Details for Patent: 8,092,828

Which drugs does patent 8,092,828 protect, and when does it expire?

Patent 8,092,828 protects VYXEOS and is included in one NDA.

Protection for VYXEOS has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has thirty-one patent family members in twenty countries.

Summary for Patent: 8,092,828

Title:	Fixed drug ratios for treatment of hematopoietic cancers and proliferative disorders
Abstract:	Provided herein are methods for treating cancer by administering a pharmaceutical composition comprising a fixed, non-antagonistic molar ratio of cytarabine and an anthracycline. Such methods are particularly useful in the treatment of patients with advanced hematologic cancers or proliferative disorders.
Inventor(s):	Arthur Louie, Christine Swenson, Lawrence Mayer, Andrew Janoff
Assignee:	Jazz Pharmaceuticals Therapeutics Inc
Application Number:	US12/032,583
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,092,828
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Drug Patent 8,092,828: Claim Scope, Vyxeos Protection, Expiration and Generic Entry Risk

US Patent No. 8,092,828 protects a highly specific liposomal cytarabine-daunorubicin treatment regimen. The patent is directed to the product later commercialized as Vyxeos, a fixed-ratio liposomal formulation of cytarabine and daunorubicin used for acute myeloid leukemia.

The core protection requires all of the following: a human leukemia patient; intravenous administration; liposomal encapsulation; a cytarabine-to-daunorubicin molar ratio of about 5:1; maintenance of that ratio in plasma for at least four hours; a DSPC:DSPG:cholesterol lipid ratio of 7:2:1; administration on days 1, 3 and 5; and a cytarabine dose of 32-134 mg/m² per administration.

The patent is therefore narrower than a general claim to cytarabine-daunorubicin combination therapy. A competing product or regimen that omits the specified lipid composition, changes the dosing schedule, uses a different molar ratio, or fails to maintain the ratio in plasma may avoid literal infringement.

What drug does US Patent 8,092,828 protect?

US 8,092,828 protects a liposomal fixed-ratio combination of cytarabine and daunorubicin. The protected product corresponds to Vyxeos, also known as CPX-351, developed by Celator Pharmaceuticals and commercialized by Jazz Pharmaceuticals.

Item	Description
Patent	US 8,092,828
Technology	Liposomal cytarabine-daunorubicin combination
Commercial product	Vyxeos
Active ingredients	Cytarabine and daunorubicin citrate
Drug class	Liposomal antineoplastic combination
Principal disease	Therapy-related AML and AML with myelodysplasia-related changes
FDA approval	August 3, 2017
Administration	Intravenous infusion
Standard schedule	Days 1, 3 and 5
Commercial ratio	5:1 cytarabine to daunorubicin on a molar basis
Lipid system in the patent claims	DSPC:DSPG:cholesterol at 7:2:1

The FDA-approved Vyxeos label describes administration by intravenous infusion over 90 minutes on days 1, 3 and 5 for induction therapy. Consolidation therapy uses a different dosing schedule, generally days 1 and 3. The issued claims quoted in the question are focused on the three-dose induction cycle. [2]

What are the independent claim limitations in US 8,092,828?

Claim 1 is the controlling method claim. It requires a combination of product, pharmacokinetic, dosing and patient-treatment limitations.

Claim element	Required limitation
Patient	Human patient
Disease	Leukemia
Route	Intravenous administration
Dosage form	Liposome-encapsulated composition
Active ingredients	Cytarabine and daunorubicin
Drug ratio	About 5:1 molar ratio
Plasma behavior	Ratio maintained for at least four hours
Lipid composition	DSPC:DSPG:cholesterol at 7:2:1 molar ratio
Infusion period	Eight hours or less
Cytarabine dose	32-134 mg/m² per administration
Total cycle dose	96-402 mg/m²
Treatment cycle	Administration on days 1, 3 and 5

Every limitation must generally be satisfied for literal infringement. The claim does not cover every liposomal formulation containing the two active ingredients. It covers the specified formulation when used under the specified treatment conditions.

What does the 5:1 ratio limitation mean?

The claim requires cytarabine and daunorubicin to be present at an approximately 5:1 molar ratio. This is a ratio of molecules, not a weight ratio. Because cytarabine and daunorubicin have different molecular weights, a formulation can satisfy the molar ratio without having a 5:1 weight ratio.

The claim also requires that the fixed ratio remain in plasma for at least four hours. This limitation distinguishes the claimed formulation from conventional co-administration, where the two drugs are infused separately or have materially different pharmacokinetic profiles.

The plasma-ratio requirement is important for enforcement. A generic developer could challenge infringement by arguing that its product does not maintain the ratio for four hours, although the evidentiary issue would likely require pharmacokinetic testing and expert analysis.

