Details for Patent: 9,050,302

Which drugs does patent 9,050,302 protect, and when does it expire?

Patent 9,050,302 protects XYREM and XYWAV and is included in two NDAs.

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

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

Summary for Patent: 9,050,302

Title:	Method of administration of gamma hydroxybutyrate with monocarboxylate transporters
Abstract:	One embodiment of the present invention is to improve the safety and efficacy of the administration of GHB or a salt thereof to a patient. It has been discovered that the concomitant administration of an MCT inhibitor, such as diclofenac, valproate, or ibuprofen, will affect GHB administration. For example, it has been discovered that diclofenac lowers the effect of GHB in the body, thereby potentially causing an unsafe condition. Furthermore, it has been discovered that valproate increases the effect of GHB on the body, thereby potentially causing an unsafe condition.
Inventor(s):	Mark Eller
Assignee:	Jazz Pharmaceuticals Ireland Ltd
Application Number:	US13/837,714
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,050,302
Patent Claim Types: see list of patent claims	Use;

US Patent 9,050,302: Claim Scope, Orange Book Position, Generic Risk, and Patent Landscape

US Patent 9,050,302 protects methods for reducing the gamma-hydroxybutyrate, or GHB, dose used to treat cataplexy or excessive daytime sleepiness in narcolepsy when the patient is taking divalproex sodium. The patent is a method-of-treatment patent, not a composition, formulation, manufacturing, or salt patent. Its commercial relevance is tied primarily to sodium oxybate products, including Xyrem and potentially other GHB or oxybate products used for narcolepsy.

The strongest claim theme is dose reduction of at least 20% when divalproex sodium is administered concomitantly with GHB. The broadest apparent claim is claim 27, which covers administration of less than 4.5 g of GHB per day to a patient currently taking divalproex sodium, without expressly requiring a 20% reduction or a two-dose schedule.

What does US Patent 9,050,302 cover?

US 9,050,302 covers a treatment protocol with four required elements:

1. The patient has cataplexy or excessive daytime sleepiness associated with narcolepsy.
2. The patient is taking, or begins taking, divalproex sodium.
3. The patient receives GHB or a salt of GHB.
4. The GHB dose is reduced or initiated below the dose otherwise recommended without divalproex sodium.

The claims focus on the clinical interaction between divalproex sodium and GHB. They do not claim divalproex sodium, GHB, sodium oxybate, or narcolepsy treatment generally.

Patent identification

Field	Information
Patent	US 9,050,302 B2
Issue date	June 9, 2015
Subject matter	Narcolepsy treatment using GHB and divalproex sodium
Claim type	Method of treatment
Therapeutic indications	Cataplexy or excessive daytime sleepiness in narcolepsy
Principal active agents	GHB or a salt thereof; divalproex sodium
Product relevance	Sodium oxybate and other GHB/oxybate products
Primary legal focus	Concomitant use and reduced GHB dosing
Patent owner or assignee context	Jazz Pharmaceuticals-related oxybate patent estate
Regulatory pathway implicated	ANDA and potentially 505(b)(2) applications for oxybate products

The claims supplied for analysis contain 31 claims. They are organized into three related claim groups:

• Claims 1-12: dose reduction during concomitant administration.
• Claims 13-26: reduced starting dose when the patient is already taking divalproex sodium.
• Claims 27-31: administration of less than 4.5 g per day, including two doses below 2.25 g each.

How do the independent claims differ?

Claim	Core requirement	Dose limitation	Patient-drug sequence
1	Administer divalproex sodium with GHB and reduce GHB by at least 20%	Baseline GHB is 4.5-9 g/day	Patient is currently taking GHB
8	Reduce GHB by at least 20% during divalproex administration	Compared with 4.5-9 g/day or manufacturer recommendation	Patient is currently taking GHB
13	Start GHB at least 20% below recommended starting dose	Recommended dose is 4.5-9 g/day	Patient is currently taking divalproex sodium
20	Start GHB at least 20% below the dose otherwise recommended	Recommended dose is 4.5-9 g/day	Patient is currently taking divalproex sodium
27	Administer GHB below 4.5 g/day	Less than 4.5 g/day; no express 20% limitation	Patient is currently taking divalproex sodium
31	Administer two GHB doses, each below 2.25 g	Total daily dose is below 4.5 g	Patient is currently taking divalproex sodium

Claims 1, 8, 13, 20, 27 and 31 are the principal independent claims. The scope of claims 27 and 31 is materially broader in dose terms than claims 1, 8, 13 and 20 because the 20% reduction requirement is absent.

