection?
Stage 3/4 is in dependent claim 12, with additional lesion descriptors in claims 27 and 28.

4) Does the patent cover container type and dilution logistics?
Yes. Dependent claims specify PVC infusion bags and a ~100 mL volume of 0.9% NaCl in the infusion bag.

5) Can a different iloprost concentration avoid the patent?
Claim 1 requires a final concentration of about 1 µg/mL after dilution, so using a different final concentration could avoid literal coverage.

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References

1. US Patent 12,409,183. (United States Patent and Trademark Office).

Drugs Protected by US Patent 12,409,183

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Btg Intl	AURLUMYN	iloprost	SOLUTION;INTRAVENOUS	217933-001	Feb 13, 2024		RX	Yes	Yes	12,409,183					TREATMENT OF SEVERE FROSTBITE IN ADULTS TO REDUCE THE RISK OF DIGIT AMPUTATIONS

International Family Members for US Patent 12,409,183

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
China	121772928
Denmark	202630963
European Patent Office	4746889
World Intellectual Property Organization (WIPO)	2025019625