What does the lipid limitation require?

The liposome must comprise:

• DSPC, or distearoylphosphatidylcholine;
• DSPG, or distearoylphosphatidylglycerol; and
• cholesterol.

The claim specifies a 7:2:1 molar ratio. A formulation using another phospholipid, a different lipid ratio, or a materially different liposome architecture could fall outside the literal scope of claim 1.

The wording "comprise" generally permits additional components unless another claim limitation excludes them. It does not, however, eliminate the requirement that the named lipid components be present at the claimed ratio.

How do claims 2 through 4 narrow the patent scope?

Claims 2 through 4 impose administration restrictions or specify the route.

Claim	Added limitation
Claim 2	Each administration step is completed in three hours or less
Claim 3	Each administration step is completed in 90 minutes or less
Claim 4	Administration is by IV drip

Claim 3 is particularly relevant to Vyxeos because the FDA label uses a 90-minute infusion. A product administered over 90 minutes or less may fall within both claim 3 and the broader administration-period limitations in claim 1.

The claims do not require a particular infusion pump, hospital setting or infusion volume. The relevant issue is whether the product is administered intravenously within the specified time period.

Which leukemia indications are covered by claims 5 through 8?

Claim 5 identifies acute lymphocytic leukemia, acute myeloid leukemia and acute promyelocytic leukemia. Claims 6 through 8 narrow the patient population to previously treated or relapsed patients.

Claim	Patient or disease limitation
Claim 5	ALL, AML or APL
Claim 6	Prior anticancer regimen or previous remission
Claim 7	Relapse within 18 months after prior therapy
Claim 8	Relapse within six months after prior therapy

The patent is not limited to newly diagnosed patients. It reaches certain relapsed or previously treated patients, provided the product and regimen limitations are also met.

These claims can create method-of-use exposure even where a generic manufacturer does not promote every covered indication. Under US law, inducement questions can turn on labeling, prescribing information, distribution practices and the relationship between the patented use and the approved label.

Are claims 9 through 11 enforceable treatment limitations?

Claims 9 through 11 concern treatment outcomes and safety measurements.

Claim 9 refers to measuring therapeutic effect through:

• Increased complete remission rate;
• Longer complete remission duration;
• Longer time to progression; or
• Longer survival.

Claim 10 requires measuring an improved safety result through reduced non-hematologic toxicities. Claim 11 identifies mucositis and alopecia as examples.

The legal significance of these claims depends on claim construction. The wording may be argued to require actual measurement as part of the treatment method, rather than merely requiring that the treatment produce an outcome. A generic product using the same regimen could face a more difficult infringement case under these dependent claims if the claimed measurement is absent from clinical use or labeling.

Claims 9 through 11 are less commercially central than claim 1 because ordinary clinical administration may not expressly include the claimed measurement steps. They may still strengthen the patent against protocols, clinical studies or promotional materials that expressly evaluate the specified efficacy and toxicity endpoints.

What formulations are protected by US 8,092,828?

The principal formulation protection is defined by the combination of active ingredients, lipid composition and pharmacokinetic behavior.

A potentially infringing formulation would generally need to satisfy the following profile:

1. Cytarabine and daunorubicin are co-encapsulated in liposomes.
2. The active ingredients have an approximately 5:1 molar ratio.
3. The liposomes use DSPC, DSPG and cholesterol.
4. The lipid components are present at a 7:2:1 molar ratio.
5. The formulation maintains the active-ingredient ratio in plasma for at least four hours.
6. The product is administered under the claimed schedule and dose.

A formulation may present design-around opportunities if it uses:

• Separate liposomes for the two active ingredients;
• A different drug ratio;
• A different lipid composition;
• A different lipid molar ratio;
• Non-liposomal co-administration;
• A different administration schedule; or
• A dose outside the claimed per-administration range.

A design-around is not automatically safe. The patent family, continuation patents, claim construction and doctrine of equivalents must be reviewed as a group.

How does the patent compare with conventional cytarabine-daunorubicin therapy?

The patent’s commercial distinction is the coordinated delivery of both drugs in a fixed ratio.

Characteristic	Conventional 7+3 therapy	US 8,092,828 regimen
Cytarabine	Continuous or prolonged infusion	Liposome-encapsulated
Daunorubicin	Separate administration	Encapsulated with cytarabine
Drug ratio	May vary over time	Approximately fixed at 5:1 molar
Lipid carrier	None	DSPC:DSPG:cholesterol liposomes
Administration	Separate chemotherapy components	Single liposomal product
Typical induction schedule	Cytarabine for seven days, anthracycline for three days	Days 1, 3 and 5
Pharmacokinetic objective	Separate exposure profiles	Maintained plasma ratio
Main patent risk	Usually outside the claimed formulation	High if all claim elements are met

The patent does not broadly prevent physicians from using cytarabine and daunorubicin together. Its commercial value comes from controlling a particular delivery system and treatment schedule.

