# US Patent 10,487,330: HAO1 siRNA Scope, Lumasiran Coverage, Expiration and Competitive Patent Landscape

US Patent No. 10,487,330 protects specific double-stranded RNA interference constructs directed to HAO1, including 21/23-nucleotide duplexes, two-nucleotide 3' overhangs, chemical modifications, phosphorothioate linkages, and GalNAc conjugation. The patent also covers pharmaceutical compositions and methods of reducing HAO1 expression, including subcutaneous treatment of primary hyperoxaluria type 1 (PH1).

The claims closely track the molecular architecture and therapeutic use of lumasiran, marketed by Alnylam Pharmaceuticals as Oxlumo. The strongest commercial claims are claims 1, 6, 7, 12, 13, 18, 19, 20, 21 and 30. The patent is composition-focused but also creates method-of-use exposure for products that use the claimed HAO1 sequence or a qualifying complementary sequence.

What drug does US Patent 10,487,330 protect?

US Patent 10,487,330 protects HAO1-directed RNAi agents. HAO1 encodes glycolate oxidase, an enzyme involved in hepatic oxalate production. Reducing HAO1 expression lowers glycolate oxidase activity and can reduce oxalate accumulation in patients with PH1.

The patent is directly relevant to lumasiran, an N-acetylgalactosamine-conjugated small interfering RNA, or siRNA, that targets HAO1 mRNA in hepatocytes.

Patent identification

Item	Detail
Patent	US 10,487,330
Likely title	Compositions and methods for inhibiting HAO1 gene expression
Technology	HAO1-targeting RNA interference
Modality	Chemically modified, GalNAc-conjugated siRNA
Principal commercial product	Lumasiran, marketed as Oxlumo
Patent holder	Alnylam Pharmaceuticals, Inc., or an affiliated Alnylam entity
Grant date	November 26, 2019
Therapeutic indication	Primary hyperoxaluria type 1
FDA approval of Oxlumo	November 23, 2020
Regulatory pathway	New drug application
Key target	Hepatic HAO1 mRNA

The claims supplied for analysis identify SEQ ID NO: 1823 as the relevant HAO1 target sequence. A product does not necessarily need to reproduce every disclosed sequence or modification to create risk. Claims 9 and 24 are drafted more functionally and may reach alternative oligonucleotide sequences that are sufficiently complementary to the specified HAO1 target region and reduce HAO1 expression.

What are the independent claims in US 10,487,330?

The principal independent claims are claims 1, 9, 10, 11, 12, 22, 23, 24 and 30. They fall into four categories: defined duplex structures, broader HAO1-complementary oligonucleotides, pharmaceutical compositions, and therapeutic methods.

Claim 1: defined 21/23-nucleotide duplex

Claim 1 requires:

A first strand of 21 nucleotides.
A second strand of 23 nucleotides.
A duplex structure.
At least 15 nucleotides of the second strand that are 100% complementary to SEQ ID NO: 1823.
A two-nucleotide 3' overhang on the second strand.

This is a structural composition claim. It does not require GalNAc, phosphorothioates, 2'-O-methyl groups, 2'-fluoro groups, a pharmaceutical carrier, or administration to a patient.

The claim is therefore potentially broad within the defined length and sequence relationship. A competing siRNA could avoid literal infringement by changing the strand length, eliminating the precise two-nucleotide overhang, using a different target segment, or reducing complementarity below the claimed threshold. Whether such changes remain vulnerable under the doctrine of equivalents would depend on the claim construction, prosecution history and technical effect of the modification.

Claim 9: broader HAO1-complementary oligonucleotide

Claim 9 covers a 21- to 23-nucleotide oligonucleotide that:

Is sufficiently complementary to a target region of HAO1 mRNA.
Corresponds to a region having the sequence of SEQ ID NO: 1823.
Has at least 15 nucleotides of qualifying complementarity.
Contains one or more modified nucleotides.
Reduces HAO1 mRNA expression when introduced into a cell.

Claim 9 is broader than claim 1 in structural terms. It does not expressly require a 21/23 duplex, a two-nucleotide overhang, a guide strand, or a GalNAc ligand. It can therefore present greater design-around risk for alternative HAO1 siRNA formats.

