Details for Patent: 8,592,462

Which drugs does patent 8,592,462 protect, and when does it expire?

Patent 8,592,462 protects ESBRIET and is included in two NDAs.

This patent has sixty-four patent family members in thirty-nine countries.

Summary for Patent: 8,592,462

Title:	Pirfenidone treatment for patients with atypical liver function
Abstract:	Methods are provided for administering pirfenidone to a patient that has exhibited abnormal biomarkers of liver function in response to pirfenidone administration. The methods include administering to a patient pirfenidone at doses lower than the full target dosage for a time period, followed by administering to the patient pirfenidone at the full target dosage. The methods also include administering pirfenidone at the full target dose with no reduction and administering permanently reduced doses of pirfenidone.
Inventor(s):	Williamson Ziegler Bradford, Javier Szwarcberg
Assignee:	Legacy Pharma Inc Sezc
Application Number:	US13/312,746
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,592,462
Patent Claim Types: see list of patent claims	Use;

United States Patent 8,592,462: Pirfenidone Liver-Event Retreatment Claims, Scope, Expiration, and Competitive Patent Landscape

U.S. Patent No. 8,592,462 protects a narrow method of retreating an IPF patient with pirfenidone after a clinically defined liver-function abnormality during an earlier course of treatment. The patent does not broadly cover pirfenidone, IPF treatment, or the 2,403 mg/day commercial dose. Its central limitation is the sequence: first pirfenidone exposure, specified hepatic biomarker elevation, followed by renewed pirfenidone administration at 1,600 mg/day or more.

The strongest claim coverage is concentrated in claims 1, 16, 21 and 26. The dependent claims add dose levels, temporary interruption, stepwise re-titration, treatment until liver biomarkers normalize, and administration three times daily with food. The estate is commercially relevant to generic pirfenidone products that reproduce the labeled or customary management of liver-enzyme elevations.

What does U.S. Patent 8,592,462 cover?

The patent covers a method of administering pirfenidone to a patient with idiopathic pulmonary fibrosis after the patient experiences a defined liver-function abnormality during an earlier administration.

The core elements are:

Required element	Scope of the claims
Active ingredient	Pirfenidone
Disease	Idiopathic pulmonary fibrosis
Treatment sequence	A first administration followed by a second administration
Prior event	Elevated liver biomarkers or a Grade 2 liver-function abnormality
Quantitative threshold	About 2.5-fold to about 5-fold above the upper limit of normal in certain claims
Retreatment dose	At least 1,600 mg/day
Specific doses	About 1,800 mg/day, 2,400 mg/day or 2,403 mg/day
Reintroduction protocol	Lower doses, temporary discontinuation, or treatment until biomarkers normalize
Administration schedule	Three times daily with food in dependent claims

The claims are method-of-treatment claims. They do not claim the pirfenidone molecule, a pirfenidone composition, a tablet, a capsule, or a manufacturing process.

What are the independent claims in Patent 8,592,462?

The patent has four principal independent claims:

Claim	Triggering liver event	Required retreatment
1	ALT or AST increase of about 2.5-fold to about 5-fold above ULN	Pirfenidone at least 1,600 mg/day
16	One or more liver-function biomarkers at about 2.5-fold to about 5-fold above ULN	Pirfenidone at least 1,600 mg/day
21	Grade 2 abnormality in one or more liver-function biomarkers	Pirfenidone at least 1,600 mg/day
26	Grade 2 abnormality in ALT or AST	Pirfenidone at least 1,600 mg/day

Claims 1 and 26 are narrower with respect to the biomarker category because they expressly identify ALT and AST. Claim 16 is broader in biomarker selection because it covers one or more biomarkers of liver function. Claim 21 also uses the broader biomarker formulation but substitutes the Grade 2 classification for the numerical 2.5-to-5-fold range.

How do the dependent claims narrow the patent?

The dependent claims create multiple retreatment protocols.

