US Patent 11,628,162: Pemigatinib CYP3A4 Avoidance Claims, Exclusivity, and Patent Landscape
US Patent 11,628,162 protects methods of treating cancer with pemigatinib when the patient avoids concomitant administration of specified CYP3A4-interacting drugs. Its claims are method-of-treatment claims, not composition, formulation, manufacturing, or biomarker claims. The commercially important coverage concerns pemigatinib treatment in the presence of a prohibited CYP3A4 perpetrator, particularly a strong CYP3A4 inhibitor, a moderate-to-strong CYP3A4 inducer, itraconazole, or rifampin.
The patent creates a use-based barrier for a generic pemigatinib product if the generic label, prescribing instructions, or actual use encourages the claimed administration conditions. It does not independently prevent all pemigatinib manufacture or use.
What does US Patent 11,628,162 cover?
The patent covers administering a therapeutically effective amount of pemigatinib to a cancer patient while avoiding concomitant administration of specified CYP3A4-interacting agents.
The principal claim groups are:
| Claim group |
Covered subject matter |
Scope |
| Claim 1 |
Pemigatinib administered while avoiding a CYP3A4 perpetrator |
Broadest independent claim |
| Claim 2 |
Pemigatinib administered while avoiding a strong CYP3A4 inhibitor |
Independent claim |
| Claim 3 |
Pemigatinib administered while avoiding a moderate-to-strong CYP3A4 inducer |
Apparently intended as a dependent claim to claim 1 |
| Claim 4 |
Pemigatinib administered while avoiding itraconazole |
Independent claim |
| Claim 5 |
Pemigatinib administered while avoiding rifampin |
Independent claim |
| Claim 6 |
Claim 1 cancer indications |
Broad cancer list |
| Claims 7-9 |
8p11 myeloproliferative syndrome, cholangiocellular carcinoma, and bladder cancer |
Narrower disease claims |
| Claim 10 |
Continuous daily dosing or a 14-days-on/7-days-off cycle |
Dosing-regimen claim |
| Claim 11 |
Liver cancer |
Narrower disease claim |
The user-supplied text for claim 3 appears internally defective: it begins, “The method of claim 1,” and then repeats an independent-method formulation. Claim dependency should be confirmed against the issued patent rather than relying on a transcription.
What is the core technical concept of the patent?
The technical concept is management of pemigatinib exposure through avoidance of CYP3A4 perpetrators.
Pemigatinib is primarily metabolized by CYP3A4. A strong CYP3A4 inhibitor can increase pemigatinib exposure, while a moderate-to-strong CYP3A4 inducer can reduce exposure. The patent claims treatment that excludes those interacting drugs from the patient’s concomitant medication regimen.
The claims therefore combine four elements:
- A patient in need of cancer treatment.
- Administration of a therapeutically effective amount of pemigatinib.
- Avoidance of concomitant administration of a defined CYP3A4-interacting drug or drug class.
- For dependent claims, a specified cancer or dosing schedule.
The claims do not require a particular pemigatinib salt, tablet strength, excipient, formulation, biomarker, FGFR alteration, or manufacturing process.
How broad is claim 1?
Claim 1 is potentially broad because “CYP3A4 perpetrator” can encompass drugs that inhibit or induce CYP3A4. The claim does not limit the cancer type, pemigatinib dose, route of administration, or treatment line.
Its practical breadth depends on how “perpetrator” is construed in the patent specification and prosecution history. The term is pharmacology-specific but is not necessarily self-defining. A court would likely examine:
- The patent’s definition of “CYP3A4 perpetrator.”
- Whether the term includes weak inhibitors or weak inducers.
- Whether the term covers only drugs with a clinically meaningful effect on pemigatinib exposure.
- Whether “avoiding” requires a deliberate prescriber instruction or merely the absence of concomitant administration.
- The meaning of “concomitant,” including same-day, overlapping, or clinically relevant exposure periods.
- Whether a patient’s incidental use of an interacting drug falls within the claim.