What is the FDA and Orange Book status of Vyxeos?

Vyxeos received FDA approval in 2017 for adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. The product was approved through an NDA rather than an ANDA pathway. [2]

Vyxeos is a small-molecule liposomal combination product, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply. A competing developer would generally pursue an ANDA or, depending on product differences, a 505(b)(2) application.

The Orange Book identifies patents and exclusivity associated with approved drug products. For Vyxeos, the relevant analysis includes both listed patents and non-patent regulatory exclusivity. Orange Book patent listings must be checked against the current FDA edition because listing status, expiration data and certification information can change. [3]

What regulatory exclusivity applied to Vyxeos?

Vyxeos received orphan-drug designation for the approved AML population. Orphan exclusivity generally runs for seven years from approval under section 527 of the Federal Food, Drug, and Cosmetic Act, subject to statutory exceptions. The product also benefited from FDA approval-related exclusivity associated with its regulatory classification. [2][4]

Regulatory exclusivity and patent protection operate independently. Expiration of one does not necessarily terminate the other. An ANDA applicant must account for the latest-ending applicable barrier, including patent litigation and any pediatric extension.

When does US 8,092,828 lose exclusivity?

The patent’s effective expiration date depends on its earliest effective nonprovisional filing date, patent-term adjustment, patent-term extension and any applicable pediatric extension. A patent number alone does not establish the final enforceable expiration date.

Public patent records have associated US 8,092,828 with an expiration period in the mid-2020s. The practical generic-entry date can be later than the nominal expiration if:

• FDA exclusivity remains active;
• A valid patent-term adjustment applies;
• A pediatric extension adds six months;
• A later continuation patent remains enforceable;
• An ANDA applicant enters a litigation stay; or
• A settlement agreement restricts launch.

For diligence purposes, the relevant date is the latest enforceable barrier affecting the proposed product, not simply the expiration date printed against one patent family member.

How strong is the patent estate for Vyxeos?

US 8,092,828 is commercially meaningful but technically narrow.

Strength factor	Assessment
Product specificity	Strong; the lipid and drug ratios are highly defined
Regimen specificity	Strong; days 1, 3 and 5 and dose limits narrow the claim
Pharmacokinetic limitation	Potentially strong but testing-intensive
Design-around risk	Material because alternative lipids or ratios may avoid literal infringement
Clinical relevance	High for the Vyxeos induction regimen
Biosimilar exposure	Not applicable
ANDA exposure	Applicable
Continuation-family risk	Must be reviewed separately
Method-of-use risk	Meaningful for AML labeling and promotion
Manufacturing barrier	Potentially significant because liposome loading, stability and ratio retention are difficult to reproduce

The patent’s strength is highest against a directly substitutive product that copies the Vyxeos formulation and label. Its strength is lower against a different liposomal architecture or a combination product with separate dosing and altered pharmacokinetics.

Which companies are challenging Vyxeos patents?

A reliable assessment of Paragraph IV challengers requires current FDA Orange Book records, ANDA litigation dockets and patent-holder disclosures. The claim record supplied does not establish a current named challenger, a filing date or a settlement term.

The principal legal pathway for a generic challenge would be an ANDA containing a Paragraph IV certification alleging that a listed patent is invalid, unenforceable or not infringed. The patent holder could file an infringement action within 45 days, triggering a statutory FDA approval stay of up to 30 months under the Hatch-Waxman framework. [5]

A 505(b)(2) applicant could face a similar patent-certification process if it relies on the reference product while seeking approval for a modified formulation, dosage or indication.

What Paragraph IV risks exist for generic launch?

A generic applicant would likely assess several noninfringement positions:

1. The proposed liposome does not use DSPC:DSPG:cholesterol at 7:2:1.
2. The product does not maintain a 5:1 plasma ratio for at least four hours.
3. The product uses a different cytarabine-daunorubicin ratio.
4. The proposed label omits a patented indication or regimen.
5. The dosage or infusion schedule falls outside the claimed ranges.
6. The product does not co-encapsulate both active ingredients.

Invalidity arguments could target written description, enablement, obviousness, indefiniteness and claim construction. The fixed-ratio delivery concept, specific lipid system and clinical dosing schedule would likely be analyzed against earlier liposomal anthracycline, cytarabine and combination-therapy disclosures.

The most important practical question is whether the competing product is pharmaceutically equivalent to Vyxeos. If it is, the product may encounter both formulation-patent and method-of-use exposure.

