United States Patent 7,816,383: Pirfenidone–Fluvoxamine Interaction Claims, Scope, Expiration and Patent Landscape
U.S. Patent No. 7,816,383 protects selected methods of using pirfenidone when a patient is also receiving, or may require, fluvoxamine or another strong CYP1A2 inhibitor. The patent does not claim pirfenidone itself, the compound’s composition, or every use of pirfenidone in idiopathic pulmonary fibrosis (IPF). Its principal commercial relevance is a method-of-use barrier tied to avoiding fluvoxamine co-administration, discontinuing fluvoxamine before treatment, using the approved 800/801 mg three-times-daily regimen, and providing specified drug-interaction counseling.
The patent was issued to InterMune, Inc. on October 19, 2010. Its nominal patent term runs into 2027, subject to the official term calculation, any patent-term adjustment, and subsequent legal events recorded by the USPTO. Roche acquired InterMune in 2014 and commercialized pirfenidone as Esbriet.
What does U.S. Patent 7,816,383 protect?
The patent protects treatment protocols rather than a chemical composition. Its claims require a combination of:
- Pirfenidone administration.
- A patient who is also in need of fluvoxamine therapy, or who is receiving fluvoxamine.
- Avoidance or discontinuation of fluvoxamine.
- In several claims, treatment of IPF.
- In the narrower claims, a daily pirfenidone dose of 2,400 or 2,403 mg, administered as 800 or 801 mg three times daily with food.
- In claims 11 through 20, specified counseling or warnings concerning CYP-mediated drug interactions.
The patent has three independent claim groups:
| Claim group |
Independent claim |
Core subject matter |
| Avoidance |
1 |
Administer pirfenidone while avoiding fluvoxamine co-administration |
| Discontinuation |
5 |
Stop fluvoxamine, then begin pirfenidone |
| Treatment and counseling |
11 |
Treat IPF with 2,400/2,403 mg per day while avoiding fluvoxamine and provide specified advice |
Claims 2 through 4 narrow claim 1. Claims 6 through 10 narrow claim 5. Claims 12 through 20 narrow claim 11.
What are the key limitations in the patent claims?
Claims 1 through 4: avoiding co-administration
Claim 1 requires a patient who is both:
- In need of pirfenidone therapy; and
- In need of fluvoxamine therapy.
The method requires administration of pirfenidone while avoiding co-administration of fluvoxamine.
This language creates several limits. A pirfenidone prescription for a patient with no fluvoxamine-related treatment need would not meet the express “patient ... also in need of fluvoxamine therapy” limitation. Likewise, treatment of a patient taking another CYP1A2 inhibitor would not literally satisfy the fluvoxamine-specific requirement, although other patents or regulatory theories could become relevant.
Claim 2 adds IPF. Claims 3 and 4 add the commercial Esbriet dosing regimen:
- 2,400 or 2,403 mg per day; or
- 800 or 801 mg three times daily, with food.
The 2,403 mg regimen corresponds to 801 mg three times daily. The 2,400 mg alternative corresponds to 800 mg three times daily.
Claims 5 through 10: sequencing discontinuation and treatment
Claim 5 requires:
- Discontinuing fluvoxamine;
- To avoid an adverse interaction with pirfenidone; and
- Then administering a therapeutically effective amount of pirfenidone.
The temporal sequence is important. The claim is not limited to a general warning against co-administration. It requires discontinuation before pirfenidone treatment begins.
Claims 9 and 10 narrow the discontinuation period to:
- Within one month before starting pirfenidone; or
- Within two weeks before starting pirfenidone.
These timing claims may be difficult to apply where the medical record does not establish when fluvoxamine was stopped or whether the discontinuation was undertaken for the claimed interaction-avoidance purpose.
Claims 11 through 20: treatment plus counseling
Claim 11 is narrower than claims 1 and 5 because it requires:
- A patient with IPF;
- A patient also in need of fluvoxamine therapy;
- 2,400 or 2,403 mg of pirfenidone per day;
- Avoidance of fluvoxamine; and
- At least one specified counseling statement.
