Scope and claims of US Patent 12,151,020 (neostigmine plus glycopyrrolate/glycopyrronium impurity control) and how the patent estate can block generics

US 12,151,020 is directed to a ready-to-use, stable injectable fixed-dose combination of a neostigmine component with an antimuscarinic component (glycopyrrolate/glycopyrronium) at tightly defined concentrations, using formulation design rules aimed at suppressing degradation to “Glycopyrrolate Impurity C” below a specified threshold after storage under accelerated conditions. The independent claim sets the enforceable core: (1) concentrations (≈1 mg/mL neostigmine + ≈0.2 mg/mL glycopyrrolate), (2) presence of a tonicity modifier and a pharmaceutically acceptable liquid vehicle, and (3) an impurity control performance requirement at 40°C/75% RH for 6 months (<1%). Dependent claims narrow to specific tonicity (sodium chloride), container closure formats (ampoule/vial/prefilled syringe), dosage form (solution/suspension/emulsion), routes (SC/IV/IM), pH range (3.0 to 4.0), and a specific chemical pairing (neostigmine methylsulfate + glycopyrronium bromide).

What does US 12,151,020 claim for stable ready-to-use neostigmine–glycopyrrolate injectables?

Short answer: It claims a particular composition (not a device or use method) defined by (a) two drug concentrations in a liquid vehicle, (b) tonicity modifier, and (c) stability validated by impurity acceptance criteria after storage, with optional narrowing to pH and specific salt forms.

Independent claim 1: what are the enforceable ingredients and the stability metric?

Claim 1 recites:

Active concentrations
- Neostigmine: about 1 mg/mL (or pharmaceutically acceptable salt, solvate, hydrate)
- Glycopyrrolate: about 0.2 mg/mL (or pharmaceutically acceptable salt, solvate, hydrate)
Formulation components
- Pharmaceutically acceptable liquid vehicle
- Tonicity modifier (unspecified in claim 1)
Container/administration status
- “Ready-to-use injectable pharmaceutical composition” (not explicitly limiting to route in claim 1, though dependent claims add that)
Critical stability/performance requirement
- “Glycopyrrolate Impurity C” level < 1% after storage at:
  - 40°C
  - 75% relative humidity
  - for 6 months

Practical scope of claim 1: any liquid injectable meeting the recited concentration “about” ranges, containing a tonicity modifier and achieving the impurity control threshold under the specified accelerated condition falls within the claim, regardless of the specific vehicle composition, if the vehicle is a pharmaceutically acceptable liquid vehicle. The “Impurity C <1%” limitation is a major narrowing feature that can be used both offensively (infringement via stability testing) and defensively (non-infringement by showing impurity exceeds the limit under the test protocol).

Independent claim 8: same concept with explicit salt pairing and added pH adjusting agent

Claim 8 is a second independent claim with the same impurity-performance requirement, but it specifies:

Neostigmine methylsulfate: about 1 mg/mL
Glycopyrronium bromide: about 0.2 mg/mL
Pharmaceutically acceptable liquid vehicle
Tonicity modifier
pH adjusting agent (added requirement in claim 8)
Impurity acceptance: “Glycopyrrolate Impurity C” < 1% after 40°C/75% RH for 6 months

This claim is narrower than claim 1 in two ways:

it locks the salt forms to neostigmine methylsulfate and glycopyrronium bromide, and
it requires a pH adjusting agent.

How broad is the claim scope: concentrations “about,” impurity threshold, and “liquid vehicle”?

“About 1 mg/mL” and “about 0.2 mg/mL”

The use of “about” typically provides some latitude around nominal concentrations, but it is not unlimited. In infringement analysis, “about” is assessed via prosecution history and claim construction. Even without file history, the enforceable takeaway is that the formulation must be in the vicinity of the stated strengths and designed for fixed-dose combination dosing.

“Glycopyrrolate Impurity C less than 1%” is the highest-friction limiter

This is the single most testable constraint. It defines the patent’s stability boundary, effectively turning the claim into a performance-claim for product quality.

