US Patent 11,230,530: Berotralstat Angioedema Treatment Claims and Patent Landscape
US Patent No. 11,230,530 protects once-daily oral treatment of angioedema, particularly hereditary angioedema, using berotralstat or a pharmaceutically acceptable salt. The claims cover the active compound broadly, the individual enantiomers, hydrochloride and bis(hydrochloride) salts, capsule dosage forms, and once-daily administration. The patent is associated with BioCryst Pharmaceuticals' berotralstat product, Orladeyo.
The patent is a method-of-treatment patent. It does not, based on the supplied claims, claim the chemical compound itself, a specific formulation composition, a manufacturing process, or a particular dose strength.
What drug does US Patent 11,230,530 cover?
The compound described by the claims is berotralstat, also known as BCX7353, a plasma kallikrein inhibitor developed for prophylaxis against hereditary angioedema attacks. The marketed product is Orladeyo, supplied as oral capsules containing berotralstat hydrochloride.
| Item |
Information |
| U.S. patent |
US 11,230,530 |
| Patent title |
Methods of treating angioedema |
| Patent holder or associated innovator |
BioCryst Pharmaceuticals, Inc. |
| Active compound |
Berotralstat |
| Development code |
BCX7353 |
| Product |
Orladeyo |
| FDA indication |
Routine prophylaxis to prevent attacks of hereditary angioedema in adults and pediatric patients 12 years and older |
| FDA approval |
December 3, 2020 |
| Dosage form |
Oral capsule |
| FDA-approved regimen |
150 mg orally once daily with food |
| Pharmacologic class |
Plasma kallikrein inhibitor |
| Patent type |
Method of treatment |
FDA approved Orladeyo as an orally administered prophylactic treatment for hereditary angioedema. The approved product contains berotralstat hydrochloride, although the claims in US 11,230,530 are drafted to reach the free compound, enantiomeric forms, and specified salts. [1]
What are the independent and dependent claims?
Claim 1 is the operative broad claim. It covers:
- Treating or preventing angioedema.
- Oral administration.
- An oral dosage form.
- A therapeutically effective amount of the claimed compound or a pharmaceutically acceptable salt.
The remaining claims narrow claim 1 by adding treatment characteristics or chemical forms.
| Claim group |
Added limitation |
Commercial relevance |
| Claim 1 |
Oral treatment or prevention of angioedema |
Broad method claim |
| Claims 2-3 |
Once-daily dosing; capsule dosage form |
Directly aligned with Orladeyo use |
| Claims 4-6 |
Hereditary angioedema |
Matches the FDA-approved indication |
| Claims 7-10 |
(+)-enantiomer |
Covers one stereochemical form |
| Claims 11-14 |
(-)-enantiomer |
Covers the opposite stereochemical form |
| Claims 15-18 |
Hydrochloride salt |
Covers a principal commercial salt form |
| Claims 19-22 |
Bis(hydrochloride) salt |
Covers an additional salt form |
Claims 2 through 22 are dependent claims. They do not create separate inventions independent of claim 1. Their value is narrowing and fallback protection. If a court invalidated or narrowed claim 1, a dependent claim could remain enforceable if its additional limitations supplied patentable distinction.
How broad is the scope of US 11,230,530?
The scope is commercially significant because claim 1 is not limited to hereditary angioedema. It recites angioedema generally, including treatment or prevention. A competing product could potentially fall within claim 1 if it used the claimed compound orally for another angioedema indication.
The claims are broader than the current FDA label in several respects:
- They cover treatment or prevention, while the approved label is directed to routine prophylaxis.
- They recite angioedema generally, while the approved indication is hereditary angioedema.
- They cover the compound and pharmaceutically acceptable salts.
- They cover both identified enantiomers.
- They cover once-daily administration but do not recite the FDA-approved 150 mg strength.
- They cover capsules but do not require the exact excipient system used in Orladeyo.
The claims are narrower than a compound patent because they require a therapeutic use. A party making or selling berotralstat for a non-angioedema indication might avoid literal infringement of the method claims, although inducement, contributory infringement, label language, clinical evidence, and product marketing would remain relevant.
Does the patent cover Orladeyo?
Yes. Orladeyo appears to fall within multiple claim paths:
- Claim 1: oral berotralstat or a pharmaceutically acceptable salt for angioedema prevention.