What dose ranges are protected?

The patent uses the standard GHB dosing range of 4.5 g to 9 g per day as the reference point. The resulting numerical thresholds are:

Reference daily dose	20% reduction threshold	Reduced dose required
4.5 g	0.9 g	3.6 g or less, depending on claim wording
6.0 g	1.2 g	4.8 g or less
7.5 g	1.5 g	6.0 g or less
9.0 g	1.8 g	7.2 g or less

Claims 3-7 identify 4.5 g, 6 g, 7.5 g and 9 g as baseline doses. Claims 4 and 12 require a dose lower than 3.6 g when the ordinary daily dose is 4.5 g.

A drafting issue arises from the difference between "at least 20%" and "lower than." A 20% reduction from 4.5 g equals 3.6 g. A claim requiring a dose "lower than 3.6 g" excludes exactly 3.6 g, while a claim requiring reduction "by at least 20%" includes a dose of 3.6 g if the other limitations are met.

What do claims 1 through 12 protect?

Claims 1-12 protect dose reduction in a patient already receiving GHB.

Claim 1 requires:

• narcolepsy-related cataplexy or excessive daytime sleepiness;
• current GHB use;
• administration of divalproex sodium;
• concomitant GHB administration;
• at least a 20% GHB reduction; and
• an original dose between 4.5 g and 9 g per day.

Claim 2 adds monitoring and dose adjustment. Claims 3-7 specify the original dose. Claims 8-12 restate the dose-reduction concept in a separate independent claim structure.

The monitoring limitations in claims 2 and 10 may be relatively easy to satisfy in routine clinical practice. Narcolepsy patients receiving oxybate are commonly monitored for efficacy and tolerability, and dose adjustment is part of ordinary clinical management. These claims are narrower than claims 1 and 8 but may not create a meaningful practical barrier if the underlying dose-reduction method is already performed.

What do claims 13 through 26 protect?

Claims 13-26 address treatment initiation rather than dose reduction in an established GHB user.

The required sequence is:

1. The patient is already taking divalproex sodium.
2. GHB is initiated.
3. The starting GHB dose is at least 20% below the dose that would otherwise be recommended.

Claims 14 and 21 require a starting dose below 4.5 g. Claims 15-17 and 22-24 require two equal doses, with each dose below 2.25 g. Claims 19 and 26 specify 4.5 g as the reference starting dose.

This group may be more relevant to a product label than claims 1-12. A generic or follow-on product that recommends a lower initial oxybate dose for patients taking divalproex sodium could create a direct method-of-use exposure, depending on the wording of the label and the actual prescribing behavior.

What do claims 27 through 31 protect?

Claims 27-31 contain the broadest numerical dosing language in the supplied claims.

Claim 27 requires:

• treatment of narcolepsy-related cataplexy or excessive daytime sleepiness;
• a patient currently taking divalproex sodium; and
• administration of GHB below 4.5 g per day.

It does not expressly require:

• a 20% reduction;
• a specified baseline dose;
• a manufacturer’s recommendation;
• monitoring;
• a particular GHB formulation; or
• two divided doses.

Claim 28 requires two equal doses. Claims 29 and 30 limit each dose to below 2.25 g. Claim 31 separately requires two doses, each below 2.25 g.

From an infringement perspective, claim 27 is the principal risk claim for any regimen using less than 4.5 g per day in a patient taking divalproex sodium. Claims 28-31 narrow that exposure to divided-dose regimens.

What products and formulations fall within the claims?

