US Patent 9,023,790: Posaconazole Intravenous Formulation Scope, Claims, Exclusivity and Patent Landscape
US Patent No. 9,023,790 protects a narrow intravenous posaconazole formulation centered on acidic aqueous solution, sulfobutylether-beta-cyclodextrin, and defined concentration ranges. The strongest commercial claim is claim 8, which recites a formulation materially aligned with the Noxafil intravenous product: approximately 18 mg/mL posaconazole, 400 mg/mL sulfobutylether-beta-cyclodextrin sodium, 0.2 mg/mL EDTA, and pH 2.6.
The patent is formulation-focused. It does not broadly cover posaconazole as a molecule, all posaconazole dosage forms, or every intravenous posaconazole product. Its principal enforcement risk is directed at an injectable product using the claimed cyclodextrin carrier, concentration profile, acidic pH, and, for narrower claims, EDTA and the specified stability or pharmacokinetic results.
What does US Patent 9,023,790 protect?
The patent has four principal claim groups:
| Claim group |
Claims |
Protected subject matter |
| Intravenous composition |
1-8, 12 |
Posaconazole aqueous formulation with sulfobutylether-beta-cyclodextrin |
| Treatment method |
9-11, 13-18 |
Administration of the composition to treat fungal or parasitic infections |
| Stability and dosing |
6, 7, 12-16 |
Pharmacokinetic outcomes, precipitation resistance, and 180-220 mg dosing |
| Infusion kit |
19 |
Breakable container inside an infusion bag containing diluent |
Claim 1 is the central composition claim. It requires all of the following:
- Posaconazole or a pharmaceutically acceptable salt.
- Modified beta-cyclodextrin comprising sulfobutylether-beta-cyclodextrin.
- Degree of substitution of approximately 6.5.
- Molecular weight of approximately 2,163 g/mol.
- Aqueous solution.
- pH between approximately 2.0 and 3.5.
- Posaconazole concentration between approximately 14 and 22 mg/mL.
- Cyclodextrin concentration between approximately 350 and 450 mg/mL.
- Suitability for intravenous administration.
A competing product that omits any one of these limitations may avoid literal infringement of claim 1, although the doctrine of equivalents could remain relevant depending on the substituted excipient, concentration, and technical effect.
How narrow are the key composition claims?
Claim 1: broadest practical formulation claim
Claim 1 covers a defined formulation window rather than one exact recipe. Its numerical scope includes:
| Parameter |
Claimed range |
| pH |
About 2.0-3.5 |
| Posaconazole |
About 14-22 mg/mL |
| Sulfobutylether-beta-cyclodextrin |
About 350-450 mg/mL |
| Cyclodextrin degree of substitution |
About 6.5 |
| Cyclodextrin molecular weight |
About 2,163 g/mol |
The claim is narrower than a generic claim to an injectable posaconazole solution because it requires a particular solubilizer and a specific acidic concentration regime.
The cyclodextrin limitation is likely the most important technical boundary. Sulfobutylether-beta-cyclodextrin is commonly identified commercially as Captisol. A formulation using hydroxypropyl-beta-cyclodextrin, randomly methylated beta-cyclodextrin, or another solubilizer would not literally satisfy this limitation.
Claims 3-5: EDTA and formulation-specific narrowing
Claim 3 requires:
- Posaconazole free base;
- EDTA as the chelating agent; and
- pH of approximately 2.3-3.0.
Claim 4 narrows EDTA to approximately 0.1-0.3 mg/mL. Claim 5 recites the commercially significant target composition:
- Posaconazole: about 18 mg/mL;
- Sulfobutylether-beta-cyclodextrin: about 400 mg/mL; and
- EDTA: about 0.2 mg/mL.
Claim 5 is easier to test analytically than claim 1 because it identifies a discrete formulation target. It is also more vulnerable to design-around strategies involving omission of EDTA, substitution of another chelator, or movement outside the claimed concentration ranges.
Claim 8: exact composition claim
Claim 8 recites quantities and processing components:
- Posaconazole: about 18 mg/mL;
- Sulfobutylether-beta-cyclodextrin sodium salt: about 400 mg/mL;
- Molecular weight: 2,163 g/mol;
- Degree of substitution: 6.5;
- Disodium edetate: about 0.2 mg/mL;
- Hydrochloric acid and sodium hydroxide in quantities sufficient to adjust pH to about 2.6;
- Water to one milliliter.
This claim is commercially important because it captures a complete injectable formulation rather than only a combination of active ingredient and excipient. The acid and base limitations are likely interpreted as pH-adjustment components, not necessarily as residual quantities that must remain at a specific concentration.