Key enforcement consequence:

To prove infringement, a challenger/claimant would typically test finished product stored for 6 months at 40°C/75% RH and quantify Impurity C using the patent’s analytical method (not provided in your excerpt).
To design around, a generic would aim to show either:
- the impurity exceeds 1% under the same storage protocol, or
- the impurity species is not “Glycopyrrolate Impurity C” as characterized in the patent (claim construction depends on definitions in the specification).

“Pharmaceutically acceptable liquid vehicle” is broad

Claim 1 leaves vehicle formulation open, so long as it is pharmaceutically acceptable and can support impurity control. That broad vehicle language increases enforceability, because design-around efforts must still satisfy the impurity threshold under accelerated storage.

What do the dependent claims add: tonicity modifier, pH, container closure, and route?

Tonicity modifier specificity

Claim 2: tonicity modifier is sodium chloride
This is a narrower design point that, if satisfied, supports infringement of claim 2 specifically. However, claim 1 already covers any tonicity modifier, so sodium chloride is not required unless one is analyzing claim 2 independently.

Container format limitations

Claim 3 / Claim 11: sealed container selected from:
- ampoule
- vial
- pre-filled syringe

This means claim 3 and claim 11 are not limited to bulk liquids, syringes without prefill, or other packaging like cartridges unless they fit these categories.

Dosage form category

Claim 4 / Claim 12: composition is in the form of:
- solution
- suspension
- emulsion

So the patent does not limit to solutions only. That increases its coverage across common injectable liquid dosage technologies.

Route of administration

Claim 5 / Claim 13: suitable for:
- subcutaneous
- intravenous
- intramuscular

This is a formulation suitability limitation, not an administered method claim. It still can matter for infringement arguments if product labeling or intended use is contested.

Specific salt pairing (claim 6)

Claim 6: composition comprises:
- neostigmine methylsulfate
- glycopyrronium bromide

This dependent claim aligns with claim 8’s salt-specific structure, but claim 1 covers other salts/hydrates/solvates of neostigmine and glycopyrrolate/glycopyrronium.

pH range (claim 7 and claim 14)

Claim 7: pH 3.0 to 4.0
Claim 14: same pH range 3.0 to 4.0

These dependent claims require a relatively acidic formulation. This is important because pH is one of the typical control knobs affecting degradation and impurity formation.

What “design around” paths are implied by the claim language?

1) Substitute tonicity modifier

Claim 1 does not require sodium chloride.
A design-around that removes sodium chloride may still infringe claim 1 if another tonicity modifier is used and the impurity threshold is met.
Only if the alternate tonicity strategy fails the <1% impurity requirement under the specified storage test would it exit claim 1.

2) Change pH

pH 3.0 to 4.0 is only required in dependent claims (7 and 14).
A product outside that pH window could still infringe claim 1/8 if it meets the impurity threshold and other elements.

3) Use different packaging

Claim 3/11 restrict to ampoule/vial/prefilled syringe.
A product packaged differently could avoid those dependent claims while still potentially infringing claim 1/8 if those independent claims do not require those packaging types. (Your excerpt indicates packaging only in dependent claims.)

4) Avoid the specific impurity metric

Because the claims hinge on “Glycopyrrolate Impurity C <1%,” the most realistic design-around is analytical and formulation-stability-based:

engineer a formulation where the measured Impurity C at 40°C/75% RH for 6 months is ≥1%, or
redefine/avoid the specific impurity species being labeled as “Impurity C” per the patent’s analytical definition (which depends on the specification and method, not shown in your excerpt).

What likely enforceable claim types are present: composition stability/performance + salt/concentration ranges

Based on the claims provided, the patent is primarily a:

composition claim (fixed combination strength in a liquid vehicle),
with a stability-performance limitation (Impurity C acceptance after accelerated storage),
plus dependent narrowing to salt forms, pH window, tonicity modifier identity, and packaging.

That structure is characteristic of patents intended to protect commercial ready-to-use injectables where the key commercial barrier is shelf-life and impurity control, not just the active ingredients.

