Details for Patent: 12,419,867

Which drugs does patent 12,419,867 protect, and when does it expire?

Patent 12,419,867 protects VIVIMUSTA and is included in one NDA.

Summary for Patent: 12,419,867

Title:	Stable pharmaceutical compositions of bendamustine
Abstract:	Stable, injectable pharmaceutical compositions are provided, which are useful as ready-to-dilute (RTD) or ready-to-use (RTU) liquid injectable compositions comprising bendamustine or a pharmaceutically acceptable salt thereof, and which are suitable for intravenous administration. Preferably, solution formulations comprise (a) bendamustine, or pharmaceutically acceptable salts, solvates, or hydrates thereof, (b) at least one pharmaceutically acceptable non-aqueous solvent; (c) optionally, at least one pharmaceutically acceptable excipient, and (d) optionally, a pH adjuster, where the pharmaceutical composition is antioxidant-free, and formulated as a ready-to-dilute or ready-to-use liquid composition suitable for parenteral administration. The invention further relates to methods for manufacturing stable, antioxidant-free injectable solutions of bendamustine.
Inventor(s):	Harish Govindaraja Setty CHINNARI, Somashekhar BATTINI, Sumitra Ashokkumar PILLAI, Lourdu Chinnu Thippabattuni, BALASUBRAMANIAN Satheesh
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US18/758,225
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 12,419,867 (Method of Treating CLL/Indolent B-Cell NHL With Liquid, Antioxidant-Free Bendamustine at 25 mg/mL) Scope and Claim-by-Claim Patent Landscape

Executive summary: U.S. Patent 12,419,867 is a US-method-of-treatment and liquid-formulation claim set built around a specific bendamustine concentration (about 25 mg/mL), specific non-aqueous solvent sets (ethanol, glycerine, PEG, propylene glycol, DMAc, NMP, mixtures), optional pH adjustment windows, and two stability/impurity performance gates tied to storage at 2°C to 8°C for 6 months by HPLC. The claims further lock in antioxidant-free status for both the undiluted and diluted compositions, creating a narrow but potentially defensible formulation boundary against competitors that use antioxidants, different solvent systems, or different impurity profiles.

What does US Patent 12,419,867 claim for bendamustine liquid formulations used to treat CLL and indolent B-cell NHL?

Core claim position (Claim 1): The patent’s principal protection is not a bare “bendamustine for CLL” method. It is a method of treating where the treatment is executed with a very specific dosing vehicle: a liquid composition (undiluted concentrate) that is later diluted with a parenterally acceptable diluent prior to administration. The exclusivity risk zone is the intersection of:

1. Therapeutic indication: CLL or indolent B-cell non-Hodgkin’s lymphoma
2. Drug concentration: about 25 mg/mL bendamustine (or salt)
3. Vehicle: non-aqueous solvent selected from a constrained list, at least one chosen
4. Optional pH adjuster and pH ranges in dependent claims
5. Performance attributes after refrigerated storage for 6 months: total impurities ≤ 5% w/w, ethyl ester impurity ≤ 0.5% w/w, mono-substituted impurity ≤ 3.5% w/w
6. Antioxidant-free condition for both the concentrate and diluted compositions

How Claim 1 is structured legally (what limits infringement)

Claim 1 is drafted as an “administering” claim tied to a vehicle definition. That typically narrows infringement to scenarios where a competitor’s product is (i) used for the claimed indications and (ii) meets the composition + impurity + antioxidant + storage attributes.

Key limiting elements:

• Liquid composition vs. reconstituted lyophilized drug: Claim 1 requires a liquid composition at dosing strength, not a solid-to-liquid conversion scheme.
• Undiluted concentrate and diluted composition both antioxidant-free: This blocks straightforward “concentrate without antioxidants, but diluted admixture includes antioxidants” workarounds (and vice versa).
• Refrigerated 2–8°C for 6 months and impurity acceptance thresholds: Competitors must meet or avoid those thresholds under the same measured conditions (HPLC; the claim states “when stored” for 6 months at 2–8°C).
• Non-aqueous solvent list is “at least one”: The claim is broad as to which of the listed solvents is used, but narrow as to the allowed solvent classes (no aqueous solvents as the main vehicle are recited; also there is no open-ended “selected from” beyond the listed options).
• “About 25 mg/mL” bendamustine: This is a concentration anchor. Even if “about” introduces tolerance, the numeric center is clear and can be used in claim construction for infringement analysis.

What exactly is the vehicle definition in Claim 1?