What are the method-of-treatment claims?
Claims 9-18 extend the patent beyond the formulation itself. They cover administration of the claimed composition to treat infections in an animal, including humans.
Claim 11 lists a broad infection set, including:
- Oropharyngeal and esophageal candidiasis;
- Invasive aspergillosis and candidiasis;
- Fusariosis and scedosporiosis;
- Infections caused by dimorphic fungi, zygomycetes, rare molds and yeasts;
- Refractory or intolerant patients;
- Hematologic malignancy and transplant-related infections;
- Chagas disease; and
- Leishmaniasis.
Claims 13-16 specify doses of approximately 180-220 mg or approximately 200 mg, administered once or twice daily. These claims may be difficult to enforce against a manufacturer without evidence of the intended dosing regimen. They may be more useful in a product-label or induced-infringement analysis where the approved label recommends the claimed dose.
Claims 17 and 18 cover combination treatment with another active ingredient, including antifungals, antibacterials, antivirals, steroids, chemotherapeutics, antiemetics, and listed antifungal classes.
What do the pharmacokinetic and stability claims cover?
Claims 6 and 7 use pharmacokinetic limitations:
| Claim |
Cmax |
AUC |
| 6 |
About 1,176-18,375 ng/mL |
About 21,600-33,750 hr·ng/mL |
| 7 |
About 1,470 ng/mL |
About 27,000 hr·ng/mL |
The claim text supplied for claim 6 uses “AUCiast,” while claim 7 uses “AUClast.” That terminology difference may create claim-construction and indefiniteness issues if the issued patent does not define the measurement convention. The extraordinarily broad Cmax range in claim 6 also reduces its practical selectivity compared with claim 7.
Claim 12 requires that no visible posaconazole precipitate form after the composition is injected into an infusion bag, mixed with infusate, and allowed to stand for up to 24 hours. This is a functional stability limitation. In an infringement dispute, the relevant testing protocol would need to address:
- Infusion-bag material;
- Diluent identity;
- Mixing conditions;
- Temperature;
- Observation method;
- Storage duration; and
- Meaning of “visible” precipitate.
The claim does not necessarily require chemical or subvisible-particle stability. Its express limitation is the absence of visible posaconazole precipitation.
What does claim 19 protect?
Claim 19 covers a kit containing:
- A small breakable container;
- An infusion bag;
- The claimed posaconazole composition in the breakable container; and
- Normal saline or 5% dextrose in the infusion bag.
The breakable container is placed directly inside the bag so that breaking it releases the formulation into the diluent. This is a packaging and administration-system claim. It is distinct from the composition claims and could be infringed by a kit even if the product is distributed as a complete infusion system rather than as a conventional vial.
The claim is commercially narrower than standard vial-based packaging. A manufacturer using a conventional vial and separately supplied infusion bag would likely avoid literal infringement of claim 19 while remaining exposed under claims 1-8.
What is the relationship to Noxafil intravenous injection?
Noxafil is posaconazole, marketed by Merck for oral suspension, delayed-release tablets, and intravenous injection. FDA labeling identifies the intravenous product as a concentrated solution requiring dilution before administration. The product uses sulfobutylether-beta-cyclodextrin as a solubilizing excipient and is administered intravenously after dilution in an appropriate infusion solution (U.S. Food and Drug Administration [FDA], 2024).
The claimed formulation is closely directed to the technical profile of the intravenous product:
| Product characteristic |
Patent claims |
Noxafil IV product profile |
| Active ingredient |
Posaconazole |
Posaconazole |
| Route |
Intravenous |
Intravenous |
| Solubilizer |
Sulfobutylether-beta-cyclodextrin |
Sulfobutylether-beta-cyclodextrin |
| Concentration |
14-22 mg/mL in claim 1; about 18 mg/mL in claims 5 and 8 |
Approximately 18 mg/mL |
| Acidic pH |
About 2.0-3.5 |
Acidic formulation |
| EDTA |
About 0.1-0.3 mg/mL in claim 4 |
Relevant to the claimed formulation profile |
| Dose |
About 200 mg |
Standard labeled dose in relevant treatment settings |
| Dilution |
Infusion-bag administration |
Required before infusion |
The overlap is strongest for claims 1, 5 and 8. Commercial exposure depends on the exact approved formulation, current product composition, patent listing, and the status of any applicable terminal disclaimer or patent-term adjustment.
When does US Patent 9,023,790 lose exclusivity?
