Details for Patent: 11,020,363

Which drugs does patent 11,020,363 protect, and when does it expire?

Patent 11,020,363 protects EVOMELA and is included in one NDA.

This patent has twenty-three patent family members in fourteen countries.

Summary for Patent: 11,020,363

Title:	Injectable nitrogen mustard compositions comprising a cyclodextrin derivative and methods of making and using the same
Abstract:	The present disclosure is directed to pharmaceutical compositions comprising a nitrogen mustard and a cyclodextrin derivative, and methods of making and using the same.
Inventor(s):	James D. Pipkin, Stephen G. Machatha
Assignee:	Acrotech Biopharma LLC , Cydex Pharmaceuticals Inc
Application Number:	US14/229,523
Patent Claim Types: see list of patent claims	Composition; Formulation;

Scope and claims analysis for US Patent 11,020,363 (melphalan + sulfobutyl ether-β-cyclodextrin injectable aqueous formulation)
US 11,020,363 claims a specific melphalan injectable aqueous formulation at pH 5 with defined sodium chloride content, a defined sulfobutyl ether-β-cyclodextrin (SBE-β-CD) to melphalan weight ratio (≥54:1), and performance requirements. The enforceable core is not “melphalan plus cyclodextrin,” but a narrow combination of (i) quantitative formulation composition parameters and (ii) stability and exposure (AUC0-t) advantages over an otherwise equivalent melphalan formulation lacking SBE-β-CD.

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What is US Patent 11,020,363 claiming for melphalan injectable formulation with SBE-β-cyclodextrin?

Answer: Aqueous injectable melphalan at pH 5 with SBE-β-CD:mELPHALAN weight ratio ≥54:1, containing melphalan at 5 mg/mL (or, in dependent/alternate claims, 0.45 mg/mL after dilution for dosing comparison), and meeting two linked functional requirements:

1. Room-temperature stability (threshold on % melphalan degraded after defined holds), and
2. PK exposure enhancement: after dilution with 9 g/L NaCl to 0.45 mg/mL, administration yields melphalan AUC0-t ≥20% higher than an equivalent-dose melphalan formulation without SBE-β-CD.

The independent-claim architecture

The provided claims show two independent claim families:

1. Claim 1: formulation composition described in terms of an 8.5 mL dose volume formulation at pH 5 with 9 g/L NaCl, containing SBE-β-CD and melphalan at melphalan 5 mg/mL and SBE-β-CD:melphalan ≥54:1, plus stability for ≥1 hour at room temperature, and a dilution-to-dose PK superiority (AUC0-t ≥20%).

2. Claim 4: same basic concept but recasts the formulation as a pH 5 aqueous solution at melphalan 0.45 mg/mL and SBE-β-CD and melphalan only (the claim says the solution “consisting of” those components), with stability for ≥4 hours at room temperature, and the same AUC0-t ≥20% advantage over an equivalent-dose melphalan formulation lacking SBE-β-CD.

A third formulation variant appears in Claim 7, using a higher NaCl level and a fixed SBE-β-CD concentration.

Composition elements that drive claim scope

Across Claims 1, 4, and 7, the key structural limitations are:

• Dosage form: injectable aqueous pharmaceutical formulation (solution)
• pH: 5
• Sodium chloride:
  • Claim 1: 9 g/L NaCl
  • Claim 7: 9 mg/mL NaCl (numerically equivalent to 9 g/L, same concentration in different units)
• Melphalan concentration:
  • Claim 1: 5 mg/mL in the injectable formulation
  • Claim 4: 0.45 mg/mL in the injectable formulation (post-dilution form, by claim framing)
  • Claim 7: 5 mg/mL in the injectable formulation, with the claim describing a further dilution to 0.45 mg/mL
• Cyclodextrin: sulfobutyl ether-β-cyclodextrin (SBE-β-CD)
• Stoichiometry: SBE-β-CD:melphalan weight ratio ≥54:1
• PK advantage criterion: after dilution using NaCl solution to prepare a composition with 0.45 mg/mL melphalan, administration yields melphalan AUC0-t at least 20% greater than a matched melphalan formulation without SBE-β-CD
• Stability criterion: room temperature hold with % degradation limits (Claims 2, 3, 5, 6 specify thresholds at 5h and 10h)

Functional limitations tied to evidence

The claims are performance-driven. The “comprising” language remains present, but the “consisting of” language in certain claims narrows allowable excipients to none beyond specified components.

• Stability requirement in independent claims:
  • Claim 1: stable at room temperature for at least one hour
  • Claim 4: stable at room temperature for at least 4 hours
  • Claim 7: stable at room temperature for at least one hour
• Specific degradation cutoffs in dependent claims:
  • <2% melphalan degraded after 5h (Claims 2 and 5)
  • <4% melphalan degraded after 10h (Claims 3 and 6)

Because these are quantitative performance measures, infringement tends to depend on laboratory data under specified conditions, not just formulation ingredients.

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How broad are the independent claims (1, 4, and 7) given the numerical limitations?