What manufacturing and geographic IP barriers matter?

The claims are enforceable in the United States only. Foreign counterparts must be analyzed separately by jurisdiction, including patent term, prosecution history, supplementary protection certificates and national claim scope.

Manufacturing risk is higher than for a conventional tablet or injectable mixture. A competing manufacturer may need to reproduce:

• Drug loading into the liposome;
• Encapsulation efficiency;
• Particle-size distribution;
• Lipid-ratio control;
• Stability during storage;
• Release kinetics;
• Sterility and pyrogen control; and
• Maintenance of the in-plasma ratio.

These technical barriers can delay market entry even where a patent design-around appears available. They also increase the probability that a 505(b)(2) applicant, rather than a conventional ANDA applicant, will be used if the proposed product differs materially from Vyxeos.

What patent litigation or settlement issues should investors monitor?

The key diligence items are:

• Current Orange Book listings for Vyxeos;
• Patent-term adjustment and extension records;
• Continuation and divisional patents in the Celator/Jazz family;
• Paragraph IV notices;
• District-court complaints filed after certification;
• 30-month-stay dates;
• Trial and appellate decisions;
• Authorized-generic provisions;
• Launch dates in settlement agreements; and
• Any pediatric exclusivity attached to the product.

A settlement may permit an earlier launch than patent expiration while restricting the generic to a specified date, supply arrangement or authorized-generic structure. The settlement date should not be confused with the patent expiration date.

Key Takeaways

• US 8,092,828 is a method patent centered on the Vyxeos liposomal cytarabine-daunorubicin regimen.
• Claim 1 requires a 5:1 molar ratio, four-hour plasma-ratio maintenance, DSPC:DSPG:cholesterol at 7:2:1, intravenous administration and a day 1/3/5 cycle.
• Claims 2 and 3 narrow the infusion period to three hours and 90 minutes, respectively.
• Claims 5 through 8 cover specified leukemia types and previously treated or rapidly relapsed patients.
• Claims 9 through 11 address efficacy and non-hematologic toxicity measurements.
• The patent does not broadly cover all cytarabine-daunorubicin combinations.
• Biosimilar competition is not the relevant pathway because Vyxeos is a small-molecule liposomal drug.
• Generic competition would most likely proceed through an ANDA or, for a materially different product, a 505(b)(2) application.
• The patent’s practical strength is highest against a product that copies both the Vyxeos formulation and the labeled induction regimen.
• Final market-entry timing depends on the complete patent family, Orange Book records, regulatory exclusivity, patent-term adjustments, litigation stays and settlements.

FAQs About US Patent 8,092,828 and Vyxeos

Does US 8,092,828 cover ordinary 7+3 AML chemotherapy?

No. The claims require a liposomal fixed-ratio formulation and the specified day 1, 3 and 5 administration cycle. Conventional separate cytarabine and daunorubicin administration generally does not satisfy those limitations.

Can a different cytarabine-to-daunorubicin ratio avoid infringement?

Potentially. A materially different ratio may avoid literal infringement, but the complete claim language, prosecution history and doctrine of equivalents must be analyzed.

Is CPX-351 the same product as Vyxeos?

Yes. CPX-351 is the development code for the fixed-ratio liposomal cytarabine-daunorubicin product marketed as Vyxeos.

Can a generic company use a Paragraph III certification instead of Paragraph IV?

A Paragraph III certification accepts that the listed patent is valid and enforceable until its expiration. A Paragraph IV certification challenges validity, enforceability or infringement and can trigger patent litigation.

Are European or Canadian rights automatically covered by US 8,092,828?

No. US 8,092,828 creates rights only in the United States. Foreign national patents, supplementary protection certificates and local regulatory exclusivity must be reviewed separately.

References

1. United States Patent and Trademark Office. (2012). U.S. Patent No. 8,092,828, methods for treating leukemia using liposomal cytarabine and daunorubicin.
2. U.S. Food and Drug Administration. (2023). Vyxeos (daunorubicin and cytarabine) liposome for injection prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360cc.
5. Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 8,092,828

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Jazz Pharms Therap	VYXEOS	cytarabine; daunorubicin	POWDER;INTRAVENOUS	209401-001	Aug 3, 2017		RX	Yes	Yes					Y

International Family Members for US Patent 8,092,828

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3300601		301185	Netherlands
European Patent Office	3300601		CA 2022 00030	Denmark
European Patent Office	3300601		2022C/528	Belgium
European Patent Office	3300601		LUC00271	Luxembourg
European Patent Office	3300601		122022000044	Germany
European Patent Office	3300601		27/2022	Austria
European Patent Office	3300601		C20220023 00369	Estonia