Details for Patent: 12,303,506

Which drugs does patent 12,303,506 protect, and when does it expire?

Patent 12,303,506 protects EVDI and is included in one NDA.

This patent has one patent family member in one country.

Summary for Patent: 12,303,506

Title:	Trabectedin composition
Abstract:	The present disclosure provides a stable, ready-to-dilute injectable pharmaceutical composition comprising trabectedin and at least one pharmaceutically acceptable excipient, wherein the composition is free of ethanol.
Inventor(s):	Krishna Mohan Chilakala, Nagamalleswara Rao BEERAKA, Ramesh MANTRI, Hanumantha Rao Kamma, Janos Vaczi
Assignee:	Extrovis AG
Application Number:	US17/931,831
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound;

Scope and Claims Analysis for US Patent 12,303,506 (Trabectedin Stable Ready-to-Dilute Injectable Composition)
US 12,303,506 claims a narrow formulation space for a stable, ethanol-free, ready-to-dilute injectable trabectedin composition with defined concentration, pH window, impurity limits after 3-month storage, and selectable solvent/pH/stabilizer components. The patent’s enforceable perimeter is largely determined by three hard anchors: (1) trabectedin at ~0.05 mg/mL, (2) pH ~2.5–5 with ethanol excluded, and (3) impurity acceptance criteria for desacetyl and dehydroxy impurities after 3 months at 2–8°C or 25°C.

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What does US Patent 12,303,506 claim for stable ready-to-dilute trabectedin injections? (Claim-scope map)

Claim 1 is the independent claim and sets the core formulation definition. Claims 2–8 and 9–10 refine component selection and a purity retention attribute.

Claim 1: the primary scope anchor

Independent claim elements (all must be present):

1. Product form: “stable ready-to-dilute injectable pharmaceutical composition.”
2. Active concentration: trabectedin at about 0.05 mg/mL.
3. Ethanol condition: free of ethanol.
4. Carrier composition is limited to:
   • one pharmaceutically acceptable solvent
   • one pharmaceutically acceptable pH-adjusting agent
   • one pharmaceutically acceptable stabilizing agent
5. pH window: about 2.5 to about 5.
6. Stability/impurities after storage:
   • stored 3 months at 2–8°C or 3 months at 25°C
   • must satisfy:
     • total impurities ≤ 3.0%
     • desacetyl trabectedin impurity ≤ 0.5%
     • dehydroxy trabectedin impurity ≤ 0.5%

Practical claim read-through for infringement risk: a accused product must match the concentration, be ethanol-free, operate in the specified pH range, and demonstrate the specified impurity outcomes at both storage conditions (or at least whichever is claimed as part of the “wherein when stored… the composition has…” requirement).

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What specific formulation limitations narrow or expand US 12,303,506 claim 1?

Claim 1 narrows scope through a stack of quantitative and categorical limitations, but it also expands scope via “one solvent” and broad solvent/pH/stabilizer lists in dependent claims.

A. Concentration limitation

• Trabectedin is fixed at about 0.05 mg/mL.
• “About” creates some latitude, but the claim is not open-ended; it targets a specific formulation strength.

B. Ethanol exclusion

• “Free of ethanol” is a bright-line limitation.
• Any ethanol-containing formulation is outside claim 1’s literal scope.

C. pH window

• pH is limited to ~2.5 to ~5.
• pH outside that band avoids literal infringement, even if other components are similar.

D. Stability outcome limitations

The most litigable part is the impurity performance after defined storage:

• Total impurities ≤ 3.0%
• Desacetyl impurity ≤ 0.5%
• Dehydroxy impurity ≤ 0.5%

This creates a “function/spec” requirement that depends on analytical method and conditions used in testing. In claim construction, the specification’s analytical definitions (and the method’s validation) often become central, even though those method details are not included in the claim text you provided.

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Which dependent claims expand coverage within US 12,303,506? (solvent, pH, stabilizer)

Claim 2: solvent selection expands the claim set

Claim 2 limits the “one pharmaceutically acceptable solvent” to a list, including:

• propylene glycol
• polyethylene glycol
• dimethyl acetamide
• solketal
• glycerol formal
• acetone
• glycerol
• glycofurol
• diethylene glycol monoethyl ether
• dimethyl sulfoxide
• N-methyl-2-pyrrolidone
• water for injection
• dimethyl formamide
• aqueous solutions of disaccharides
• mixtures thereof

Effect on scope: many excipient substitutions remain within the claim as long as only one solvent is used (and the chosen solvent is in the listed group).

Claim 3: propylene glycol is singled out

Claim 3 narrows further:

• solvent is specifically propylene glycol.

This gives a distinct, stronger basis for enforcement against products using propylene glycol even if other solvents could also qualify.

Claim 4: quantitative solvent amount limitation

Claim 4 requires solvent present at:

• ~0.001 mL to ~1 mL per mL of composition.

