Details for Patent: 8,980,853

Which drugs does patent 8,980,853 protect, and when does it expire?

Patent 8,980,853 protects SPINRAZA and is included in one NDA.

This patent has sixty-nine patent family members in twenty-four countries.

Summary for Patent: 8,980,853

Title:	Compositions and methods for modulation of SMN2 splicing in a subject
Abstract:	Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.
Inventor(s):	C. Frank Bennett, Gene Hung, Frank Rigo, Adrian R. Krainer, Yimin Hua, Marco A. Passini, Lamya Shihabuddin, Seng H. Cheng, Katherine W. Klinger
Assignee:	Cold Spring Harbor Laboratory , Biogen MA Inc
Application Number:	US13/380,021
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,980,853
Patent Claim Types: see list of patent claims	Use;

US Patent 8,980,853: Claim Scope, Nusinersen Exclusivity, and the Spinal Muscular Atrophy Patent Landscape

US Patent 8,980,853 protects a highly specific method of treating infantile-onset type I spinal muscular atrophy with nusinersen, the antisense oligonucleotide marketed as Spinraza. The patent does not broadly cover every antisense treatment for SMA. Its independent claim requires a defined patient population, intrathecal bolus administration, the exact 18-nucleotide SMN2-targeting sequence, complete phosphorothioate internucleoside linkages, 2'-MOE sugar modifications, and clinical amelioration of an SMA symptom.

The patent was issued to Ionis Pharmaceuticals and is associated with the Biogen commercial product Spinraza. Its practical importance is greatest for generic developers seeking to market the same active oligonucleotide for infantile-onset type I SMA by intrathecal injection.

What does US Patent 8,980,853 protect?

US 8,980,853 protects a treatment method using the nusinersen oligonucleotide sequence:

5'-TCACTTTCATAATGCTGG-3'

The claim requires all of the following elements:

Claim element	Required limitation
Disease	Infantile-onset type I SMA
Administration route	Intrathecal
Administration mode	Bolus injection
Active agent	Antisense compound consisting of the specified 18 linked nucleosides
Sequence	SEQ ID NO: 1
Internucleoside chemistry	Every linkage is phosphorothioate
Sugar chemistry	Every nucleoside is 2'-MOE
Therapeutic result	Amelioration of at least one SMA symptom

This combination corresponds to nusinersen, an 18-mer antisense oligonucleotide that binds an intronic splicing silencer region in SMN2 pre-mRNA. The treatment promotes inclusion of exon 7 and increases production of full-length SMN protein.

The patent is therefore a method-of-use patent with substantial structural limitations. It is not, based on the quoted claims, a general composition patent covering all antisense oligonucleotides that modulate SMN2 splicing.

How broad is the independent claim of US 8,980,853?

The independent claim is narrow in sequence and chemistry but commercially important because it tracks the approved Spinraza product.

A potential infringement analysis would require proof that the accused product or treatment satisfies each limitation. The claim has six principal narrowing features.

Exact sequence requirement

The oligonucleotide must have the nucleobase sequence identified as SEQ ID NO: 1. A sequence with one or more substitutions, deletions, additions, or a different targeting region would fall outside the literal scope of the claim.

The sequence requirement materially limits the claim against:

• Alternative SMN2 antisense sequences
• Shorter or longer oligonucleotides
• Mismatched or chemically modified analogues with altered nucleobase sequences
• RNA interference products
• Small molecules that increase SMN2 exon 7 inclusion

A generic nusinersen product, however, would be expected to use the same sequence because the reference product itself is defined by this active ingredient.

Complete phosphorothioate linkage requirement

Every internucleoside linkage must be phosphorothioate. A molecule containing a mixed backbone, such as phosphorothioate linkages combined with phosphodiester or other internucleoside linkages, may avoid literal infringement of this limitation.

The all-phosphorothioate requirement also gives a potential design-around route. That route may not be commercially attractive because phosphorothioate chemistry contributes to nuclease resistance, tissue distribution, and pharmacokinetic behavior.

Complete 2'-MOE nucleoside requirement

Each nucleoside must be a 2'-MOE nucleoside. The claim does not cover an oligonucleotide containing a different sugar modification, such as 2'-O-methyl, locked nucleic acid, constrained ethyl, or a mixed sugar pattern, unless another claim or doctrine of equivalents applies.

