Details for Patent: 11,110,054

Which drugs does patent 11,110,054 protect, and when does it expire?

Patent 11,110,054 protects PREVDUO and is included in one NDA.

Summary for Patent: 11,110,054

Title:	Ready-to-use injectable pharmaceutical compositions comprising neostigmine and glycopyrrolate
Abstract:	The present invention provides stable, ready-to-use injectable pharmaceutical compositions, comprising the combination of neostigmine, glycopyrrolate, a stabilizing amount of one or more aminopolycarboxylic acids, and a pharmaceutically acceptable liquid vehicle. Other aspects of the invention relate to methods for making such compositions and methods of using such compositions for reversing the effects of non-depolarizing neuromuscular blocking agents. Preferably, the composition comprises neostigmine methylsulfate, glycopyrronium bromide, ethylenediaminetetraacetic acid (EDTA) and a pharmaceutically acceptable liquid vehicle, and is provided in a pre-filled, ready-to-use sealed container, such as a pre-filled syringe, suitable for intravenous administration.
Inventor(s):	Rahul Dhulaji Bhise, Ajay Kumar Singh, Mahadeo Vasant Mahadik, Ashish Anilrao DUBEWAR, Molugu Prashanth Reddy
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US16/170,948
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound;

US Patent 11,110,054 (Claims on Ready-to-Use Neostigmine/Glycopyrrolate for Reversal of Non-Depolarizing NMBAs): Scope, Claim Strength, and Landscape

United States Patent 11,110,054 claims a stable, ready-to-use injectable composition for reversing non-depolarizing neuromuscular blocking agents (NMBAs), defined by a tight drug-dose ratio, a specific tonicity modifier (sodium chloride), an explicit acid/base pH control, and a specific impurity control requirement under accelerated storage (40°C/75% RH for 3 months). The independent claim set is structurally built around: (1) neostigmine at ~1 mg/mL, (2) glycopyrrolate/glycopyrronium bromide at ~0.2 mg/mL, (3) sodium chloride tonicity adjustment, and (4) impurity C in glycopyrrolate held below 1% after storage.

This produces a landscape where infringement risk clusters around formulation-level matches (not just the API combination), while competitors can often reduce exposure by changing dose ratios, tonicity control, pH targets, or storage-stability/impurity profiles.

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What does Claim 1 actually cover (independent claim scope)?

Core subject matter

Claim 1 is an apparatus-free, formulation-defined product claim:

A stable ready-to-use injectable pharmaceutical composition for reversing non-depolarizing NMBAs, comprising:

• (i) neostigmine: about 1 mg/mL (or pharmaceutically acceptable salt/solvate/hydrate)
• (ii) glycopyrrolate: about 0.2 mg/mL (or pharmaceutically acceptable salt/solvate/hydrate)
• (iii) pharmaceutically acceptable liquid vehicle
• (iv) tonicity modifier: sodium chloride
• (v) pH adjusting agent: sodium hydroxide, hydrochloric acid, or mixture thereof
• Stability/impurity condition:
  • glycopyrrolate Impurity C < 1% after storage at 40°C and 75% relative humidity for 3 months
• Ready-to-use injectable compositions are further scoped by dependent claims to container formats and administration routes.

Key constraints that define infringement

Claim 1 is not just “neostigmine + glycopyrrolate injection.” It is limited by multiple conjunctive limitations:

1. Fixed concentration bands by “about” terms

   • Neostigmine: ~1 mg/mL
   • Glycopyrrolate: ~0.2 mg/mL
   • This sets a 5:1 neostigmine:glycopyrrolate concentration ratio.

2. Tonicity modifier must be sodium chloride

   • Use of other tonicity agents (for example, dextrose, mannitol, etc.) is outside the literal claim if not captured by “tonicity modifier” definition.

3. pH adjustment must be NaOH and/or HCl

   • Buffers and other pH agents are not stated as acceptable unless they still fall within “pH adjusting agent” language (the claim names specific agents).

4. Impurity C acceptance criterion

   • Requires that glycopyrrolate Impurity C remains <1% after 40°C/75% RH for 3 months.

5. Purpose/functional context

   • “for reversing the effects of non-depolarizing neuromuscular blocking agents”
   • This typically does not change formulation mechanics but supports product identity and claim interpretation.

Impurity limitation is a decisive enforcement lever

The most enforceable, product-differentiating element is the stability test linked to a specific impurity:

• Glycopyrrolate Impurity C < 1% after accelerated storage.

That requirement can be used to distinguish competing products that otherwise match concentration and formulation excipients but fail the impurity/spec condition.

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How does Claim 7 change the chemical form language (scope continuity vs. substitution)?

Claim 7 is another independent composition claim with materially aligned features but introduces a more specific salt pairing:

• Neostigmine: about 1 mg/mL of neostigmine methylsulfate
• Glycopyrrolate: about 0.2 mg/mL of glycopyrronium bromide (spelling in your text: “glycopyrronium bromide”)
• Vehicle, tonicity modifier, and pH adjusting agent are the same:
  • sodium chloride
  • sodium hydroxide, hydrochloric acid, or mixture thereof
• Same impurity and storage condition:
  • Impurity C <1% after 40°C/75% RH for 3 months
• Claim 10 converts this into a “consisting of” form, tightening exclusions.

