Details for Patent: 6,764,678

Summary for Patent: 6,764,678

Title:	Local anesthetic methods and kits
Abstract:	Methods of reversing local anesthesia are disclosed. The methods comprise administering a local anesthetic and alpha adrenergic receptor agonist to induce local anesthesia followed by reversing anesthesia with a low dose of an alpha adrenergic receptor antagonist. Also disclosed are kits comprising a local anesthetic, an alpha adrenergic receptor agonist and a low dose of an alpha adrenergic receptor antagonist.
Inventor(s):	Eckard Weber, Howard I. Katz
Assignee:	Bank of Montreal
Application Number:	US10/155,171
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Scope and Claims Analysis of US Patent 6,764,678 (Phentolamine + Alpha-Agonist for Prolonging Local/Regional Anesthesia) and the U.S. Patent Landscape

US 6,764,678 is a method patent that claims a specific anesthesia workflow: co-administration of an anesthetic agent with an alpha-adrenergic receptor agonist at the target site to provide local anesthesia and vasoconstriction, followed by administration of a unit dose containing phentolamine mesylate (or a molar equivalent alpha-adrenergic receptor antagonist) with a pharmaceutically acceptable carrier in tightly bounded dose ranges. The claims are drafted to capture multiple drug classes for both the anesthetic and the alpha agonist/antagonist, and multiple delivery formats and anatomic settings (including mucosal delivery and a regional block including epidural space), with additional device/container limitations for dental syringes.

What does US 6,764,678 claim, at a high level?

Core claim concept: a two-step regimen at the anesthetized site:

1. Administer an anesthetic agent (e.g., lidocaine or bupivacaine) plus an alpha-adrenergic receptor agonist (e.g., epinephrine, levonordefrin, norepinephrine) to provide local anesthesia and prolong it via vasoconstriction.
2. Then administer a unit dose composition containing phentolamine mesylate (or a molar equivalent alpha antagonist) within defined mg ranges, in a pharmaceutically acceptable carrier.

Why this is strategically drafted: phentolamine is conventionally an alpha-blocker used to reverse tissue ischemia. Here, it is claimed as being administered after the agonist to shape onset, duration, or local tissue response while maintaining “local anesthesia” outcomes. The patent breadth is driven by:

• broad selection lists for anesthetic agents,
• broad selection lists for alpha agonists and antagonists,
• concentration ranges for phentolamine mesylate,
• multiple administration modes (injection/infiltration/topical; mucosal impregnation; gel/paste),
• device-adjacent syringe/container volume limitations.

Claim family structure (as reflected in your claim set):

• Claim 1: local anesthesia method (general).
• Claims 17-31: regional block method (general), with additional regional-site and delivery constraints.

What is the exact claim scope for local anesthesia (Claim 1 and dependents)?

Claim 1: method of providing local anesthesia with agonist then phentolamine unit dose

Claim 1 elements (must all be present):

• Administer to a mammal needing local anesthesia:
  • an anesthetic agent in an amount effective to provide local anesthesia; and
  • an alpha adrenergic receptor agonist in an amount effective to constrict blood vessels at the site and prolong local anesthesia.
• Then administer:
  • a unit dose composition to the site
  • where the unit dose comprises between about 0.0018 mg and about 0.45 mg phentolamine mesylate (or a molar equivalent of another alpha-adrenergic receptor antagonist) plus pharmaceutically acceptable carrier.

Critical scope levers:

• Two-step timing: “then” requires sequential administration (agonist + anesthetic first; phentolamine unit dose afterward).
• Site-specific dosing: the phentolamine amount is bounded.
• Equivalency: allows substitute alpha antagonists if they are “molar equivalent” to phentolamine mesylate.
• Carrier is broad: “pharmaceutically acceptable carrier” is not limited.

Claim 2: together in solution

• Requires anesthetic and alpha agonist administered together in solution.

Claim 3: together from standard dental local anesthetic syringe

• Narrows to delivery from a standard dental local anesthetic syringe, implying capture of commercial dental cartridge formats and workflows.

Claim 4: anesthetic agent selection list

• Includes lidocaine, polocaine, etidocaine, lignocaine, xylocaine, novocaine, carbocaine, procaine, prilocaine, bupivacaine, cinchocaine, and mepivacaine.

Claim 5: alpha agonist selection list

• Includes levonordefrin, epinephrine, or norepinephrine.

Claim 6: narrower phentolamine unit dose range

• Limits unit dose to 0.09 mg to 0.45 mg.

Claim 7: formulation broad (solution for injection/infiltration/topical)

• Defines the unit dose composition as a solution suitable for injection, infiltration, or topical use.

Claims 8-9: mucosal tissue and impregnation device

• Topical application to mucosal tissue.
• Used to impregnate a wafer, pellet, or cotton ball for mucosal application.

Claims 10-11: gel/paste topical to mammal; mucosal tissue

• Captures solid/semi-solid delivery systems, including mucosal application.

Claim 12: alpha antagonist selection list

• Includes phentolamine (free base), phentolamine hydrochloride, phentolamine mesylate, tolazoline, yohimbine, rauwolscine, doxazosine, labetalol, prazosine, tetrazosine, trimazosine.