This limitation separates the claimed compound from many newer antisense platforms. It also reinforces the connection between the patent and nusinersen, which uses a fully 2'-MOE-modified phosphorothioate backbone.

Infantile-onset type I SMA requirement

The patient must have infantile-onset type I SMA. This is narrower than SMA generally and excludes, on its face, later-onset type II or type III SMA patients.

The limitation creates a potentially material defense for an accused treatment directed solely to:

• Type II SMA
• Type III SMA
• Adult-onset SMA
• Presymptomatic patients who do not yet have the claimed disease presentation

Clinical documentation, labeling, treatment protocols, and prescribing records would be relevant to determining whether the patient population falls within the claim.

Intrathecal bolus injection requirement

The drug must be administered by bolus injection into the intrathecal space. The claim does not expressly cover all possible delivery methods.

Potentially distinct routes include:

• Intravenous administration
• Subcutaneous administration
• Intramuscular administration
• Continuous intrathecal infusion
• Intracerebroventricular delivery
• Local spinal delivery through an implant or pump

The word "bolus" is commercially significant. The FDA-approved Spinraza regimen uses intermittent intrathecal injection rather than continuous infusion. A competing product using a materially different delivery format could present a noninfringement position, subject to claim construction and equivalents analysis.

Therapeutic-result requirement

The method requires that administration ameliorate at least one symptom of SMA. This is a functional limitation. In practice, infringement may be assessed through the treatment protocol and expected clinical outcome rather than requiring proof of improvement in every treated patient.

The claim does not specify a particular symptom, motor milestone, survival endpoint, or SMN protein threshold. That breadth makes the result limitation less restrictive than the sequence and administration limitations.

What do dependent claims 2, 3, and 4 add?

What dose is covered by claim 2?

Claim 2 requires a dose of 0.5 to 10 mg per kilogram of body weight.

This range is broad relative to the approved fixed-dose regimen for Spinraza. It can cover different patient weights and dosing practices, provided the treatment otherwise satisfies claim 1.

The claim does not expressly define:

• Number of doses
• Dosing interval
• Loading-dose schedule
• Maintenance schedule
• Total lifetime dose
• Whether the dose is calculated using actual or nominal body weight

Because claim 2 depends on claim 1, it retains the type I SMA, intrathecal bolus, exact sequence, complete phosphorothioate, and complete 2'-MOE limitations.

What biological result is covered by claim 3?

Claim 3 requires increased inclusion of exon 7 of SMN2 mRNA in a motoneuron.

This claim ties the treatment to the recognized mechanism of nusinersen. Binding near the intronic splicing silencer downstream of exon 7 redirects SMN2 pre-mRNA splicing toward exon 7 inclusion.

The claim is technically narrower than claim 1 because it requires the specified molecular effect. It could become relevant where an accused product uses the same oligonucleotide but disputes whether the treatment increases exon 7 inclusion in motoneurons.

What dose is covered by claim 4?

Claim 4 requires administration of a 5 mg to 20 mg dose of antisense compound.

The claim covers a fixed-dose range rather than a weight-based range. It overlaps with claim 2 for patients whose dose falls within both ranges.

The approved Spinraza dose is generally 12 mg of nusinersen administered intrathecally. The 12 mg dose falls within claim 4 and, depending on patient weight, may also fall within claim 2.

What is the FDA status of nusinersen and Spinraza?

The FDA approved Spinraza on December 23, 2016, for the treatment of SMA in pediatric and adult patients. The product is administered intrathecally through a loading regimen followed by maintenance dosing approximately every four months (U.S. Food and Drug Administration, 2016).

The approved regimen includes:

Treatment phase	Dose
Loading dose 1	12 mg
Loading dose 2	12 mg, 14 days later
Loading dose 3	12 mg, 14 days after dose 2
Loading dose 4	12 mg, 30 days after dose 3
Maintenance	12 mg every four months

This regimen fits claim 4's 5 mg to 20 mg range. It also fits the independent claim's intrathecal bolus requirement and the claimed nusinersen structure.

