Details for Patent: 11,382,923

Which drugs does patent 11,382,923 protect, and when does it expire?

Patent 11,382,923 protects FRINDOVYX and is included in one NDA.

This patent has one patent family member in one country.

Summary for Patent: 11,382,923

Title:	Stable liquid formulations of cyclophosphamide and processes to prepare the same
Abstract:	The present invention relates to stable liquid pharmaceutical formulations of cyclophosphamide comprising cyclophosphamide and at least one pharmaceutically acceptable excipient wherein moisture content of the liquid formulation is less than about 2.0% by weight. The invention further relates to stable liquid formulations of cyclophosphamide prepared by a process comprising a step of reducing the moisture content from cyclophosphamide or liquid compositions of cyclophosphamide or both. The invention further relate to method of using such stable liquid formulations of cyclophosphamide for parenteral administration either as ready-to-use or ready-to-dilute for treating various cancer disorders.
Inventor(s):	Riyaz Ahmed Shaik, Ananya SAHA, SVB Janardhan Garikipati, Akash CHAURASIYA, Bhavesh Vallabhbhai PATEL, Harshal BHAGWATWAR, Sumitra Ashok Pillai
Assignee:	Avyxa Holdings LLC
Application Number:	US15/402,712
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound;

US Patent 11,382,923: Cyclophosphamide Liquid Formulation Claims, Scope and Patent Landscape

US Patent 11,382,923 is directed to a low-moisture, refrigerated liquid formulation of cyclophosphamide. Its commercial significance lies in the combination of five limitations: liquid dosage form, cyclophosphamide concentration, moisture below about 2%, refrigerated six-month impurity control, and exclusion of polyol organic solvents and citric acid. The patent does not broadly claim cyclophosphamide, cyclophosphamide monohydrate, or every injectable cyclophosphamide product.

The strongest practical coverage is likely claim 1, supported by narrower claims covering moisture below 1%, concentration of 0.5 g/mL, specific impurity limits, cyclophosphamide monohydrate, and listed excipients. Claim 9 appears to duplicate the six-month stability limitation already present in claim 1.

What does US Patent 11,382,923 protect?

The patent protects a stable liquid pharmaceutical formulation of cyclophosphamide that satisfies all limitations of claim 1:

Claim element	Scope
Active ingredient	Cyclophosphamide
Dosage form	Liquid pharmaceutical formulation
Excipients	At least one pharmaceutically acceptable excipient
Moisture	Less than about 2.0% by weight
Stability condition	Stable after moisture is reduced below about 2.0%
Refrigerated stability	Total impurities below about 6.0% by weight at 2-8°C for at least six months
Exclusions	No polyol organic solvent and no citric acid

The claim uses “comprising,” which generally leaves the formulation open to additional ingredients unless another limitation excludes them. A competing product could therefore contain excipients beyond those expressly identified in claim 8, provided the product still satisfies the core moisture, impurity, stability, and exclusion limitations.

The claim is formulation-specific. It does not claim:

• Cyclophosphamide as a chemical compound;
• Cyclophosphamide monohydrate in every dosage form;
• A lyophilized cyclophosphamide product;
• A dry powder for reconstitution;
• A manufacturing process in the claims supplied;
• A method of treating cancer;
• A vial, syringe, bag, or other container independently of the formulation;
• A liquid formulation containing citric acid or a polyol organic solvent.

How do claims 1 through 9 differ?

Claim 1: Core composition and stability claim

Claim 1 is the principal independent claim in the supplied text. An accused product would need to meet each material limitation.

The most important limitations are cumulative. A formulation may contain cyclophosphamide and an excipient but remain outside the claim if:

• Its moisture content is 2.0% or higher;
• Its total impurities reach or exceed approximately 6.0% after the specified storage period;
• It contains citric acid;
• It contains a polyol organic solvent;
• It is not a liquid formulation;
• It does not remain stable after moisture reduction.

The phrase “about” creates a potential claim-construction issue. The enforceable boundary for “about 2.0%” and “about 6.0%” would depend on the specification, prosecution history, analytical method, and technical meaning in the field.

Claims 2 through 4: Moisture and concentration limitations

Claim	Added limitation	Commercial effect
2	Moisture below about 1.0%	Narrows claim 1 to a lower-moisture formulation
3	Cyclophosphamide concentration at least 0.1 g/mL	Excludes lower-concentration liquid products
4	Cyclophosphamide concentration of 0.5 g/mL	Targets a specific high-strength formulation

Claim 4 depends on claim 1 and therefore retains every limitation of claim 1. A 0.5 g/mL product is not within claim 4 unless it also meets the moisture, impurity, stability, excipient, and exclusion requirements.

