Details for Patent: 9,758,783

Which drugs does patent 9,758,783 protect, and when does it expire?

Patent 9,758,783 protects AMONDYS 45 and is included in one NDA.

This patent has fifty-four patent family members in twenty-one countries.

Summary for Patent: 9,758,783

Title:	Antisense molecules and methods for treating pathologies
Abstract:	An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 59.
Inventor(s):	Stephen Donald Wilton, Sue Fletcher, Abbie Adams, Penny Meloni
Assignee:	University of Western Australia
Application Number:	US14/944,886
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,758,783
Patent Claim Types: see list of patent claims	Use; Composition; Delivery;

US Patent 9,758,783: Scope, Claim Analysis and Exon 45-Skipping Patent Landscape

US Patent 9,758,783 covers exon 45-skipping treatment of Duchenne muscular dystrophy using specified morpholino antisense oligonucleotides targeting the H45A region of dystrophin pre-mRNA. Its broadest practical coverage is directed to 17 sequence-length and annealing-site configurations, while later claims narrow protection to the 22-base sequence corresponding to casimersen, the active oligonucleotide in Amondys 45.

The patent is commercially relevant to exon 45-skipping products, but literal infringement analysis depends on the precise chemical structure, sequence orientation, conjugation status, formulation, patient genotype and administration method. The claims do not cover every exon 45-skipping oligonucleotide. They are constrained by the listed H45A target sites, morpholino chemistry and, in several claims, PEG conjugation or a 5-substituted pyrimidine modification.

What does US Patent 9,758,783 protect?

US Patent 9,758,783 protects methods of treating DMD patients whose mutations are amenable to exon 45 skipping. The claimed intervention is administration of a morpholino antisense oligonucleotide that hybridizes to exon 45 of human dystrophin pre-mRNA and induces exon skipping.

The claim set has four principal layers:

Claim group	Claims	Primary subject matter
Broad sequence/site method claims	1-4	17 morpholino oligonucleotide configurations defined by H45A annealing site and length
Explicit sequence claims	5-10	17 corresponding sequences, uniformly modified with a 5-substituted pyrimidine base
Reading-frame restoration claims	11-14	Exon 45 skipping to restore the dystrophin mRNA reading frame and induce dystrophin
Casimersen-specific claims	15-30	The 22-base SEQ ID NO: 63, with morpholino chemistry and, in most claims, PEG conjugation

The patent therefore combines functional limitations, target-site limitations, sequence limitations, chemical-structure limitations and treatment-method limitations.

How many antisense oligonucleotides are covered by the patent?

Claims 1, 5 and 11 each identify 17 distinct oligonucleotide configurations. They are not necessarily 17 different pharmacologically meaningful products because several sequences overlap substantially and differ by extension at the 5' or 3' end.

The listed lengths are:

Configuration	H45A annealing site	Length
1	-09+25	34 bases
2	-03+25	28 bases
3	-06+25	31 bases
4	-12+19	31 bases
5	-03+19	22 bases
6	-09+19	28 bases
7	-12+16	28 bases
8	-14+25	39 bases
9	-08+19	27 bases
10	-07+25	32 bases
11	-12+22	34 bases
12	-09+22	31 bases
13	-09+30	39 bases
14	-06+22	28 bases
15	-06+28	34 bases
16	-03+22	25 bases
17	-03+28	31 bases

Claims 5 and 11 provide sequence-defined versions of these configurations. The sequence language is narrower than the site-and-length language because it requires the listed base sequence and a uniform 5-substituted pyrimidine modification.

What is the key casimersen sequence in US 9,758,783?

The central species is the 22-base oligonucleotide in SEQ ID NO: 63:

CAA UGC CAU CCU GGA GUU CCU G

This sequence corresponds to casimersen, also known as SRP-4045 and marketed in the United States as Amondys 45. Casimersen is a phosphorodiamidate morpholino oligomer, or PMO, designed to induce exon 45 skipping in dystrophin pre-mRNA.