Spinraza received orphan-drug designation and pediatric regulatory protections. FDA approval was supported by clinical evidence showing improved motor outcomes and survival-related benefits in infants with SMA compared with sham procedures and natural-history expectations (U.S. Food and Drug Administration, 2016).

When does US Patent 8,980,853 lose exclusivity?

US 8,980,853 was issued on March 17, 2015. Public patent records identify a December 27, 2024 patent-term expiration date for the patent family, subject to any applicable patent-term adjustment or pediatric extension recorded by the USPTO or FDA.

The key exclusivity dates are:

Protection	Date or period
Patent issue date	March 17, 2015
FDA approval	December 23, 2016
Five-year new chemical entity exclusivity	Through December 23, 2021
Orphan-drug exclusivity	Generally through December 23, 2023
Patent expiration reported for US 8,980,853	December 27, 2024
Potential pediatric extension	Six additional months if awarded and applicable

Regulatory exclusivity and patent exclusivity are separate. The end of FDA orphan or new chemical entity exclusivity does not eliminate patent protection. Conversely, patent expiration does not automatically guarantee generic approval if other listed patents or regulatory barriers remain.

What is the Orange Book status of US 8,980,853?

US 8,980,853 has been associated with FDA Orange Book patent listings for Spinraza. Its relevance is as a method-of-use patent covering treatment of SMA with nusinersen by intrathecal administration.

An Orange Book listing can require a generic applicant to address the patent through:

• Paragraph I certification, if the patent information is not available
• Paragraph II certification, if the patent has expired
• Paragraph III certification, accepting approval only after patent expiration
• Paragraph IV certification, asserting that the patent is invalid, unenforceable, or not infringed
• A section viii statement, where the applicant seeks approval without the patented method

For a product whose proposed labeling includes the patented infantile-onset type I SMA use, a Paragraph IV challenge would create litigation risk. A generic applicant may instead attempt a skinny-label strategy that omits the patented indication, subject to induced-infringement and labeling analysis.

The commercial value of the patent listing depends on whether the listing remains the only enforceable barrier. Spinraza has been associated with a broader patent estate, including related patents directed to antisense compounds, SMN2 splicing, dosing, and treatment methods.

Which patents form the broader Spinraza patent landscape?

The relevant landscape includes several categories rather than a single patent.

Patent category	Typical protected subject matter	Commercial relevance
Composition patents	Nusinersen sequence and chemical structure	Can block manufacture and sale of the active ingredient
Splicing patents	Antisense modulation of SMN2 exon 7 inclusion	Can cover mechanism and sequence variants
Treatment patents	Administration to SMA patients	Relevant to marketed indications
Dosing patents	Loading and maintenance regimens	Can delay or complicate generic labeling
Formulation patents	Injectable oligonucleotide compositions	Relevant to product manufacture and stability
Manufacturing patents	Oligonucleotide synthesis, purification, and formulation	May create process-level barriers
Delivery patents	Intrathecal or CNS delivery systems	Relevant to alternative administration technologies

Publicly associated members of the Ionis/Biogen SMA patent family include US 8,361,977 and US 8,980,853, along with later continuation or divisional patents. The exact scope, expiration, terminal disclaimers, patent-term adjustments, and Orange Book status must be reviewed patent by patent. A later-issued continuation may remain enforceable after US 8,980,853 expires if it claims a distinct subject matter and has a later expiration date.

How strong is the patent estate for nusinersen?

The estate is strongest against a conventional generic that reproduces the reference product and seeks approval for the same SMA population and route of administration.

Strengths

The estate has several practical strengths:

1. The claimed sequence is the marketed active ingredient.
2. The chemistry limitations correspond closely to the reference product.
3. The FDA label uses intrathecal bolus administration.
4. The approved 12 mg dose falls directly within claim 4.
5. The treatment mechanism is well matched to claim 3.
6. The product has a defined commercial indication and established clinical use.

Potential weaknesses

The quoted claims also contain litigation vulnerabilities:

• The type I patient limitation may not cover every proposed use.
• The bolus limitation may distinguish continuous-delivery systems.
• The all-2'-MOE and all-phosphorothioate requirements permit chemistry-based design-arounds.
• The "ameliorates at least one symptom" limitation may raise enablement, written-description, or definiteness arguments depending on the asserted claim construction.
• Earlier publications concerning SMN2 splicing and antisense oligonucleotides could support invalidity attacks based on anticipation or obviousness.
• A generic may omit the claimed indication from its labeling and rely on a section viii statement, although that strategy carries induced-infringement risk.