Patent landscape risks: what can other patents cover vs. what this one specifically covers?

Without a bibliographic record for US 12,151,020 (application number, filing date, specification-defined Impurity C definition, and whether there are continuation/divisional family members), only the boundaries of the given claims can be analyzed.

Likely “overlap” with other formulation patents

shelf-life/impurity suppression improvements for neostigmine + glycopyrrolate/glycopyrronium combinations
pH-adjusted injectable stability improvements
specific concentration ratio combinations and ready-to-use packaging formats

This patent would be most differentiated where it:

specifies the concentration ratio,
includes “Impurity C” as a named degradation product,
and uses a fixed storage condition and threshold.

What this patent probably does NOT cover based on the claim text

broad methods of administering neostigmine/glycopyrronium
devices or dosing regimens (no method-of-use claim in your excerpt)
non-ready-to-use dry products or kits (claim language is “ready-to-use injectable pharmaceutical composition” but dependent claims don’t address kits)
combination products with different concentration ratios (claim requires about 1 mg/mL and about 0.2 mg/mL)

If a generic or biosimilar question arises, where is the Paragraph IV style risk?

This patent reads like a small-molecule injectable formulation and would be litigated in the Hatch-Waxman small-molecule context (Orange Book, ANDA route), not biosimilar pathways.

However, infringement risk depends on whether the generic’s product meets the performance metric (Impurity C < 1%) under the specific accelerated conditions. Many formulation patents become “conditional” in litigation because the generic’s stability data under the patent’s protocol is determinative.

Claim-level risk profile

High if the generic uses the same or similar ratio and formulation design to meet shelf-life, because that often also drives down named impurities.
Medium to lower if the generic cannot reproduce the impurity performance or if its analytics show different impurity profiles that do not map to “Impurity C.”

Exclusivity timeline: when does protection end?

Your excerpt does not include the patent’s filing date, grant date, priority dates, or any terminal disclaimer/effective term adjustments. Without that data, a precise exclusivity and expiration timeline cannot be produced.

Key takeaways

US 12,151,020 protects a specific ready-to-use injectable combination: about 1 mg/mL neostigmine and about 0.2 mg/mL glycopyrrolate (or corresponding salts), in a liquid vehicle with a tonicity modifier.
The independent claim’s core narrowing feature is performance at 40°C/75% RH for 6 months: Glycopyrrolate Impurity C < 1%.
Dependent claims tighten coverage to sodium chloride, pH 3.0–4.0, ampoule/vial/prefilled syringe packaging, solution/suspension/emulsion, and SC/IV/IM suitability, plus a salt-specific pairing in at least one dependent claim.
Design-around is most plausibly achieved through failure to meet the Impurity C threshold under the same storage conditions or by producing a product whose degradation profile does not satisfy the claim-defined “Impurity C” limitation.

FAQs

1) Can a product with a different tonicity modifier than sodium chloride still infringe claim 1?
Yes. Claim 1 requires a tonicity modifier but does not limit it to sodium chloride. Sodium chloride is only required for claim 2.

2) Does the patent require a specific pH to infringe claim 1?
No. pH 3.0–4.0 is limited to dependent claims (7 and 14). Claim 1 and claim 8 do not, on the face of the excerpt, require that pH range.

3) What is the single most litigable limitation in these claims?
The stability requirement: Glycopyrrolate Impurity C <1% after 40°C/75% RH for 6 months.

4) Are ampoules/vials/prefilled syringes required for infringement of the independent claims?
Based on the excerpt, packaging is recited only in dependent claims (3 and 11). Independent claim infringement is not expressly limited to those containers in the provided language.

5) Is this patent drafted like a method-of-use or a formulation patent?
Formulation. The claims are directed to the composition and its stability/impurity profile, not an administration method.

References (APA)

United States Patent and Trademark Office. US Patent 12,151,020. Claims provided in user prompt.

