US Patent 10,512,657: Scope, Claims, Expiration, and PFIC2 Patent Landscape
US Patent 10,512,657 protects pediatric treatment of progressive familial intrahepatic cholestasis type 2, or PFIC2, with an apical sodium-dependent bile acid transporter inhibitor, or ASBTI. The patent is primarily a method-of-treatment patent. Its broadest claims cover administering an ASBTI to a pediatric PFIC2 patient while achieving at least a 20% reduction in serum or hepatic bile acid levels. Dependent claims add pruritus, pediatric formulations, dosing ranges, ages, low systemic absorption, combination therapy, and higher bile-acid reduction thresholds.
The patent is commercially relevant to odevixibat, marketed by Ipsen as Bylvay. Odevixibat is an orally administered, minimally absorbed ASBTI approved by the FDA for PFIC and Alagille syndrome. The patent’s reported nominal expiration date is January 10, 2034, subject to any applicable patent-term adjustment, patent-term extension, terminal disclaimer, or later legal determination.
What does US Patent 10,512,657 cover?
US Patent 10,512,657 covers methods for treating or ameliorating pediatric PFIC2 using an ASBTI. The claims do not identify only one named molecule. They use the broader functional class of ASBTIs, subject to the patent’s specification and claim construction.
The core elements are:
| Claim element |
Scope |
| Disease |
Pediatric progressive familial intrahepatic cholestasis type 2 |
| Patient |
Pediatric subject |
| Therapeutic agent |
ASBTI or pharmaceutically acceptable salt |
| Primary result |
At least 20% reduction in serum and/or hepatic bile acid levels |
| Administration |
Direct administration or administration through a pharmaceutical composition |
| Key dependent limitations |
Pruritus, pediatric dosage form, dose, age, low systemic absorption, combination with bile-acid binder, and greater reductions in bile acids |
The patent therefore reaches beyond a particular product label. A product can fall within the claim scope if it is an ASBTI, is administered to a pediatric PFIC2 patient, and satisfies the claimed bile-acid reduction limitation.
What are the independent claims in US Patent 10,512,657?
Claims 1, 2, and 3 are the principal independent claims.
Claim 1: PFIC2 treatment
Claim 1 covers administering an ASBTI to a pediatric subject to treat or ameliorate PFIC2, where the ASBTI produces at least a 20% decrease in serum and/or hepatic bile acid levels from baseline.
This claim is broad because it does not limit the ASBTI to odevixibat, a specific chemical structure, a particular formulation, or a single dosing schedule. It also covers treatment of PFIC2 generally rather than one specific symptom.
Claim 2: Pruritus treatment
Claim 2 covers treating or ameliorating pruritus in a pediatric PFIC2 patient using an ASBTI. The claimed efficacy requirement remains a reduction of at least 20% in serum and/or hepatic bile acid levels.
The claim does not require a measured reduction in pruritus as its express efficacy threshold. A treatment may therefore implicate the claim if it is directed to PFIC2-associated pruritus and meets the bile-acid reduction limitation, even if the clinical evidence is framed primarily around bile acids rather than a pruritus score.
Claim 3: Pharmaceutical composition
Claim 3 covers administering a pharmaceutical composition containing an ASBTI to a pediatric PFIC2 patient. It carries the same 20% bile-acid reduction requirement.
Claim 3 is important for commercial products because it is directed to a composition-based administration route rather than administration of the active ingredient in isolation. The claim does not, on its face, require a particular excipient, dosage form, concentration, or release profile.
How broad are the dependent claims?
The dependent claims create several overlapping infringement positions.
| Claims |
Limitation |
Commercial relevance |
| 4 |
Reduction of xanthoma, lipoprotein X, liver enzymes, bilirubin, intraenterocyte bile acids, or hepatic damage |
Adds secondary biological or clinical outcomes |
| 5 |
Pediatric dosage form |
Targets child-oriented product presentation |
| 6 |
Solution, syrup, suspension, chewable, gummy, lollipop, sachet, oral powder, and other forms |
Broad formulation coverage |
| 7 |
About 10 to 300 micrograms/kg/day |
Broad dose range |
| 8 |
About 14 to 280 micrograms/kg/day |
Narrower dose range |
| 9 |
About 14 to 140 micrograms/kg/day |
Narrowest stated weight-based range |
| 10 |
0.1 to 20 mg ASBTI per dosage form |
Unit-dose formulation coverage |
| 11 |
PFIC2 symptoms and disease manifestations |
Expands disease-characterization coverage |
| 12 |
Pediatric patient aged 6 months to 12 years |
Defines a specific pediatric population |
| 13 |
Less than 10% systemic absorption |
Targets gut-restricted ASBTIs |
| 14 |
Combination with a bile-acid sequestrant or binder |
Covers combination therapy |
| 15 |
At least 30% reduction in bile acids |
Higher efficacy threshold |
| 16 |
At least 40% reduction |
Higher efficacy threshold |
| 17 |
At least 50% reduction |
Highest stated efficacy threshold |
Claims 15 through 17 are not independent alternatives to claim 1. They narrow claim 1 by requiring progressively greater reductions in serum or hepatic bile acids.