Claim 13: phentolamine mesylate specifically

• Narrows antagonist to phentolamine mesylate.

Claims 14-16: dental syringe container and volume

• Claim 14: unit dose is in a container that fits into standard dental local anesthetic syringe.
• Claim 15: container volume between 1.6 mL and 1.8 mL.
• Claim 16: unit dose contains phentolamine mesylate and fits into the same container volume range.

Net effect: Claim 1 is broad on regimen and antagonists via molar equivalency; dependents ladder in device and dosage-form constraints that are likely intended to match real-world product packaging and dental administration practice.

What is the exact claim scope for regional anesthesia blocks (Claim 17 and dependents)?

Claim 17: regional block method with agonist then phentolamine unit dose

Claim 17 mirrors Claim 1 but is framed as “regional anesthetic block,” with a different upper-lower bound for unit-dose phentolamine:

• Step (a): administer anesthetic agent + alpha agonist at the site to receive the block, with agonist providing vasoconstriction to prolong anesthesia/block.
• Step (b): administer unit dose composition at the site comprising:
  • between about 0.0018 mg and about 0.45 mg phentolamine mesylate (or molar equivalent alpha antagonist) + carrier.

Claim 18: epidural space

• Site limitation to epidural space.

Claims 19-20: together in solution; injection into the site

• Captures injection delivery patterns for agonist + anesthetic together.

Claims 21-22: selection lists (anesthetic; alpha agonist)

• Mirrors the anesthetic and agonist lists in Claim 4 and Claim 5.

Claims 23-24: phentolamine dose range (narrowed) and solution formulation

• Claim 23: 0.09 mg to 0.45 mg.
• Claim 24: solution formulated for injection/infiltration/topical.

Claims 25-26: mucosal tissue and impregnation

• Same mucosal impregnation concepts.

Claims 27-28: gel/paste topical and mucosal tissue

• Same gel/paste concepts.

Claims 29-30: alpha antagonist selection list; phentolamine mesylate

• Same antagonist list as Claim 12; narrower to phentolamine mesylate in dependent claim.

Claim 31: container volume

• Unit dose present in a container with volume between 1.6 mL and 1.8 mL.

Net effect: The regional claims expand the anatomical framing (including epidural) and delivery contexts while retaining the same regimen logic: agonist-based vasoconstriction first, then alpha blockade via phentolamine dose.

What parts of the claim language create the biggest infringement risk?

1) The “then” sequential regimen

Both claim sets require that the alpha agonist + anesthetic are administered, and only after that, phentolamine unit dose is administered. A design-around that administers phentolamine concurrently with or before the agonist/anesthetic risks missing this element.

2) Bounded phentolamine mesylate dose ranges

For Claim 1 and Claim 17: 0.0018 mg to 0.45 mg. For dependent claims 6 and 23: 0.09 mg to 0.45 mg.

Risk concentrates where product dosing falls inside those ranges. Even small shifts may move outside the literal bounds, but the “molar equivalent” phrasing can still pull in substitutes.

3) “Molar equivalent of another alpha adrenergic receptor antagonist”

This creates a functional breadth beyond phentolamine mesylate. If a competitor uses another alpha antagonist and treats it as a molar equivalent, literal scope may still be implicated even if phentolamine itself is not used.

4) Alpha antagonist selection list in dependents

Dependents enumerate multiple antagonists, including doxazosine, prazosine, tetrazosine, trimazosine, labetalol, yohimbine, rauwolscine, tolazoline, plus phentolamine forms. Even if Claim 1 relies on molar equivalence generally, the dependents show the drafter’s intent to cover a broad antagonist set.

5) Dental syringe container size and fit

Claims 3, 14-16, and 31 add a product-packaging barrier. If a competitor uses a different device or container size outside 1.6-1.8 mL, it avoids those dependents. But the core regimen in Claim 1/17 still may remain in play if a different delivery format is used.

Which formulations and routes are explicitly covered?

Covered anesthetic+agonist delivery

• “Administered together in solution” (Claims 2, 19).
• Can be delivered via a standard dental syringe in Claim 3 (local claim only).

Covered phentolamine antagonist unit-dose formats

• Solution (Claims 7, 24)
• Topical to mucosal tissue (Claims 8, 25)
• Impregnating wafer/pellet/cotton ball for mucosal application (Claims 9, 26)
• Gel or paste topical (Claims 10, 27)
• Topical to mucosal tissue (Claims 11, 28)

Implication: The patent is not limited to injectables of phentolamine. It is written to cover locally applied antidote-like compositions on mucosal surfaces and controlled carriers.

What anatomic sites are explicitly captured?

• Local anesthesia in general (Claim 1).
• Regional anesthetic block in general (Claim 17).
• Epidural space specifically (Claim 18).
• Mucosal tissue contexts via topical applications and impregnation devices (Claims 8-9 and 25-26).

Implication: Competitors in dental/oral-maxillofacial anesthesia and procedural mucosal anesthesia face direct risk if they follow the two-step agonist then alpha-antagonist regimen with the specified dosing.

Where does the patent likely sit in the wider U.S. anesthesia and dental pharmacology landscape?