Claim 30: commercial lumasiran-type construct

Claim 30 is the most commercially significant claim. It requires:

A 21-nucleotide first strand.
A 23-nucleotide second strand.
A duplex structure.
A second strand 100% complementary to SEQ ID NO: 1823.
A two-nucleotide 3' overhang.
A GalNAc moiety conjugated to the 3' terminal nucleotide of the first strand.
A reduction in HAO1 mRNA levels after administration.

This claim combines the siRNA architecture with the hepatocyte-targeting ligand and therapeutic result. A product that uses the same sequence architecture and 3' terminal GalNAc configuration would face a high literal infringement risk if the claim remains enforceable and is not narrowed through litigation or prosecution history.

How do the dependent claims narrow the patent scope?

The dependent claims add chemical, biological and clinical limitations.

Claim group	Added limitation	Commercial significance
Claim 2	At least two phosphorothioate internucleotide linkages in the second strand	Covers nuclease-stability and pharmacokinetic modifications
Claims 3-5	Modified nucleotides, including 2'-O-methyl and 2'-fluoro	Captures standard siRNA chemistry
Claims 6-7	GalNAc conjugation, including attachment to the 3' terminal nucleotide	Covers hepatocyte delivery architecture
Claim 8	Guide strand complexes with RISC and promotes target RNA cleavage	Defines the intended RNAi mechanism
Claims 10 and 22	Pharmaceutical composition with pharmaceutically acceptable carrier	Supports product-level formulation claims
Claims 11 and 23	In-vitro HAO1 gene or mRNA reduction	Covers cell-based use
Claims 12 and 24	Administration to a subject	Covers in-vivo therapeutic use
Claims 13 and 25	PH1 patient population	Links the method to the approved disease
Claims 14-17	Glycolate oxidase, oxalate, kidney deposits and urinary glycolate/creatinine outcomes	Adds disease-relevant pharmacodynamic and clinical endpoints
Claims 18 and 26	Dose of 0.3 to 10 mg/kg	Covers a broad dosing range
Claims 19 and 27	HAO1 mRNA reduction detectable 29 days after administration	Supports durable RNAi activity
Claims 20 and 28	At least 80% HAO1 mRNA reduction	Adds a quantitative efficacy threshold
Claims 21 and 29	Subcutaneous administration	Relevant to commercial Oxlumo dosing
Claim 30	Defined duplex, full sequence complementarity, GalNAc attachment and HAO1 reduction	Strong product-specific combination claim

The dependent claims do not all require every feature of claim 1. A product avoiding a particular dependent limitation may still infringe claim 1 or claim 9.

What formulations are protected by US 10,487,330?

The patent claims pharmaceutical compositions containing the claimed HAO1 oligonucleotides and a pharmaceutically acceptable carrier. The supplied claims do not identify a particular excipient, concentration, buffer, pH, vial, prefilled syringe, or dosage form.

This distinction matters. Patent 10,487,330 is not principally a formulation patent in the conventional small-molecule sense. It protects the active RNA construct in a pharmaceutical composition. A generic or follow-on manufacturer may need to assess separate patents covering:

Specific Oxlumo concentrations.
Buffer systems.
Stabilizers and excipients.
Injectable presentations.
Manufacturing and purification processes.
GalNAc linker chemistry.
Conjugation intermediates.
Solid-state or storage characteristics, if applicable.

A product using a different carrier may still fall within claims 10 or 22 because those claims require only a pharmaceutically acceptable carrier, subject to construction of the underlying nucleic-acid claim.

Does the patent cover lumasiran?

Yes, the supplied claims are directed to the core structural and therapeutic characteristics associated with lumasiran.

Lumasiran is a GalNAc-conjugated siRNA designed to reduce hepatic HAO1 expression. Its clinical effect is to suppress glycolate oxidase and reduce oxalate production. The product is administered subcutaneously for PH1, consistent with claims 12, 13, 14, 15, 16, 18, 19, 20 and 21. The product’s 21/23 duplex and GalNAc conjugation are also consistent with claims 1 and 30.