Claim 1 is stronger against conduct that clearly follows the claimed regimen. It is less predictable where the patient receives a drug with disputed CYP3A4 classification or where the drugs are separated in time.
What do claims 2 through 5 add?
Strong CYP3A4 inhibitors
Claim 2 narrows the prohibited drug class to strong CYP3A4 inhibitors. This is narrower than claim 1 but may be easier to enforce because regulatory and pharmacology references commonly classify strong inhibitors.
Claim 4 identifies itraconazole specifically. Itraconazole is a strong CYP3A4 inhibitor and is a concrete species within the inhibitor-focused claim set. A claim directed to itraconazole avoids some classification disputes but is limited to that drug.
CYP3A4 inducers
Claim 3 addresses moderate-to-strong CYP3A4 inducers. Claim 5 identifies rifampin, a strong CYP3A4 inducer, as a specific example.
Rifampin is an important claim species because it is a well-established strong inducer and has a clear pharmacokinetic rationale for reducing pemigatinib exposure. The claim does not appear to cover every antibiotic or every rifamycin unless the relevant drug also satisfies the claim’s CYP3A4-inducer limitation.
Negative limitations
The phrase “while avoiding” is a negative limitation. It requires the treatment method to omit the specified concomitant drug or drug class. The patent does not claim that the patient must receive an alternative CYP3A4-neutral drug, nor does it require therapeutic drug monitoring or a measured pemigatinib plasma concentration.
What cancers and dosing regimens are protected?
Claims 6 through 9 and 11 expand the treatment method into disease-specific embodiments.
The listed cancers include cholangiocarcinoma, liver cancer, bladder cancer, breast cancer, colorectal cancer, lung cancer, pancreatic cancer, hematologic malignancies, glioblastoma, melanoma, sarcoma, and other solid tumors and blood cancers.
The commercially significant disease claims are likely:
- Cholangiocellular carcinoma.
- Liver cancer.
- Myeloid/lymphoid neoplasms with FGFR1 rearrangement, including 8p11 myeloproliferative syndrome.
- Bladder cancer, if pemigatinib is used in that setting.
Claim 10 covers two dosing structures:
- Continuous daily administration of an intended or adjusted amount.
- A 21-day cycle consisting of 14 days of daily administration followed by seven days without pemigatinib.
The 14-days-on/7-days-off regimen corresponds to the labeled dosing architecture for Pemazyre in relevant indications. The “intended amount or adjusted amount” language may cover dose modifications made for toxicity, drug interactions, organ impairment, or other clinical reasons, subject to the claim construction and specification.
What is the FDA regulatory status of pemigatinib?
Pemigatinib is marketed in the United States as Pemazyre by Incyte Corporation. The FDA granted accelerated approval in April 2020 for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement, as determined by an FDA-approved test.[2]
The FDA later approved pemigatinib for adults with relapsed or refractory myeloid/lymphoid neoplasms with an FGFR1 rearrangement.[3] The FDA label identifies clinically relevant CYP3A drug-interaction restrictions and instructs prescribers to avoid specified CYP3A inhibitors and inducers or to manage dosing according to the label.[1]
The regulatory label is important to patent analysis because a generic sponsor may need to address the same drug-interaction instructions in its abbreviated new drug application labeling.
What is the Orange Book status of US Patent 11,628,162?
The Orange Book is the relevant FDA listing source for patents associated with approved small-molecule drug products. Patent 11,628,162 should be assessed together with the other patents listed for Pemazyre and its approved indications, rather than in isolation.[4]
The patent’s claims are method-of-use claims. Orange Book relevance depends on whether the patent is listed against the applicable Pemazyre NDA and whether its claims cover an approved method of use. A listed method patent can require a generic applicant to submit a Paragraph IV certification or a section viii statement, depending on the relationship between the patent claims and the proposed generic labeling.
The exact commercial impact depends on:
- Whether Patent 11,628,162 remains listed.
- The NDA indication and use code associated with the listing.
- The patent expiration date recorded by FDA.