Effect on scope: this prevents arguments that any “trace” or “solvent-as-formulation-medium” approach is automatically covered or automatically avoided. It also creates a measurable boundary.

Claim 5: pH-adjusting agents are limited

Claim 5 limits the pH-adjuster to a long listed group including:

• organic acids: acetic acid, tartaric acid, lactic acid, maleic acid, malic acid, citric acid, gluconic acid, succinic acid, fumaric acid
• mineral acids/bases: hydrochloric acid, sulfuric acid, phosphoric acid, sodium hydroxide, sodium carbonate, sodium bicarbonate
• salts/buffers and inorganic agents: sodium carbonate/bicarbonate, dibasic/monobasic phosphate salts, magnesium oxide, magnesium carbonate, calcium carbonate, boric acid, magnesium aluminium silicates
• amines: triethanolamine, monoethanolamine, diethanolamine
• mixtures

Claim 6: lactic acid is singled out

Claim 6:

• pH-adjusting agent is lactic acid.

This is an explicit sub-scope that tracks claim 9’s preferred embodiment.

Claim 7: stabilizing agent is limited

Claim 7 limits the stabilizer to one of:

• amino acids: glycine, 1-arginine, phenylalanine, histidine, acetylcysteine, citrulline, lysine, isoleucine, methionine, cysteine
• and pharmaceutically acceptable salts

Effect on scope: stabilizer swaps are bounded to this list.

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What does “ready-to-dilute” do to enforceability for US 12,303,506?

“Ready-to-dilute injectable” can be argued to mean:

• a concentrate intended to be diluted by the end user (or by a healthcare facility) into an infusion solution.

From a scope perspective, this term is typically used to distinguish from:

• premixed infusion solutions, and
• lyophilized products requiring reconstitution rather than dilution.

But the literal claim text you provided does not state the diluent, dilution factor, or target infusion concentration. Enforcement will therefore focus on the claimed formulation “as supplied,” and whether the product is presented as a ready-to-dilute concentrate.

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What is the added coverage in Claims 9 and 10? (specific embodiment with PG + lactic acid + glycine)

Claim 9 is another independent claim with a more specific carrier stack:

• trabectedin (therapeutically effective amount)
• propylene glycol
• lactic acid sufficient to provide pH 2.5 to 5.0
• glycine
• sterile water for injection
• ethanol is not explicitly stated in the claim text as provided for claim 9, but Claim 9 is framed as “stable ready-to-dilute injectable pharmaceutical composition” with stability outcomes identical to claim 1.

It then requires:

• after 3 months at 2–8°C or 25°C:
  • total impurities ≤ 3.0%
  • desacetyl impurity ≤ 0.5%
  • dehydroxy impurity ≤ 0.5%

Claim 10 adds:

• at least ~90% trabectedin purity retained after storage at 2–8°C.

How claims 9/10 change the litigation posture

• Claim 1 is broad on solvent/pH/stabilizer via dependent lists, but uses the specific trabectedin concentration “about 0.05 mg/mL.”
• Claim 9 is composition-specific (propylene glycol + lactic acid + glycine + sterile water) and still depends on the same impurity stability requirements.
• If an accused product uses this exact combination, it is more directly captured by claim 9, even if the concentration differs from claim 1’s “about 0.05 mg/mL” anchor (depending on how “therapeutically effective amount” is construed and the factual product strength).

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How strong is the patent estate for ethanol-free stable trabectedin concentrates? (coverage strength vs substitution risk)

Based on the claim language provided:

What is strongly covered

1. Ethanol-free trabectedin concentrates with pH 2.5–5.
2. Products meeting tight impurity thresholds for desacetyl and dehydroxy species after defined storage.
3. Formulations using specific excipient families when they also satisfy the overall composition rules:
   • solvents from the Claim 2 list (or specifically propylene glycol in Claims 3/4/9)
   • pH adjusters from Claim 5 list (or specifically lactic acid in Claims 6/9)
   • stabilizers from Claim 7 list (or specifically glycine in Claim 9)

What can design around easily

• Add ethanol: breaches the “free of ethanol” limitation (but may be incompatible with safety/labeling).
• Adjust pH outside ~2.5–5: avoids literal scope.
• Use different excipient categories not in the Claim 2/5/7 lists: may avoid dependent claim capture, though Claim 1 could still be asserted if the component fits the “one pharmaceutically acceptable solvent/pH-adjusting agent/stabilizing agent” concept without matching the dependent lists.
• Improve stability with different mechanisms but still remain within the same pH/solvent/stabilizer lists: if improved stability still keeps impurity under the same thresholds, that does not avoid infringement. Stability-by-better formulation often does not provide a design-around if the claim is framed by the stability outcome.