- Claim 4: use for hereditary angioedema.
- Claim 5: once-daily administration.
- Claim 6: once-daily capsule administration.
- Claim 15: hydrochloride salt.
- Claim 16: hydrochloride salt for hereditary angioedema.
- Claim 17: hydrochloride salt administered once daily.
- Claim 18: hydrochloride salt in a once-daily capsule.
The strongest commercial overlap is claims 4-6 and 15-18. Those claims track the labeled product and regimen more closely than the broader claims.
What patents protect berotralstat and Orladeyo?
US 11,230,530 is one component of the broader berotralstat estate. The estate may include separate patent families directed to the compound, stereochemistry, pharmaceutical salts, treatment methods, formulations, and manufacturing processes.
| Protection category |
Relevance to berotralstat |
Relationship to US 11,230,530 |
| Core compound patents |
Protect berotralstat chemical matter |
Usually broader against unauthorized manufacture and sale |
| Stereochemical patents |
Protect a selected enantiomer or stereochemical composition |
US 11,230,530 expressly recites both enantiomers in dependent claims |
| Salt patents |
Protect hydrochloride or other salt forms |
US 11,230,530 includes hydrochloride and bis(hydrochloride) method claims |
| Method-of-use patents |
Protect treatment or prevention of angioedema |
Primary subject of US 11,230,530 |
| Formulation patents |
Protect capsule composition, release profile, excipients, or stability |
Not apparent from the supplied claims |
| Manufacturing patents |
Protect synthetic routes, intermediates, crystallization, or salt formation |
Not apparent from the supplied claims |
| Regulatory listing patents |
Support restrictions on abbreviated generic approval |
Depends on FDA Orange Book listing and product-specific applicability |
The supplied claims do not establish that US 11,230,530 protects a specific formulation. A generic manufacturer could still face separate formulation, compound, salt, process, or method-of-use patents even if it designed around the capsule limitations.
What is the patent expiration date?
The patent was granted on February 1, 2022. Its relevant priority chain reaches back to July 2014. The effective expiration date must be determined from the patent family, the earliest nonprovisional or international filing date controlling U.S. patent term, any terminal disclaimer, and any patent-term adjustment.
A provisional priority date is not itself the ordinary starting point for the 20-year U.S. patent term. The grant date also is not the expiration date. For commercial diligence, the controlling date should be taken from the USPTO Patent Center patent-term calculation and the current FDA Orange Book listing rather than inferred from the priority date. [2]
The patent's practical exclusivity period may differ from its ordinary term because:
- The patent may have patent-term adjustment.
- A continuation may be subject to a terminal disclaimer.
- Patent-term extension under 35 U.S.C. ยง 156 may apply to an eligible product patent, although method-of-treatment patents require separate analysis.
- Pediatric exclusivity, if granted for the product, could add six months to applicable listed patents.
- Orange Book listing status can change independently of the patent's underlying validity.
What is the Orange Book status of US 11,230,530?
A patent's eligibility for Orange Book listing depends on whether it claims the approved drug, a drug substance, a drug product, or an approved method of use under FDA regulations. Method-of-use patents can be listed when they claim an approved use and satisfy FDA listing requirements.
US 11,230,530 is especially relevant to Orange Book analysis because its claims expressly cover:
- Hereditary angioedema.
- Oral administration.
- Once-daily administration.
- Capsules.
- The hydrochloride salt used in Orladeyo.
The patent number, however, is not enough by itself to establish current Orange Book status. The current product-specific patent table, FDA patent-use code, and any subsequent delisting or correction must control. [3]
For an abbreviated new drug application, a generic applicant would need to assess whether the patent is listed for Orladeyo and whether its proposed labeling overlaps an FDA-listed method of use.
When does berotralstat lose regulatory exclusivity?