The counseling alternatives cover:
- Advising that fluvoxamine should be avoided or discontinued;
- Warning about inhibitors of CYP1A2 combined with CYP2C9, CYP2C19 or CYP3A4;
- Advising that pirfenidone and fluvoxamine can alter therapeutic or adverse-effect profiles;
- Advising that fluvoxamine use is contraindicated;
- Advising that co-administration caused a six-fold increase in pirfenidone exposure;
- Advising that fluvoxamine caused a two-fold increase in average pirfenidone Cmax; or
- Advising that strong CYP1A2 inhibitors may reduce pirfenidone clearance.
Claims 12 through 20 are dependent counseling claims. Claim 19 adds avoidance of a strong CYP1A2 inhibitor. Claim 20 adds discontinuation of that inhibitor.
How strong are the claims in U.S. Patent 7,816,383?
The patent has meaningful commercial relevance but a narrower scope than a core composition or broad IPF-use patent.
Strengths
The claims track the approved clinical regimen and FDA-recognized drug-interaction information. That alignment can support an infringement theory where a generic label instructs physicians to avoid fluvoxamine or directs treatment of IPF patients using the patented dose.
The claims also cover both avoidance and discontinuation. A generic sponsor cannot necessarily avoid all exposure by removing an express instruction to discontinue fluvoxamine if the product labeling still recommends the patented treatment protocol.
The counseling claims create additional coverage around interaction warnings. They may be relevant to induced-infringement theories if a label actively encourages physicians, pharmacists or patients to perform the claimed counseling.
Weaknesses
The claims contain patient-status and conduct limitations that may complicate infringement proof. A claimant must establish that the patient was also in need of fluvoxamine therapy, not merely that the patient was taking another antidepressant.
The claims also require avoidance or discontinuation. A generic label that omits fluvoxamine information may reduce literal inducement exposure, although the analysis depends on the full label and the treatment steps encouraged by that label.
Claims 11 through 20 are particularly vulnerable to noninfringement arguments because they require both the 2,400/2,403 mg dose and one of several specific counseling statements. General pharmacokinetic warnings may not necessarily satisfy every precise statement in the claims.
The patent does not cover:
- Pirfenidone as a molecule;
- Every pirfenidone formulation;
- Every pirfenidone treatment for IPF;
- Treatment with pirfenidone when fluvoxamine is not clinically relevant;
- All CYP1A2 inhibitor combinations;
- A specific tablet strength as a composition claim; or
- Manufacture of pirfenidone.
What is the patent expiration date for U.S. Patent 7,816,383?
| Event |
Date |
| Priority date reported for the patent family |
March 24, 2006 |
| U.S. application filing |
March 23, 2007 |
| U.S. publication |
November 1, 2007 |
| Patent issuance |
October 19, 2010 |
| Nominal 20-year term based on earliest priority |
March 24, 2027 |
The expected nominal expiration is March 24, 2027, based on the earliest priority date and the standard 20-year term under 35 U.S.C. §154. The operative expiration date should be confirmed against the USPTO patent-term record, including any patent-term adjustment or terminal disclaimer. The patent does not receive pediatric exclusivity merely because pirfenidone has FDA approval.
What is the FDA and Orange Book status of the patent?
The patent is associated with the pirfenidone product Esbriet, which received FDA approval for adults with IPF. The FDA prescribing information identifies fluvoxamine as a strong CYP1A2 inhibitor and warns against the combination with pirfenidone. The label also discusses reduced pirfenidone clearance and increased exposure when pirfenidone is administered with relevant CYP inhibitors. [2]
An Orange Book method-of-use listing can affect ANDA approval and paragraph IV litigation, but it does not prevent approval of an ANDA with a valid section viii label carve-out. The practical question is whether the patented fluvoxamine-avoidance information is necessary for the generic label or can be removed without making the generic product less safe or less effective for its remaining indications.
| Regulatory issue |
Relevance to Patent 7,816,383 |
| Active ingredient |
Pirfenidone |
| Reference product |
Esbriet |
| FDA indication |
Adults with IPF |
| Patent type |
Method of treatment and drug-interaction management |
| Orange Book relevance |
Potential method-of-use listing |
| ANDA pathway |
Paragraph IV challenge or section viii carve-out |
| Biologic pathway |
Not applicable |
| FDA exclusivity |
Separate from patent rights |
| Label issue |
Whether fluvoxamine and CYP1A2 information must remain in the generic label |
The FDA’s labeling position is commercially important because it mirrors the patent’s central clinical premise. A label that says to avoid or discontinue fluvoxamine may provide evidence for induced infringement, while a label that omits the patented use may support a section viii strategy.