Claims 15-26 repeatedly recite this 22-base species. Claims 27-30 define the same 22-base target by length, complementarity and H45A(-03+19) annealing site rather than by SEQ ID NO. 63 alone.

This creates overlapping but distinct claim positions:

• Claims 15-17 cover treatment with the 22-base sequence, a morpholino, a uniform 5-substituted pyrimidine modification and PEG linkage.
• Claims 18-20 cover reading-frame restoration using the same modified and PEG-linked species.
• Claims 21-26 add a pharmaceutical composition and carrier.
• Claims 27-30 cover a 22-base morpholino complementary to H45A(-03+19), with PEG linkage in the dependent claims.

The sequence-only claims are not entirely equivalent to the H45A site claims. A product may satisfy one definition but not another depending on sequence orientation, nomenclature and chemical modification.

What are the broadest enforceable claim limitations?

The practical scope of independent claim 1 is defined by the following required elements:

1. A method of treating a DMD patient.
2. The patient has a DMD mutation amenable to exon 45 skipping.
3. The administered agent is one of 17 listed antisense oligonucleotide configurations.
4. The oligonucleotide is a morpholino antisense oligonucleotide.
5. It is 100% complementary to the specified exon 45 target region.
6. It specifically hybridizes to the H45A annealing site.
7. The hybridization induces exon 45 skipping.

The claim is not a composition claim covering the oligonucleotide as an article of manufacture. It is a method-of-treatment claim. Liability generally requires performance of the claimed treatment method, although supplying or promoting the relevant product may create separate inducement or contributory-infringement issues under applicable facts.

The phrase "amenable to exon 45 skipping" is a material patient-selection limitation. The patent is directed primarily to mutation classes in which removal of exon 45 restores the dystrophin reading frame or otherwise produces a therapeutically useful dystrophin transcript. Treatment of a DMD patient whose mutation is not amenable to exon 45 skipping would not satisfy this limitation.

How do claims 1, 5, 11 and 27 differ?

Claims 1 and 11: site-defined treatment methods

Claim 1 requires one of the listed lengths and H45A target regions. Claim 11 uses substantially the same oligonucleotide group but adds the biological result of restoring the mRNA reading frame and inducing dystrophin production.

Claim 11 is narrower in one respect because the claimed method expressly requires the reading-frame restoration and dystrophin-production result. The result may also create proof issues in litigation because the patentee may need to establish that the administered product produces the claimed biological effect in the relevant patient population.

Claim 5: sequence-defined treatment methods

Claim 5 identifies the 17 sequences by SEQ ID NO. It also requires a morpholino uniformly modified to comprise a 5-substituted pyrimidine base.

This language may cover PMOs containing uniformly substituted bases, such as 5-methylcytosine substitutions, but chemical-structure analysis is essential. "5-substituted pyrimidine" is a structural limitation, not simply a description of any modified antisense oligonucleotide.

Claims 27 and 29: focused 22-base coverage

Claim 27 defines the 22-base H45A(-03+19) oligonucleotide through target-site complementarity and morpholino structure. Claim 29 adds a pharmaceutical composition.

These claims can be more commercially important than the 17-species Markush claims because they focus on the species associated with casimersen. They also provide alternative claim-construction positions if a dispute arises over the sequence listing or SEQ ID NO. 63.

What formulations are protected by US 9,758,783?

The patent has limited formulation coverage. Claims 9 and 21-26 require a pharmaceutical composition containing the relevant antisense oligonucleotide and a pharmaceutically acceptable carrier.

The composition claims do not recite a detailed buffer, pH, concentration, tonicity agent, container, dosage strength or manufacturing process. They therefore do not independently create a complete formulation barrier around every commercial presentation.

The patent does contain a recurring PEG limitation:

• Claim 3 depends from claim 1 and requires chemical linkage to a polyethylene glycol chain.
• Claim 7 depends from claim 5 and adds the same PEG requirement.
• Claim 13 depends from claim 11 and adds PEG.
• Claims 15-26 expressly require the PEG-linked 22-base species, subject to the alternative salt language in several claims.
• Claim 28 and claim 30 add PEG to the H45A(-03+19) 22-base species and composition.