Practical effect

• Claim 1 uses neostigmine and glycopyrrolate broadly with “pharmaceutically acceptable salt, solvate or hydrate thereof.”
• Claim 7 explicitly fixes the salts: neostigmine methylsulfate and glycopyrronium bromide.
• From an infringement standpoint:
  • A product using different salts/hydrates could still fall under Claim 1 if it uses “pharmaceutically acceptable salt/solvate/hydrate thereof.”
  • Claim 7 captures the salt-specific embodiments, making it easier to enforce where those salts are used.

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What do Claims 2-6 add (narrowing features)?

Claim 2: sealed container type

Claim 2 depends on Claim 1 and narrows packaging:

• sealed container selected from:
  • ampoules
  • vials
  • pre-filled syringes

This limits literal coverage to those packaging categories.

Claim 3: dosage form (solution/suspension/emulsion)

Claim 3 depends on Claim 1 and allows the composition to be:

• solution, suspension, or emulsion

So the claim is not restricted to one physical dosage form.

Claim 4: route of administration

Claim 4 depends on Claim 1 and states suitability for:

• subcutaneous, intravenous, or intramuscular administration

This can matter if competitors market an alternate route or argue lack of “suitable for” use.

Claim 5: explicit salt pairing inside the general claim

Claim 5 depends on Claim 1 and specifies:

• neostigmine methylsulfate and glycopyrronium bromide

It functionally overlaps with Claim 7, but by dependency it narrows within the Claim 1 framework.

Claim 6: pH range

Claim 6 depends on Claim 1 and requires:

• pH ranging from about 3.0 to about 4.0

This is another enforcement boundary. If a competitor-formulated product operates outside that pH window, it may fall outside Claim 6 even if Claim 1 could still be argued.

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What does Claim 8-10 add (additional narrowing and “consisting of”)?

Claim 8

Claim 8 depends on Claim 7 and narrows packaging in the same way:

• sealed container: ampoules, vials, pre-filled syringes

Claim 9

Claim 9 depends on Claim 7 and fixes:

• pH about 3.0 to about 4.0

Claim 10: “consisting of” formulation closure

Claim 10 is the tightest claim form and functions as the most exclusionary literal claim:

• consisting of:
  • (i) about 1 mg/mL neostigmine methylsulfate
  • (ii) about 0.2 mg/mL glycopyrronium bromide
  • (iii) pharmaceutically acceptable liquid vehicle
  • (iv) sodium chloride as tonicity modifier
  • (v) sodium hydroxide, hydrochloric acid or mixture as pH adjusting agent
• impurity/stability condition:
  • Impurity C <1% after 40°C/75% RH for 3 months

“Consisting of” generally limits inclusion of additional active/pharmaceutical ingredients beyond the listed elements (while still allowing typical formulation excipients if they are treated as part of the listed components; the claim language explicitly includes “liquid vehicle,” but does not name other excipients). Practically, this claim is designed to block “variant formulations” that try to add buffers/pH agents beyond NaOH/HCl or alter tonicity beyond NaCl.

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Claim scope map (who is in vs out) using the claim’s own limiting terms

In-literal-likelihood zone

A product likely falls within the core claims if it meets all of the following simultaneously:

• Dose ratio/levels
  • neostigmine at ~1 mg/mL
  • glycopyrrolate/glycopyrronium bromide at ~0.2 mg/mL
• Use context
  • intended to reverse non-depolarizing NMBAs
• Tonicity
  • sodium chloride used as the tonicity modifier
• pH adjustment
  • pH set using NaOH and/or HCl
• Stability/impurity
  • glycopyrrolate Impurity C <1% after 40°C/75% RH for 3 months
• Form factor
  • injectable and “ready-to-use” (and, if the container/route matters, matches Claims 2/4/8 accordingly)

Out-literal-likelihood zone (typical design-arounds that attack specific limitations)

Competitor formulations can reduce literal exposure by changing at least one of the conjunctive limitations:

• Replace or remove sodium chloride as tonicity modifier (use alternative tonicity systems).
• Use different pH agents (introduce buffers or other acid/base systems) if not captured under “pH adjusting agent” as claimed.
• Operate at pH values outside ~3.0 to ~4.0 (important for dependent Claims 6 and 9).
• Fail the impurity target:
  • products with Impurity C ≥1% after the specified accelerated condition would not meet the claim’s stability criterion.
• Change concentration outside “about” bounds:
  • materially different neostigmine or glycopyrrolate concentrations can push outside the claim definition (this hinges on construction of “about”).

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What is the patent landscape shaped by this claim set?