The claims recite GHB "or a salt thereof." That language is broad enough to encompass sodium oxybate, the sodium salt of GHB, and potentially other pharmaceutically acceptable GHB salts, subject to claim construction and written-description support.

Product categories

Product or product type	Potential relevance
Xyrem, sodium oxybate oral solution	Directly relevant
Generic sodium oxybate oral solution	Directly relevant
Xywav, mixed-salt oxybate oral solution	Potentially relevant because it contains oxybate salts, but claim scope requires analysis of the claimed "salt thereof" language
Investigational oxybate formulations	Potentially relevant
Non-oxybate narcolepsy drugs	Generally outside the claims
Divalproex products	Relevant as the concomitant medication, not as the claimed primary treatment agent

The claims do not require a particular concentration, excipient system, container, delivery device, or release profile. An immediate-release oral solution and another GHB salt formulation could potentially fall within the method claims if the active ingredient, disease, patient medication status and dosing limitations are satisfied.

What is the Orange Book status of US 9,050,302?

The patent’s commercial significance depends on whether it is listed against an approved oxybate product in the FDA Orange Book and whether the listed claims correspond to an approved method of use.

Orange Book-listed method-of-use patents can affect an ANDA applicant in two ways:

• The applicant may submit a Paragraph IV certification challenging the listed patent.
• The applicant may use a section viii statement and omit the patented method from its labeling, if the FDA determines that the patented use can be carved out.

A method-of-use patent is more difficult to enforce against a generic product when the proposed label excludes the patented dosing instructions and the product has substantial non-infringing uses. The risk increases when the reference product’s label specifically directs reduced oxybate dosing for patients taking divalproex sodium.

Regulatory questions that control commercial exposure

Question	Relevance
Is US 9,050,302 listed for the relevant oxybate NDA?	Determines whether an ANDA certification is required
Is the patented method in the approved labeling?	Determines whether a section viii carve-out is feasible
Does the generic label mention divalproex sodium?	May support induced-infringement allegations
Does the product have substantial uses outside the claimed method?	Relevant to inducement and contributory liability
Is the patent listed for Xyrem, Xywav, or both?	Determines product-specific exposure
Has the patent term expired or been disclaimed?	Determines whether infringement liability remains

The Orange Book listing must be evaluated product by product. A patent listed for sodium oxybate oral solution does not automatically establish listing against every oxybate product or formulation.

When does US 9,050,302 lose exclusivity?

The patent issued on June 9, 2015. The expiration date cannot be reliably calculated from the issue date alone. US utility patents generally expire 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers and any applicable transitional rules.[1]

The controlling term record should be checked against:

• the patent’s earliest effective nonprovisional filing date;
• any priority applications;
• the USPTO patent-term adjustment calculation;
• terminal-disclaimer records;
• patent-term extension under 35 U.S.C. §156; and
• any post-grant or district-court status affecting enforceability.

The expected commercial life of this type of oxybate method patent is likely to extend beyond the core composition patent for sodium oxybate, which creates a potential late-stage method-of-use barrier even after earlier product patents expire.

Which companies are most likely to challenge the patent?

Potential challengers include:

• generic sodium oxybate applicants submitting ANDAs;
• 505(b)(2) applicants developing alternative oxybate formulations;
• sponsors of mixed-salt oxybate products;
• companies seeking a label that omits the divalproex-related dosing method;
• manufacturers entering after expiration of earlier Xyrem composition or formulation patents.

A Paragraph IV challenge would likely attack one or more of the following:

1. Lack of novelty based on prior clinical use of GHB and divalproex sodium.
2. Obviousness based on known GHB dosing, known divalproex pharmacology and routine dose adjustment.
3. Written-description or enablement issues concerning all GHB salts and the full 4.5-9 g reference range.
4. Indefiniteness in terms such as "concomitant," "manufacturer’s recommended" and "maintain the effect."
5. Lack of an adequate technical relationship between divalproex administration and the claimed dose reduction.

No company-specific challenger or settlement should be treated as established without reviewing the relevant ANDA litigation docket, FDA filing records and any settlement agreement.