- Any patent-term adjustment or pediatric exclusivity.
- Whether the generic applicant carves out the patented use.
- Whether the proposed label still encourages the patented CYP3A4-avoidance regimen.
A definitive Orange Book conclusion requires the current FDA listing and use-code entry. The patent document alone does not establish current listing status.
When does pemigatinib lose exclusivity?
Patent expiration and regulatory exclusivity are separate.
| Exclusivity category |
Relevance to pemigatinib |
| New chemical entity exclusivity |
Blocks ANDA approval for the statutory period after the first approval of the active moiety |
| Orphan-drug exclusivity |
May protect an approved orphan indication for seven years, subject to statutory exceptions |
| Patent exclusivity |
Depends on each listed patent’s expiration, term adjustment, and enforceability |
| Pediatric exclusivity |
May add six months if FDA requirements are satisfied |
| Method-of-use protection |
May delay or constrain generic labeling for the patented indication or regimen |
US Patent 11,628,162 was issued on February 21, 2023. Its effective patent term must be calculated from the relevant nonprovisional filing and priority chain, not simply from the grant date. The controlling expiration date is the term shown in the USPTO record and, if listed, the FDA Orange Book entry. A grant date does not equal an expiration date.
The patent is likely to have a later expiration than pemigatinib’s earliest composition or core-compound patents because it appears directed to a later-developed clinical-use concept. That can make it relevant to late-stage generic launch planning even after earlier compound protection expires.
Are there Paragraph IV challenges to this patent?
A Paragraph IV challenge is legally possible if the patent is listed for Pemazyre and remains relevant to an ANDA applicant’s proposed use. The applicant could allege that the patent is invalid, unenforceable, or not infringed.
Potential challenge theories include:
- Lack of novelty based on prior clinical or pharmacokinetic disclosures.
- Obviousness based on known CYP3A4 metabolism and label-directed avoidance of inhibitors and inducers.
- Indefiniteness involving “perpetrator,” “concomitant,” or “avoiding.”
- Written-description or enablement challenges across the broad cancer list.
- Noninfringement based on a carved-out label.
- Lack of infringement where the generic label does not instruct administration under the claimed conditions.
The strongest validity question is likely obviousness. If prior art already disclosed pemigatinib’s CYP3A4 metabolism, contraindicated or discouraged co-medications, and the clinical consequences of exposure changes, an ANDA challenger could argue that the claimed avoidance regimen was predictable.
The patent holder would likely argue that the claimed regimen reflects clinically meaningful pharmacokinetic findings and a specific treatment protocol, not merely routine application of CYP3A4 knowledge.
No litigation or settlement conclusion should be inferred from the patent’s existence. Patent litigation status must be verified through the FDA Orange Book, PACER, and district-court docket records.
What formulation and manufacturing patents protect pemigatinib?
Patent 11,628,162 does not claim:
- A pemigatinib tablet formulation.
- A particular crystal or polymorphic form.
- A salt, solvate, or particle-size distribution.
- A synthetic intermediate.
- A manufacturing process.
- A packaging system.
- A fixed-dose combination.
- A pharmaceutical composition defined by excipients.
Those protections, if present, would reside in separate patent families. A generic sponsor must conduct a separate composition, formulation, process, and solid-state search. The CYP3A4 patent is a use patent and should not be treated as the full pemigatinib patent estate.
How strong is the patent estate for pemigatinib?
The estate appears strongest where four conditions coincide:
- Pemigatinib is used for an FDA-approved cancer indication.
- The patient receives the labeled dose or an adjusted dose.
- The patient avoids a clearly classified strong CYP3A4 inhibitor or inducer.
- The generic label reproduces or encourages the same interaction-management instructions.
The estate is weaker where a generic applicant can omit the patented indication or interaction-specific language without undermining safe use for an unpatented indication. However, a labeling carve-out may be difficult if FDA requires the CYP3A4 warning for all pemigatinib use.