This distinction is commercially significant. Amondys 45 is an intravenously administered casimersen PMO product. The FDA-approved product description must be compared directly with the claimed PEG-linked structure. A product can contain the casimersen sequence and PMO backbone without necessarily satisfying a claim that requires chemical linkage to PEG.

Does the patent cover casimersen and Amondys 45?

The patent has a strong sequence-level relationship to casimersen because SEQ ID NO: 63 is the 22-base H45A(-03+19) sequence recited repeatedly in claims 15-30. The claims also refer to the same exon 45-skipping mechanism used by casimersen.

The infringement question is not resolved by sequence identity alone. A full analysis must examine:

Issue	Relevance
Sequence	Whether the commercial oligonucleotide is the claimed 22-base sequence
Backbone	Whether it is a phosphorodiamidate morpholino
Base chemistry	Whether pyrimidines are uniformly 5-substituted
Conjugation	Whether PEG is chemically linked, rather than present only as an excipient
Patient population	Whether the treated mutation is amenable to exon 45 skipping
Administration	Whether treatment is performed intravenously where required by a dependent claim
Product form	Whether the commercial product is a composition containing the claimed agent and carrier

The claims most directly relevant to a standard casimersen product are claims 5, 27 and potentially claims 1 and 11, depending on the precise construction of the site, sequence and chemical limitations. The PEG-dependent claims are narrower.

When does US Patent 9,758,783 lose exclusivity?

US Patent 9,758,783 issued on September 12, 2017. Its ordinary patent term is generally calculated from the earliest effective nonprovisional or international filing date in the priority chain, not from the issue date. The projected expiration is in the early 2030s, subject to the patent's complete continuity record, patent-term adjustment and any patent-term extension.

A reliable expiration analysis must distinguish:

Term issue	Effect
Earliest effective filing date	Establishes the basic 20-year term
Patent-term adjustment	Can extend the term for USPTO delays
Patent-term extension	May be available for regulatory review, subject to statutory limits
Terminal disclaimer	Can shorten the enforceable term if applicable
Reexamination or post-grant proceedings	May alter claim validity or scope, but not automatically the expiration date
Continuation patents	May have different expiration treatment depending on the priority chain

The issued patent's commercial life should therefore be analyzed together with any continuation, divisional or related patents, particularly patents directed to casimersen composition, dosing, manufacturing or approved-product labeling.

What is the Orange Book status of US 9,758,783?

A patent's inclusion in the FDA Orange Book is separate from issuance and enforceability. Orange Book listing depends on whether the NDA holder submitted the patent and whether the patent claims the drug substance, drug product or an approved method of use under FDA listing rules.

Amondys 45 was approved by FDA in February 2021 under NDA 214117. FDA describes casimersen as an antisense oligonucleotide indicated for DMD patients with a confirmed mutation amenable to exon 45 skipping (U.S. Food and Drug Administration, 2021).

The relevant regulatory questions are:

• Whether US 9,758,783 is listed against NDA 214117.
• Which claims are identified as covering the approved method of use.
• Whether the listing has been superseded by later Sarepta patents.
• Whether a generic or follow-on applicant would face a Paragraph IV certification.
• Whether later patents listed for Amondys 45 extend beyond the scope of US 9,758,783.

The supplied claim text alone does not establish the patent's current Orange Book listing status, any listing date or whether a later patent has replaced it in the NDA record.

Are Paragraph IV challenges likely for casimersen?

A Paragraph IV challenge could target any listed patent alleged to cover casimersen, its composition, formulation or approved use. The practical entry barrier is higher than for a conventional small-molecule generic because casimersen is a complex PMO product requiring control of sequence, stereochemical and chemical attributes, impurity profile, analytical comparability and clinical pharmacology.