The likely battleground

The impurity thresholds are outcome-based. In practice, dispute typically centers on:

• impurity quantification method (assay/LC conditions)
• how desacetyl and dehydroxy impurities are defined and measured
• whether the accused product is truly tested “when stored for 3 months at about 2°C to about 8°C, or for 3 months at about 25°C” under comparable conditions
• whether “total impurities” is calculated per the same definition and includes/omits specific peaks

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What generic entry risks exist for trabectedin ready-to-dilute injectables under this patent?

For a generic or biosimilar-adjacent entry (trabectedin is a small molecule, so “generic” not “biosimilar”), risk analysis focuses on:

Literal infringement pathways

• A generic that prepares an ethanol-free trabectedin ready-to-dilute injectable at ~0.05 mg/mL, with pH 2.5–5, and uses a listed solvent and stabilizer and achieves impurity thresholds after the storage window is at high risk.

Common generic development trajectories that fail to avoid scope

• Switching solvent among Claim 2’s list without changing pH and without removing ethanol (or switching to ethanol-free but still meeting impurity thresholds) can remain covered.
• Narrow reformulation toward the same impurity profile can still satisfy “≤0.5%” and “≤3.0%” limits and therefore remain within claim reach.

Design-around levers that reduce risk

• Introduce ethanol (if acceptable for the product profile) to break claim 1’s “free of ethanol.”
• Shift pH outside the claimed band.
• Use excipients not in the dependent lists, while also arguing that the dependent claim limitations do not apply and that the independent claim element mapping fails (this is more complex because Claim 1’s carrier language is broader than the dependent lists).

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How does US 12,303,506 compare with typical trabectedin stability IP? (what the claims emphasize)

This patent’s emphasis is consistent with a formulation patent strategy built around:

• solvent system selection
• pH control
• amino-acid stabilization
• storage impurity suppression
• ethanol exclusion (often a meaningful formulation differentiator)

Relative to patents that focus only on composition ingredients, this one has strong “specification-by-performance” constraints through impurity limits after storage, which can be more resistant to superficial excipient substitution.

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What is the Orange Book status of US 12,303,506?

No Orange Book status can be stated from the claim text alone. US 12,303,506 may or may not be listed in the Orange Book for a particular NDC associated with trabectedin, and the relationship between the patent and any listed drug product (and whether it is for drug substance vs drug product vs method) is not provided in the input.

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Patent expiration timeline for US 12,303,506

No expiration timeline can be stated from the claim text alone. Patent expiration depends on application filing date, priority dates, patent term adjustments, and whether terminal disclaimers apply. Those facts are not provided.

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Key Takeaways

• US 12,303,506 is a formulation-performance patent for ethanol-free, pH-controlled, ready-to-dilute trabectedin concentrates.
• Claim 1 is the core: trabectedin at about 0.05 mg/mL, pH ~2.5–5, ethanol-free, and strict impurity caps after 3 months at 2–8°C or 25°C.
• Dependent claims expand enforcement coverage through defined excipient lists: specific solvents, pH adjusters, and stabilizing amino acids.
• Claims 9/10 provide a narrower “preferred” embodiment: propylene glycol + lactic acid + glycine + sterile water for injection, with the same impurity thresholds and a ≥90% purity retention feature (at least at 2–8°C).
• Design-around is most likely via pH shift and/or ethanol introduction; excipient substitution alone may not avoid infringement if the stability outcome remains within the claimed impurity limits.

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FAQs

1) If an accused product matches the pH and excipients but fails impurity limits slightly, is it outside the claims?
Yes for literal scope if total impurities or desacetyl/dehydroxy impurity thresholds exceed the claimed caps under the defined storage conditions.

2) Does “about 0.05 mg/mL” allow meaningful deviation in trabectedin concentration?
It provides some latitude, but infringement risk increases as the product concentration approaches the claimed target; the fact pattern would drive how “about” is construed against the accused concentration.

3) Can a formulation using ethanol avoid claim 1 but still be asserted under other dependent claims?
Claim 1 contains the ethanol-free requirement. Dependent claims tied to Claim 1 generally inherit that limitation; ethanol-containing products are typically positioned to avoid the Claim 1-based lineage.

4) Are the impurity limits tied to specific storage conditions, or can testing at other times be used to argue non-infringement?
The claim text requires performance “when stored for 3 months at about 2°C to about 8°C, or for 3 months at about 25°C.” Testing outside those windows would not directly satisfy the claim language.

5) How does “therapeutically effective amount” in claim 9 affect scope compared with claim 1’s fixed concentration?
It is broader than a fixed concentration, which can widen claim 9’s capture of different strength embodiments that still satisfy the stability and component requirements.

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References

1. User-provided claim text for US 12,303,506 (claims 1–10).

Drugs Protected by US Patent 12,303,506

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Apotex	EVDI	trabectedin	SOLUTION;INTRAVENOUS	220837-001	May 1, 2026		RX	Yes	Yes			Y

International Family Members for US Patent 12,303,506

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	4215184