Title:	Ready-to-use injectable pharmaceutical compositions comprising neostigmine and glycopyrrolate
Abstract:	Stable, ready-to-use injectable pharmaceutical compositions are provided, comprising the combination of neostigmine, glycopyrrolate, and a pharmaceutically acceptable liquid vehicle, optionally with additional pharmaceutically acceptable excipients. 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, 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:	US18/444,310
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,151,020
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound;
Patent landscape, scope, and claims:	Scope and claims of US Patent 12,151,020 (neostigmine plus glycopyrrolate/glycopyrronium impurity control) and how the patent estate can block generics US 12,151,020 is directed to a ready-to-use, stable injectable fixed-dose combination of a neostigmine component with an antimuscarinic component (glycopyrrolate/glycopyrronium) at tightly defined concentrations, using formulation design rules aimed at suppressing degradation to “Glycopyrrolate Impurity C” below a specified threshold after storage under accelerated conditions. The independent claim sets the enforceable core: (1) concentrations (≈1 mg/mL neostigmine + ≈0.2 mg/mL glycopyrrolate), (2) presence of a tonicity modifier and a pharmaceutically acceptable liquid vehicle, and (3) an impurity control performance requirement at 40°C/75% RH for 6 months (<1%). Dependent claims narrow to specific tonicity (sodium chloride), container closure formats (ampoule/vial/prefilled syringe), dosage form (solution/suspension/emulsion), routes (SC/IV/IM), pH range (3.0 to 4.0), and a specific chemical pairing (neostigmine methylsulfate + glycopyrronium bromide). What does US 12,151,020 claim for stable ready-to-use neostigmine–glycopyrrolate injectables? Short answer: It claims a particular composition (not a device or use method) defined by (a) two drug concentrations in a liquid vehicle, (b) tonicity modifier, and (c) stability validated by impurity acceptance criteria after storage, with optional narrowing to pH and specific salt forms. Independent claim 1: what are the enforceable ingredients and the stability metric? Claim 1 recites: Active concentrations Neostigmine: about 1 mg/mL (or pharmaceutically acceptable salt, solvate, hydrate) Glycopyrrolate: about 0.2 mg/mL (or pharmaceutically acceptable salt, solvate, hydrate) Formulation components Pharmaceutically acceptable liquid vehicle Tonicity modifier (unspecified in claim 1) Container/administration status “Ready-to-use injectable pharmaceutical composition” (not explicitly limiting to route in claim 1, though dependent claims add that) Critical stability/performance requirement “Glycopyrrolate Impurity C” level < 1% after storage at: 40°C 75% relative humidity for 6 months Practical scope of claim 1: any liquid injectable meeting the recited concentration “about” ranges, containing a tonicity modifier and achieving the impurity control threshold under the specified accelerated condition falls within the claim, regardless of the specific vehicle composition, if the vehicle is a pharmaceutically acceptable liquid vehicle. The “Impurity C <1%” limitation is a major narrowing feature that can be used both offensively (infringement via stability testing) and defensively (non-infringement by showing impurity exceeds the limit under the test protocol). Independent claim 8: same concept with explicit salt pairing and added pH adjusting agent Claim 8 is a second independent claim with the same impurity-performance requirement, but it specifies: Neostigmine methylsulfate: about 1 mg/mL Glycopyrronium bromide: about 0.2 mg/mL Pharmaceutically acceptable liquid vehicle Tonicity modifier pH adjusting agent (added requirement in claim 8) Impurity acceptance: “Glycopyrrolate Impurity C” < 1% after 40°C/75% RH for 6 months This claim is narrower than claim 1 in two ways: it locks the salt forms to neostigmine methylsulfate and glycopyrronium bromide, and it requires a pH adjusting agent. How broad is the claim scope: concentrations “about,” impurity threshold, and “liquid vehicle”? “About 1 mg/mL” and “about 0.2 mg/mL” The use of “about” typically provides some latitude around nominal concentrations, but it is not unlimited. In infringement analysis, “about” is assessed via prosecution history and claim construction. Even without file history, the enforceable takeaway is that the formulation must be in the vicinity of the stated strengths and designed for fixed-dose combination dosing. “Glycopyrrolate Impurity C less than 1%” is the highest-friction limiter This is the single most