Lower-dose reintroduction

Claims 2, 6, 9, 10, 13, 14, 17 and 27 require a lower-dose period before the patient reaches the claimed maintenance dose. The specified reintroduction doses include:

• About 800 mg/day or 801 mg/day.
• About 1,600 mg/day or 1,602 mg/day.
• Doses below 1,600 mg/day.
• Doses below 2,400 mg/day.

The claims generally require this lower-dose phase to continue for approximately one week or until liver-function biomarkers return to normal limits.

Treatment interruption

Claims 7, 8, 12, 18, 23 and 28 require discontinuation of the first pirfenidone administration before the second administration begins. The interruption lasts approximately one week or until liver biomarkers return to normal limits.

This creates a potential distinction between:

1. A patient whose treatment is interrupted and then restarted.
2. A patient whose dose is reduced without a formal interruption.
3. A patient who receives a direct second administration at the claimed dose.

The patent has claims directed to each of these pathways.

Specific daily doses

The dose limitations are:

Dose	Relevant claims
At least 1,600 mg/day	Claims 1, 16, 21 and 26, plus dependents
About 1,800 mg/day	Claims 5, 20, 25 and 30
About 2,400 mg/day or 2,403 mg/day	Claims 3, 4, 12, 13, 14 and 15
About 800 mg/day or 801 mg/day	Claims 9 and 13
About 1,600 mg/day or 1,602 mg/day	Claims 10 and 14

The 2,403 mg/day limitation corresponds to 801 mg administered three times daily. The 1,602 mg/day limitation corresponds to 534 mg administered three times daily. The 801 mg/day limitation corresponds to 267 mg administered three times daily.

Food and three-times-daily administration

Claims 11, 15, 19, 24 and 29 require pirfenidone to be administered three times daily with food. These claims align closely with the FDA-approved Esbriet dosing architecture, which uses dose escalation to 801 mg three times daily, or 2,403 mg/day, in patients who tolerate treatment.[1]

What is the claim construction risk for Patent 8,592,462?

The principal infringement issue is whether a generic product's prescribing information directs physicians to perform the patented retreatment sequence after the claimed liver-function event.

A product does not necessarily infringe merely because its label permits pirfenidone dose reduction or interruption. The asserted claim requires a defined patient history and a particular second administration. The following limitations are likely to control infringement analysis:

Patient-specific sequence

The patient must have received a first pirfenidone administration and then experienced the specified abnormality. A generic label that discusses liver monitoring without directing retreatment after the relevant event may create a narrower inducement case.

Numerical liver-function threshold

Claims 1 and 16 require an increase of about 2.5-fold to about 5-fold above ULN. A label that uses only "elevated liver enzymes," "greater than three times ULN," or another threshold may not map cleanly onto every claim.

The phrase "about" creates claim-construction and equivalence questions. A value slightly outside the stated range could become relevant, but the numerical range remains a material limitation.

Grade 2 abnormality

Claims 21 and 26 depend on the meaning of "Grade 2." The applicable grading framework and the biomarker value used to classify the event would be important. The claim does not simply cover every elevation in ALT or AST.

Retreatment at 1,600 mg/day or more

The second administration must reach at least 1,600 mg/day. A label limited to permanent discontinuation, or to a lower maintenance dose, would not satisfy that limitation without additional evidence of induced use.

"Second administration"

The claims use a first and second administration framework. A court could examine whether the second administration requires a formal treatment restart, a resumption after interruption, or any later dosing course after the first course. The dependent claims support an interpretation involving retreatment after interruption or dose reduction, but the independent claims do not always expressly require discontinuation.

What is the FDA and Orange Book status of Patent 8,592,462?

