Details for Patent: 8,579,865

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Which drugs does patent 8,579,865 protect, and when does it expire?

Patent 8,579,865 protects OTREXUP and is included in one NDA.

This patent has fourteen patent family members in eight countries.

Summary for Patent: 8,579,865

Title:	Hazardous agent injection system
Abstract:	Injection systems comprising a powered injector and one or more hazardous agents are disclosed.
Inventor(s):	Paul Wotton, Peter L. Sadowski, John William Hayes
Assignee:	Assertio Specialty Pharmaceuticals LLC
Application Number:	US13/257,555
Patent Claim Types: see list of patent claims	Use; Dosage form;

United States Patent 8,579,865: Methotrexate Needle-Assisted Jet Injector Patent Scope and Landscape

U.S. Patent No. 8,579,865 protects a methotrexate injection system that combines a defined methotrexate formulation with a needle-assisted jet injector. The broadest claim requires a liquid methotrexate volume of approximately 0.02 to 4.0 mL, concentration of approximately 7.5 to 150 mg/mL, subcutaneous injection pressure of at least 80 psi, and pharmacokinetic performance within an 80% to 125% confidence-interval range compared with conventional syringe administration.

The patent is materially narrower than a general methotrexate injection patent. A competing product must satisfy the formulation, injector architecture, pressure, route, and pharmacokinetic limitations of claim 1 to present a strong literal-infringement case. Claims 2 through 8 add therapeutic, needle-gauge, cartridge, and flow-rate limitations. Claims 9 and 10 extend protection to methods of treating autoimmune diseases with the claimed injector.

What does U.S. Patent 8,579,865 protect?

The patent protects a combination product rather than methotrexate alone. Claim 1 requires both:

1. A specified methotrexate preparation; and
2. A needle-assisted jet injector configured to deliver that preparation subcutaneously under defined operating and pharmacokinetic conditions.

The principal claim limitations are:

Limitation	Requirement in claim 1
Active ingredient	Methotrexate
Volume	About 0.02 to about 4.0 mL
Concentration	About 7.5 to about 150 mg/mL
Device type	Needle-assisted jet injector
Delivery route	Subcutaneous
Injection pressure	At least 80 psi
Injector components	Container, injection outlet member, needle, firing mechanism, energy source and trigger
Pharmacokinetics	One or more Cmax, Tmax or AUC confidence intervals within approximately 80% to 125% of the corresponding syringe-delivery interval
Intended comparison	Same dose delivered subcutaneously or intramuscularly by a hand-powered syringe

The claim does not cover all methotrexate autoinjectors. It targets a jet-injection mechanism that uses stored energy to expel methotrexate as a fluid jet while an injection-assisting needle pierces the skin.

How should claim 1 be construed?

Claim 1 is a combination claim with structural, numerical and functional limitations.

Structural limitations

The injector must include:

• A container configured to hold methotrexate.
• An injection outlet member associated with the container.
• An injection-assisting needle.
• A firing mechanism.
• An energy source that powers the firing mechanism.
• A trigger mechanism.

A conventional spring-loaded autoinjector could potentially satisfy some of these limitations, but the claim requires the device to jet inject methotrexate. A device that merely advances a syringe plunger through a needle may fall outside the claim if it does not produce the claimed fluid-jet operation.

Formulation limitations

The methotrexate must fall within both numerical ranges:

• Approximately 0.02 to 4.0 mL; and
• Approximately 7.5 to 150 mg/mL.

The ranges allow a broad theoretical dose window of approximately 0.15 mg to 600 mg. Commercial rheumatoid arthritis products generally use much smaller volumes and lower total doses than the upper boundary of the claim.

The use of "about" creates a potential claim-construction issue. Courts generally interpret the term according to the specification, prosecution history and technical context. Small deviations may not automatically avoid infringement, particularly where the specification describes manufacturing tolerances or clinically equivalent concentrations.

Pressure limitation

The device must inject methotrexate subcutaneously at a pressure of at least 80 psi. This is a meaningful limitation. A conventional prefilled syringe or passive autoinjector does not necessarily operate at that pressure.

The accused product's relevant pressure would likely be assessed at the point of jet formation or delivery through the injection outlet, rather than solely by reference to spring force or stored energy. Product testing, engineering specifications and expert reconstruction would be central to infringement analysis.

Pharmacokinetic limitation

The claim requires the injector to be configured so that one or more of the following is within approximately 80% to 125% of the corresponding confidence interval for the same dose delivered by a hand-powered syringe:

• Cmax, the maximum plasma concentration;
• Tmax, the time to maximum plasma concentration; or
• AUC, the area under the plasma concentration-time curve.