The patent is commercially strong because it maps onto the reference product. Its legal strength depends on the asserted claim, prior art, prosecution history, Orange Book listing, and the actual generic label.

What generic entry risks exist for Spinraza?

A conventional generic faces four main risks.

Paragraph IV litigation

A Paragraph IV applicant could assert that US 8,980,853 is invalid or not infringed. The most likely theories would involve:

• Anticipation or obviousness based on earlier SMN2 antisense disclosures
• Failure to demonstrate patentable distinction over known 2'-MOE phosphorothioate oligonucleotides
• Noninfringement based on patient population or dosing
• Noninfringement based on a modified formulation or manufacturing process

The patent holder would likely focus on the close correspondence between the proposed product, the FDA label, and the claimed nusinersen structure.

Skinny-label entry

A generic may seek approval for unpatented uses while carving out the patented method. The risk is highest where the remaining label, promotional activity, dosing instructions, or clinical practice would still encourage the patented treatment.

Alternative chemistry

A product using a different sugar modification or mixed backbone could avoid the literal composition limitations. It would face substantial development risk because changes to oligonucleotide chemistry may alter potency, distribution, safety, clearance, and immunogenicity.

Alternative delivery

A non-bolus intrathecal system could avoid the express administration limitation. Continuous pumps and implantable systems introduce their own regulatory, manufacturing, device, and safety barriers.

Is there biosimilar risk for nusinersen?

Nusinersen is a chemically synthesized antisense oligonucleotide, not a conventional protein biologic. A competing product would generally proceed through the drug generic pathway rather than the FDA's section 351(k) biosimilar pathway.

The primary competitive threat is therefore an ANDA-based generic or a follow-on oligonucleotide product. The absence of a biosimilar pathway does not eliminate competition. It shifts the central issues to:

• Pharmaceutical equivalence
• Active-ingredient characterization
• Oligonucleotide impurity profiles
• Bioequivalence and pharmacokinetics
• Intrathecal administration
• Clinical bridging
• Patent certifications
• Labeling carve-outs

How does Spinraza compare with competing SMA products?

Product	Active ingredient	Modality	Administration	Patent risk relative to US 8,980,853
Spinraza	Nusinersen	Antisense oligonucleotide	Intrathecal injection	Directly implicated
Evrysdi	Risdiplam	Small-molecule SMN2 splicing modifier	Oral	Outside the claimed oligonucleotide structure and route
Zolgensma	Onasemnogene abeparvovec	AAV gene-replacement therapy	Intravenous or intrathecal depending on product/use	Outside the claimed chemistry, but subject to separate gene-therapy patents

Spinraza competes clinically with oral risdiplam and gene-replacement therapy. Those products do not directly practice the quoted method because they do not administer the claimed 18-mer 2'-MOE phosphorothioate oligonucleotide by intrathecal bolus injection.

Their competitive impact is commercial rather than direct infringement. They can reduce the addressable population for a nusinersen generic by shifting physicians and patients to oral or gene-therapy alternatives.

What litigation and settlement issues affect the patent?

Patent litigation risk is concentrated around ANDA filings, Orange Book certifications, and later continuation patents. A settlement can establish a future generic launch date without invalidating the patent. The relevant commercial analysis should distinguish:

• Patent expiration
• Regulatory exclusivity expiration
• Litigation settlement date
• Authorized-generic arrangements
• License rights
• Geographic launch restrictions
• Pediatric and orphan exclusivity

No license or settlement should be assumed solely from the existence of the patent family. A definitive assessment requires the specific ANDA litigation docket, settlement filing, and FDA patent record for the relevant period.

What geographic coverage does the patent provide?

US 8,980,853 provides rights only in the United States. Corresponding international and national-phase patents may exist in Europe, Japan, Canada, Australia, and other jurisdictions, but each must be assessed separately.

Geographic differences may involve:

• Different claim scope
• Different patent-term dates
• Patent-term extensions
• Supplementary protection certificates
• Opposition or revocation proceedings
• Local enablement standards
• Different treatment of method-of-use claims
• Different regulatory exclusivity periods

A US patent does not block manufacture, sale, or use outside the United States unless separate foreign rights apply.

