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Patent landscape, scope, and claims summary: |
United States Patent 10,166,244 (NC_Cа-ATP Channel Inhibitors as SUR1 and/or TRPM4 Antagonists with Bolus-to-Maintenance Infusion Ratios): Claim Map and US Patent Landscape
US Patent 10,166,244 is directed to treating or reducing ischemic damage by administering an NC_Ca-ATP channel inhibitor where the inhibitor is a SUR1 antagonist and/or a TRPM4 antagonist, delivered as a loading bolus followed by a constant infusion maintenance dose where the bolus is 30–90x the maintenance dose. Dependent claims narrow the SUR1 antagonist to a broad set of sulfonylureas (notably glyburide/gli(b)enclamide and other agents with overlapping SUR1 pharmacology), define example TRPM4 antagonist chemotypes, and add use-context (transplant organ preservation, angina, kidney reperfusion), delivery modalities (systemic and local), adjunct therapy, and specific dose constraints for SUR1 agents.
This filing is structurally important for infringement analysis because the claim is framed as a specific dosing regimen (30–90x bolus-to-maintenance) + infusion format (constant infusion) applied to ischemia using SUR1 and/or TRPM4 antagonists. Patent strength and attack surfaces therefore track to (i) whether prior art already disclosed the same regimen proportions and infusion pattern with SUR1/TRPM4 antagonists for ischemia, (ii) whether the prior art disclosed the dual-target concept (SUR1 and TRPM4 inhibition within NC_Ca-ATP channel modulation), and (iii) whether the claim’s broad genus of antagonists and delivery options invites obviousness or anticipation by earlier therapeutic and dosing publications.
What does US Patent 10,166,244 claim in plain terms? (Independent Claim 1 dosing + NC_Ca-ATP/SUR1/TRPM4 mechanism)
Claim 1 elements (structured for claim charting):
- Method of treating or reducing ischemic damage in a subject.
- Administer an inhibitor of an NC_Ca-ATP channel that is:
- a SUR1 antagonist and/or
- a TRPM4 antagonist.
- Administration format:
- loading bolus dose followed by
- constant infusion maintenance dose.
- Bolus-to-maintenance ratio constraint:
- bolus dose is 30–90 times the maintenance dose.
- This regimen is within the ischemia setting (the claim does not restrict indication beyond ischemic damage).
Key claim levers:
- The claim is not just “use SUR1/TRPM4 antagonists for ischemia.”
- It is “use SUR1/TRPM4 antagonists for ischemia with a defined infusion regimen (constant infusion + 30–90x bolus).”
- That combination can narrow prior art overlap, but it also creates a single-point failure for validity and an infringement gating issue for competitors: changing the ratio, avoiding constant infusion, or changing the bolus structure can potentially move outside Claim 1, depending on doctrine of equivalents and claim construction.
What is the critical infringement scope of the 30–90x bolus-to-maintenance constant infusion limitation?
Where infringement is likely to concentrate
- Any protocol using SUR1 antagonists and delivering an initial bolus then switching to a continuous infusion will need to be checked for the numeric ratio.
- If a competitor uses a bolus but then transitions to intermittent dosing or to an infusion without maintaining a ratio in the 30–90 range, they may avoid Claim 1.
Potential design-around candidates (conceptual)
- Altering the bolus-to-maintenance ratio outside 30–90.
- Using a loading dose conceptually but not paired with a maintenance constant infusion that maps to the claim’s “maintenance dose” as construed.
- Avoiding constant infusion by using intermittent maintenance schedules.
(For litigation posture, the ratio and the “constant infusion” definitions typically become claim-construction and expert testimony targets.)
Which SUR1 antagonists are explicitly covered by Claim 2, and what does that do to freedom-to-operate?
Claim 2 lists SUR1 antagonists including:
- glibenclamide (glyburide)
- tolbutamide, acetohexamide, chlorpropamide, tolazimide
- glipizide, gl(i)quidone
- repaglinide, nateglinide, meglitinide, gliclazide, glimepiride, mitiglinide
- pharmaceutically acceptable salts and active metabolites
FTO implication: Claim 2 broadens beyond one active. A company using any of the enumerated SUR1 antagonists (or salts/metabolites) in the Claim 1 regimen context faces an explicit dependent-claim hook, meaning that even if a primary assertion focuses on Claim 1, the dependent set materially constrains negotiation positions.
How broadly does Claim 3 cover TRPM4 antagonists beyond flufenamic acid and mefanimic acid?
Claim 3 TRPM4 antagonist set includes:
- flufenamic acid
- mefanimic acid
- niflumic acid
- antagonists of VEGF, MMP, NOS, TNFα, NFκB, and/or thrombin
Claim construction risk points:
- The last clause (“antagonists of VEGF, MMP, NOS, TNFα, NFκB, and/or thrombin”) may create a functional or pathway-based expansion. That can broaden coverage beyond classic TRPM4 direct blockers, depending on how the claim interprets “TRPM4 antagonist” in relation to VEGF/MMP/NOS/TNFα/NFκB/thrombin pathway antagonism.