Landscape axis 1: formulation stability and impurity control

The claims anchor enforceability to an analytical attribute: glycopyrrolate Impurity C under a defined storage stress. This creates a landscape where:

• Generic or follow-on products cannot assume a “formulation shell” match is enough.
• The key differentiator becomes whether the product formulates and stabilizes impurity levels to satisfy <1% after the defined test.

Landscape axis 2: product identity built from salt pairing and concentration

Because Claim 7 and Claim 10 fix:

• neostigmine methylsulfate
• glycopyrronium bromide
• concentrations at ~1 mg/mL and ~0.2 mg/mL the competitive set likely includes:
• branded and generic offerings that use those exact salts and concentration ratios.
• formulations that deviate either via different salt selection (if still “pharmaceutically acceptable”) or via different dosing concentrations.

Landscape axis 3: “consisting of” narrows variant formulations

Claim 10’s “consisting of” formulation language increases the risk for competitors that try to:

• add alternative pH modifiers
• alter tonicity agent systems
• include extra active/functional ingredients beyond the listed categories

The landscape implication is that variant formulations may still face claim coverage under Claim 1/7, but Claim 10 is positioned to force a more radical reformulation rather than minor tweaks.

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How strong are these claims relative to typical formulation-IP risk points?

Strong points

• Multiple conjunctive limitations (dose, tonicity, pH agents, impurity spec, storage condition).
• Specific impurity and storage protocol: creates a concrete testable boundary.
• Independent claims exist in two versions:
  • broader salt/solvate/hydrate language (Claim 1)
  • fixed salts (Claim 7)
• “consisting of” closes escape routes for minor excipient additions (Claim 10).

Potential attack points in practice (what challengers usually focus on)

Even without examining validity arguments, the structure implies typical challenge targets:

• construction of “about” for concentrations
• whether accused products meet impurity measurement definitions and test conditions
• whether “pH adjusting agent” captures all relevant buffer/pH systems used in commercial formulations

These are not asserted weaknesses; they are the predictable focal points in claim interpretation and infringement testing.

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Actionable enforcement and diligence checklist (claim-driven)

If you are evaluating freedom-to-operate

Prioritize technical comparison to these claim elements:

1. Concentration and ratio
   • neostigmine at ~1 mg/mL
   • glycopyrrolate at ~0.2 mg/mL
2. Chemical form
   • salt forms: neostigmine methylsulfate and glycopyrronium bromide
   • if different, assess Claim 1 coverage via “pharmaceutically acceptable salt/solvate/hydrate”
3. Tonicity modifier
   • verify whether tonicity is sodium chloride
4. pH control chemistry
   • identify whether pH is adjusted using NaOH and/or HCl
5. Impurity C spec
   • glycopyrrolate Impurity C <1% after 40°C/75% RH for 3 months
6. Product presentation
   • container type and readiness-to-use format (for Claims 2 and 8)
7. Operational pH
   • pH between ~3.0 and ~4.0 (for Claims 6 and 9)

If you are assessing competitive risk from a new product entrant

Treat the impurity specification as the primary “go/no-go” comparator. A competitor that matches concentration and excipients but fails the impurity target is less likely to infringe, even if the product concept is the same.

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Key Takeaways

• US 11,110,054 is a formulation-stability patent for a ready-to-use injectable neostigmine + glycopyrrolate/glycopyrronium reversal composition for non-depolarizing NMBAs, defined by dose levels (~1 mg/mL neostigmine, ~0.2 mg/mL glycopyrrolate), sodium chloride tonicity, and pH adjusted using NaOH and/or HCl.
• The claims are anchored by a hard stability/impurity criterion: glycopyrrolate Impurity C <1% after 40°C/75% RH for 3 months, which is likely the most differentiating element in the patent landscape.
• Claim 10 uses “consisting of” to tighten boundaries against formulation variants.
• Landscape risk concentrates on products that match both formulation chemistry and stability/impurity performance, not just the API combination.

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FAQs

1. Does the patent cover any neostigmine and glycopyrrolate injection?
   No. The claims require specific concentration levels, sodium chloride tonicity, NaOH/HCl pH adjustment, and Impurity C <1% after 40°C/75% RH for 3 months.

2. What is the most powerful claim limitation for design-arounds?
   The glycopyrrolate Impurity C limit tied to 40°C/75% RH for 3 months.

3. Is sodium chloride only a “recommended” excipient?
   No. It is a claimed tonicity modifier.

4. Does “consisting of” in Claim 10 make infringement easier?
   Yes. It narrows permissible formulation elements to those listed (with “liquid vehicle” included), which increases predictability for literal-coverage analysis.

5. Can changing pH avoid dependent claims?
   Yes for Claims 6 and 9 because they require pH about 3.0 to about 4.0. Independent claims still require the specified pH adjusting agents and impurity/stability performance.

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References

[1] United States Patent and Trademark Office. US Patent 11,110,054 (claims and text as provided).

Drugs Protected by US Patent 11,110,054

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	PREVDUO	glycopyrrolate; neostigmine methylsulfate	SOLUTION;INTRAVENOUS	216903-001	Feb 23, 2023		RX	Yes	Yes	11,110,054		Y