testable constraint. It defines the patent’s stability boundary, effectively turning the claim into a performance-claim for product quality. Key enforcement consequence: To prove infringement, a challenger/claimant would typically test finished product stored for 6 months at 40°C/75% RH and quantify Impurity C using the patent’s analytical method (not provided in your excerpt). To design around, a generic would aim to show either: the impurity exceeds 1% under the same storage protocol, or the impurity species is not “Glycopyrrolate Impurity C” as characterized in the patent (claim construction depends on definitions in the specification). “Pharmaceutically acceptable liquid vehicle” is broad Claim 1 leaves vehicle formulation open, so long as it is pharmaceutically acceptable and can support impurity control. That broad vehicle language increases enforceability, because design-around efforts must still satisfy the impurity threshold under accelerated storage. What do the dependent claims add: tonicity modifier, pH, container closure, and route? Tonicity modifier specificity Claim 2: tonicity modifier is sodium chloride This is a narrower design point that, if satisfied, supports infringement of claim 2 specifically. However, claim 1 already covers any tonicity modifier, so sodium chloride is not required unless one is analyzing claim 2 independently. Container format limitations Claim 3 / Claim 11: sealed container selected from: ampoule vial pre-filled syringe This means claim 3 and claim 11 are not limited to bulk liquids, syringes without prefill, or other packaging like cartridges unless they fit these categories. Dosage form category Claim 4 / Claim 12: composition is in the form of: solution suspension emulsion So the patent does not limit to solutions only. That increases its coverage across common injectable liquid dosage technologies. Route of administration Claim 5 / Claim 13: suitable for: subcutaneous intravenous intramuscular This is a formulation suitability limitation, not an administered method claim. It still can matter for infringement arguments if product labeling or intended use is contested. Specific salt pairing (claim 6) Claim 6: composition comprises: neostigmine methylsulfate glycopyrronium bromide This dependent claim aligns with claim 8’s salt-specific structure, but claim 1 covers other salts/hydrates/solvates of neostigmine and glycopyrrolate/glycopyrronium. pH range (claim 7 and claim 14) Claim 7: pH 3.0 to 4.0 Claim 14: same pH range 3.0 to 4.0 These dependent claims require a relatively acidic formulation. This is important because pH is one of the typical control knobs affecting degradation and impurity formation. What “design around” paths are implied by the claim language? 1) Substitute tonicity modifier Claim 1 does not require sodium chloride. A design-around that removes sodium chloride may still infringe claim 1 if another tonicity modifier is used and the impurity threshold is met. Only if the alternate tonicity strategy fails the <1% impurity requirement under the specified storage test would it exit claim 1. 2) Change pH pH 3.0 to 4.0 is only required in dependent claims (7 and 14). A product outside that pH window could still infringe claim 1/8 if it meets the impurity threshold and other elements. 3) Use different packaging Claim 3/11 restrict to ampoule/vial/prefilled syringe. A product packaged differently could avoid those dependent claims while still potentially infringing claim 1/8 if those independent claims do not require those packaging types. (Your excerpt indicates packaging only in dependent claims.) 4) Avoid the specific impurity metric Because the claims hinge on “Glycopyrrolate Impurity C <1%,” the most realistic design-around is analytical and formulation-stability-based: engineer a formulation where the measured Impurity C at 40°C/75% RH for 6 months is ≥1%, or redefine/avoid the specific impurity species being labeled as “Impurity C” per the patent’s analytical definition (which depends on the specification and method, not shown in your excerpt). What likely enforceable claim types are present: composition stability/performance + salt/concentration ranges Based on the claims provided, the patent is primarily a: composition claim (fixed combination strength in a liquid vehicle), with a stability-performance limitation (Impurity C acceptance after accelerated storage), plus dependent narrowing to salt forms, pH window, tonicity modifier identity, and packaging. That structure is characteristic of patents intended to protect commercial ready-to-use injectables where the key commercial barrier is shelf-life and impurity control, not just the