US Patent 9,023,790 was granted on May 5, 2015. A United States utility patent generally expires 20 years after the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments (35 U.S.C. §§ 154, 156).
| Item |
Data |
| Patent |
US 9,023,790 |
| Grant date |
May 5, 2015 |
| Technology |
Intravenous posaconazole formulation |
| Patent type |
Utility patent |
| Principal owner lineage |
Schering/Merck patent portfolio |
| Basic term rule |
20 years from earliest effective nonprovisional filing |
| Possible extensions |
PTA, PTE, terminal disclaimer analysis required |
| Regulatory exclusivity |
Separate from patent term |
The patent’s precise expiration date should be taken from the USPTO Patent Center record and the face of the issued patent. The grant date alone does not establish expiration. FDA regulatory exclusivity also does not automatically track the patent term.
What is the Orange Book status of US Patent 9,023,790?
The Orange Book treats patent listing at the approved-product level. A patent may be relevant to a drug product without being listed for every dosage form or strength. Composition patents, method-of-use patents and packaging claims are subject to FDA listing rules under 21 C.F.R. § 314.53.
For Noxafil, the relevant Orange Book analysis should distinguish:
- Oral suspension;
- Delayed-release tablets;
- Intravenous injection;
- Drug substance patents;
- Formulation patents; and
- Method-of-use listings.
US 9,023,790 is technically most relevant to the intravenous dosage form. Its claims do not naturally map to the oral suspension or delayed-release tablet products. An Orange Book listing for one Noxafil presentation would not automatically create a listing for all posaconazole products.
How strong is the patent estate for posaconazole?
The posaconazole estate has several technical layers:
| Layer |
Typical protection |
Relevance to generic entry |
| Compound |
Posaconazole molecule and salts |
Generally expired or near-expired relative to later formulation patents |
| Oral formulation |
Suspension and absorption-enhancing systems |
Relevant to oral suspension competitors |
| Solid oral dosage form |
Delayed-release tablet formulation |
Relevant to tablet ANDAs |
| Intravenous formulation |
Cyclodextrin-based aqueous injection |
Directly relevant to injectable products |
| Method of use |
Treatment of invasive fungal infections and prophylaxis |
Label-dependent exposure |
| Packaging and administration |
Infusion kit and dilution system |
Narrower, product-configuration risk |
US 9,023,790 is strongest against an injectable product that copies the claimed concentration, pH, cyclodextrin grade and EDTA profile. It is weaker against:
- A different cyclodextrin;
- A nonaqueous formulation;
- A materially different posaconazole concentration;
- A different pH outside the claimed ranges;
- A formulation without EDTA for claims 3-5 and 8;
- A conventional vial-based administration system for claim 19.
The patent does not block all posaconazole generic development. A generic company could pursue a formulation that falls outside the claims, subject to stability, safety, bioequivalence, manufacturing and regulatory requirements.
What Paragraph IV challenges and litigation risks exist?
An ANDA applicant seeking approval before patent expiration could file a Paragraph IV certification against relevant Orange Book-listed patents. The likely invalidity and noninfringement arguments for US 9,023,790 would include:
Anticipation and obviousness
A challenger could argue that prior art disclosed:
- Posaconazole in injectable form;
- Sulfobutylether-beta-cyclodextrin as a solubilizer;
- Acidic pH adjustment;
- EDTA or another chelator;
- Comparable concentration ranges; or
- Dilution into infusion solutions.
The patent’s defense would focus on the combined formulation window and the technical result of maintaining posaconazole in solution after dilution. A combination of individually known excipients can still be patentable if the prior art did not make the claimed combination obvious with a reasonable expectation of success.
Written description and enablement
The broad ranges in claim 1 and the broad pharmacokinetic range in claim 6 could attract written-description or enablement challenges. The patent owner would rely on examples, formulation testing and clinical data to establish possession and operability across the claimed scope.
Indefiniteness
Potential issues include:
- “About” applied to multiple quantitative limitations;
- The meaning of molecular weight for a distribution of cyclodextrin species;
- “Degree of substitution of 6.5”;
- “No visible precipitate”;
- The claim 6 AUC terminology; and
- The measurement conditions for Cmax and AUC.
Infringement proof
A product-specific case would require analysis of the ANDA, proposed labeling, formulation records and potentially batch testing. FDA approval alone would not establish infringement of every formulation limitation.
No reliable conclusion on a current Paragraph IV challenge, district-court litigation, or settlement agreement follows from the claim text alone. Current case status must be determined from PACER, USPTO records, FDA Orange Book updates and the relevant ANDA litigation docket.