Does the patent cover odevixibat and Bylvay?
The patent is highly relevant to odevixibat because Bylvay is an orally administered ASBT inhibitor used in pediatric cholestatic disease. Odevixibat is designed to act locally in the intestinal lumen and has limited systemic exposure, which corresponds closely to the subject matter of claims 1, 7 through 9, 12, and 13.
The FDA approved Bylvay in 2021 for the treatment of cholestatic pruritus due to PFIC in patients three months of age and older. The FDA later expanded the product’s approved use to cholestatic pruritus associated with Alagille syndrome. The PFIC approval is the most direct regulatory overlap with the patent claims. [1]
The patent claims are not limited to the Bylvay label. They can potentially cover other ASBTIs used for pediatric PFIC2 if the claimed efficacy and patient limitations are met.
What formulations are protected by US Patent 10,512,657?
The patent does not claim one narrow formulation architecture. Claim 6 lists a wide range of pediatric dosage forms, including:
- Oral solutions and syrups
- Suspensions and elixirs
- Powders for reconstitution
- Dispersible and effervescent tablets
- Chewable tablets
- Gummies and lollipops
- Freezer pops and troches
- Oral thin strips
- Orally disintegrating tablets
- Sachets
- Soft gelatin capsules
- Sprinkle powders and granules
This creates broad method-of-treatment coverage for pediatric product formats. The claims do not necessarily establish separate composition patents for each dosage form. Instead, they cover use of an ASBTI-containing composition in the claimed pediatric PFIC2 treatment method.
The Bylvay product is supplied in oral pellets and capsules. FDA labeling identifies weight-based dosing and administration instructions for pediatric patients. [2]
What doses fall within the patent claims?
Claims 7 through 9 establish overlapping weight-based ranges:
| Claim |
Dose range |
| 7 |
Approximately 10 to 300 micrograms/kg/day |
| 8 |
Approximately 14 to 280 micrograms/kg/day |
| 9 |
Approximately 14 to 140 micrograms/kg/day |
These ranges are broad enough to cover common pediatric weight-based dosing strategies for odevixibat and potentially other gut-restricted ASBTIs.
Claim 10 separately covers dosage forms containing 0.1 to 20 mg of ASBTI. That limitation is directed to the amount per dosage unit rather than the daily dose expressed by body weight.
A product can implicate multiple claims simultaneously. For example, a pediatric odevixibat product administered at a weight-based dose and producing a 30% bile-acid reduction could fall within claims 1, 7, 8, 9, and 15, depending on the actual dose and evidence.
When does US Patent 10,512,657 expire?
The reported nominal expiration date is January 10, 2034. The patent’s enforceable term must be assessed against the official USPTO patent record, including any patent-term adjustment and terminal-disclaimer information. Patent expiration can also be affected by patent-term extension under 35 U.S.C. § 156, although orphan-drug regulatory exclusivity is separate from patent term. [3]
The commercial exclusivity timeline is therefore:
| Event |
Date or period |
| US patent |
US 10,512,657 |
| Reported nominal patent expiration |
January 10, 2034 |
| FDA PFIC approval for Bylvay |
July 20, 2021 |
| Orphan-drug exclusivity for the PFIC approval |
Generally through July 20, 2028 |
| Expected patent-based protection |
Potentially through January 2034, subject to official term calculations |
The seven-year orphan exclusivity period blocks FDA approval of the same drug for the same orphan indication unless an exception applies. It does not prevent all competing ASBTI development and does not prevent patent challenges. [1]
What is the Orange Book status of US Patent 10,512,657?
US Patent 10,512,657 has been associated with Bylvay’s US intellectual-property position and is relevant to the FDA-approved drug. Orange Book listing status must be checked against the current FDA publication because listed patents, delisting events, use codes, and product records can change. [4]
The patent is a method-of-use patent rather than a classic active-ingredient composition-of-matter patent. Its commercial effect therefore depends on:
- The FDA-approved use code.
- Whether a proposed generic seeks the PFIC indication.
- Whether the generic applicant uses a section viii statement to omit the patented indication.
- Whether the proposed label nevertheless encourages or induces the patented use.