Orladeyo received FDA approval on December 3, 2020. Berotralstat received new chemical entity exclusivity if FDA classified it as an NCE, which ordinarily blocks approval of an ANDA or 505(b)(2) application containing the same active moiety for five years from approval, subject to the statutory Paragraph IV exception. That five-year period would ordinarily run to December 3, 2025. [1, 4]
Regulatory exclusivity and patent exclusivity are separate:
| Protection |
Approximate basis |
Commercial effect |
| NCE exclusivity |
Five years from FDA approval, subject to Paragraph IV rules |
Blocks certain ANDA and 505(b)(2) approvals |
| Patent protection |
Depends on each listed patent's term |
Can block approval or commercial launch after NCE expiry |
| Pediatric exclusivity |
Six months if granted |
Extends applicable exclusivity or patent protection |
| Orphan-drug exclusivity |
Depends on FDA orphan designation and indication |
Can block approval of the same drug for the same disease or condition |
The NCE period does not determine the last possible generic launch date. Listed patents and litigation outcomes are usually more important after the regulatory exclusivity period ends.
What Paragraph IV challenges and generic entry risks exist?
A generic applicant seeking approval for berotralstat could use one or more ANDA certification strategies:
- Paragraph I: no patent information has been submitted.
- Paragraph II: the listed patent has expired.
- Paragraph III: the applicant will wait until patent expiration.
- Paragraph IV: the listed patent is invalid, unenforceable, or will not be infringed.
- Section viii statement: the applicant will carve out a patented method of use where FDA permits the carve-out.
For US 11,230,530, the principal technical challenge would likely concern method-of-use infringement. A generic label directed only to an indication or dosing regimen outside the listed method might attempt a section viii carve-out. That strategy is more difficult where the entire approved use is hereditary angioedema prophylaxis and the patent claims cover that same use.
A Paragraph IV certification could attack:
- Written description or enablement.
- Obviousness of treating hereditary angioedema with the compound.
- Novelty of the claimed enantiomer or salt.
- Definiteness of the chemical structure.
- Infringement based on the proposed label.
- Enforceability issues arising from prosecution conduct.
The once-daily and capsule limitations may create design-around arguments, but a product labeled for oral berotralstat treatment of hereditary angioedema could still implicate claim 1 or claim 4 even if it avoided a dependent claim requiring once-daily capsule administration.
Which companies are challenging the Orladeyo patent estate?
The supplied information does not identify a filed Paragraph IV notice, ANDA applicant, district-court complaint, or settlement agreement involving US 11,230,530. No challenger should be treated as established solely because the patent is nearing the end of its NCE period.
The relevant public records for litigation diligence are:
- FDA Orange Book patent certifications.
- FDA Paragraph IV litigation notifications.
- PACER district-court complaints.
- Hatch-Waxman docket activity.
- BioCryst securities filings.
- Patent-term and listing records.
Without a verified litigation record, the commercial assumption should be that the patent remains an enforceable barrier until expiration, invalidation, settlement, or a successful noninfringement position.
How strong is the patent estate?
US 11,230,530 has moderate-to-strong product relevance but limited standalone breadth compared with a composition-of-matter patent.
Strengths
- The independent claim reaches oral use of the identified compound for angioedema.
- Dependent claims align closely with the approved hereditary angioedema indication.
- The hydrochloride salt claims map onto the marketed product.
- Once-daily capsule claims correspond to the commercial regimen.
- A generic product would likely use labeling that overlaps the claimed indication.
Limitations
- The claims are method claims, not direct composition-of-matter claims.
- The claims do not recite the marketed 150 mg strength.
- The supplied claims do not protect a defined excipient formulation.
- Enantiomer claims may invite stereochemical, written-description, or obviousness challenges depending on the specification and prior art.
- A narrow label carve-out may reduce infringement exposure if FDA permits it.
- Validity cannot be assessed from claim text alone; the specification, prosecution history, cited art, and related family patents control.
What manufacturing and IP barriers affect generic entry?
A generic manufacturer would face several independent barriers:
- Regulatory approval after the NCE period.
- Orange Book patent certifications.
- Potential Hatch-Waxman litigation.
- Access to a commercially viable synthesis and salt-formation process.
- Control of polymorph, purity, stereochemistry, and stability attributes.
- Avoidance of separate compound, formulation, and process patents.
- Labeling that does not induce infringement of a listed method claim.
The method claims do not prevent every form of chemical manufacture. A generic could still need to resolve non-method patents before launching. Conversely, a successful challenge to US 11,230,530 would not necessarily clear the entire berotralstat estate.