Claims 5 and 6: Impurity-specific limitations

Claim 5 requires impurity D below about 1.5%. Claim 6 requires impurity B below about 1.5%.

These claims may provide narrower protection against a formulation that satisfies the total-impurity limit but has controlled levels of a particular degradation product. The supplied claim text does not identify the chemical structures of impurity B or impurity D. That omission prevents a reliable assessment of:

• Whether the impurities are cyclophosphamide degradation products;
• Whether the limits are measured by HPLC, another method, or a specified pharmacopeial procedure;
• Whether the impurity nomenclature corresponds to a recognized regulatory impurity classification;
• Whether the claims are vulnerable to indefiniteness or written-description arguments.

Claim 7: Cyclophosphamide monohydrate

Claim 7 narrows the active ingredient to cyclophosphamide monohydrate. This claim is relevant because the hydrate form can affect solubility, water activity, degradation, and moisture measurement.

A product containing an anhydrous form of cyclophosphamide could potentially remain within claim 1 while falling outside claim 7, assuming all other claim 1 limitations are met.

Claim 8: Excipients

Claim 8 identifies the following excipients or excipient classes:

• Ethanol;
• Polysorbates;
• Cyclodextrins;
• Dimethyl acetamide;
• Polyethoxylated castor oil;
• Combinations of these materials.

The word “selected from” generally narrows the dependent claim to the listed excipient categories. Claim 1, by contrast, covers at least one pharmaceutically acceptable excipient without limiting the excipient to the claim 8 list, subject to the express exclusion of polyol organic solvent and citric acid.

Ethanol is not a polyol. Cyclodextrins are cyclic oligosaccharides and may raise a separate interpretive question if a particular cyclodextrin or formulation component is characterized as a polyol organic solvent. That issue would turn on the patent specification, technical evidence, and the relevant claim-construction record.

Claim 9: Six-month refrigerated stability

Claim 9 repeats the limitation that total impurities remain below about 6.0% after storage at 2-8°C for six months. Claim 1 already requires total impurities below about 6.0% when stored at 2-8°C for at least six months.

On the supplied language, claim 9 adds little or no substantive scope. “At least six months” in claim 1 includes six months. The duplication may reflect prosecution drafting, claim-set consolidation, or an attempt to preserve a separately worded stability limitation.

What formulation characteristics create infringement risk?

A liquid cyclophosphamide product presents the highest literal infringement risk when it has the following profile:

Product characteristic	Risk under the supplied claims
Cyclophosphamide concentration of 0.5 g/mL	High, if all claim 1 limits are met
Moisture below 1.0%	Higher risk under claim 2
Cyclophosphamide monohydrate	Higher risk under claim 7
Ethanol, polysorbate, cyclodextrin, dimethyl acetamide, or polyethoxylated castor oil	Higher risk under claim 8
Total impurities below 6% at 2-8°C for six months	Required for claim 1
Impurity B or D below 1.5%	Higher risk under claims 5 or 6
Citric acid present	Potential design-around to the express exclusion
Polyol organic solvent present	Potential design-around to the express exclusion
Moisture at or above approximately 2%	Potential design-around
Lyophilized dosage form	Outside the liquid-formulation requirement

The technical evidence should focus on the formulation as marketed, not only the initial bulk solution. Moisture and impurity values may differ between bulk manufacture, filled containers, stability samples, and finished packaged product.

What are the principal patent-validity issues?

Is the low-moisture limitation definite?

The claims use “less than about 2.0%” and “less than about 1.0%.” A validity or enforcement dispute could focus on:

• The analytical method used to measure moisture;
• Whether moisture means total water, free water, residual water, or water activity;
• The acceptable analytical variation;
• The meaning of “about” at the claimed thresholds;
• Whether the specification provides sufficient examples around the boundaries.

Karl Fischer titration, loss-on-drying, and other methods can produce different results. The patent specification and prosecution history would control the legal interpretation.

Is the stability limitation definite and enabled?

“Stable when the moisture content is reduced” is potentially important but imprecise. A challenger could examine whether the patent defines:

• The starting moisture level;
• The process used to reduce moisture;
• The time between moisture reduction and stability testing;
• The impurity assay;
• The total-impurity calculation;
• The accepted storage container;
• The sampling protocol;
• The meaning of “stable.”