FTO implication: A competitor using inhibitors of those pathways may argue they are not TRPM4 antagonists. A patentee will argue functional TRPM4 inhibition or target linkage. This clause is a key battleground for litigation because it can expand the covered chemical space beyond the named TRPM4 blockers.
Do the administration route and timing limitations in Claims 4–6 narrow or expand infringement risk?
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Claim 4: delivery by IV, subcutaneous, intramuscular, intracutaneous, intragastric, or oral.
- This is expansive and reduces route-based design-around leverage.
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Claim 5: administration prior to or concurrent with an ischemic episode.
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Claim 6: administration following an ischemic episode.
- Together, Claims 5 and 6 eliminate timing-based carveouts. Most ischemic intervention protocols (pre-, peri-, post-event) would fall somewhere inside the dependent set.
What do the “direct to organ/tissue,” preservation, extraction, and transplantation sub-claims add for enforceability?
Claims 7–10: local and transplant workflow coverage
- Claim 7: deliver inhibitor directly to the organ or tissue.
- Claim 8: deliver prior to extraction, during extraction.
- Claim 9: combinations including before, during, and/or after extraction relative to the respective organ or tissue.
- Claim 10: deliver to a recipient prior to transplantation, during transplantation, and/or after transplantation.
Enforcement impact:
- These claims create multiple potential infringement pathways in a single product’s lifecycle: donor, preservation/extraction, and recipient perioperative periods.
- Local delivery also complicates competitor defenses that rely on systemic-only protocols.
Claim 11: ischemic damage context
Claim 11 specifies ischemic damage related to:
- organ preservation for transplantation
- angina pectoris
- kidney reperfusion injury
That narrows the “ischemic damage” universe at least in dependent-claim theory. Even so, Claim 1 already covers ischemic damage generally; Claim 11 is best used to show that the patented regimen is tied to commercial and clinical use-cases with predictable regulatory and medical affairs narratives.
How do adjunct therapy claims (Claims 12–14) affect product bundling and settlement leverage?
- Claim 12: method further comprises delivering an additional therapeutic agent.
- Claim 13: additional agent can be antacid, immunosuppressant, antiviral, antibacterial, antifungal.
- Claim 14: specifically enumerates transplant and immunology agents such as:
- anti-thymocyte globulin
- basiliximab
- methylprednisolone
- tacrolimus
- mycophenolate mofetil
- prednisone
- sirolimus/rapamycin
- azathioprine
Business effect: This sort of dependent set supports broad “combination” infringement arguments even if the defendant tries to sell a mono-therapy or to position the accused protocol as part of multi-drug standard of care. In licensing, it tends to increase leverage for the patent holder because it reduces the chance that “we didn’t deliver the combination” defeats a method claim theory.
Do the specific dosage caps in Claims 15–16 narrow the regimen enough to matter?
- Claim 15: SUR1 antagonist dosage is < 3.5 mg/day.
- Claim 16: SUR1 antagonist dosage is < 0.8 mg/kg body weight within a 24-hour period.
These caps may be clinically plausible for some infusion plans, but they also introduce a second numeric gating mechanism besides the 30–90 bolus-to-maintenance ratio. In litigation, both numbers become potential defenses:
- If a protocol exceeds either cap, it may avoid dependent claims (though Claim 1 still exists without these caps).
- Even when dependent claims are avoided, the independent claim can still be asserted if the accused protocol satisfies Claim 1’s ratio and constant infusion elements and uses a SUR1 antagonist/TRPM4 antagonist.
What is the role of Claims 17–19 duration requirements in limiting infringement?
- Claim 17: maintenance dose is administered as constant infusion.
- Claim 18: maintenance duration 6 hours or more.
- Claim 19: maintenance duration 24 hours or more.
This is likely the most important dependent-claim set after the bolus-to-maintenance ratio because it maps to operational protocol design. Competitors can reduce risk by:
- shortening maintenance infusion duration below claimed thresholds, and/or
- avoiding true “constant infusion” administration.
Still, the risk profile depends on whether Claim 1 is asserted independently of duration (it is). Claims 18–19 constrain dependent coverage; they do not necessarily eliminate independent-claim exposure.
Critical legal analysis: where the patent is most vulnerable and where it is most defensible
Likely vulnerability vectors
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Obviousness based on known SUR1/TRPM4 ischemia biology plus known bolus/infusion regimen concepts
- If prior art already combined SUR1 antagonists (e.g., glibenclamide/glyburide) with ischemia models and used loading/maintenance dosing with continuous infusion, the remaining question becomes whether the specific 30–90 ratio and constant infusion add enough non-obviousness.
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Anticipation by dosing-regimen disclosures
- Numeric ratio claims often fail if any publication, protocol, or clinical practice disclosure describes the same regimen window.
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Functional TRPM4 expansion via pathway antagonists (Claim 3)
- If prior art separately disclosed VEGF/MMP/NOS/TNFα/NFκB/thrombin antagonists without tying them to TRPM4 antagonism, defendants can attack the claim breadth on enablement/claim scope or argue lack of direct disclosure.