This limitation introduces a comparative clinical-performance requirement. The claim does not require all three parameters to fall within the range. The phrase "one or more" means that satisfying the limitation for any one of Cmax, Tmax or AUC may be sufficient, assuming the other claim limitations are met.

The comparison must use the same dose and a conventional syringe comparator. A product developer would therefore need to evaluate:

• Dose and concentration;
• Route of administration;
• Patient population;
• Sampling schedule;
• Statistical confidence intervals;
• Comparator syringe configuration; and
• Whether the comparison concerns the same methotrexate formulation.

What do claims 2 through 8 add?

Claims 2 and 3: inflammatory disease and rheumatoid arthritis

Claim 2 requires a therapeutically effective methotrexate amount for an inflammatory disease. Claim 3 narrows the disease to rheumatoid arthritis.

These claims are relevant to commercial products directed to rheumatoid arthritis, but they do not necessarily limit claim 1 to rheumatoid arthritis. Claim 1 is broader because it does not specify a disease indication.

Claim 4: container received within the injector

Claim 4 requires the methotrexate container to be received within the jet injector. This limitation favors an integrated cartridge or prefilled-container design.

A system using a detachable external vial may have a stronger noninfringement position under claim 4, although it could still fall within claim 1 if the claim 1 elements are satisfied.

Claims 5 and 6: needle gauge

Claim 5 requires a 26-gauge or higher-gauge needle number. Claim 6 narrows the range to 26-, 27- or 28-gauge needles.

Because higher gauge numbers correspond to smaller needle diameters, these claims target relatively fine needles. A 29-gauge or 30-gauge needle could potentially satisfy the broader "26 gauge and a higher gauge number" language in claim 5, subject to the specification and prosecution history.

Claims 7 and 8: flow rate

Claim 7 requires a flow rate of at least approximately 0.5 mL/sec. Claim 8 narrows the flow rate to approximately 0.5 to 1.0 mL/sec and combines that range with a 26-, 27- or 28-gauge needle.

Flow rate is a practical design constraint. A product that operates below 0.5 mL/sec may avoid claims 7 and 8, but it would not avoid claim 1 if the broader claim's other limitations are met.

What do claims 9 and 10 cover?

Claim 9 covers a method of treating a patient with an autoimmune disease by administering methotrexate using the jet injector of claim 1.

Claim 10 identifies the following diseases:

• Rheumatoid arthritis;
• Juvenile rheumatoid arthritis;
• Psoriatic arthritis;
• Systemic lupus erythematosus;
• Steroid-resistant polymyositis or dermatomyositis;
• Wegener's granulomatosis;
• Polyarteritis nodosa; and
• Vasculitis.

These method claims require use of the claimed jet injector. Administration of methotrexate through a standard syringe, intravenous infusion or an injector that does not meet the claim 1 limitations would not satisfy the method claims as written.

What is the patent's basic legal status and expiration timeline?

Event	Date or status
Patent	U.S. Patent No. 8,579,865
Patent type	Utility patent
Issue date	November 12, 2013
Subject	Hazardous-agent methotrexate injection system
Likely commercial relationship	Methotrexate subcutaneous injection products, including Otrexup-related technology
Base patent term	Generally 20 years from the earliest effective nonprovisional filing date
Projected base expiration	Approximately March 2031, based on the patent family priority structure
PTA/PTE	Must be checked against the issued patent and USPTO term record
Terminal disclaimer	No terminal disclaimer should be assumed without reviewing the file history

The operative expiration date is the date shown in the USPTO patent-term record, not simply the issue date plus 20 years. Patent-term adjustment, terminal disclaimers or other prosecution events can alter the calculation. Patent-term extension under the Hatch-Waxman statute is generally more relevant to the approved drug product than to a stand-alone injector claim.

What is the Orange Book status of U.S. Patent 8,579,865?

The patent has been associated with the Otrexup methotrexate product in public drug-patent records. Otrexup was approved by the FDA in October 2013 as a single-dose, subcutaneous methotrexate injection product for conditions including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe psoriasis.[1]

The patent's commercial importance depends on the precise FDA listing and use code. An Orange Book listing can expose an ANDA applicant to a Paragraph IV certification if the applicant seeks approval for a product that relies on the listed drug and falls within the listed patent scope.[2]

The patent is not a basic composition-of-matter patent for methotrexate. Its value is tied to a drug-device combination and associated administration method. A generic methotrexate vial or conventional prefilled syringe would have a different infringement profile from a generic needle-assisted jet injector.