- Whether the patent remains enforceable when an ANDA is filed.
A generic applicant seeking approval only for a non-PFIC indication could attempt to avoid the listed method of use. A product labeled for pediatric PFIC2 treatment would face a more direct patent risk.
Are there Paragraph IV challenges or patent litigation?
A Paragraph IV certification would assert that the patent is invalid, unenforceable, or not infringed. If the patent is listed for Bylvay and an ANDA applicant makes a Paragraph IV certification, the patent holder could bring an infringement action under the Hatch-Waxman framework.
The principal litigation issues would likely include:
- Whether the accused active ingredient qualifies as an ASBTI under the patent specification.
- Whether the patient has PFIC2 as claimed.
- Whether the patient is within the pediatric limitation.
- Whether administration produces the required bile-acid reduction.
- Whether “at least 20%” is measured against an appropriate baseline.
- Whether serum and hepatic bile-acid measurements are interchangeable for claim purposes.
- Whether the claims are enabled across the full ASBTI genus.
- Whether the efficacy threshold and pediatric PFIC2 use were obvious from earlier ASBTI and cholestasis disclosures.
No publicly documented Paragraph IV judgment or final settlement concerning US Patent 10,512,657 is identified in the cited records. The absence of a reported judgment does not eliminate future ANDA litigation risk.
How strong is the patent estate?
The estate is strongest where a competing product has all of the following characteristics:
- An ASBTI mechanism.
- Pediatric PFIC2 treatment.
- Oral administration.
- Low systemic absorption.
- Weight-based pediatric dosing.
- A demonstrated reduction of at least 20% in serum or hepatic bile acids.
The estate is weaker against products that:
- Treat a non-PFIC indication.
- Use a different mechanism.
- Are administered only to adults.
- Avoid the claimed PFIC2 indication in the FDA label.
- Do not produce the claimed bile-acid reduction.
- Challenge the breadth or enablement of the ASBTI genus.
The absence of a narrow chemical structure in the independent claims creates breadth, but it also creates potential validity exposure. A defendant could argue that the specification does not adequately support or enable every ASBTI, every pediatric PFIC2 patient, every covered formulation, and every claimed efficacy level.
What other ASBTIs compete with odevixibat?
The principal competitive landscape includes other ASBTIs, although regulatory status differs substantially.
| Product or molecule |
Company |
Status relevant to PFIC |
| Odevixibat, Bylvay |
Ipsen, formerly Albireo |
FDA-approved for PFIC and Alagille syndrome |
| Maralixibat, Livmarli |
Mirum Pharmaceuticals |
FDA-approved for Alagille syndrome; not equivalent to an FDA PFIC approval |
| Elobixibat |
EA Pharma and regional partners |
Approved in Japan for constipation; not a US PFIC product |
| Linerixibat |
GSK |
Investigational ASBTI program for cholestatic pruritus |
| Other ASBTIs |
Multiple developers |
Development status varies by molecule and indication |
Maralixibat is the closest commercial comparator by mechanism and pediatric cholestatic-disease focus. Its FDA approval for Alagille syndrome does not automatically establish approval for PFIC2. A competitor could still face the patent if its label or actual use reaches pediatric PFIC2 and the drug satisfies the claim limitations.
Does the patent create biosimilar risk?
No. Bylvay contains a small-molecule active ingredient, odevixibat. The relevant competitive pathway is an abbreviated new drug application, not a biosimilar application under the Public Health Service Act.
The main regulatory risks are generic substitution, Paragraph IV litigation, skinny-label strategies, and possible approval of another ASBTI for a different indication. The patent’s method-of-treatment structure makes labeling and induced-use analysis more important than biosimilar interchangeability.
What manufacturing and intellectual-property barriers remain?
US Patent 10,512,657 does not appear to be a manufacturing-process patent based on the supplied claims. It does not directly claim:
- Odevixibat synthesis.
- A specific crystalline form.
- A defined impurity profile.
- A manufacturing process.
- A particular excipient system.
- A release-control technology.
Manufacturing barriers may therefore arise from separate patents, trade secrets, regulatory specifications, know-how, or the cost of producing a sufficiently pure ASBTI. The patent itself is principally an indication, patient-population, dosing, efficacy, and formulation-use right.
How does US Patent 10,512,657 compare with competing patent rights?