When does generic pirfenidone lose exclusivity risk from this patent?
A generic sponsor faces several possible launch scenarios.
Scenario 1: Paragraph IV challenge
The ANDA applicant certifies that the patent is invalid, unenforceable or will not be infringed. The patent holder may sue within 45 days, triggering a statutory stay of approval of up to 30 months under the Hatch-Waxman Act, subject to court action and regulatory events. [3]
Likely invalidity theories would focus on:
- Obviousness based on known CYP1A2 metabolism and fluvoxamine inhibition;
- Written-description or enablement issues for the counseling alternatives;
- Indefiniteness in phrases such as “in need of fluvoxamine therapy” and “alter the therapeutic effect or adverse reaction profile”; and
- Double-patenting or terminal-disclaimer issues, if applicable.
Scenario 2: Section viii carve-out
The applicant omits the patented interaction-management use from its label while retaining noninfringing IPF treatment information. This strategy is strongest where the FDA permits removal of the fluvoxamine-specific use and the remaining label does not encourage the claimed method.
The strategy becomes more difficult if the FDA requires warnings about fluvoxamine for safe use. A warning can create litigation risk if it instructs physicians to perform the patented avoidance or discontinuation steps.
Scenario 3: Launch after expiration
A launch after the patent’s operative expiration eliminates ordinary infringement risk from the patent, although other active patents, regulatory exclusivities, manufacturing rights and contractual restrictions may remain relevant.
Which other patents compete with U.S. Patent 7,816,383?
The pirfenidone estate has historically included several distinct patent categories:
| Patent category |
Typical protected subject matter |
Relationship to 7,816,383 |
| Compound patents |
Pirfenidone molecule and chemical synthesis |
Generally separate and earlier-expiring |
| IPF-use patents |
Use of pirfenidone to treat IPF or pulmonary fibrosis |
Broader disease-use coverage |
| Dosing patents |
Titration, dose escalation or maintenance dosing |
May cover initiation and tolerability protocols |
| Interaction patents |
CYP1A2 inhibitors, fluvoxamine and related warnings |
7,816,383 is in this category |
| Formulation patents |
Tablets, excipients, dissolution and stability |
Relevant to product design and ANDA substitution |
| Manufacturing patents |
Processes for producing pirfenidone or intermediates |
Relevant to API sourcing and supply |
The main competitive risk is claim overlap between an interaction patent and broader IPF-use or dosing patents. A generic sponsor that defeats or carves out 7,816,383 may still face another listed method patent covering IPF treatment, titration, or the marketed dosage regimen.
A complete freedom-to-operate analysis therefore requires review of the entire Orange Book listing, patent-family continuations, terminal disclaimers, reissue records, and litigation history. Patent 7,816,383 should not be treated as the entire Esbriet estate.
What patent litigation affects pirfenidone generic entry?
Pirfenidone generic entry has been shaped by Hatch-Waxman litigation involving Roche and former InterMune patent rights. The central litigation issues have included:
- Whether generic labeling induces use of patented IPF treatment methods;
- Whether interaction warnings can be carved out;
- Whether dose and administration instructions remain within the scope of listed patents;
- Whether asserted claims are obvious in view of pirfenidone pharmacology and known CYP inhibition; and
- Whether settlements permit launch before patent expiration.
A specific litigation conclusion cannot be inferred from the claim text alone. The controlling analysis requires the ANDA label, the paragraph IV notice, asserted claims, claim-construction rulings, settlement terms, and any final judgment.
Do biosimilars create risk for pirfenidone?
No. Pirfenidone is a synthetic small-molecule drug, not a biologic. Biosimilar approval under the Biologics Price Competition and Innovation Act is not applicable.
The relevant competitive pathway is an ANDA for generic pirfenidone under section 505(j) of the Federal Food, Drug, and Cosmetic Act. The principal barriers are listed patents, labeling restrictions, bioequivalence, API supply, tablet manufacturing, and any settlement-based launch limitations.