Pirfenidone was approved by the FDA as Esbriet for the treatment of IPF. The reference product was developed by InterMune, which Roche acquired in 2014.[1,2]

Patent 8,592,462 is associated with the U.S. Esbriet intellectual-property estate and has been treated as a method-of-use patent relevant to generic pirfenidone competition. Orange Book listings must be evaluated by product, patent-use code and the FDA’s current publication data because listing status, delisting, and use-code information can change.[3]

The regulatory significance is greater for an ANDA applicant that seeks approval for IPF treatment than for a company pursuing an unrelated pirfenidone use. Under the Hatch-Waxman framework, an ANDA applicant must address listed patents through a certification or a statement that the applicant will omit the patented use.[4]

Does Patent 8,592,462 cover all FDA-approved pirfenidone use?

No. The patent is narrower than the FDA-approved indication. It covers a particular liver-event retreatment protocol within IPF therapy. It does not independently claim:

• Initial pirfenidone treatment for IPF.
• Pirfenidone treatment for other diseases.
• Pirfenidone generally.
• Every dose of pirfenidone.
• Every adverse-event dose adjustment.
• Every patient with abnormal liver tests.

When does Patent 8,592,462 lose exclusivity?

The patent issued on November 26, 2013.[5] Its term is governed by the U.S. patent-term rules applicable to the relevant application and priority filings, subject to any patent-term adjustment, terminal disclaimer, patent-term extension or other official adjustment.[6]

Public patent records associate the patent family with InterMune and an effective patent term reaching into 2027. The operative expiration date for freedom-to-operate and ANDA planning should be taken from the current USPTO Patent Center record and the FDA Orange Book listing, including any listed patent-term adjustment. The 2027 expiration horizon is commercially important because it places the patent after the loss of the principal small-molecule exclusivity period for Esbriet.

What FDA exclusivities protected Esbriet?

Esbriet received FDA approval in 2014. The drug was eligible for five-year new chemical entity exclusivity, subject to the statutory rules governing the approved active ingredient and indication. That regulatory exclusivity period expired before the expected expiration of the later method-of-use patent estate.[1,4]

The commercial protection therefore shifted from regulatory exclusivity to patent enforcement and label-based generic-entry disputes.

Which patents compete with Patent 8,592,462 in the Esbriet estate?

The relevant competitive estate includes patents directed to treatment methods, dosing, and related clinical-use limitations. Patent 8,592,462 is best understood as the liver-safety retreatment patent within that broader estate.

Patent category	Typical protected subject matter	Relevance to generic entry
Initial-use method patents	Use of pirfenidone for IPF	Can support a Paragraph IV dispute
Dose-regimen patents	Titration, maintenance dose and administration schedule	Relevant to full-label ANDAs
Liver-event patents	Dose interruption, reintroduction and retreatment after abnormal tests	Directly relevant to Patent 8,592,462
Formulation patents	Tablets, capsules, excipients or release characteristics	Relevant if the ANDA uses a protected formulation
Manufacturing patents	Synthesis, purification or solid-state forms	Usually separate from physician-use inducement
Use-code patents	Specific FDA-approved use identified in the Orange Book	Determine whether a section viii carve-out is feasible

The principal competitive question is whether the applicant can omit the patented liver-management instructions while still obtaining approval for a commercially viable IPF label.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV certification asserts that a listed patent is invalid, unenforceable or will not be infringed by the proposed ANDA product.[4] For this patent, an ANDA applicant could challenge:

• Written description and enablement.
• Anticipation by prior pirfenidone dosing and safety disclosures.
• Obviousness based on known liver-enzyme monitoring and dose interruption practices.
• Indefiniteness of terms such as "about," "Grade 2," "second administration" and "until biomarkers ... are within normal limits."
• Lack of induced infringement if the proposed label does not instruct the patented retreatment protocol.

The patent holder could respond with an infringement theory based on the full clinical label, physician behavior, dosing instructions, or downstream substitution practices.

Can a generic use a section viii statement?

Potentially, if the generic applicant can carve out the patented method from its labeling while retaining approval for non-patented aspects of pirfenidone treatment. The viability of that strategy depends on:

1. The exact Orange Book use code.
2. Whether the patented method is separable from the core IPF indication.
3. Whether the FDA accepts the proposed labeling omission.
4. Whether the remaining label still induces use of the claimed retreatment protocol.