How does Orladeyo compare with competing hereditary angioedema products?
| Product |
Active ingredient |
Route |
Primary use |
Competitive distinction |
| Orladeyo |
Berotralstat |
Oral |
Routine prophylaxis |
Once-daily oral plasma kallikrein inhibition |
| Takhzyro |
Lanadelumab |
Subcutaneous injection |
Routine prophylaxis |
Long-acting monoclonal antibody |
| Haegarda |
C1 esterase inhibitor |
Subcutaneous injection |
Prophylaxis |
Replacement therapy |
| Cinryze |
C1 esterase inhibitor |
Intravenous injection |
Prophylaxis |
Intravenous administration |
| Firazyr |
Icatibant |
Subcutaneous injection |
Acute attack treatment |
On-demand bradykinin B2-receptor antagonism |
| Ruconest |
C1 esterase inhibitor |
Intravenous injection |
Acute attack treatment |
Acute treatment rather than routine oral prophylaxis |
Orladeyo's commercial differentiation is oral administration and once-daily dosing. Those attributes also make the method claims more directly relevant to a generic oral competitor than to injectable HAE products.
What is the revenue exposure from US 11,230,530?
The patent is linked to the U.S. commercial use of Orladeyo, but patent-level revenue exposure cannot be calculated from the claims alone. The relevant variables are:
- U.S. Orladeyo net sales.
- U.S. versus international revenue mix.
- Gross-to-net discounts.
- Patient access and reimbursement.
- Duration of patent protection.
- Generic launch timing.
- Settlement terms, if any.
- Alternative prophylactic products.
- Ability to shift patients to other presentations or indications.
Because the claims cover the approved indication, a successful generic launch could materially affect U.S. product sales. The magnitude would depend on whether the generic entrant receives a first-filer 180-day exclusivity period, whether the generic label includes the HAE indication, and whether other patents remain in force.
Key Takeaways
- US 11,230,530 is a method-of-treatment patent associated with berotralstat and Orladeyo.
- Claim 1 broadly covers oral treatment or prevention of angioedema using berotralstat or a pharmaceutically acceptable salt.
- Claims 4-6 most directly cover hereditary angioedema treated with a once-daily oral capsule.
- Claims 15-18 specifically cover the hydrochloride salt used in the commercial product.
- The patent does not, from the supplied claims, establish protection for a particular formulation, excipient system, dose strength, manufacturing process, or compound composition.
- Orladeyo's five-year NCE exclusivity period ordinarily ran from December 3, 2020, subject to statutory exceptions and any applicable pediatric exclusivity.
- A Paragraph IV challenge would likely focus on validity, label-based infringement, and possible design-around of the once-daily capsule limitations.
- Clearing this patent would not necessarily clear the broader berotralstat patent estate.
- Current Orange Book listing, patent-term calculations, and litigation records are controlling for launch timing.
FAQs
What is US Patent 11,230,530's main claim?
Its main claim covers orally administering a therapeutically effective amount of berotralstat or a pharmaceutically acceptable salt to treat or prevent angioedema.
Does US 11,230,530 cover the 150 mg Orladeyo dose?
The supplied claims do not expressly recite 150 mg. They require a therapeutically effective amount. The approved Orladeyo regimen is 150 mg once daily with food.
Does the patent cover acute hereditary angioedema treatment?
The claims recite treatment or prevention of angioedema, but Orladeyo's FDA-approved use is routine prophylaxis. Whether an acute-treatment use falls within a particular claim depends on the facts of administration and claim construction.
Can a generic avoid the patent by using a tablet instead of a capsule?
A tablet may avoid dependent claims requiring a capsule, but it could still fall within claim 1 or other claims that do not require a capsule. Dosage-form design alone may not avoid the patent.
Are biosimilars relevant to Orladeyo?
No. Berotralstat is a small-molecule drug, so competing products would generally use the ANDA or 505(b)(2) pathways rather than the biosimilar pathway under the Public Health Service Act.
References
-
U.S. Food and Drug Administration. (2020). Orladeyo (berotralstat) prescribing information. FDA.
-
United States Patent and Trademark Office. (2022). U.S. Patent No. 11,230,530, Methods of treating angioedema. USPTO.
-
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
-
U.S. Food and Drug Administration. (n.d.). Small business assistance: Frequently asked questions on the Patent Term Restoration and Patent Term Extension Act. FDA.