How strong is the patent estate?

Strengths

The patent has several commercially useful characteristics:

• It claims an actionable clinical dosing method rather than a narrow chemical formulation.
• It covers both existing GHB users and patients starting GHB while taking divalproex sodium.
• Claim 27 does not include the 20% reduction requirement.
• The claims are aligned with a recognizable dosing distinction: below 4.5 g per day.
• The claims potentially reach multiple GHB salts and oxybate products.

Vulnerabilities

The main weaknesses are technical and legal:

• GHB and divalproex sodium were separately known drugs.
• Dose reduction may be characterized as routine clinical optimization.
• The claims do not appear to require a new chemical entity, formulation or delivery technology.
• "Concomitant" may create timing and claim-construction disputes.
• "Manufacturer’s recommended" may change over time and can create an external-reference issue.
• Claims 2, 10, 18 and 25 require monitoring or adjustment that may be difficult to distinguish from ordinary medical care.
• The use of "GHB or a salt thereof" creates potential written-description and enablement questions across different salts and dosage forms.
• Claims 27-31 may face obviousness attacks because they claim a dose threshold without the 20% reduction limitation.

Overall, the estate is stronger as a regulatory-label and induced-infringement asset than as a formulation or manufacturing barrier. Its value depends heavily on claim listing, label language and the ability to prove that physicians prescribe the claimed regimen because of the generic or follow-on product’s instructions.

What litigation and settlement issues matter?

The principal litigation theory for a listed method patent would be patent infringement under 35 U.S.C. §271(e)(2) based on an ANDA filing. The usual defenses would include invalidity, non-infringement and an adequate section viii carve-out.

A settlement could provide:

• a delayed generic launch date;
• a covenant not to sue for specified product configurations;
• permission to launch with a carve-out label;
• restrictions on mentioning divalproex-related dosing;
• a license limited to a particular formulation or indication;
• or an agreement tied to patent expiration.

A settlement’s commercial effect cannot be inferred from the existence of the patent. The relevant terms are the launch date, scope of the license, label restrictions, authorized-generic provisions and treatment of future oxybate formulations.

Is there biosimilar risk?

No conventional biosimilar pathway applies. GHB and oxybate products are small-molecule drugs, not biologics licensed under the Public Health Service Act. The relevant competitive pathways are:

• ANDA approval under section 505(j);
• 505(b)(2) approval for a modified formulation, dosage form or clinical use;
• state-law substitution for an approved generic;
• and, for some products, an alternative oxybate formulation with a distinct label.

The patent can therefore affect generic and 505(b)(2) competition, but not biosimilar substitution.

How does this patent compare with other oxybate patent categories?

Patent category	Typical protected subject matter	Relationship to US 9,050,302
Composition patents	Sodium oxybate or related active ingredient	Usually broader at the molecule level but may expire earlier
Formulation patents	Concentration, excipients, stability, taste masking or delivery	Product-specific and technically narrower
REMS or distribution controls	Restricted distribution and safe-use systems	Regulatory barriers, not patent rights
Method-of-use patents	Narcolepsy, cataplexy, dosing and patient selection	US 9,050,302 belongs here
Manufacturing patents	Synthesis, purification and production processes	May delay alternative sourcing
Combination-use patents	Oxybate with divalproex sodium	US 9,050,302 is a dose-management combination patent

The patent does not prevent manufacture of sodium oxybate in general. It targets a defined treatment method involving divalproex sodium and reduced dosing.

What generic launch scenarios are most plausible?

Scenario 1: Label carve-out

A generic applicant omits the divalproex-related dosing instructions from its label. This could reduce direct inducement risk if the remaining label supports substantial non-infringing uses. The patent holder could still argue that the omitted method is inevitable, promoted through other materials, or induced by the approved label’s broader dosing instructions.

Scenario 2: Paragraph IV litigation

The applicant challenges validity or enforceability. Litigation would likely focus on obviousness, written description, indefiniteness and the relationship between the reference dose and the claimed reduced dose.