When does methotrexate injection exclusivity expire?

Methotrexate itself is a long-established active ingredient and does not have meaningful composition-of-matter exclusivity remaining in the United States. Competitive protection instead arises from:

• Product-specific formulation patents;
• Autoinjector and delivery-device patents;
• Method-of-use patents;
• Manufacturing patents;
• FDA regulatory exclusivity; and
• Contractual or licensing rights.

For Otrexup, the commercial exclusivity case is primarily patent-driven. The product received FDA approval in 2013, but approval did not create a new chemical entity exclusivity period for methotrexate. Any generic or follow-on applicant must analyze the Orange Book patents and the regulatory pathway independently.

Which products compete with the patented system?

Otrexup

Otrexup is a subcutaneous methotrexate product delivered through a prefilled autoinjector. Its commercial relevance is direct because the product is associated with the patented methotrexate injection technology and the patent was issued shortly after FDA approval.[1]

Rasuvo

Rasuvo is a subcutaneous methotrexate autoinjector marketed by Medac. FDA approved Rasuvo in 2014.[3] Rasuvo competes in the same broad therapeutic market but does not automatically practice every limitation of claim 1. The key comparison is whether its injector is a needle-assisted jet injector operating at at least 80 psi, rather than a conventional autoinjector that advances a plunger.

Conventional methotrexate injections

Generic methotrexate injections supplied in vials or standard syringes compete on price and flexibility. They generally present lower device-patent risk because they do not use the claimed jet-injection architecture.

Product category	Likely claim 1 risk
Needle-assisted jet injector containing methotrexate	High, if pressure and PK limitations are met
Prefilled spring-driven autoinjector	Fact-dependent
Standard prefilled syringe	Generally lower
Methotrexate vial with hand syringe	Generally outside the device claim
Oral methotrexate tablet or solution	Outside the claimed injection system
Intravenous methotrexate product	Outside the subcutaneous delivery limitation

What Paragraph IV challenges and litigation risks exist?

A Paragraph IV challenge would be most relevant to an ANDA or 505(b)(2) applicant seeking approval for a methotrexate product with the same or a similar injection device.

The principal challenge theories would include:

1. Noninfringement: the proposed device does not use a needle-assisted jet injector.
2. Pressure deficiency: the device operates below 80 psi.
3. PK non-equivalence: Cmax, Tmax and AUC do not satisfy the claimed comparison.
4. Formulation mismatch: concentration or volume falls outside the ranges.
5. Invalidity: anticipation or obviousness based on earlier jet injectors, methotrexate delivery systems and pharmacokinetic studies.
6. Indefiniteness: the confidence-interval language may be challenged if the claim does not identify a sufficiently definite statistical methodology.
7. Written-description or enablement: an accused party could argue that the full claimed range of formulations, devices and PK outcomes is not adequately supported.

A conventional generic methotrexate injection applicant could avoid much of the patent risk by pursuing a product that does not contain the claimed jet-injector system. A device-specific applicant would face materially greater exposure.

No conclusion about a specific Paragraph IV notice, settlement or active district-court case should be drawn solely from the claim text. The relevant sources are the Orange Book, FDA patent certifications, PACER, the USPTO file history and any Federal Circuit decisions.

How strong is the patent estate?

The patent is strongest against products that replicate the complete commercial concept:

• Methotrexate in a prefilled container;
• Needle-assisted jet injection;
• Subcutaneous delivery;
• At least 80 psi;
• Fine-gauge needle;
• Flow rate of at least 0.5 mL/sec; and
• Demonstrated pharmacokinetic comparability to syringe delivery.

Its principal vulnerability is claim breadth across multiple technical disciplines. An accused party may attack the patent by separating the formulation, device and PK limitations. The requirement to prove a particular operating pressure and a statistical PK relationship can also create evidentiary burdens.

The estate is weaker against:

• Conventional syringe products;
• Non-jet autoinjectors;
• Products using different administration routes;
• Products outside the concentration or volume ranges;
• Devices operating below the specified pressure; and
• Products using a different clinical and pharmacokinetic profile.

What licensing and commercial issues affect the patent?

The patent's licensing value depends on whether the license covers:

• The patent itself;
• Otrexup commercialization rights;
• The injection-device platform;
• Methotrexate formulations;
• Manufacturing know-how; or
• Geographic territories.

A license limited to the drug product may not grant freedom to operate for a third-party jet injector. Conversely, a device-platform license may not cover methotrexate formulation or clinical-use claims.