Key Takeaways

• US 8,980,853 is a narrow but commercially important method-of-treatment patent tied closely to nusinersen and Spinraza.
• The claim requires infantile-onset type I SMA, intrathecal bolus injection, the exact SEQ ID NO: 1 sequence, all-phosphorothioate linkages, all-2'-MOE nucleosides, and symptom amelioration.
• Claim 4 directly covers the approved 12 mg Spinraza dose.
• Claim 3 covers increased SMN2 exon 7 inclusion in motoneurons.
• The patent is a method-of-use right, not a broad monopoly over all SMA therapies.
• A generic using the same oligonucleotide and seeking the same label faces direct Paragraph IV and induced-infringement risk.
• Alternative chemistry, alternative delivery, and skinny-label strategies may reduce literal infringement exposure.
• Nusinersen is an antisense drug, so competitive entry is generally an ANDA issue rather than a biosimilar issue.
• The broader Ionis/Biogen estate, including continuation patents, must be reviewed before concluding that US 8,980,853 is the only remaining barrier.
• Public records identify a December 27, 2024 expiration date for US 8,980,853, subject to any applicable term adjustment or pediatric extension.

FAQs About US Patent 8,980,853 and Spinraza

Does US 8,980,853 cover all uses of nusinersen?

No. The quoted claims are limited to specific treatment conditions, including infantile-onset type I SMA and intrathecal bolus administration.

Can a generic avoid US 8,980,853 by changing the dose?

Possibly, but only if the changed dose falls outside all asserted claims. Changing the dose alone may not avoid claim 1 because claim 1 does not specify a numerical dose.

Does the patent cover risdiplam or onasemnogene abeparvovec?

No. Those products use different active modalities and do not contain the claimed 18-nucleotide antisense oligonucleotide.

Can a continuous intrathecal infusion avoid the patent?

It may avoid the express "bolus injection" limitation, but the outcome would depend on claim construction, the facts of use, and any other asserted patent.

What is the main patent risk for a nusinersen generic after patent expiration?

The main risk is that a related continuation, formulation, dosing, manufacturing, or method-of-use patent may remain enforceable after US 8,980,853 expires.

References

1. Biogen Inc. (2016). Spinraza (nusinersen) injection, prescribing information. U.S. Food and Drug Administration.

2. Ionis Pharmaceuticals, Inc. (2015). Antisense modulation of SMN2 splicing, U.S. Patent No. 8,980,853. United States Patent and Trademark Office.

3. Ionis Pharmaceuticals, Inc. (2013). Antisense modulation of SMN2 splicing, U.S. Patent No. 8,361,977. United States Patent and Trademark Office.

4. U.S. Food and Drug Administration. (2016). FDA approves first drug for spinal muscular atrophy. https://www.fda.gov

5. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugsatfda.

Drugs Protected by US Patent 8,980,853

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Biogen	SPINRAZA	nusinersen sodium	SOLUTION;INTRATHECAL	209531-001	Dec 23, 2016		RX	Yes	Yes	8,980,853					TREATMENT OF INFANTILE-ONSET SPINAL MUSCULAR ATROPHY
Biogen	SPINRAZA	nusinersen sodium	SOLUTION;INTRATHECAL	209531-002	Mar 27, 2026		RX	Yes	Yes	8,980,853					TREATMENT OF INFANTILE-ONSET SPINAL MUSCULAR ATROPHY
Biogen	SPINRAZA	nusinersen sodium	SOLUTION;INTRATHECAL	209531-003	Mar 27, 2026		RX	Yes	Yes	8,980,853					TREATMENT OF INFANTILE-ONSET SPINAL MUSCULAR ATROPHY

Foreign Priority and PCT Information for Patent: 8,980,853

PCT Information
PCT Filed	June 17, 2010	PCT Application Number:	PCT/US2010/039077
PCT Publication Date:	December 23, 2010	PCT Publication Number:	WO2010/148249

International Family Members for US Patent 8,980,853

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3449926		2020008	Norway
Australia	2010262862
Australia	2016200344
Canada	2765396
China	102665731