A challenger would likely assess:

1. Invalidity based on anticipation or obviousness of exon 45-skipping PMOs.
2. Written-description and enablement issues across the 17-species group.
3. Indefiniteness of terms such as "amenable to exon 45 skipping," "specifically hybridizes" and "inducing exon 45 skipping."
4. Noninfringement based on absence of PEG linkage or differences in pyrimidine modification.
5. Patent-term and Orange Book listing defects.
6. FDA's requirements for demonstrating equivalence or biosimilarity-like comparability for a PMO.

No conventional biosimilar pathway applies to casimersen because it is not a biologic licensed under the Public Health Service Act. A competing product would generally be evaluated through an abbreviated or full NDA strategy, depending on FDA's determination of the appropriate pathway and the available reference-product data.

Which companies are challenging the exon 45-skipping market?

Sarepta Therapeutics is the principal commercial company associated with casimersen and Amondys 45. The broader DMD exon-skipping market includes:

Product	Active agent	Exon target	Company	Regulatory status
Amondys 45	Casimersen	45	Sarepta Therapeutics	FDA approved
Exondys 51	Eteplirsen	51	Sarepta Therapeutics	FDA approved
Vyondys 53	Golodirsen	53	Sarepta Therapeutics	FDA approved
Viltepso	Viltolarsen	53	NS Pharma	FDA approved
Elevidys	Delandistrogene moxeparvovec	DMD gene replacement	Sarepta Therapeutics	FDA approved with expanded indication
Duvyzat	Givinostat	Non-exon-skipping mechanism	Italfarmaco	FDA approved

No competing FDA-approved exon 45-skipping product is identified in the supplied record. The most direct competitive threat is therefore a future casimersen or exon 45 PMO entrant, rather than substitution by another approved exon 45 oligonucleotide.

How strong is the patent estate for exon 45 skipping?

US 9,758,783 has meaningful claim density around the casimersen sequence, but its strength is narrower than a broad platform patent.

Strengths

• It identifies a clinically relevant exon 45-skipping sequence.
• It includes both target-site and explicit sequence definitions.
• It covers treatment and reading-frame restoration.
• It includes composition claims for selected embodiments.
• It provides repeated claims to the 22-base SEQ ID NO. 63 species.
• It ties the method to the genotype-selected DMD population used for the approved indication.

Vulnerabilities

• The independent claims are method claims rather than broad product claims.
• Many dependent claims require PEG conjugation that may not match the commercial product.
• The 17-species group may face written-description or obviousness scrutiny if the prior art disclosed exon 45 targets and routine PMO optimization.
• Functional terms may generate claim-construction disputes.
• The patent does not, from the supplied claims, establish broad protection for every PMO chemistry, formulation, dose or manufacturing process.
• The claims do not expressly cover non-morpholino antisense chemistries such as 2'-O-methyl phosphorothioate or peptide-conjugated alternatives unless they otherwise satisfy the morpholino limitation.

The strongest commercial position is the combination of the explicit 22-base sequence, the PMO backbone, the exon 45-skipping mechanism and patient-genotype limitation. The weakest positions are likely the PEG-dependent claims if the marketed product lacks a covalent PEG conjugate, and the broader 17-species coverage if challenged on predictability or written description.

What manufacturing and IP barriers affect generic entry?

Casimersen manufacturing presents technical barriers independent of patent scope. A competing PMO supplier would need to reproduce or match:

• Sequence identity and chain-length distribution.
• Base substitution pattern.
• End-group chemistry.
• Residual coupling reagents and truncated sequences.
• Aggregation and stability profile.
• Sterility and particulate controls.
• Pharmacokinetic behavior after intravenous administration.
• Exon-skipping activity in relevant cellular systems.
• Dystrophin-production evidence.

Separate patents may cover synthesis intermediates, coupling methods, purification, sterile drug product, dosing regimens or delivery technologies. These rights can create a layered barrier even if US 9,758,783 expires or is invalidated.

Geographic risk also differs. US claims are enforceable only in the United States. Foreign family members may have different claim scope, prosecution histories, opposition outcomes and expiration dates. A global launch requires separate review of Europe, Japan, China, Australia and other jurisdictions in which exon 45-skipping rights were pursued.