The patent is stronger if its examples establish repeatable results across the claimed excipients and concentrations. It is weaker if the examples cover only a narrow formulation but claim 1 extends to every pharmaceutically acceptable excipient.

Could the claims face an obviousness challenge?

Potential prior-art combinations would likely involve:

1. Earlier liquid cyclophosphamide formulations;
2. Known refrigerated storage of cyclophosphamide;
3. Moisture reduction as a strategy for controlling degradation;
4. Known solubilizers or surfactants;
5. Prior impurity-control studies.

The patentability question would not turn solely on whether each element appeared separately in the prior art. The relevant issue would be whether a skilled person would have combined the elements with a reasonable expectation of achieving the claimed six-month impurity profile.

Evidence supporting validity would include unexpected stability, a non-linear relationship between moisture and degradation, or an excipient-specific effect. Evidence supporting invalidity would include prior formulations already using the same excipients and routine optimization of water content and storage conditions.

When does US Patent 11,382,923 expire?

A precise expiration date cannot be calculated from the claims supplied. US utility-patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to terminal disclaimers, patent-term adjustment, patent-term extension, and other statutory adjustments. The grant date alone does not establish the expiration date. The operative record is the USPTO front page, Patent Center file history, and any terminal-disclaimer or patent-term-adjustment data.[2]

The patent number indicates a US patent issued in 2022, but that fact does not establish whether the patent has:

• Patent-term adjustment;
• A terminal disclaimer;
• A continuation or divisional relationship;
• A foreign priority claim;
• A patent-term extension;
• Any post-grant claim amendment.

What is the Orange Book status of cyclophosphamide patent 11,382,923?

The supplied claims do not establish an Orange Book listing. Orange Book listing is product-specific and depends on the approved NDA, patent submission, statutory listing requirements, and FDA publication practice.[3]

The patent covers a formulation, so it could be relevant to an approved liquid cyclophosphamide product if the NDA holder submitted it and FDA accepted the listing. It would not automatically appear in the Orange Book merely because it claims an FDA-regulated drug formulation.

For a Paragraph IV challenge, a generic applicant would need to address any properly listed patent identified for the reference-listed drug. The relevant certification would depend on the NDA’s current patent-listing record, not on the existence of US Patent 11,382,923 alone.

Are biosimilars relevant to this patent?

No. Cyclophosphamide is a small-molecule drug. Competitors would generally use the abbreviated new drug application pathway, not the biosimilar pathway under the Public Health Service Act.

The relevant market-entry issues are:

• Abbreviated new drug applications;
• Paragraph I, II, III, or IV certifications;
• Hatch-Waxman litigation;
• 30-month stays;
• First-filer exclusivity;
• Formulation and method-of-use patent listings;
• Non-infringement and invalidity positions.[4]

Which companies may challenge the patent?

The supplied information does not identify a filed Paragraph IV notice, ANDA applicant, district-court action, International Trade Commission investigation, settlement, or license involving US Patent 11,382,923. No particular challenger, licensee, or settlement counterparty can be attributed to this patent from the claim text.

Potential challengers would be companies developing:

• Premixed liquid cyclophosphamide;
• High-concentration injectable cyclophosphamide;
• Refrigerated liquid products;
• Alternative solvent systems;
• Low-moisture formulations;
• Ready-to-use oncology products.

A generic applicant could pursue a design-around rather than challenge the patent, particularly by using a different moisture level, excipient system, dosage form, or stability profile.

What design-arounds are available?

The most apparent design-around paths are:

1. Use a moisture content at or above the relevant claim threshold.
2. Use citric acid or a qualifying polyol organic solvent, subject to regulatory and formulation feasibility.
3. Develop a lyophilized product for reconstitution.
4. Use a concentration outside the narrower claims, such as below 0.1 g/mL.
5. Use a different active form than cyclophosphamide monohydrate to avoid claim 7.
6. Use excipients outside claim 8 while addressing the broader claim 1 limitations.
7. Accept a different refrigerated impurity profile, provided the product remains within applicable quality specifications.
8. Use packaging or manufacturing controls that produce a different formulation state.

A design-around must avoid the complete combination in claim 1. Avoiding only claim 8 does not avoid claim 1, because claim 8 is dependent and the broader claim does not require one of the listed excipients.

How strong is the patent estate?

Based solely on the supplied claims, the estate appears concentrated rather than broad.