The patent has meaningful commercial relevance because the claimed avoidance condition may be embedded in standard prescribing information. That creates potential inducement risk even when the generic product itself is chemically identical and the generic manufacturer does not control the physician’s ultimate prescribing decision.
Which companies are challenging pemigatinib exclusivity?
Pemigatinib is a small molecule, so the relevant challengers are generic-drug manufacturers filing ANDAs, not biosimilar sponsors. Biosimilar pathways under section 351(k) do not apply.
Publicly confirmed challenger identities, ANDA filing dates, Paragraph IV notices, and settlement terms require current regulatory and court-record verification. The patent number alone does not identify an ANDA challenger or establish that a Paragraph IV notice has been served.
What generic launch scenarios exist?
A generic pemigatinib launch could occur through several routes:
Full-label launch
The applicant keeps the interaction-management language and challenges the relevant patent under Paragraph IV. This creates the highest litigation exposure but preserves the broadest commercial market.
Section viii or skinny-label launch
The applicant omits a patented indication or method of use if FDA permits the carve-out. This may reduce infringement risk but can leave the generic unable to market the full approved label.
Post-expiration launch
The applicant accepts the listed patent and launches after expiration or after a settlement-defined date. This removes Paragraph IV litigation risk but delays market entry.
Indication-limited launch
The applicant markets only non-patented indications or dosing uses. This approach is commercially viable only if the remaining label supports meaningful prescribing and does not incorporate the patented method by implication.
Key Takeaways
- US Patent 11,628,162 is a pemigatinib method-of-treatment patent.
- Its central limitation is avoiding concomitant CYP3A4 perpetrators.
- Claims 2 through 5 focus on strong inhibitors, moderate-to-strong inducers, itraconazole, and rifampin.
- Claims 6 through 11 narrow the method by cancer type and dosing schedule.
- The patent does not cover pemigatinib’s chemical structure, formulation, solid state, or manufacturing process.
- Its commercial value depends heavily on Orange Book listing, use codes, FDA labeling, and generic-label carve-out options.
- A Paragraph IV challenge could focus on obviousness, indefiniteness, enablement, or noninfringement.
- Pemigatinib requires generic, not biosimilar, competition.
- The precise expiration date and any active litigation or settlement must be taken from current USPTO, FDA, and court records.
FAQs
Does Patent 11,628,162 cover all pemigatinib use?
No. It covers treatment methods that include avoiding specified CYP3A4-interacting drugs. It does not independently cover every administration of pemigatinib.
Does the patent cover pemigatinib for FGFR2-positive cholangiocarcinoma?
Potentially, where the treatment also satisfies the CYP3A4-avoidance limitation and the relevant disease and dosing limitations. The patent should be compared with the applicable Orange Book use code.
Can a generic manufacturer avoid the patent by omitting itraconazole from its label?
Possibly, but omission of one named drug may not avoid broader claims covering strong CYP3A4 inhibitors or CYP3A4 perpetrators. The complete proposed labeling and patent claims must be analyzed together.
Is rifampin prohibited during pemigatinib treatment under the patent?
Claim 5 specifically requires avoiding concomitant administration of rifampin. The FDA label also identifies clinically important CYP3A interaction management for pemigatinib.[1]
Does this patent protect a new pemigatinib dose?
Not as a standalone dose claim. Claim 10 protects specified administration schedules, including continuous daily dosing and a 14-days-on/7-days-off cycle, subject to the claim’s other limitations.
References
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U.S. Food and Drug Administration. (2024). Pemazyre (pemigatinib) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
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U.S. Food and Drug Administration. (2020). FDA grants accelerated approval to pemigatinib for metastatic cholangiocarcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/
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U.S. Food and Drug Administration. (2022). FDA approves pemigatinib for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. https://www.fda.gov/drugs/resources-information-approved-drugs/
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
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United States Patent and Trademark Office. (2023). U.S. Patent No. 11,628,162. https://patents.google.com/patent/US11628162B2/en
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U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation resources. https://www.uspto.gov/patents/laws/patent-term-adjustment---