What geographic protection does the patent provide?
U.S. Patent 7,816,383 provides rights only in the United States. Foreign counterparts may exist, but their enforceability and expiration dates must be assessed separately.
| Jurisdiction |
Effect of U.S. Patent 7,816,383 |
| United States |
Direct enforceability against covered U.S. activity |
| European Union |
No direct effect |
| Japan |
No direct effect |
| China |
No direct effect |
| Canada |
No direct effect |
| Other markets |
Require separate national patent review |
For international launches, the relevant analysis includes national equivalents, supplementary protection certificates, local drug-label rules, and whether the claimed method is enforceable against physicians, hospitals, pharmacists or suppliers.
What manufacturing and IP barriers remain after this patent?
The patent does not create a manufacturing monopoly over pirfenidone. A competitor can potentially source or manufacture noninfringing pirfenidone API and develop a bioequivalent product without practicing the claimed fluvoxamine-management method.
The principal remaining barriers may include:
- Active formulation patents;
- Tablet manufacturing patents;
- Process patents for API production;
- Other method-of-use patents;
- FDA approval requirements;
- API qualification and impurity controls;
- Stability data;
- Supply-chain qualification; and
- Labeling restrictions.
The 7,816,383 claims are therefore more significant for regulatory labeling and physician-directed treatment conduct than for chemical or manufacturing freedom to operate.
Key Takeaways
- U.S. Patent 7,816,383 is a method-of-treatment patent focused on pirfenidone and fluvoxamine interaction management.
- Its independent claims cover avoidance of co-administration, discontinuation of fluvoxamine before pirfenidone, and specified counseling.
- Claims 2, 6 and 11 through 20 are directed specifically or principally to IPF patients.
- Claims 3, 4, 7, 8 and 11 through 20 track the 800/801 mg three-times-daily regimen.
- The nominal patent expiration is March 24, 2027, subject to the official USPTO term calculation.
- The principal generic-entry strategies are paragraph IV litigation, a section viii label carve-out, or launch after expiration.
- The patent does not claim pirfenidone itself, all IPF treatment, pirfenidone formulations, or pirfenidone manufacturing.
- Pirfenidone is a small molecule, so biosimilar risk does not apply.
- The commercial strength of the patent depends heavily on the generic label and whether FDA-required interaction warnings practice the claimed methods.
- Other Esbriet patents covering IPF use, dosing, formulations and manufacturing must be evaluated separately.
FAQs
Can a generic manufacturer sell pirfenidone for IPF without infringing Patent 7,816,383?
Yes, potentially. The manufacturer may pursue a section viii carve-out or establish that its label does not encourage the claimed fluvoxamine-related method. Other pirfenidone patents may still block approval or launch.
Does prescribing pirfenidone alone infringe the patent?
Generally, not on the claim language provided. The claims require a patient also in need of fluvoxamine therapy, avoidance or discontinuation of fluvoxamine, and, for several claims, specified dosing or counseling.
Does the patent cover all strong CYP1A2 inhibitors?
No. The broadest claims expressly identify fluvoxamine. Claims 11, 13 and 18 discuss broader CYP inhibitor categories, but those claims retain additional IPF, dose and counseling limitations.
Can a physician be liable for following the Esbriet label?
Potentially, if the physician performs all elements of an asserted claim and the patent remains enforceable. In practice, liability would depend on the label, patient facts, counseling conduct, intent, and the governing infringement record.
Is the 801 mg dose itself patented by U.S. Patent 7,816,383?
No. The patent claims methods using 801 mg three times daily in specified circumstances. It does not claim an 801 mg pirfenidone tablet as a composition or formulation.
References
- United States Patent and Trademark Office. (2010). U.S. Patent No. 7,816,383, Methods for treating patients with pirfenidone.
- U.S. Food and Drug Administration. (2023). Esbriet (pirfenidone) prescribing information. Genentech USA, Inc.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
- United States Code. (2024). 35 U.S.C. §154: Contents and term of patent; provisional rights.
- United States Code. (2024). 21 U.S.C. §355: New drugs.