Product-to-claim mapping

Lumasiran characteristic	Relevant claims
HAO1-targeting siRNA	1, 8, 9, 11-12, 23-24, 30
21/23-nucleotide duplex	1 and 30
Two-nucleotide 3' overhang	1 and 30
Chemically modified nucleotides	3-5
Phosphorothioate linkages	2
GalNAc conjugation	6, 7 and 30
HAO1 mRNA reduction	9, 11, 12, 19, 20, 24, 27, 28 and 30
PH1 treatment	13, 25 and 30
Subcutaneous administration	21 and 29
Dose range of 0.3-10 mg/kg	18 and 26
Reduction in glycolate oxidase or oxalate burden	14-17

The claim analysis should distinguish the marketed product from the full patent disclosure. A claim can cover an HAO1 RNAi agent without covering every aspect of the approved product label.

When does US Patent 10,487,330 lose exclusivity?

The patent’s expected expiration is determined principally from its earliest effective nonprovisional or international filing date, subject to patent-term adjustment, terminal disclaimers and any applicable patent-term extension.

Public patent records should be used to confirm the final expiration date. Based on the patent’s priority structure, the ordinary patent term is expected to extend into approximately 2036. The exact Orange Book expiration date may differ from a simple 20-year calculation if the patent received patent-term adjustment or is subject to a terminal disclaimer.

Relevant exclusivity periods for Oxlumo

Exclusivity type	Expected timing
US patent term	Approximately 2036, subject to USPTO term calculation
FDA new chemical entity exclusivity	Five years from November 23, 2020 approval
FDA orphan-drug exclusivity	Seven years from November 23, 2020 approval, subject to statutory exceptions
Regulatory exclusivity end	NCE exclusivity approximately November 23, 2025; orphan exclusivity approximately November 23, 2027

FDA regulatory exclusivity and patent protection are separate. Expiration of NCE or orphan exclusivity does not remove a later-expiring patent. Conversely, patent expiration does not necessarily end all FDA exclusivity.

What is the Orange Book status of US 10,487,330?

Oxlumo is an FDA-approved prescription drug, and its patent protection must be evaluated through the FDA Orange Book and the underlying patent records. The relevant listing analysis should identify whether US 10,487,330 is listed for the approved product, the listed patent expiration date, and any use codes associated with PH1 treatment.

The supplied claims include both product claims and method-of-use claims. A method-of-use listing may affect the scope of an ANDA applicant’s certification and labeling obligations. A generic applicant could seek a paragraph IV certification against a listed patent, a section viii statement for a carved-out use where legally available, or defer approval until the patent and regulatory exclusivity barriers expire.

For Oxlumo, the commercial risk is likely concentrated in patents covering:

The specific lumasiran sequence.
The 21/23 duplex structure.
GalNAc attachment and ligand chemistry.
Formulation and injectable presentation.
HAO1 reduction for PH1.
Manufacturing and conjugation processes.

Patent 10,487,330 is therefore one component of the Orange Book estate rather than necessarily the entire estate.

Are there Paragraph IV challenges or patent litigation involving Oxlumo?

The supplied information does not establish a particular Paragraph IV notice letter, ANDA filing, district-court complaint, settlement agreement or final judgment involving US 10,487,330.

A complete litigation assessment must separate:

Patent infringement complaints.
Declaratory-judgment actions.
Paragraph IV notice activity.
Inter partes review petitions.
Post-grant review.
License or settlement agreements.
FDA approval dates for any abbreviated application.

The absence of a litigation event in the supplied record should not be treated as evidence that no challenge exists. For business planning, the relevant trigger is an ANDA applicant’s paragraph IV notice, which can create a 45-day window for the patent owner to file an infringement action and potentially obtain a 30-month FDA approval stay under the Hatch-Waxman framework.

How strong is the patent estate for lumasiran?

Patent 10,487,330 has meaningful strength because it combines sequence identity, duplex geometry, chemical modification, delivery ligand and therapeutic use. Its strength varies by claim type.