• Bendamustine: about 25 mg/mL of bendamustine or a pharmaceutically acceptable salt
• Solvent system: at least one non-aqueous solvent selected from:
  • ethanol
  • glycerine
  • PEG
  • propylene glycol
  • dimethylacetamide (DMAc)
  • N-methyl-pyrrolidone (NMP)
  • mixtures thereof
• pH adjuster: “optionally” included
• Antioxidant-free: liquid composition and diluted liquid composition are antioxidant-free
• Impurity acceptance at storage:
  • Total impurities ≤ 5% w/w after 6 months at 2–8°C (HPLC)

How do the dependent claims narrow composition and performance (pH, solvents, impurity profiles) for U.S. 12,419,867?

pH limitations

Claims specify pH ranges for the liquid composition:

• Claim 2: pH about 3.0 to 5.0
• Claim 3: pH about 2.0 to 5.0
• Claim 4: pH about 2.7 to 3.7

These create multiple claim “hooks” depending on which pH window the product targets. A product outside all windows (if reliably established) reduces direct alignment with those dependent claims.

Specific solvent embodiments

• Claim 5: PEG is PEG-400
• Claim 6: ethanol is dehydrated ethanol
• Claim 8: solvent contains a mixture of ethanol and PEG
• Claim 9: ethanol 2–25% w/w, PEG 75–98% w/w
• Claim 10: ethanol 2–5% w/w, PEG 90–98% w/w
• Claim 11: solvent contains 39.45 mg/mL ethanol

These dependent claims matter for non-infringement design because they provide numeric compositions that can be avoided by changing ethanol fraction, ethanol grade definition (dehydrated vs not), or PEG selection (PEG-400 vs other PEG grades).

Specific salt selection

• Claim 7: bendamustine is bendamustine hydrochloride

This is narrower than Claim 1’s “bendamustine or salt” and is likely useful in enforcement against products using the HCl salt but less useful against free base or other salts.

Expanded pH adjuster universe

• Claim 12: pH adjuster selected from:
  • sodium hydroxide, potassium hydroxide, magnesium hydroxide
  • sodium carbonate, tromethamine
  • sodium linoleate, sodium oleate
  • potassium carbonate, potassium linoleate, potassium oleate
  • mixtures

Even though these are listed, Claim 1 says pH adjuster is optional, so absence of pH adjustment can still fall within Claim 1, while the dependent claim requires the specific listed adjuster types.

More specific impurity constraints

Claim 1 covers total impurities ≤5% w/w. Dependent claims add specific impurity classes:

• Claim 13: ethyl ester impurity ≤ 0.5% w/w after 6 months at 2–8°C (HPLC)
• Claim 14: mono-substituted impurity ≤ 3.5% w/w after 6 months at 2–8°C (HPLC)

These are high-leverage because impurity profiles often differ based on process, packaging, and solvent/pH stress chemistry. A competitor could try to remain within total impurity but exceed a specific impurity category, or vice versa. The claim architecture lets the patentee assert either or both.

What is the therapeutic scope: does US 12,419,867 cover only CLL or also indolent B-cell NHL?

Claim 1 covers both:

• chronic lymphocytic leukemia (CLL)
• indolent B-cell non-Hodgkin’s lymphoma

Claims 15 and 16 narrow the method to the particular indication:

• Claim 15: patient treated for CLL
• Claim 16: patient treated for indolent B-cell non-Hodgkin’s lymphoma

This matters for enforcement strategy: a challenger could attempt to argue non-infringement by using the formulation for other indications. The claim set does not speak to other indications.

How broad is the claim coverage on solvent systems and what workarounds does that create?

What the claim permits

Claim 1 allows at least one non-aqueous solvent among the listed group. That is broader than a formulation that is locked to a single solvent.

Where the claim remains narrow

• Non-aqueous solvents are from a closed list. A competitor changing to a solvent outside the list could avoid Claim 1 if the alternative is material and legally qualifies as not “consisting of” an allowed solvent set.
• Antioxidant-free is a hard qualifier for both undiluted and diluted compositions. If any antioxidant is present in either, the claim language points away from infringement.

Practical design-around angles implied by the wording

• Keep ethanol out (or change ethanol grade) to avoid dependent claims, though Claim 1 can still be infringed if another allowed solvent is used and the product meets other limits.
• Use a permitted solvent list but alter pH outside all dependent ranges; still, Claim 1 does not require a pH window.
• Create an impurity profile that violates one threshold (ethyl ester or mono-substituted) while keeping total impurities ≤5%; depends on which dependent claims are asserted.

Patent landscape: how to map the estate around US 12,419,867 (claims, continuity risk, and likely blocking points)

You provided only the claim text, not the patent bibliographic record (application number, priority date, assignee, related family members, or prosecution history). Without those, the landscape must be limited to what is inferable from claim scope alone: the likely estate structure that would support such a drafting choice.