A narrow method patent can be commercially significant even when a label carve-out is legally available. If the omitted information concerns routine safety management, physicians may still use the product in the patented manner, creating inducement and contributory-infringement issues.

What generic launch scenarios are most likely?

Scenario	Commercial result	Risk to patent holder
No challenge until patent expiry	Generic launch follows expiry	Low litigation risk, delayed competition
Paragraph IV challenge with full IPF label	Potential 30-month stay and patent litigation	High litigation cost and earlier entry opportunity
Section viii carve-out	Approval without the patented liver-retreatment use	Reduced patent exposure, potentially narrower label
Settlement with delayed entry	Entry date set by agreement	Revenue erosion begins on settlement date
Court invalidation or noninfringement finding	Earlier unrestricted launch	High revenue impact
Label-based infringement finding	Injunction or damages exposure	Launch delayed or restricted

The commercial impact depends on whether the patented protocol is included in the proposed label and whether physicians commonly follow the protocol after liver-enzyme elevations.

How strong is the patent estate for Patent 8,592,462?

The patent has meaningful but narrow enforcement value.

Strengths

• Four independent claims cover different formulations of the liver-event trigger.
• The claims include both numerical biomarker thresholds and Grade 2 abnormalities.
• The 1,600 mg/day threshold overlaps the commercially relevant pirfenidone dosing range.
• Dependent claims track the FDA dosing schedule, including 801 mg three times daily and 2,403 mg/day.
• The claims cover both dose reduction and treatment interruption before retreatment.

Weaknesses

• The claims are heavily dependent on patient history and clinical documentation.
• Infringement may occur in treatment decisions made by physicians rather than in the manufacture or sale of the product.
• The liver-management concepts may face obviousness challenges based on known hepatotoxicity monitoring and dose-rechallenge practices.
• "About" ranges and Grade 2 classifications may create factual disputes.
• A carefully drafted generic label may reduce direct inducement evidence.
• The patent does not block initial IPF treatment or pirfenidone products used under a non-infringing label.

The patent is stronger as a barrier to a full-label generic launch than as a standalone barrier to every pirfenidone product.

What manufacturing and geographic barriers remain?

Patent 8,592,462 does not claim pirfenidone synthesis, crystalline form, tablet composition or manufacturing equipment. It therefore presents limited manufacturing-IP risk by itself.

Its geographic scope is also limited to the United States. Parallel patent families may exist in Europe, Japan, Canada and other jurisdictions, but foreign claims, expiration dates and enforcement standards must be assessed separately. A U.S. launch decision cannot be based solely on the existence or expiration of a foreign counterpart.

For U.S. manufacturers, the main exposure is method-of-use inducement associated with the product label and commercial promotion. For API suppliers, the patent presents less direct risk unless the supplier participates in downstream use promotion or product instructions.

What licensing deals and litigation affect the patent?

InterMune commercialized Esbriet before Roche acquired InterMune for approximately $8.3 billion in 2014.[2] The acquisition transferred control of the Esbriet commercial and patent portfolio to Roche and its Genentech organization.

No separate license is required to practice the patented method for internal research under ordinary circumstances, but commercial licensing, settlement and launch rights depend on the specific agreement and litigation record. Patent disputes involving generic pirfenidone products have generally centered on the Orange Book estate, Paragraph IV certifications, label scope and the timing of generic entry.

A complete litigation conclusion cannot be drawn from the claim text alone. The operative status depends on the current USPTO record, FDA Orange Book data, ANDA litigation docket and any settlement terms.