Claim type	Relative strength	Main vulnerability
Claim 1 structural duplex	High	Design-around through strand length, overhang or target region
Claim 2 phosphorothioate limitation	Moderate	Alternative backbone chemistry
Claims 3-5 modified nucleotides	Moderate to high	Prior-art and obviousness challenges involving known siRNA chemistry
Claims 6-7 GalNAc conjugation	High commercially	Alternative ligand attachment site or delivery system
Claim 9 broad complementary oligonucleotide	Moderate	Written-description, enablement and obviousness issues
Claims 12-21 therapeutic methods	Moderate to high	Induced-infringement and treatment-step proof issues
Claims 24-29 broader treatment methods	Moderate	Functional limitations and patient-use evidence
Claim 30 product-specific combination	High if sequence and conjugation match	Narrower literal scope and possible prosecution-history limits

The strongest enforcement position generally arises where a competing product copies the exact target sequence, duplex lengths and GalNAc conjugation. Broader functional claims may be valuable against alternative HAO1 siRNA designs but are more exposed to validity challenges.

Which companies are challenging or competing with Oxlumo?

Oxlumo has no approved direct HAO1 siRNA competitor identified in the supplied record. The competitive landscape includes other approaches to PH1 and other forms of primary hyperoxaluria.

RNAi and genetic competitors

Novo Nordisk’s acquisition of Dicerna brought RNAi capabilities directed to metabolic and liver targets. Dicerna’s nedosiran program targets LDHA rather than HAO1 and represents a mechanistically distinct RNAi approach.
Ionis Pharmaceuticals and other antisense developers have pursued liver-directed oligonucleotide platforms, but an antisense product does not necessarily implicate the claims of patent 10,487,330.
Gene-editing and gene-replacement approaches could avoid HAO1 siRNA claims but may encounter separate delivery, manufacturing and patent barriers.

Non-RNAi treatments

PH1 treatment also involves pyridoxine in responsive patients, hydration, dietary management, urinary alkalinization and, in advanced disease, dialysis or transplantation. These alternatives do not generally create direct infringement risk under the supplied composition claims.

What generic launch risks exist for lumasiran?

A generic or follow-on lumasiran would face four principal barriers.

Sequence and architecture risk

A product using the same HAO1-targeting sequence, 21/23 duplex and two-nucleotide overhang could fall within claims 1 and 30.

Chemical modification risk

Use of 2'-O-methyl, 2'-fluoro and phosphorothioate modifications could implicate claims 2-5. These are common RNAi modifications, which increases commercial relevance but may also increase prior-art exposure.

Delivery risk

A 3' terminal GalNAc conjugate creates substantial risk under claims 6, 7 and 30. A different ligand, linker or attachment position might avoid literal infringement, but it could affect liver uptake, potency, dosing and regulatory comparability.

Method-of-use risk

A product labeled for PH1, HAO1 suppression, glycolate oxidase reduction or reduction of calcium oxalate accumulation could implicate claims 12-21 and 24-29. A labeling carve-out may be difficult if the only commercially viable use is treatment of PH1.

How does the patent compare with alternative HAO1 and PH1 strategies?

Strategy	Likely relation to US 10,487,330	Commercial assessment
Same lumasiran sequence and GalNAc format	High infringement risk	Direct generic threat only after challenge or expiration
Different HAO1 siRNA sequence	Potential claim 9 or 24 exposure	Requires sequence-by-sequence analysis
HAO1 antisense oligonucleotide	Usually outside structural siRNA claims	Separate patent and regulatory analysis required
HAO1 small-molecule inhibitor	Outside nucleic-acid claims	Separate mechanism and patent estate
LDHA RNAi such as nedosiran	Generally outside HAO1 claims	Competing mechanism, not a direct substitute at the patent level
Gene editing of HAO1	Outside supplied claims	Different safety, delivery and manufacturing risks
Pyridoxine or transplantation	Outside supplied claims	Clinical alternatives rather than molecular substitutes

What manufacturing and geographic IP barriers remain?

The patent claims can create manufacturing risk even where a competitor does not sell the exact finished product. Relevant activities include:

Synthesis of the two RNA strands.
Incorporation of 2'-O-methyl and 2'-fluoro nucleotides.
Installation of phosphorothioate linkages.
Duplex annealing.
GalNAc-linker synthesis.
Conjugation to the 3' terminal nucleotide.
Purification and impurity control.
Manufacture of injectable pharmaceutical compositions.