What generic launch scenarios exist?
| Scenario |
Exposure under US 9,023,790 |
| Generic copies approximately 18 mg/mL IV formulation with 400 mg/mL SBECD and 0.2 mg/mL EDTA |
High |
| Generic uses SBECD but concentration is materially outside 350-450 mg/mL |
Reduced, subject to equivalents |
| Generic uses a different cyclodextrin |
Reduced for literal infringement |
| Generic uses same formulation but different packaging |
Claims 1-8 remain relevant |
| Generic uses a conventional vial rather than breakable infusion container |
Claim 19 risk reduced |
| Generic changes pH outside 2.0-3.5 |
Claim 1 risk reduced |
| Generic omits EDTA |
Claims 3-5 and 8 risk reduced; claim 1 may remain relevant |
| Generic relies on a different IV solubilization technology |
Lower direct risk |
The main commercial barrier is not only patent coverage. Injectable generic development also requires control of precipitation after dilution, container compatibility, particulate matter, extractables and leachables, sterility, endotoxins, stability and IV administration instructions.
How does the patent compare with competing antifungal estates?
Posaconazole competes with voriconazole, isavuconazonium sulfate, amphotericin B products and echinocandins. US 9,023,790 differs from many competing estates because it protects a formulation architecture rather than a broad active pharmaceutical ingredient claim.
| Drug |
Formulation-patent profile |
Generic or biosimilar issue |
| Posaconazole |
Oral and IV formulation claims |
ANDA and formulation design-around risk |
| Voriconazole |
Compound, formulation and use claims |
Conventional generic pathway |
| Isavuconazonium |
Prodrug and injectable/oral product claims |
More complex prodrug and formulation analysis |
| Amphotericin B |
Liposomal and colloidal delivery systems |
Delivery-system manufacturing barriers |
| Echinocandins |
Compound and injectable formulation estates |
Conventional sterile injectable risk |
Biosimilar risk is not material for posaconazole because posaconazole is a small-molecule drug regulated through the ANDA pathway, not a biologic regulated under the biosimilar pathway. The relevant competitive threat is generic injectable entry.
Key Takeaways
- US 9,023,790 is a targeted formulation patent for intravenous posaconazole.
- Claim 1 requires acidic aqueous solution, SBECD with a defined substitution and molecular weight profile, and specific concentration ranges.
- Claims 5 and 8 most closely capture the commercially important 18 mg/mL posaconazole formulation with approximately 400 mg/mL SBECD and 0.2 mg/mL EDTA.
- Claims 6, 7 and 12 add pharmacokinetic and precipitation-stability limitations that may complicate infringement testing.
- Claim 19 separately covers a breakable-container infusion kit.
- The patent does not broadly cover all posaconazole products or all intravenous formulations.
- A generic using the same SBECD-based formulation has the highest risk.
- Design-around opportunities include changing the cyclodextrin, pH, concentration, chelator, or packaging configuration.
- Exact patent expiration, Orange Book listing and current Paragraph IV or litigation status require review of the current USPTO, FDA and court records.
FAQs About US Patent 9,023,790
Does US Patent 9,023,790 cover oral Noxafil tablets?
No. Its core claims require a pharmaceutical composition suitable for intravenous administration. Oral suspension and delayed-release tablet patents must be analyzed separately.
Can a generic use sulfobutylether-beta-cyclodextrin without infringing?
Possibly. The concentration, molecular-weight profile, degree of substitution, pH and posaconazole concentration must be evaluated together. Use of SBECD alone does not determine infringement.
Is EDTA required in every claim?
No. EDTA is required by claims 3-5 and 8. Claim 1 does not require EDTA, so omission of EDTA does not by itself avoid claim 1.
Does the patent cover a 200 mg posaconazole dose?
Claims 6, 7 and 13-16 expressly address approximately 200 mg dosing or pharmacokinetic results associated with that dose. The composition claims remain dependent on the formulation limitations.
Are posaconazole biosimilars expected?
No. Posaconazole is a small molecule. Competitors would generally seek FDA approval through the ANDA pathway rather than the biosimilar pathway.
References
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U.S. Patent No. 9,023,790. (2015). Posaconazole formulations. United States Patent and Trademark Office. https://patents.google.com/patent/US9023790
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U.S. Food and Drug Administration. (2024). Noxafil (posaconazole) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
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U.S. Patent and Trademark Office. (2024). Patent Center. https://patentcenter.uspto.gov/
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Code of Federal Regulations. (2024). 21 C.F.R. § 314.53, submission of patent information.
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United States Code. (2024). 35 U.S.C. §§ 154 and 156.