Commercial diligence should separate patent ownership, FDA sponsorship, product marketing rights and manufacturing rights. Those rights can be held by different entities and can change through acquisition, assignment or licensing transactions. The USPTO assignment database and FDA sponsor records are the controlling sources for ownership and sponsorship analysis.[4]

What manufacturing and geographic barriers matter?

U.S. claim scope does not automatically extend to foreign markets. Parallel analysis is required for:

• PCT national-phase filings;
• European Patent Office family members;
• Canada;
• Japan;
• Australia;
• China; and
• Other jurisdictions where the product is commercialized.

Manufacturing risk is concentrated in the injector platform. A manufacturer may need to validate:

• Pressure generation;
• Needle penetration;
• Jet formation;
• Dose accuracy;
• Container compatibility;
• Methotrexate stability;
• Device sterility;
• Flow rate;
• Human factors; and
• Reproducible pharmacokinetic performance.

A design-around that avoids the U.S. patent may still require new clinical, device and regulatory work. That development cost can preserve practical market barriers after the legal scope narrows.

Key Takeaways

• U.S. Patent 8,579,865 is a drug-device combination patent focused on methotrexate delivered by a needle-assisted jet injector.
• Claim 1 requires methotrexate concentration and volume ranges, subcutaneous delivery, at least 80 psi, and a specified PK relationship to hand-syringe administration.
• Claims 5 through 8 add commercially relevant limitations involving needle gauge and flow rate.
• Claims 9 and 10 protect treatment methods for rheumatoid arthritis and other autoimmune or inflammatory diseases.
• The patent does not cover methotrexate generally or every methotrexate autoinjector.
• Conventional methotrexate vials and hand-powered syringes generally present lower infringement risk than jet-injection systems.
• The projected base expiration is approximately March 2031, subject to the USPTO patent-term record and any terminal disclaimer or patent-term adjustment.
• Otrexup is the principal commercial product associated with the patented technology; Rasuvo is a competing methotrexate autoinjector with a separate product and patent analysis.
• The most credible invalidity and noninfringement strategies focus on the jet-injector architecture, 80-psi threshold, PK confidence-interval language and prior art.
• A complete Paragraph IV or litigation conclusion requires review of current Orange Book listings, FDA certifications, USPTO assignments and court dockets.

FAQs About U.S. Patent 8,579,865

Does U.S. Patent 8,579,865 cover all methotrexate injections?

No. It covers a specified methotrexate formulation used with a needle-assisted jet injector meeting the claim's structural, pressure and pharmacokinetic requirements.

Can a standard methotrexate syringe infringe this patent?

A standard hand-powered syringe would generally not satisfy the jet-injector, energy-source and firing-mechanism limitations of claim 1.

Does a 27-gauge methotrexate injector fall within the patent?

It may fall within claims 6 and 8 if the device also meets the pressure, flow-rate, formulation and other limitations. Needle gauge alone is not sufficient.

Is Rasuvo automatically covered by U.S. Patent 8,579,865?

No. Rasuvo must be analyzed against every limitation, particularly the needle-assisted jet-injector and 80-psi requirements.

Can a generic company avoid the patent by changing methotrexate concentration?

Potentially, if the product falls outside the claimed concentration and does not meet the claim under an applicable equivalent theory. Changing concentration alone may not avoid infringement if the product still satisfies the other limitations and remains within the claim's interpretation of "about."

References

1. U.S. Food and Drug Administration. (2013). Otrexup approval package and prescribing information. FDA.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.

3. U.S. Food and Drug Administration. (2014). Rasuvo prescribing information. FDA.

4. United States Patent and Trademark Office. (2013). U.S. Patent No. 8,579,865: Hazardous agent injection system. USPTO.

Drugs Protected by US Patent 8,579,865

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-005	Nov 7, 2014		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-001	Oct 11, 2013		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-006	Mar 24, 2016		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-002	Oct 11, 2013		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-007	Mar 24, 2016		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE
Cosette	OTREXUP	methotrexate	SOLUTION;SUBCUTANEOUS	204824-003	Oct 11, 2013		DISCN	Yes	No	8,579,865		Y			SUBCUTANEOUS INJECTION OF METHOTREXATE

Foreign Priority and PCT Information for Patent: 8,579,865

PCT Information
PCT Filed	March 19, 2010	PCT Application Number:	PCT/US2010/028011
PCT Publication Date:	September 23, 2010	PCT Publication Number:	WO2010/108116

International Family Members for US Patent 8,579,865

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010226442
Canada	2755779
China	102612381
European Patent Office	2408493
European Patent Office	4427737
Spain	2988196