Most defensible aspects
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The bolus-to-maintenance numeric window coupled to constant infusion
- This is a relatively specific dosing regimen. If prior art only used one of: bolus without constant infusion, or infusion without the ratio window, then Claim 1 can remain distinct.
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Multiple delivery and timing forms
- The broad route/timing/local delivery set supports breadth across clinical and perioperative workflows.
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Explicit transplant workflows
- Claims 7–10 and Claim 11 anchor enforceability to high-value, well-documented clinical operations where evidence of protocols may exist.
How the claim architecture supports licensing leverage (and potential settlement structure)
From a settlement standpoint, the patent’s architecture provides multiple “hooks”:
- core: Claim 1 method with ratio and constant infusion
- corroboration: dependent claims specifying SUR1 antagonist identity, TRPM4 antagonist classes, and transplant/ischemia contexts
- monetization: adjunct therapy claims can support broader combination settlement licensing
- operational: duration and dose caps can inform product label or protocol negotiations
This structure allows the patent holder to pursue:
- protocol-specific licensing (if accused conduct matches Claim 1 regimen),
- class-level licensing (if competitor uses sulfonylureas as SUR1 antagonists and includes similar infusion schemes),
- indication-level licensing (transplant preservation and kidney reperfusion).
Which prior-art categories should matter most for challenging US 10,166,244 (without relying on uncertain citation targets)
Since you provided the claims but not the patent’s prosecution history, specification details, or cited references, the critical validity analysis should focus on classes of disclosures that most directly collide with the claim’s novel elements:
- Ischemic cardiology and renal reperfusion studies using SUR1 antagonists with continuous infusion
- Donor organ preservation and ex vivo perfusion approaches with SUR1/TRPM4 modulation
- TRPM4 blocker literature that pairs loading doses with infusion maintenance
- General drug-delivery and infusion protocols describing bolus-to-maintenance ratios in the same numeric range for similar pharmacologic classes
- Mechanistic bridging showing TRPM4 antagonism attributable to VEGF/MMP/NOS/TNFα/NFκB/thrombin pathway antagonists
The most effective invalidity record typically requires a document that discloses the combination of: ischemia indication + SUR1/TRPM4 antagonism + dosing regimen with continuous infusion + the 30–90 ratio window.
Orange Book status, FDA regulatory posture, and biosimilar/generic risk
No actionable determination can be made here because the prompt does not provide the drug name(s) or FDA application linkages for the patent’s covered product. Without those, it is not possible to reliably map:
- Orange Book listing status (if any),
- the FDA approval pathway (NDA/BLA/505(b)(2)),
- potential Paragraph IV timing,
- biosimilar relevance (if biologic),
- generic formulation constraints tied to the infusion regimen.
Because method claims can attach to an approved regimen without a direct Orange Book analog, a missing product identifier blocks the regulatory-exclusivity analysis needed for business decisions.
Key takeaways
- US 10,166,244 is anchored on a specific infusion regimen: loading bolus + constant infusion maintenance with bolus = 30–90x maintenance, applied to ischemic damage using NC_Ca-ATP channel inhibitors that are SUR1 antagonists and/or TRPM4 antagonists.
- Dependent claims substantially widen the covered agent set by naming many SUR1 antagonists (notably glyburide/gibenclamide) and by expanding TRPM4 antagonism beyond a short list of TRPM4-associated acids to include VEGF/MMP/NOS/TNFα/NFκB/thrombin antagonists.
- The strongest enforceability lever is the numeric dosing window combined with constant infusion, while the most sensitive vulnerability lever is whether prior art already disclosed that regimen with SUR1/TRPM4 targeting for ischemia.
- Operational protocol parameters in dependent claims (dose caps and maintenance duration 6+ or 24+ hours) can create design-around opportunities for defendants, but do not eliminate independent-claim exposure if Claim 1 elements are met.
FAQs
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How does changing the bolus-to-maintenance ratio affect infringement risk under US 10,166,244?
Avoiding the 30–90 window is the most direct way to challenge Claim 1 coverage if claim construction ties “maintenance dose” and “bolus dose” to specific measurable dosing events.
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If a competitor uses a SUR1 antagonist but delivers it without a constant infusion, does that avoid the patent?
If “maintenance dose is administered as a constant infusion” is treated as a strict regimen requirement, using intermittent dosing can be an infringement defense, though doctrine of equivalents may still be argued depending on claim interpretation.
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Do the transplant-related dependent claims require ex vivo perfusion or in vivo dosing?
The claim set includes both pre- and during extraction delivery and recipient peri-transplant delivery, so the patent is not limited to one of those scenarios.
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How could defendants attack Claim 3’s “TRPM4 antagonist” definition for VEGF/MMP/NOS/TNFα/NFκB/thrombin antagonists?
The attack focus is whether such pathway antagonists are sufficiently disclosed as acting as TRPM4 antagonists in the sense required by the claim.
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What is the litigation strategy focus for a validity challenge to US 10,166,244?
Prior art must be shown to disclose the ischemia use plus SUR1/TRPM4 antagonism plus the specific infusion regimen, especially the 30–90 bolus-to-maintenance ratio.
References
- Provided patent claims only (no bibliographic sources supplied).
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