Key Takeaways

• U.S. Patent 8,592,462 is a method-of-treatment patent, not a compound or formulation patent.
• Its central concept is retreating an IPF patient with pirfenidone after a defined liver-function abnormality.
• Claims 1, 16, 21 and 26 are the primary independent claims.
• The principal dose threshold is at least 1,600 mg/day.
• Dependent claims cover 800/801 mg/day, 1,600/1,602 mg/day, 1,800 mg/day and 2,400/2,403 mg/day regimens.
• Temporary discontinuation, stepwise re-titration and administration three times daily with food are separately claimed.
• The patent is most relevant to a full-label generic pirfenidone ANDA for IPF.
• A section viii carve-out may reduce exposure if FDA labeling permits omission of the patented retreatment instructions.
• The patent’s commercial term reaches into the 2027 period, subject to the official USPTO and Orange Book term records.
• The principal enforcement risk is inducement based on generic labeling and physician-directed retreatment.

FAQs About U.S. Patent 8,592,462

Does Patent 8,592,462 cover Esbriet’s 2,403 mg/day dose by itself?

No. The patent covers 2,403 mg/day only when the other claim limitations are satisfied, including prior pirfenidone administration and the specified liver-function event.

Is Patent 8,592,462 a formulation patent?

No. It is directed to methods of administering pirfenidone. It does not claim a particular tablet, capsule, excipient system or dissolution profile.

Does an elevated ALT automatically satisfy the patent?

No. The relevant claims require a defined elevation, a Grade 2 abnormality or both ALT/AST and the other patient-treatment limitations stated in the applicable claim.

Can a generic sell pirfenidone before the patent expires?

Possibly, through a successful Paragraph IV challenge, an accepted section viii label carve-out, a settlement permitting early entry or a court determination of noninfringement or invalidity.

Does the patent block pirfenidone treatment outside idiopathic pulmonary fibrosis?

No. The claims expressly require treatment of a patient with IPF. They do not cover use of pirfenidone for an unrelated disease.

References

1. U.S. Food and Drug Administration. (2014). Esbriet prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205832s000lbl.pdf
2. Roche. (2014). Roche to acquire InterMune for $74 per share in cash. https://www.roche.com/media/releases/med-cor-2014-08-24
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
4. 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications. https://www.law.cornell.edu/uscode/text/21/355
5. U.S. Patent and Trademark Office. (2013). U.S. Patent No. 8,592,462, Methods for treating idiopathic pulmonary fibrosis. https://patents.google.com/patent/US8592462
6. 35 U.S.C. §§ 154, 156. Patent term and patent-term extension. https://www.law.cornell.edu/uscode/text/35/154

Drugs Protected by US Patent 8,592,462

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Legacy	ESBRIET	pirfenidone	CAPSULE;ORAL	022535-001	Oct 15, 2014	AB	RX	Yes	Yes						CONTINUED DOSING OR DOSAGE MODIFICATION FOLLOWING ELEVATED LIVER ENZYMES IN TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS
Legacy	ESBRIET	pirfenidone	TABLET;ORAL	208780-001	Jan 11, 2017	AB	RX	Yes	No						DOSAGE MODIFICATION FOLLOWING GRADE 2 ABNORMALITY IN BIOMARKER AST AND/OR ALT AFTER PIRFENIDONE ADMINISTRATION, BY DISCONTINUING PIRFENIDONE UNTIL BIOMARKERS OF LIVER FUNCTION ARE WITHIN NORMAL LIMITS, THEN AT LEAST 1600MG/DAY IN TREATMENT OF IPF
Legacy	ESBRIET	pirfenidone	TABLET;ORAL	208780-001	Jan 11, 2017	AB	RX	Yes	No						DOSAGE MODIFICATION FOLLOWING GRADE 2 ABNORMALITY IN LIVER FUNCTION BIOMARKER AFTER PIRFENIDONE ADMINISTRATION, BY DISCONTINUING PIRFENIDONE UNTIL BIOMARKERS ARE WITHIN NORMAL LIMITS, FOLLOWED BY ADMINISTERING AT LEAST 1600 MG/DAY IN TREATMENT OF IPF

International Family Members for US Patent 8,592,462

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	E503480
Australia	2009313302
Australia	2010212371