active ingredients. Patent landscape risks: what can other patents cover vs. what this one specifically covers? Without a bibliographic record for US 12,151,020 (application number, filing date, specification-defined Impurity C definition, and whether there are continuation/divisional family members), only the boundaries of the given claims can be analyzed. Likely “overlap” with other formulation patents shelf-life/impurity suppression improvements for neostigmine + glycopyrrolate/glycopyrronium combinations pH-adjusted injectable stability improvements specific concentration ratio combinations and ready-to-use packaging formats This patent would be most differentiated where it: specifies the concentration ratio, includes “Impurity C” as a named degradation product, and uses a fixed storage condition and threshold. What this patent probably does NOT cover based on the claim text broad methods of administering neostigmine/glycopyrronium devices or dosing regimens (no method-of-use claim in your excerpt) non-ready-to-use dry products or kits (claim language is “ready-to-use injectable pharmaceutical composition” but dependent claims don’t address kits) combination products with different concentration ratios (claim requires about 1 mg/mL and about 0.2 mg/mL) If a generic or biosimilar question arises, where is the Paragraph IV style risk? This patent reads like a small-molecule injectable formulation and would be litigated in the Hatch-Waxman small-molecule context (Orange Book, ANDA route), not biosimilar pathways. However, infringement risk depends on whether the generic’s product meets the performance metric (Impurity C < 1%) under the specific accelerated conditions. Many formulation patents become “conditional” in litigation because the generic’s stability data under the patent’s protocol is determinative. Claim-level risk profile High if the generic uses the same or similar ratio and formulation design to meet shelf-life, because that often also drives down named impurities. Medium to lower if the generic cannot reproduce the impurity performance or if its analytics show different impurity profiles that do not map to “Impurity C.” Exclusivity timeline: when does protection end? Your excerpt does not include the patent’s filing date, grant date, priority dates, or any terminal disclaimer/effective term adjustments. Without that data, a precise exclusivity and expiration timeline cannot be produced. Key takeaways US 12,151,020 protects a specific ready-to-use injectable combination: about 1 mg/mL neostigmine and about 0.2 mg/mL glycopyrrolate (or corresponding salts), in a liquid vehicle with a tonicity modifier. The independent claim’s core narrowing feature is performance at 40°C/75% RH for 6 months: Glycopyrrolate Impurity C < 1%. Dependent claims tighten coverage to sodium chloride, pH 3.0–4.0, ampoule/vial/prefilled syringe packaging, solution/suspension/emulsion, and SC/IV/IM suitability, plus a salt-specific pairing in at least one dependent claim. Design-around is most plausibly achieved through failure to meet the Impurity C threshold under the same storage conditions or by producing a product whose degradation profile does not satisfy the claim-defined “Impurity C” limitation. FAQs 1) Can a product with a different tonicity modifier than sodium chloride still infringe claim 1? Yes. Claim 1 requires a tonicity modifier but does not limit it to sodium chloride. Sodium chloride is only required for claim 2. 2) Does the patent require a specific pH to infringe claim 1? No. pH 3.0–4.0 is limited to dependent claims (7 and 14). Claim 1 and claim 8 do not, on the face of the excerpt, require that pH range. 3) What is the single most litigable limitation in these claims? The stability requirement: Glycopyrrolate Impurity C <1% after 40°C/75% RH for 6 months. 4) Are ampoules/vials/prefilled syringes required for infringement of the independent claims? Based on the excerpt, packaging is recited only in dependent claims (3 and 11). Independent claim infringement is not expressly limited to those containers in the provided language. 5) Is this patent drafted like a method-of-use or a formulation patent? Formulation. The claims are directed to the composition and its stability/impurity profile, not an administration method. References (APA) United States Patent and Trademark Office. US Patent 12,151,020. Claims provided in user prompt. More… ↓ ⤷ Start Trial

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		DISCN	Yes	No	12,151,020	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 12,151,020

Which drugs does patent 12,151,020 protect, and when does it expire?

Summary for Patent: 12,151,020