US patent rights apply to US manufacture, sale, offers for sale, importation and certain activities involving patented products. Separate family members may create coverage in Europe, Japan, China and other commercial territories. A US non-infringement position does not establish freedom to operate in foreign markets.

What licensing deals affect the lumasiran patent landscape?

Alnylam is the principal commercial rights holder for Oxlumo. The supplied claims do not identify a third-party license, field-of-use restriction or royalty-bearing arrangement affecting US 10,487,330.

Platform licenses may still matter. GalNAc delivery, RNAi chemistry and conjugation technologies can be covered by separate agreements even where Alnylam owns the product-specific patent. A freedom-to-operate review should distinguish ownership of the HAO1 sequence patent from rights to platform technology.

Key Takeaways

US 10,487,330 is a core HAO1 RNAi patent relevant to lumasiran and Oxlumo.
Claim 1 covers a 21/23-nucleotide duplex with a two-nucleotide 3' overhang and qualifying complementarity to SEQ ID NO: 1823.
Claims 6, 7 and 30 add GalNAc conjugation, with claim 30 closely matching the commercial product architecture.
Claims 9 and 24 create broader risk for alternative modified oligonucleotides that target the specified HAO1 region and reduce expression.
Claims 12-21 and 24-29 cover HAO1 suppression and PH1 treatment, including subcutaneous administration, dose, durability and efficacy limitations.
Oxlumo received FDA approval on November 23, 2020. Its five-year NCE exclusivity and seven-year orphan exclusivity are separate from patent protection.
The patent term is expected to extend into approximately 2036, subject to the USPTO’s final term calculation.
A generic lumasiran would face sequence, duplex, GalNAc, formulation, manufacturing and method-of-use barriers.
Alternative HAO1 sequences, antisense products, LDHA RNAi products and non-RNAi therapies may reduce direct infringement exposure but require separate patent analysis.

FAQs About US Patent 10,487,330

Does US 10,487,330 claim lumasiran by name?

No. The claims define nucleic-acid structures, HAO1 complementarity, GalNAc conjugation and therapeutic use rather than using the product’s brand name.

Can a different HAO1 siRNA avoid US 10,487,330?

Possibly, but the answer depends on sequence complementarity, strand length, chemical modifications, duplex structure and the scope of claims 9 and 24. A different sequence is not automatically outside the patent.

Does the patent cover an HAO1 small-molecule inhibitor?

No. The supplied claims are directed to nucleic acids, compositions containing them and methods using them.

Is a biosimilar pathway available for lumasiran?

Lumasiran is a chemically synthesized oligonucleotide drug rather than a conventional protein biologic. A follow-on applicant would generally assess the applicable small-molecule or alternative FDA pathway rather than assume that the biosimilar pathway applies.

What is the most important claim for a lumasiran competitor?

Claim 30 is the most product-specific claim because it combines the defined duplex, HAO1 sequence, two-nucleotide overhang, 3' terminal GalNAc conjugation and HAO1 mRNA reduction.

References

United States Patent and Trademark Office. (2019). United States Patent No. 10,487,330: Compositions and methods for inhibiting HAO1 gene expression. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2020). OXLUMO (lumasiran) injection, prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (2024). Regulatory exclusivity and patent information for approved drug products. FDA.
Alnylam Pharmaceuticals, Inc. (2020). Oxlumo: Lumasiran sodium prescribing information and product materials. Alnylam Pharmaceuticals.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Alnylam Pharms Inc	OXLUMO	lumasiran sodium	SOLUTION;SUBCUTANEOUS	214103-001	Nov 23, 2020		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y	Y		TREATMENT OF PRIMARY HYPEROXALURIA TYPE 1 (PH1)	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3581654	⤷ Start Trial	LUC00218	Luxembourg	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	PA2021008	Lithuania	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	301132	Netherlands	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	2021C/534	Belgium	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	CA 2021 00038	Denmark	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	122021000053	Germany	⤷ Start Trial
European Patent Office	3581654	⤷ Start Trial	C20210019 00342	Estonia	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,487,330

Which drugs does patent 10,487,330 protect, and when does it expire?

Summary for Patent: 10,487,330