Strength factor	Assessment
Product relevance	Strong for covered ready-to-use liquid formulations
Chemical-composition breadth	Limited
Dosage-form breadth	Limited to liquids
Excipient breadth	Broad in claim 1, narrower in claim 8
Stability coverage	Central and commercially relevant
Design-around risk	Material
Claim clarity	Potential issues around “about,” moisture, stability, and impurity measurement
Small-molecule generic risk	Relevant
Biosimilar risk	Not applicable
Method-of-use protection	Not present in supplied claims
Manufacturing-process protection	Not present in supplied claims
Container or device protection	Not present in supplied claims

The patent could have meaningful blocking value if the commercial product is a ready-to-use liquid containing cyclophosphamide at or near 0.5 g/mL, with low moisture and the claimed refrigerated impurity profile. Its value is lower against lyophilized products, formulations containing excluded components, or products that do not meet the six-month impurity limitation.

What patent litigation and licensing issues should be monitored?

The relevant records are:

• USPTO Patent Center for prosecution history and post-grant activity;
• FDA Orange Book for product-specific listings;
• PACER and district-court docket records for Hatch-Waxman litigation;
• Court opinions construing the moisture, impurity, and stability limitations;
• ANDA litigation settlements;
• Assignment and licensing records;
• Continuation and foreign-family applications.

The supplied claims do not show any litigation, settlement, licensing transaction, or assignment. Those matters cannot be inferred from the patent claims.

Key Takeaways

• US Patent 11,382,923 is a formulation patent for low-moisture liquid cyclophosphamide.
• Claim 1 requires cyclophosphamide, an excipient, moisture below about 2%, refrigerated six-month total impurities below about 6%, and exclusion of citric acid and polyol organic solvents.
• Claims 2 through 8 narrow the scope through moisture, concentration, impurity, hydrate-form, and excipient limitations.
• Claim 9 appears duplicative of claim 1’s six-month stability requirement.
• The patent does not broadly cover cyclophosphamide, all cyclophosphamide injections, lyophilized products, treatment methods, or manufacturing processes.
• The principal validity issues concern the meaning of “about,” moisture measurement, impurity testing, stability definitions, and the breadth of the excipient limitation.
• Generic applicants face the greatest risk with refrigerated, ready-to-use liquid products using low moisture and high cyclophosphamide concentration.
• Biosimilar competition is irrelevant because cyclophosphamide is a small molecule.
• Orange Book listing, expiration, litigation, Paragraph IV activity, licensing, and settlement status require the relevant USPTO, FDA, court, and transaction records and are not established by the supplied claim text.

FAQs

Does US Patent 11,382,923 cover cyclophosphamide powder?

No. The supplied claims require a liquid pharmaceutical formulation. A dry powder or lyophilized product is outside the literal scope of these claims.

Does a formulation with citric acid infringe claim 1?

The claim expressly excludes citric acid from the excipient system. A formulation containing citric acid would have a strong non-infringement position under the supplied claim language, subject to claim construction and any separate claims in the patent.

Does claim 1 require cyclophosphamide monohydrate?

No. Claim 7 adds the monohydrate limitation. Claim 1, as supplied, covers cyclophosphamide without expressly requiring the monohydrate form.

Is a 0.5 g/mL formulation automatically covered?

No. Claim 4 also requires every limitation of claim 1, including low moisture, the refrigerated impurity limit, the excipient requirement, and exclusion of citric acid and polyol organic solvents.

Can a generic company avoid the patent by using a different excipient?

Possibly, but changing the excipient alone may not avoid claim 1 because claim 1 is not limited to the excipients listed in claim 8. The alternative formulation would need to avoid the complete combination of claim 1 limitations.

References

1. United States Patent No. 11,382,923. (2022). Stable liquid pharmaceutical formulation of cyclophosphamide. United States Patent and Trademark Office.

2. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. https://www.uspto.gov/patents/uspto-patent-terms

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book

4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 11,382,923

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Avyxa Holdings	FRINDOVYX	cyclophosphamide	SOLUTION;INTRAVENOUS	210852-002	Jun 7, 2023		RX	Yes	Yes			Y
Avyxa Holdings	FRINDOVYX	cyclophosphamide	SOLUTION;INTRAVENOUS	210852-003	Jun 7, 2023		RX	Yes	Yes			Y
Avyxa Holdings	FRINDOVYX	cyclophosphamide	SOLUTION;INTRAVENOUS	210852-001	Jun 7, 2023		RX	Yes	Yes			Y

International Family Members for US Patent 11,382,923

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
World Intellectual Property Organization (WIPO)	2016005962