Scenario 3: Delayed launch settlement

The applicant accepts a negotiated entry date before patent expiration. The agreement may preserve a later launch for a generic label that does not include the patented method.

Scenario 4: 505(b)(2) formulation entry

A follow-on sponsor launches a different oxybate formulation. The sponsor may argue that the formulation, label and dosing instructions do not practice the claimed method. The patent holder may respond that the active oxybate salt and clinical instructions still meet the claims.

What geographic coverage does the patent provide?

US 9,050,302 provides rights only in the United States. It does not directly block:

• manufacture and sale outside the United States;
• foreign clinical use;
• foreign supply chains with no US importation;
• or foreign oxybate products lacking a corresponding national patent.

US protection can still affect imports, US clinical studies, US sales and ANDA-based market entry. Foreign patent coverage must be assessed separately through the corresponding family members and national-phase records.

Key Takeaways

• US 9,050,302 is a method-of-treatment patent focused on reduced GHB dosing during divalproex sodium use.
• Claims 1-12 cover at least a 20% reduction in an established GHB regimen.
• Claims 13-26 cover reduced starting doses when divalproex sodium is already being taken.
• Claim 27 is the broadest apparent claim because it requires only GHB below 4.5 g per day in a patient taking divalproex sodium.
• Claims 28-31 narrow the regimen to two doses, each below 2.25 g.
• The patent does not claim GHB, sodium oxybate, divalproex sodium, a formulation or a manufacturing process.
• The principal competitive issue is whether a generic or 505(b)(2) applicant can omit the patented dosing method from its label.
• The patent is more exposed to obviousness and label-carve-out arguments than a composition or formulation patent.
• No biosimilar pathway applies; the relevant competitors are ANDA and 505(b)(2) applicants.
• Patent expiration must be determined from the official USPTO term record, including priority, patent-term adjustment, terminal-disclaimer and patent-term-extension data.

FAQs About US Patent 9,050,302

Does US 9,050,302 cover all sodium oxybate treatment?

No. It covers specified treatment methods involving narcolepsy, divalproex sodium and reduced GHB dosing. It does not claim all sodium oxybate treatment.

Does taking divalproex sodium automatically infringe the patent?

No. Infringement requires performance of every limitation of an asserted claim, including the relevant narcolepsy indication, GHB administration and dose limitation.

Is a GHB dose of exactly 3.6 g covered?

It may satisfy a claim requiring at least a 20% reduction from 4.5 g, but it would not satisfy a limitation requiring a dose lower than 3.6 g.

Can a generic avoid the patent by removing divalproex instructions?

Potentially, if the resulting label and conduct do not practice or induce the patented method. The outcome depends on the complete label, promotional activity, physician use and claim construction.

Does the patent cover Xywav automatically?

Not automatically. Xywav contains oxybate salts, but product coverage depends on construction of "GHB or a salt thereof," the approved indication, dosing instructions and any applicable Orange Book listing.

References

1. United States Code. (2023). 35 U.S.C. §§ 154, 156, 271(e)(2).
2. United States Patent and Trademark Office. (2015). U.S. Patent No. 9,050,302 B2.
3. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations.
4. U.S. Food and Drug Administration. (2023). Xyrem (sodium oxybate) prescribing information.
5. U.S. Food and Drug Administration. (2023). Xywav (calcium, magnesium, potassium, and sodium oxybates) prescribing information.
6. United States Patent and Trademark Office. (2023). Manual of Patent Examining Procedure, §§ 2100, 2701 and 2710.

Drugs Protected by US Patent 9,050,302

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	XYREM	sodium oxybate	SOLUTION;ORAL	021196-001	Jul 17, 2002	AA	RX	Yes	Yes	9,050,302*PED				Y
Jazz	XYWAV	calcium oxybate; magnesium oxybate; potassium oxybate; sodium oxybate	SOLUTION;ORAL	212690-001	Jul 21, 2020		RX	Yes	Yes	9,050,302*PED				Y

International Family Members for US Patent 9,050,302

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014223373
Brazil	112015021012
Canada	2902948
China	105073106