Answer: Moderate on ingredient identity, narrow on numeric thresholds and on the specific comparative PK/stability benchmarks.

Ingredient identity limits

• Must be melphalan and SBE-β-CD. No other drug is claimed in the independent claims as written.
• Claim 4 includes a “consisting of” formulation constraint: “consisting of” the SBE-β-CD and melphalan in aqueous pH 5 composition. That phrase, if applied strictly, excludes additional components in that claim.

Numeric limitations that materially narrow design-around space

To fall within the claims, accused products likely must match or exceed:

• pH = 5 (or effectively 5 within analytical tolerance; the text is literal)
• SBE-β-CD:melphalan weight ratio ≥54:1
• melphalan concentration:
  • Claim 1/7: 5 mg/mL in the injectable formulation
  • Claim 4: 0.45 mg/mL in the injectable formulation
• stability window: at least 1 hour (Claims 1 and 7) or 4 hours (Claim 4)
• comparative AUC0-t test: ≥20% increase after dilution to 0.45 mg/mL with 9 g/L NaCl

The “AUC0-t ≥20%” requirement makes scope conditional

Even if a formulation matches the numeric composition limits, it still must meet the PK exposure superiority in the claim-defined dosing scenario. That creates a factual question for infringement tied to clinical PK/PK surrogate studies.

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What is the key performance benchmark: AUC0-t at least 20% higher than melphalan without SBE-β-CD?

Answer: The claims require a comparative pharmacokinetic advantage measured as melphalan AUC0-t.

Test design embedded in the claim text

The PK benchmark is embedded as:

• Dilute the claimed injectable with 9 g/L NaCl to prepare a dosing composition with 0.45 mg/mL melphalan
• Administer to a subject
• Compare AUC0-t against a control: “melphalan formulation containing an equivalent dose of melphalan and lacking SBE-β-CD”
• Require AUC0-t ≥20% greater for the claimed formulation

Claim implication for infringement analysis

A challenger asserting a “composition-only” equivalence likely won’t avoid the claim unless it also shows failure of the PK criterion under the same dilution and dosing framework. That shifts the debate toward whether the accused formulation produces the required exposure shift.

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Which stability claims further narrow US 11,020,363: 2% at 5 hours and 4% at 10 hours?

Answer: Dependent claims add explicit degradation thresholds at room temperature.

Dependent claim matrix

• Claim 2: <2% by weight melphalan degraded after 5 hours
• Claim 3: <4% melphalan degraded after 10 hours
• Claim 5: same thresholds as Claims 2 but tied to Claim 4’s independent framing
• Claim 6: same thresholds as Claims 3 but tied to Claim 4’s independent framing

These thresholds likely become the practical “gate” for assessing whether a competitor’s formulation is truly “room-stable” for meaningful handling windows.

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What do the different concentration versions mean: 5 mg/mL injectable vs 0.45 mg/mL injectable?

Answer: The claim set covers at least two “formulation stages” that could exist in product handling: a concentrate (5 mg/mL) and a diluted-ready solution (0.45 mg/mL).

Claim 1 pathway (concentrate then dilution)

• Injectable formulation: 5 mg/mL melphalan
• Dilution step: with 9 g/L NaCl to 0.45 mg/mL
• PK comparison uses the diluted composition.

Claim 4 pathway (diluted-ready claimed as the injectable)

• Injectable formulation: 0.45 mg/mL melphalan
• Claim ties stability and AUC0-t advantage directly to this injectable concentration.

Claim 7 provides a fixed-composition example

• It specifies:
  • 9 mg/mL NaCl (same as 9 g/L)
  • 270 mg/mL SBE-β-CD
  • 5 mg/mL melphalan
• Then claims the same stability and PK advantage after further dilution to 0.45 mg/mL.

The fixed concentrations reinforce that the ≥54:1 ratio is a central claim limiter, not a loose window.

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How many formulations does US 11,020,363 effectively cover (claim variants and equivalents)?

Answer: At least three distinct composition/dosing framings appear in the independent claims, with two stability cutoffs that can attach to either framing.

Covered formulation “buckets”

1. pH 5, 9 g/L NaCl, 5 mg/mL melphalan, SBE-β-CD:melphalan ≥54:1, stable ≥1h (Claim 1; plus degradation thresholds via Claims 2-3)
2. pH 5, “consisting of” SBE-β-CD and melphalan at 0.45 mg/mL, stable ≥4h (Claim 4; plus degradation thresholds via Claims 5-6)
3. pH 5, 9 g/L NaCl, 270 mg/mL SBE-β-CD, 5 mg/mL melphalan, stable ≥1h (Claim 7; PK comparator retained)

Practical scope

A competitor that matches one bucket but not the other could still evade if the claim’s concentration stage and “consisting of” boundaries are not met.

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What claims do competitors need to avoid to reduce risk of infringement?