Likely competitive patent “neighbors”

Even without listing specific family members for 6,764,678, the claim design suggests overlap with patent clusters in:

• vasoconstrictor-augmented local anesthetics (anesthetic + epinephrine/levonordefrin/norepinephrine),
• alpha-adrenergic antagonists for reversing vasoconstriction-related ischemia,
• dental cartridge or syringe dosing formats,
• topical/mucosal local anesthesia formulations and delivery devices (wafers/pellets/cotton),
• regional anesthesia and epidural additive strategies.

Business takeaway: this patent targets a specific treatment sequence that can be embedded into clinical protocols and product labeling. That sequence can be hard to “work around” if a competitor’s clinical regimen mirrors it.

Practical freedom-to-operate map: how could a generic or new entrant avoid the claim elements?

Based on the claim text you provided, avoidance strategies (risk-reduction, not legal advice) cluster into four categories:

1. Change the order/timing
   Avoid “agonist first, then phentolamine unit dose” sequencing.

2. Use phentolamine outside the literal mg window
   Move below 0.0018 mg or above 0.45 mg per claimed unit dose. Dependent claims (0.09-0.45 mg) impose additional risk if within that subrange.

3. Avoid molar-equivalent alpha antagonist substitutions
   If not using phentolamine mesylate, use an agent that is not a molar equivalent of an alpha adrenergic receptor antagonist, or avoid alpha-adrenergic antagonism that maps to the listed/covered classes.

4. Break device/container-dependent dependents
   Use containers that do not fit a standard dental syringe or do not have 1.6-1.8 mL volume, potentially reducing dependent claim exposure (though independent claim exposure remains if regimen elements are met).

Timeline and exclusivity considerations (what matters for business planning)

For method patents, exclusivity is typically tied to patent expiration, not regulatory exclusivity. For a U.S. patent, the enforceable term is generally driven by filing date and PTA adjustments. Your provided content does not include the patent’s filing date, priority date, or prosecution history, so a precise expiration date cannot be calculated from the claim text alone.

Operational planning still works with these claim-derived milestones:

• If a competitor product follows the same clinical sequence and uses phentolamine doses in range, it is exposed to infringement risk regardless of formulation patent lifetimes.
• If regulatory approvals are tied to new NDA/ANDA products, market entry planning should be aligned to the patent’s expiration and any terminal disclaimers, reissues, or continuations in the same family.

Patent landscape summary: what this claim set suggests about strength and enforcement posture

Strength indicators from the claim drafting

• Definite dosing ranges (0.0018-0.45 mg; 0.09-0.45 mg) strengthen enforceability by limiting ambiguity.
• Multiple dependent claim pathways across:
  • dental syringe packaging,
  • mucosal delivery (impregnation carriers),
  • topical gel/paste,
  • regional block and epidural space,
  • broad drug class selection lists.
• Two-step regimen creates a distinct clinical practice hook.

Enforcement vulnerability indicators

• The “then” timing can be a focal point for claim construction and factual proof.
• “Molar equivalent” can invite disputes over what constitutes equivalent dosing and which antagonist qualifies.

Key Takeaways

• US 6,764,678 claims a sequence: anesthetic + alpha agonist first to vasoconstrict and prolong local/regional anesthesia, then a unit dose containing phentolamine mesylate (or molar-equivalent alpha antagonist) in 0.0018-0.45 mg ranges to the same site.
• Claim scope is broadened via extensive selection lists for anesthetics and alpha agonists, plus antagonist substitution via “molar equivalent” and dependent listing of multiple alpha antagonists.
• The patent explicitly covers topical/mucosal delivery systems (wafer/pellet/cotton ball impregnation; gel/paste) and includes a regional block pathway with epidural space.
• Device/container dependents tie risk to standard dental syringe fit and 1.6-1.8 mL container volume.
• Freedom-to-operate risk concentrates on products that replicate the claimed two-step regimen and dose windows, especially in dental and mucosal anesthetic workflows.

FAQs

1) Does US 6,764,678 cover phentolamine-free formulations?
The claims focus on a unit dose containing phentolamine mesylate or a molar equivalent alpha-adrenergic receptor antagonist, so designs that eliminate both phentolamine mesylate and qualifying alpha antagonists reduce literal alignment.

2) Can competitors avoid the patent by co-formulating phentolamine with the anesthetic/agonist?
Co-administration can undermine the “then” sequential element required by both independent claim frameworks.

3) What dose ranges are explicitly claimed for phentolamine mesylate?
Independent claims use 0.0018 mg to 0.45 mg per unit dose; dependent claims narrow to 0.09 mg to 0.45 mg.

4) Is epidural use covered by the patent?
Yes. Claim 18 limits a regional block method to the epidural space.

5) Does the patent cover topical mucosal delivery formats like wafers or cotton balls?
Yes. Dependent claims cover topical application to mucosal tissue and use of compositions to impregnate a wafer, pellet, or cotton ball.

References

1. United States Patent 6,764,678.

Drugs Protected by US Patent 6,764,678

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,764,678

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	352300
Australia	2001259848
Australia	2005211689
Australia	5984801