What patent litigation affects US 9,758,783?

The supplied material does not identify a specific infringement action, Paragraph IV notice, settlement agreement or court decision involving US 9,758,783. The patent number and claim text alone cannot establish current litigation status.

For commercial diligence, the relevant litigation questions are whether:

• The patent was asserted against a generic or competing PMO developer.
• A court construed H45A(-03+19), SEQ ID NO. 63 or "uniformly modified."
• The patent was challenged in inter partes review or post-grant review.
• Sarepta entered a license or settlement covering exon 45 PMOs.
• A later patent was asserted against Amondys 45 or a proposed follow-on product.

Key Takeaways

• US 9,758,783 is an exon 45-skipping method patent for DMD.
• Claims 1, 5 and 11 identify 17 morpholino oligonucleotide configurations.
• The commercially central sequence is the 22-base SEQ ID NO. 63, associated with casimersen and Amondys 45.
• Claims 15-30 provide repeated, narrow protection for the 22-base species, including PEG-linked embodiments.
• The patent does not cover every exon 45-skipping oligonucleotide or every antisense chemistry.
• The PEG limitations may materially narrow infringement exposure for a non-PEG commercial product.
• FDA approved Amondys 45 in February 2021 for DMD patients with mutations amenable to exon 45 skipping.
• Generic entry would face both patent barriers and substantial PMO manufacturing and comparability requirements.
• The patent's exact expiration and Orange Book status require review of the complete USPTO continuity, term-adjustment and FDA listing records.
• No litigation or settlement status is established by the supplied claim text.

FAQs

Is casimersen the same as the 22-base sequence in SEQ ID NO. 63?

Yes. The 22-base sequence recited as SEQ ID NO. 63 is the sequence associated with casimersen, the active ingredient in Amondys 45.

Does US 9,758,783 cover exon 45-skipping drugs made with non-morpholino chemistry?

Generally, no. The claims expressly require a morpholino antisense oligonucleotide. A non-morpholino product would need to satisfy another claim or a separate patent family.

Does an intravenously administered product automatically infringe claims 4, 8, 10 or 14?

No. Intravenous administration is an added limitation in those dependent claims. The product must also satisfy the incorporated limitations of the parent claim.

Can a competitor avoid the patent by using the same casimersen sequence without PEG?

Potentially, depending on the claim asserted. Claims requiring PEG linkage would not be satisfied without a covalent PEG conjugate, but claims without that limitation may still present risk.

Is US 9,758,783 a biosimilar patent?

No. Casimersen is an antisense oligonucleotide drug, not a biologic subject to the statutory biosimilar pathway. A follow-on applicant would need to address FDA's applicable NDA and comparability requirements.

References

1. Sarepta Therapeutics, Inc. (2017). U.S. Patent No. 9,758,783: Methods for treating Duchenne muscular dystrophy. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2021). Amondys 45 (casimersen) prescribing information. U.S. Department of Health and Human Services.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

4. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension guidance. U.S. Department of Commerce.

Drugs Protected by US Patent 9,758,783

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sarepta Theraps Inc	AMONDYS 45	casimersen	SOLUTION;INTRAVENOUS	213026-001	Feb 25, 2021		RX	Yes	Yes	9,758,783					TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY (DMD) IN PATIENTS WHO HAVE A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 45 SKIPPING
Sarepta Theraps Inc	AMONDYS 45	casimersen	SOLUTION;INTRAVENOUS	213026-001	Feb 25, 2021		RX	Yes	Yes	9,758,783					TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY (DMD) IN PATIENTS WHO HAVE A MUTATION OF THE DMD GENE THAT IS AMENABLE TO EXON 45 SKIPPING BY RESTORING AN MRNA READING FRAME TO INDUCE DYSTROPHIN PROTEIN PRODUCTION

Foreign Priority and PCT Information for Patent: 9,758,783

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	2009905549	Nov 12, 2009

International Family Members for US Patent 9,758,783

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010317599
Australia	2016202924
Australia	2018202105
Australia	2020260498
Australia	2023203103