Likely estate components that tend to accompany this claim style

Given the claim’s blend of:

• indication method-of-use language (CLL/indolent B-cell NHL),
• vehicle specificity (25 mg/mL bendamustine in defined non-aqueous solvent systems),
• stability/impurity performance attributes (2–8°C for 6 months),
• and antioxidant-free limitations,

a typical family would include at least:

• base formulation claims (composition and method),
• dependent embodiments for solvent ratios, pH adjusters, specific grades (PEG-400; dehydrated ethanol),
• impurity-specific dependent claims reflecting HPLC-defined degradation pathways,
• and possibly process-related or packaging-related claims (not visible in your excerpt).

Competitive positioning implied by the claims

The claim is designed to capture a specific product class: ready liquid bendamustine concentrate or a liquid vehicle requiring dilution, rather than a lyophilized powder with reconstitution. If the market baseline is a powder and the competitor offers a “liquid” approach, this patent’s vehicle-definition becomes central.

When does exclusivity end and what is the remaining term for US 12,419,867?

No bibliographic data (filing date, priority date, patent term adjustments, or terminal disclaimer) is provided. Without it, a complete and accurate exclusivity/timeline analysis cannot be produced from the claim text alone.

What generic entry risks exist for liquid bendamustine in CLL/indolent B-cell NHL based on the claim language?

Direct infringement risk drivers

A generic or follow-on manufacturer faces higher risk if the product meets all of the following simultaneously:

• bendamustine concentrate around 25 mg/mL
• non-aqueous solvent system using one or more listed solvents
• antioxidant-free formulation for both concentrate and diluted admixture
• HPLC impurity acceptance after refrigerated storage for 6 months meeting total impurities ≤5% w/w (and, if asserted, ethyl ester ≤0.5% w/w and mono-substituted ≤3.5% w/w)
• indication use for CLL or indolent B-cell NHL

Lower-risk routes implied by the claim

• Avoid antioxidant-free status by using antioxidants may land outside the literal language (since the claim requires antioxidant-free).
• Use a different solvent outside the specified list.
• Adjust impurity profiles so that one of the numeric thresholds fails.

What does “antioxidant-free” do to enforcement and licensing leverage?

It is a decisive qualifier because it applies to:

• the liquid composition itself and
• the diluted liquid composition prior to administration.

That dual requirement is leverage in licensing negotiations: a licensee must ensure that both concentrate and diluted admixture maintain antioxidant-free status, which impacts:

• formulation recipes
• dilution workflows in pharmacy or automated compounding
• instructions for use (IFU) and stability data aligned to the antioxidant strategy

How is the patent likely used in litigation and what claim elements will be litigated first?

In typical claim construction and infringement, the disputed elements are usually the ones with clear numeric gates:

1. 25 mg/mL bendamustine (concentration and “about” range)
2. solvent composition compliance with the defined non-aqueous solvent list
3. antioxidant-free status of both concentrate and diluted formulation
4. impurity thresholds after 6 months at 2–8°C measured by HPLC

For dependent claims, additional disputes likely include:

• whether pH falls in the recited ranges
• whether PEG identity is PEG-400
• whether ethanol qualifies as dehydrated ethanol
• whether ethanol:PEG mass ratios match the dependent claim windows
• whether ethyl ester and mono-substituted impurities meet the dependent thresholds

Which jurisdictions are covered: is US 12,419,867 a US-only right or part of a family?

You asked specifically for the US patent 12,419,867. Without the family details, only US coverage can be asserted as your scope. Cross-jurisdiction coverage is not derivable from claim text alone.

Key Takeaways

• US 12,419,867 protects a specific bendamustine liquid vehicle used in CLL or indolent B-cell NHL, not a general therapeutic method.
• Claim 1 is anchored on: ~25 mg/mL bendamustine, defined non-aqueous solvent options, antioxidant-free status, and refrigerated stability/impurity thresholds after 6 months at 2–8°C measured by HPLC.
• Dependent claims lock down pH ranges, PEG-400, dehydrated ethanol, ethanol:PEG mass ratios, ethanol concentration, bendamustine hydrochloride, specific pH adjusters, and narrower impurity categories (ethyl ester and mono-substituted).
• Enforcement leverage is concentrated in antioxidant-free and impurity acceptance criteria. Those are the most direct product-quality and stability-data litigation points.

FAQs

1. What “antioxidant-free” means for infringement under US 12,419,867
2. How do the impurity thresholds (total vs ethyl ester vs mono-substituted) change litigation strategy
3. Can a product outside the pH dependent ranges still infringe Claim 1
4. Does “about 25 mg/mL” invite wide design-around compared with exact numeric limits in dependent claims
5. How should labeling and dilution instructions be structured to reduce risk under the “diluted liquid composition” antioxidant-free limitation

References

1. U.S. Patent 12,419,867, claim text provided by user.

Drugs Protected by US Patent 12,419,867

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	VIVIMUSTA	bendamustine hydrochloride	SOLUTION;INTRAVENOUS	212209-001	Dec 7, 2022		RX	Yes	Yes			Y