Answer: The most direct “avoidances” are to break at least one of the following claim anchors:

1. pH condition (must be 5)
2. SBE-β-CD type and ratio (must be SBE-β-CD, weight ratio ≥54:1)
3. melphalan concentration and stage (5 mg/mL concentrate vs 0.45 mg/mL injectable-ready)
4. NaCl concentration for dilution (9 g/L used in the dilution comparator)
5. stability performance (<2% degradation at 5h; <4% at 10h; stability ≥1h or ≥4h depending on claim)
6. PK exposure advantage (AUC0-t ≥20% vs melphalan without SBE-β-CD under the claim’s dilution and dosing setup)

This patent is structured so that a competitor cannot safely “design around” only the composition; it also needs to defeat the quantified performance and comparative PK requirements.

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What patent landscape questions matter for US 11,020,363 (expiration, Orange Book status, Paragraph IV, and litigation)?

Answer: None can be completed from the claim text alone. US 11,020,363 scope analysis is possible. Full “landscape” items such as Orange Book listings, FDA reference product ties, listed patents, expiration dates, and any Paragraph IV/ANDA litigation status require bibliographic and regulatory linkage data that is not present in the prompt.

Because those items are not derivable from the claims you provided, they are omitted here.

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How strong is US 11,020,363’s claim enforceability based on claim drafting?

Answer: The claims show strength in specificity and testable performance, but the enforceability will turn on proof of claim-specified thresholds, especially the AUC0-t ≥20% and degradation percentages.

Strength indicators in the claim language

• Hard numeric anchors: pH 5; ratio ≥54:1; melphalan concentration fixed.
• Testable stability: degradation percentages at timepoints.
• Comparative PK superiority: measurable outcome with defined comparator.

Risk points for both sides

• For a patentee: the need to show the accused product meets the PK threshold may require clinical PK data or highly robust bridging evidence tied to the claim’s dosing and dilution framework.
• For a defendant: even if composition is matched, a failure to demonstrate AUC0-t ≥20% can be a central factual rebuttal.

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What is the likely practical scope of “sulfobutyl ether-β-cyclodextrin” in the claims?

Answer: The claim uses a specific cyclodextrin identity: sulfobutyl ether-β-cyclodextrin. The scope likely covers the specified class material rather than generic “cyclodextrin,” but the exact SBE-β-CD substitution degree, average substitution, and product grade are not stated in the claims provided. In practice, those features can matter to whether a product meets the required weight ratio and achieves the claimed PK/stability outcomes.

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Key Takeaways

• US 11,020,363 is a composition-and-performance patent, not just an ingredient patent: it requires pH 5, SBE-β-CD, ≥54:1 SBE-β-CD:melphalan weight ratio, defined melphalan concentration (5 mg/mL or 0.45 mg/mL depending on the claim), and quantified stability at room temperature.
• The most decisive enforceability lever is the built-in comparative PK requirement: melphalan AUC0-t ≥20% higher after dilution with 9 g/L NaCl to 0.45 mg/mL, versus an equivalent-dose melphalan formulation without SBE-β-CD.
• Dependent claims add hard degradation thresholds: <2% at 5 hours and <4% at 10 hours at room temperature.
• Design-around risk cannot be evaluated without knowing the competitor’s exact formulation parameters and whether it meets the claim-defined stability and AUC0-t superiority in the same dilution/dosing framework.

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FAQs

1) Does US 11,020,363 cover melphalan formulations that include other excipients besides NaCl?
Claim 1 and Claim 7 frame composition as an aqueous solution with specified NaCl plus SBE-β-CD and melphalan. Claim 4 contains “consisting of,” which narrows allowed ingredients in that claim to only SBE-β-CD and melphalan beyond the aqueous medium and pH adjustment.

2) Is the AUC0-t advantage required for every claim in the set?
As provided, the independent claims (Claims 1, 4, and 7) include the AUC0-t ≥20% requirement. Dependent claims (Claims 2,3,5,6) narrow stability while staying within their respective independent claim frameworks, so the AUC requirement remains embedded.

3) What breaks coverage most reliably: changing the ratio or missing the stability window?
Breaking any single anchor can avoid infringement. The most reliable “outs” are generally pH deviation from 5, reducing SBE-β-CD:melphalan below 54:1, or failing to meet the timepoint stability/degradation thresholds and/or the AUC0-t ≥20% comparator requirement.

4) Do the claims require the injectable to be 8.5 mL?
Only Claim 1 includes “about 8.5 mL.” Claim 4 and Claim 7 do not include that dose-volume framing in the text provided. Coverage depends on which independent claim an accused product maps to.

5) Can a competitor argue non-infringement by changing only the dilution step?
The claims specify dilution with 9 g/L sodium chloride solution to achieve 0.45 mg/mL melphalan for the PK comparison. A competitor that uses a substantially different dilution composition or produces different concentration outcomes would need to avoid mapping into the claim’s defined test conditions and the resulting AUC0-t benchmark.

Drugs Protected by US Patent 11,020,363

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Acrotech Biopharma	EVOMELA	melphalan hydrochloride	POWDER;INTRAVENOUS	207155-001	Mar 10, 2016		RX	Yes	Yes	11,020,363		Y

International Family Members for US Patent 11,020,363

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010253905
Brazil	PI1012301
Canada	2763365
China	102458114
China	106389307