The patent’s competitive advantage is its disease-specific pediatric scope. A general ASBTI patent may cover the molecule or mechanism but not specifically cover pediatric PFIC2 treatment. Conversely, a competitor may possess a composition-of-matter patent that is stronger against all uses of its molecule but irrelevant to odevixibat.
| Protection type |
US 10,512,657 |
Typical competing right |
| Active ingredient |
Not the primary claim focus |
May be covered by separate compound patent |
| PFIC2 indication |
Directly claimed |
May be absent or separately claimed |
| Pediatric population |
Directly claimed |
May be narrower or broader |
| Dose |
Claims 7-9 |
May be product-label specific |
| Pediatric formulation |
Claims 5, 6, and 10 |
May be covered by formulation patents |
| Low systemic absorption |
Claim 13 |
Relevant to gut-restricted ASBTIs |
| Manufacturing |
Not apparent from supplied claims |
May be covered by separate process patents |
| Orphan exclusivity |
Regulatory protection for approved indication |
Depends on each product’s approval |
What generic launch scenarios exist?
Launch after patent expiration
A generic could launch after the patent expires, assuming FDA approval and no other enforceable patent or exclusivity barrier. The practical date would depend on the official patent-term calculation and any remaining regulatory exclusivity.
Skinny-label launch
A generic could seek approval while omitting PFIC2 from its labeling. This strategy would reduce direct method-of-use exposure but would not eliminate risk if the product’s label, marketing, distribution, or physician-directed use induces the patented treatment.
Paragraph IV launch
A generic could challenge the patent before expiration by asserting invalidity or noninfringement. The likely disputes would focus on claim breadth, the definition of ASBTI, efficacy measurement, written description, enablement, and obviousness.
Noninfringing alternative ASBTI use
A competitor could target a different disease, age group, or therapeutic endpoint. This scenario reduces direct exposure to the PFIC2 claims but may encounter separate patents and regulatory exclusivity.
Key Takeaways
- US Patent 10,512,657 is a broad pediatric PFIC2 method-of-treatment patent.
- The independent claims cover ASBTIs that reduce serum or hepatic bile acids by at least 20%.
- Odevixibat and Bylvay are the patent’s most commercially relevant products.
- Dependent claims cover pediatric dosage forms, doses from approximately 10 to 300 micrograms/kg/day, unit doses from 0.1 to 20 mg, ages 6 months to 12 years, low systemic absorption, combination therapy, and 30%, 40%, and 50% bile-acid reductions.
- The reported nominal expiration date is January 10, 2034.
- FDA orphan exclusivity for the PFIC indication generally runs seven years from the 2021 approval, through approximately July 20, 2028.
- The patent is a method-of-use right, not primarily a composition-of-matter or manufacturing patent.
- Generic risk will center on Orange Book use codes, Paragraph IV certifications, skinny-label strategies, and induced infringement.
- Biosimilar competition is not the relevant framework because odevixibat is a small molecule.
- Claim breadth supports substantial commercial coverage but creates potential validity challenges involving enablement, written description, obviousness, and efficacy measurement.
FAQs
Is US Patent 10,512,657 limited to odevixibat?
No. The supplied claims use the broader category of ASBTI rather than naming only odevixibat. The specification’s definition of ASBTI and the patent’s written-description support would control the ultimate scope.
Does the patent cover PFIC1 treatment?
The supplied claims specifically recite PFIC2. PFIC1 treatment would not automatically fall within the claims unless the disease were proven to satisfy the PFIC2 limitation or another claim in the patent covered PFIC1.
Can a generic avoid the patent by removing PFIC2 from its label?
Potentially, but label removal does not eliminate all risk. The generic could still face induced-infringement allegations if its labeling, marketing, distribution, or instructions encourage pediatric PFIC2 treatment.
Does claim 13 cover every minimally absorbed ASBTI?
No. Claim 13 requires less than 10% systemic absorption and depends on the broader method claim. The accused product must also satisfy the PFIC2, pediatric, ASBTI, and bile-acid reduction limitations.
Is Bylvay’s FDA approval enough to prove infringement?
No. Regulatory approval and patent infringement are separate inquiries. Infringement would depend on the product’s use, patient population, labeling, dosing, efficacy, and the construction and validity of the asserted claims.
References
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U.S. Food and Drug Administration. (2021). FDA approves first drug to treat itching from rare disease in children one year of age and older. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-itching-rare-disease-children-one-year-age-and-older
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U.S. Food and Drug Administration. (2024). Bylvay (odevixibat) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
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United States Patent and Trademark Office. (2024). Patent term adjustment and patent term extension guidance. https://www.uspto.gov/patents/laws/patent-term-adjustment
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U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
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United States Patent and Trademark Office. (2020). US Patent No. 10,512,657: Methods for treating progressive familial intrahepatic cholestasis. https://patents.google.com/patent/US10512657B2/en
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Ipsen. (2023). Ipsen completes acquisition of Albireo. https://www.ipsen.com/press-releases/ipsen-completes-acquisition-of-albireo/
